DT 290 Advanstar 201012

User Manual: DT 290

Open the PDF directly: View PDF .
Page Count: 56

Counterfeit drug war

continues 21

Voice of the Pharmacist

Study: Post-MI beta blocker

doses are too low 29

December 2010

When does compounding

become manufacturing? 42

VOL. 154 NO. 12

DrugTopics.com

Community and hospital

pharmacists prepare

to steer their course PAGE 22

2.0

CREDIT:

An update on Clostridium difﬁ cile infection

PAGE 30

Earn CE credit for this activity at DrugTopics.com

What’s most important in

outpatient pharmacies?

Keeping patients safe.

The challenges and demands of an outpatient pharmacy can

take away from patient care. QS/1®’s NRx® supports outpatient

pharmacies with easy-to-use processing and multiple inventory

management, including 340B. Our end-to-end pharmacy system

and services work together so you can work with safety and

FRQ¿GHQFH7RSURYLGHJUHDWVHUYLFH7RLPSURYHOLYHVEvery day.

1.800.231.7776

www.qs1.com

Visit us at

ASHP Booth

677

With your support, Amneal has become

the fastest growing generic manufacturer in the U.S.*

Superior quality products all made in the USA

Fully FDA cGMP-compliant manufacturing facilities

Widely recognized Customer Response team

Market-competitive pricing

*IMS Health, National Prescription Audit, June 2010 - Prescriptions of unbranded generics

DRUG TOPICS

December 2010 WWW.DRUGTOPICS.COM

EDITORIAL ADVISORY BOARD

Philip P. Burgess, RPh, MBA

Chairman

Community Pharmacy Foundation

Illinois Board of Pharmacy

Chicago, Ill.

James A. Jorgenson

RPh, MS, FASHP

Chief Pharmacy Ofﬁ cer, VP

Clarian Health

Indianapolis, Ind.

Gene Memoli Jr., RPh, FASCP

Director

Customer Development, Omnicare

Cheshire, Conn.

David J. Fong, PharmD

Former community chain store

senior pharmacy executive

Danville, Calif.

Frederick S. Mayer, RPh, MPH

President

Pharmacists Planning Service Inc.

San Rafael, Calif.

Jack Rosenberg, PharmD, PhD

Professor and Director

International Drug Information Center

Arnold & Marie Schwartz College

of Pharmacy and Health Sciences

Long Island University, Brooklyn, N.Y.

Christina Medina, PharmD

Manager

Professional and College Relations

CVS Caremark

Hollywood, Fla.

Mary E. Inguanti

RPh, MPH, FASCP

Senior Vice President, Operation

Charter Oak Health Center

Hartford, Conn.

Stephen W. Schondelmeyer

PharmD, PhD

Director, PRIME Institute

College of Pharmacy

University of Minnesota

Minneapolis, Minn.

Perry Cohen, PharmD, FAMCP

The Pharmacy Group LLC

Glastonbury, Conn.

Dennis Burton, BS Pharm, MBA

Bristol, Conn.

Marvin R. Moore, PharmD

Pharmacy manager and co-owner

The Medicine Shoppe/

Pharmacy Solutions Inc.

Two Rivers, Wisc.

EDITORIAL

DIRECTOR OF EDITORIAL Dan Schwartz

EDITOR-IN-CHIEF Julia Talsma

(440) 891-2792 jtalsma@advanstar.com

MANAGING EDITOR Julianne Stein

(440) 826-2834 jstein@advanstar.com

ASSOCIATE EDITOR Christina Phillis

(440) 891-2766 cphillis@advanstar.com

EDITORIAL ASSOCIATE Alicia Hoisington

CONTRIBUTING EDITORS Christine Blank,

Fred Gebhart, Jim Plagakis, RPh,

Gretchen L. Schwenker, PhD

SALES AND MARKETING

PUBLISHER James Granato

(732) 346-3071 jgranato@advanstar.com

ACCOUNT MANAGER Lisa Noble

(732) 346-3060 lnoble@advanstar.com

SALES SUPPORT ADMINISTRATOR Samyu Ganesh

(732) 346-3077 sganesh@advanstar.com

LIST MANAGER Tamara Phillips

(440) 891-2773 / tphillips@advanstar.com

PERMISSIONS AND LICENSING Maureen Cannon

(440) 891-2742 or (800) 225-4569 ext. 2742

Fax: (440) 891-2650 / mcannon@advanstar.com

DISPLAY AND CLASSIFIED ADS Heather Schlosser

(440) 891-2779 hschlosser@advanstar.com

CLASSIFIED RECRUITMENT Joanna Shippoli

800-225-4569 x 2615 jshippoli@advanstar.com

REPRINT SERVICES

(800) 290-5460, ext. 100 / AdvanstarReprints@theYGSgroup.com

(717) 505-9701, ext. 100 (international inquiries)

PRODUCTION

SENIOR PRODUCTION MANAGER Terri Johnstone

(218) 740-6310

CIRCULATION

SUBSCRIPTION CUSTOMER SERVICE / ADDRESS CHANGES

(877) 922-2022 / magazines@superﬁ ll.com

PO Box 6079, Duluth, MN 55806-6079, USA

24950 COUNTRY CLUB BLVD., SUITE 200

NORTH OLMSTED, OHIO 44070

MAIN NUMBER: (440) 243-8100

MAIN FAX NUMBER: (440) 891-2735

CUSTOMER SERVICE: (877) 922-2022

CLASSIFIED AND RECRUITMENT SALES:

(800) 225-4569

E-MAIL ADDRESS: DRUGTOPICS@ADVANSTAR.COM

WEBSITE: HTTP://WWW.DRUGTOPICS.COM

Joseph Loggia

CHIEF EXECUTIVE OFFICER

Tom Ehardt

EXECUTIVE VICE PRESIDENT, CHIEF ADMINISTRATIVE OFFICER

Steve Sturm

EXECUTIVE VICE PRESIDENT, CHIEF MARKETING OFFICER

Ted Alpert

EXECUTIVE VICE PRESIDENT, FINANCE, CFO

Georgiann De Cenzo

EXECUTIVE VICE PRESIDENT

Eric Lisman

EXECUTIVE VICE PRESIDENT

J. Vaughn

VICE PRESIDENT, INFORMATION TECHNOLOGY

Francis Heid

VICE PRESIDENT, MEDIA OPERATIONS

Nancy Nugent

VICE PRESIDENT, HUMAN RESOURCES

Ward D. Hewins

VICE PRESIDENT, GENERAL COUNSEL

Danny Phillips

EXECUTIVE VICE PRESIDENT

Chris DeMoulin

EXECUTIVE VICE PRESIDENT

Editorial Mission: Drug Topics, a monthly

news magazine guided by an editorial

advisory board of pharmacy experts,

reports on all phases of community, retail,

and health-system issues and trends. We

offer a forum for the bench pharmacist to

share practical ideas for better pharmacy

management and patient care.

Reference: 1. Pelletier AL, Butler AM, Gillies RA, et al. Metformin Stinks, Literally. Ann Intern Med. 2010;152:267-268.

•A blackberry-scented formulation designed to mask the

“fishy smell” associated with some metformin tablets1

•Therapeutically equivalent to Glucophage®*

•Available in 500 mg, 850 mg and 1000 mg tablets

Indication:Metformin hydrochloride tablets are indicated

as an adjunct to diet and exercise to improve glycemic

control in adults and children with type 2 diabetes mellitus.

Adverse reactions:The most common adverse reactions,

reported in > 5% of metformin-treated patients, are:

diarrhea, nausea/vomiting, flatulence, asthenia, indigestion,

abdominal discomfort, and headache.

Contraindications and precautions:

Metformin hydrochloride tablets are contraindicated in

patients with:

1. Renal disease or renal dysfunction (e.g., as suggested

by serum creatinine levels * 1.5 mg/dL [males],

* 1.4 mg/dL [females] or abnormal creatinine clearance)

which may also result from conditions such as

cardiovascular collapse (shock), acute myocardial

infarction, and septicemia.

2. Known hypersensitivity to metformin hydrochloride.

3. Acute or chronic metabolic acidosis, including diabetic

ketoacidosis, with or without coma. Diabetic ketoacidosis

should be treated with insulin.

Metformin should be temporarily discontinued in patients

undergoing radiologic studies involving intravascular

administration of iodinated contrast materials, because

use of such products may result in acute alteration of

renal function.

Before initiation of metformin therapy and at least annually

thereafter, renal function should be assessed and verified

as normal. In patients in whom development of renal

dysfunction is anticipated, renal function should be

assessed more frequently and metformin discontinued

if evidence of renal impairment is present.

WARNINGS: LACTIC ACIDOSIS

Lactic acidosis is a rare but serious, metabolic

complication that can occur because of metformin

accumulation. Reported cases have occurred primarily

in diabetic patients with significant renal insufficiency,

including both intrinsic renal disease and renal

hypoperfusion, often in the setting of multiple

concomitant medical/surgical problems and multiple

concomitant medications. The risk of lactic acidosis

may, therefore, be significantly decreased by regular

monitoring of renal function and by use of the minimum

effective dose. Other conditions that increase the risk

of lactic acidosis include: sepsis, dehydration, excess

alcohol intake, hepatic insufficiency and acute

congestive heart failure.

When lactic acidosis occurs, it is fatal in approximately

50% of cases. The reported incidence of lactic acidosis

in patients receiving metformin is very low

(approximately 0.03 cases/1000 patient-years, with

approximately 0.015 fatal cases/1000 patient years).

The onset is often subtle, accompanied only by

nonspecific symptoms such as malaise, myalgias,

respiratory distress, increasing somnolence and

nonspecific abdominal distress. Laboratory

abnormalities include low pH, increased anion gap,

and elevated blood lactate. If acidosis is suspected,

metformin should be discontinued and the patient

hospitalized immediately.

Metformin treatment should not be initiated in

patients ≥ 80 years of age unless measurement of

creatinine clearance demonstrates that renal function

is not reduced, as these patients are more susceptible

to developing lactic acidosis.

Please see adjacent Brief Summary of Prescribing

Information, including BOXED WARNING with complete

details about lactic acidosis.

Mylan Metformin is

Berry Nice.

A metformin tablet that doesn’t smell like fish.

METFORMIN HYDROCHLORIDE TABLETS, USP

500 mg, 850 mg and 1000 mg

Rx Only

BRIEF SUMMARY: Please see package insert for full prescribing information.

INDICATIONS AND USAGE: Metformin hydrochloride tablets are indicated as an adjunct to diet

and exercise to improve glycemic control in adults and children with type 2 diabetes mellitus.

CONTRAINDICATIONS: Metformin hydrochloride tablets are contraindi cated in patients with:

1. Renal disease or renal dysfunction (e.g., as suggested by serum creatinine levels

≥ 1.5 mg/dL [males], ≥ 1.4 mg/dL [females] or ab normal creatinine clearance)

which may also result from conditions such as cardiovascular collapse (shock),

acute myocardial infarction, and septicemia (see WARNINGS and PRECAUTIONS).

2. Known hypersensitivity to metformin hydrochloride.

3. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without

coma. Diabetic ketoacidosis should be treated with insulin.

Metformin should be temporarily discontinued in patients undergoing radiologic studies

involving intravascular administration of iodinated contrast materials, because use of

such products may result in acute alteration of renal function. (See also PRECAUTIONS.)

WARNINGS:

Lactic Acidosis: Lactic acidosis is a rare, but serious, metabolic complication that

can occur due to metformin accumulation during treatment with metformin; when it

occurs, it is fatal in approximately 50% of cases. Lactic acidosis may also occur in

association with a number of pathophysiologic conditions, including diabetes mellitus,

and whenever there is signiﬁ cant tissue hypoperfusion and hypoxemia. Lactic acidosis

is characterized by elevated blood lactate levels (> 5 mmol/L), decreased blood pH,

electrolyte disturbances with an increased anion gap, and an increased lactate/

pyruvate ratio. When metformin is implicated as the cause of lactic acidosis, metformin

plasma levels > 5 mcg/mL are generally found.

The reported incidence of lactic acidosis in patients receiving metformin

hydrochloride is very low (approximately 0.03 cases/1000 patient-years, with

approximately 0.015 fatal cases/1000 patient-years). In more than 20,000 patient-

years exposure to metformin in clinical trials, there were no reports of lactic acidosis.

Reported cases have occurred primarily in diabetic patients with signiﬁ cant renal

insufﬁ ciency, including both intrinsic renal disease and renal hypoperfusion, often in the

setting of multiple concomitant medical/surgical problems and multiple concomitant

medications. Patients with congestive heart failure requiring pharmacologic

management, in particular those with unstable or acute congestive heart failure who

are at risk of hypoperfusion and hypoxemia are at increased risk of lactic acidosis.

The risk of lactic acidosis increases with the degree of renal dysfunction and the

patient’s age. The risk of lactic acidosis may, therefore, be signiﬁ cantly decreased by

regular monitoring of renal function in patients taking metformin and by use of the

minimum effective dose of metformin. In particular, treatment of the elderly should be

accompanied by careful monitoring of renal function. Metformin treatment should not

be initiated in patients ≥ 80 years of age unless measurement of creatinine clearance

demonstrates that renal function is not reduced, as these patients are more susceptible

to developing lactic acidosis. In addition, metformin should be promptly withheld in the

presence of any condition associated with hypoxemia, dehydration or sepsis. Because

impaired hepatic function may signiﬁ cantly limit the ability to clear lactate, metformin

should generally be avoided in patients with clinical or laboratory evidence of hepatic

disease. Patients should be cautioned against excessive alcohol intake, either acute or

chronic, when taking metformin, since alcohol potentiates the effects of metformin on

lactate metabolism. In addition, metformin should be temporarily discontinued prior

to any intravascular radiocontrast study and for any surgical procedure (see also

PRECAUTIONS).

The onset of lactic acidosis often is subtle, and accompanied only by nonspeciﬁ c

symptoms such as malaise, myalgias, respira tory distress, increasing somnolence and

nonspeciﬁ c abdominal distress. There may be associated hypothermia, hypotension

and resistant bradyarrhythmias with more marked acidosis. The patient and the

patient’s physician must be aware of the possible importance of such symptoms and

the patient should be instructed to notify the physician immediately if they occur (see

also PRECAUTIONS). Metformin should be withdrawn until the situation is clariﬁ ed.

Serum electrolytes, ketones, blood glucose and, if indicated, blood pH, lactate levels

and even blood metformin levels may be useful. Once a patient is stabilized on any dose

level of metformin, gastrointestinal symptoms, which are common during initiation of

therapy, are unlikely to be drug-related. Later occurrence of gastrointestinal symptoms

could be due to lactic acidosis or other serious disease.

Levels of fasting venous plasma lactate above the upper limit of normal but less

than 5 mmol/L in patients taking metformin do not necessarily indicate impending

lactic acidosis and may be explainable by other mechanisms, such as poorly controlled

diabetes or obesity, vigorous physical activity or technical problems in sample handling.

(See also PRECAUTIONS.)

Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis

lacking evidence of ketoacidosis (ketonuria and ketonemia).

Lactic acidosis is a medical emergency that must be treated in a hospital setting. In

a patient with lactic acidosis who is taking metformin, the drug should be discontinued

immediately and general supportive measures promptly instituted. Because metformin

hydrochloride is dialyzable (with a clearance of up to 170 mL/min under good

hemodynamic conditions), prompt hemodialysis is recommended to correct the acidosis

and remove the accumulated metformin. Such management often results in prompt

reversal of symptoms and recovery. (See also CONTRAINDICATIONS and PRECAUTIONS.)

PRECAUTIONS: General: Macrovascular Outcomes: There have been no clinical studies

establishing conclusive evidence of macrovascular risk reduction with metformin

hydrochloride tablets or any other anti-diabetic drug.

Monitoring of Renal Function: Metformin is known to be substantially excreted by the

kidney, and the risk of metformin accumulation and lactic acidosis increases with the

degree of impairment of renal function. Thus, patients with serum creatinine levels

above the upper limit of normal for their age should not receive metformin. In patients

with advanced age, metformin should be carefully titrated to establish the minimum dose

for adequate glycemic effect, because aging is associated with reduced renal function. In

elderly patients, particularly those ≥ 80 years of age, renal function should be monitored

regularly and, generally, metformin should not be titrated to the maximum dose (see

WARNINGS and DOSAGE AND ADMINISTRATION in full prescribing information).

Before initiation of metformin therapy and at least annually thereafter, renal function

should be assessed and veriﬁ ed as normal. In patients in whom development of renal

dysfunction is anticipated, renal function should be assessed more frequently and

metformin discontinued if evidence of renal impairment is present.

Use of Concomitant Medications That May Affect Renal Function or Metformin Disposition:

Concomitant medication(s) that may affect renal function or result in signiﬁ cant hemodynamic

change or may interfere with the disposition of metformin, such as cationic drugs that are

eliminated by renal tubular secretion (see PRECAUTIONS: Drug Interactions), should be used

with caution.

Radiologic Studies Involving the Use of Intravascular Iodinated Contrast Materials

(for example, intravenous urogram, intravenous cholangiography, angiography, and

computed tomography (CT) scans with intravascular contrast materials): Intravascular

contrast studies with iodinated materials can lead to acute alteration of renal function

and have been associated with lactic acidosis in patients receiving metformin (see

CONTRAINDICATIONS). Therefore, in patients in whom any such study is planned, metformin

should be temporarily discontinued at the time of or prior to the procedure, and withheld for

48 hours subsequent to the procedure and reinstituted only after renal function has been

reevaluated and found to be normal.

Hypoxic States: Cardiovascular collapse (shock) from whatever cause, acute congestive

heart failure, acute myocardial infarction and other conditions characterized by hypoxemia

have been associated with lactic acidosis and may also cause prerenal azotemia. When such

events occur in patients on metformin therapy, the drug should be promptly discontinued.

Surgical Procedures: Metformin therapy should be temporarily suspended for any surgical

procedure (except minor procedures not associated with restricted intake of food and ﬂ uids)

and should not be restarted until the patient’s oral intake has resumed and renal function

has been evaluated as normal.

Alcohol Intake: Alcohol is known to potentiate the effect of metformin on lactate

metabolism. Patients, therefore, should be warned against excessive alcohol intake, acute

or chronic, while receiving metformin.

Impaired Hepatic Function: Since impaired hepatic function has been associated with

some cases of lactic acidosis, metformin should generally be avoided in patients with

clinical or laboratory evidence of hepatic disease.

Vitamin B12 Levels: In controlled clinical trials of metformin of 29 weeks duration, a

decrease to subnormal levels of previously normal serum vitamin B12 levels, without clinical

manifestations, was observed in approximately 7% of patients. Such decrease, possibly due

to interference with B12 absorption from the B12-intrinsic factor complex, is, however, very

rarely associated with anemia and appears to be rapidly reversible with discontinuation of

metformin or vitamin B12 supplementation. Measurement of hematologic parameters on an

annual basis is advised in patients on metformin and any apparent abnormalities should

be appropriately investigated and managed (see PRECAUTIONS: Laboratory Tests).

Certain individuals (those with inadequate vitamin B12 or calcium intake or absorption)

appear to be predisposed to developing subnormal vitamin B12 levels. In these patients,

routine serum vitamin B12 measurements at 2- to 3-year intervals may be useful.

Change in Clinical Status of Patients with Previously Controlled Type 2 Diabetes: A

patient with type 2 diabetes previously well controlled on metformin who develops laboratory

abnormalities or clinical illness (especially vague and poorly deﬁ ned illness) should be

evaluated promptly for evidence of ketoacidosis or lactic acidosis. Evaluation should

include serum electrolytes and ketones, blood glucose and, if indicated, blood pH, lactate,

pyruvate and metformin levels. If acidosis of either form occurs, metformin must be stopped

immediately and other appropriate corrective measures initiated (see also WARNINGS).

Hypoglycemia: Hypoglycemia does not occur in patients receiving metformin alone

under usual circumstances of use, but could occur when caloric intake is deﬁ cient, when

strenuous exercise is not compensated by caloric supplementation, or during concomitant

use with other glucose-lowering agents (such as sulfonylureas and insulin) or ethanol.

Elderly, debilitated or malnourished patients, and those with adrenal or pituitary insufﬁ ciency

or alcohol intoxication are particularly susceptible to hypoglycemic effects. Hypoglycemia may be

difﬁ cult to recognize in the elderly, and in people who are taking beta-adrenergic blocking drugs.

Loss of Control of Blood Glucose: When a patient stabilized on any diabetic regimen is

exposed to stress such as fever, trauma, infection, or surgery, a temporary loss of glycemic

control may occur. At such times, it may be necessary to withhold metformin and temporarily

administer insulin. Metformin may be reinstituted after the acute episode is resolved.

The effectiveness of oral antidiabetic drugs in lowering blood glucose to a targeted level

decreases in many patients over a period of time. This phenomenon, which may be due to

progression of the underlying disease or to diminished responsiveness to the drug, is known

as secondary failure, to distinguish it from primary failure in which the drug is ineffective

during initial therapy. Should secondary failure occur with either metformin or sulfonylurea

monotherapy, combined therapy with metformin and sulfonylurea may result in a response.

Should secondary failure occur with combined metformin/sulfonylurea therapy, it may be

necessary to consider therapeutic alternatives including initiation of insulin therapy.

Information for Patients: Patients should be informed of the potential risks and beneﬁ ts of

metformin and of alternative modes of therapy. They should also be informed about the

importance of adherence to dietary instructions, of a regular exercise program, and of regular

testing of blood glucose, glycosylated hemoglobin, renal function and hematologic parameters.

Page 1 of 2

The risks of lactic acidosis, its symptoms, and conditions that predispose to its

development, as noted in the WARNINGS and PRECAUTIONS sections, should be explained to

patients. Patients should be advised to discontinue metformin immediately and to promptly

notify their health practitioner if unexplained hyperventilation, myalgia, malaise, unusual

somnolence or other nonspeciﬁ c symptoms occur. Once a patient is stabilized on any dose

level of metformin, gastrointestinal symptoms, which are common during initiation of

metformin therapy, are unlikely to be drug related. Later occurrence of gastrointestinal

symptoms could be due to lactic acidosis or other serious disease.

Patients should be counselled against excessive alcohol intake, either acute or chronic,

while receiving metformin.

Metformin hydrochloride tablets alone do not usually cause hypoglycemia, although it

may occur when metformin is used in conjunction with oral sulfonylureas and insulin. When

initiating combination therapy, the risks of hypoglycemia, its symptoms and treatment,

and conditions that predispose to its development should be explained to patients and

responsible family members. (See Patient Information in full prescribing information.)

Laboratory Tests: Response to all diabetic therapies should be monitored by periodic

measurements of fasting blood glucose and glycosylated hemoglobin levels, with a goal

of decreasing these levels toward the normal range. During initial dose titration, fasting

glucose can be used to determine the therapeutic response. Thereafter, both glucose and

glycosylated hemo globin should be monitored. Measurements of glycosylated hemoglobin

may be especially useful for evaluating long-term control (see also DOSAGE AND

ADMINISTRATION in full prescribing information).

Initial and periodic monitoring of hematologic parameters (e.g., hemoglobin/hematocrit

and red blood cell indices) and renal function (serum creatinine) should be performed, at

least on an annual basis. While megaloblastic anemia has rarely been seen with metformin

therapy, if this is suspected, vitamin B12 deﬁ ciency should be excluded.

Drug Interactions (Clinical Evaluation of Drug Interactions Conducted with Metformin):

Glyburide: In a single-dose interaction study in type 2 diabetes patients, coadministration of

metformin and glyburide did not result in any changes in either metformin pharmacokinetics

or pharmacodynamics. Decreases in glyburide AUC and Cmax were observed, but were highly

variable. The single-dose nature of this study and the lack of correlation between glyburide

blood levels and pharmacodynamic effects, makes the clinical signiﬁ cance of this interaction

uncertain (see DOSAGE AND ADMINISTRATION: Concomitant Metformin Hydrochloride Tablet

and Oral Sulfonylurea Therapy in Adult Patients in full prescribing information).

Furosemide: A single-dose, metformin-furosemide drug interaction study in healthy

subjects demonstrated that pharmacokinetic parameters of both compounds were affected

by coadministration. Furosemide increased the metformin plasma and blood Cmax by 22%

and blood AUC by 15%, without any signiﬁ cant change in metformin renal clearance. When

administered with metformin, the Cmax and AUC of furosemide were 31% and 12% smaller,

respectively, than when administered alone, and the terminal half-life was decreased by 32%,

without any signiﬁ cant change in furosemide renal clearance. No information is available

about the interaction of metformin and furosemide when coadministered chronically.

Nifedipine: A single-dose, metformin-nifedipine drug interaction study in normal healthy

volunteers demonstrated that coadministration of nifedipine increased plasma metformin

Cmax and AUC by 20% and 9%, respectively, and increased the amount excreted in the

urine. Tmax and half-life were unaffected. Nifedipine appears to enhance the absorption of

metformin. Metformin had minimal effects on nifedipine.

Cationic Drugs: Cationic drugs (e.g., amiloride, digoxin, morphine, procainamide, quinidine,

quinine, ranitidine, triamterene, trimethoprim, or vancomycin) that are eliminated by

renal tubular secretion theoretically have the potential for interaction with metformin by

competing for common renal tubular transport systems. Such interaction between metformin

and oral cimetidine has been observed in normal healthy volunteers in both single- and

multiple-dose, metformin-cimetidine drug interaction studies, with a 60% increase in peak

metformin plasma and whole blood concentrations and a 40% increase in plasma and

whole blood metformin AUC. There was no change in elimination half-life in the single-dose

study. Metformin had no effect on cimetidine pharmacokinetics. Although such interactions

remain theoretical (except for cimetidine), careful patient monitoring and dose adjustment

of metformin and/or the interfering drug is recommended in patients who are taking cationic

medications that are excreted via the proximal renal tubular secretory system.

Other: Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic

control. These drugs include the thiazides and other diuretics, corticosteroids,

phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid,

sympathomimetics, calcium channel blocking drugs, and isoniazid. When such drugs are

administered to a patient receiving metformin, the patient should be closely observed for

loss of blood glucose control. When such drugs are withdrawn from a patient receiving

metformin, the patient should be observed closely for hypoglycemia.

In healthy volunteers, the pharmacokinetics of metformin and propranolol and metformin

and ibuprofen were not affected when coadministered in single-dose interaction studies.

Metformin is negligibly bound to plasma proteins and is, therefore, less likely to interact

with highly protein-bound drugs such as salicylates, sulfonamides, chloramphenicol, and

probenecid, as compared to the sulfonylureas, which are extensively bound to serum proteins.

Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term carcinogenicity studies

have been performed in rats (dosing duration of 104 weeks) and mice (dosing duration of

91 weeks) at doses up to and including 900 mg/kg/day and 1500 mg/kg/day, respectively.

These doses are both approximately four times the maximum recommended human daily

dose of 2000 mg based on body surface area comparisons. No evidence of carcinogenicity

with metformin was found in either male or female mice. Similarly, there was no tumorigenic

potential observed with metformin in male rats. There was however, an increased incidence

of benign stromal uterine polyps in female rats treated with 900 mg/kg/day.

There was no evidence of a mutagenic potential of metformin in the following

in vitro tests: Ames test (S. typhimurium), gene mutation test (mouse lymphoma cells),

or chromosomal aberrations test (human lymphocytes). Results in the in vivo mouse

micronucleus test were also negative.

Fertility of male or female rats was unaffected by metformin when administered

at doses as high as 600 mg/kg/day, which is approximately three times the maximum

recommended human daily dose based on body surface area comparisons.

Pregnancy: Teratogenic Effects. Pregnancy Category B: Recent information strongly

suggests that abnormal blood glucose levels during pregnancy are associated with a higher

incidence of congenital abnormalities. Most experts recommend that insulin be used during

pregnancy to maintain blood glucose levels as close to normal as possible. Because animal

reproduction studies are not always predictive of human response, metformin should not

be used during pregnancy unless clearly needed.

There are no adequate and well controlled studies in pregnant women with metformin.

Metformin was not teratogenic in rats and rabbits at doses up to 600 mg/kg/day. This

represents an exposure of about two and six times the maximum recommended human daily

dose of 2000 mg based on body surface area comparisons for rats and rabbits, respectively.

Determination of fetal concentrations demonstrated a partial placental barrier to metformin.

Nursing Mothers: Studies in lactating rats show that metformin is excreted into milk and

reaches levels comparable to those in plasma. Similar studies have not been conducted in

nursing mothers. Because the potential for hypoglycemia in nursing infants may exist, a

decision should be made whether to discontinue nursing or to discontinue the drug, taking

into account the importance of the drug to the mother. If metformin is discontinued, and if

diet alone is inadequate for controlling blood glucose, insulin therapy should be considered.

Pediatric Use: The safety and effectiveness of metformin for the treatment of type 2

diabetes have been established in pediatric patients ages 10 to 16 years (studies have not

been conducted in pediatric patients below the age of 10 years). Use of metformin in this

age group is supported by evidence from adequate and well controlled studies of metformin

in adults with additional data from a controlled clinical study in pediatric patients ages 10

to 16 years with type 2 diabetes, which demonstrated a similar response in glycemic control

to that seen in adults. (See CLINICAL PHARMACOLOGY: Pediatric Clinical Studies in full

prescribing information.) In this study, adverse effects were similar to those described in

adults. (See ADVERSE REACTIONS: Pediatric Patients.) A maximum daily dose of 2000 mg

is recommended. (See DOSAGE AND ADMINISTRATION: Recommended Dosing Schedule:

Pediatrics in full prescribing information.)

Geriatric Use: Controlled clinical studies of metformin did not include sufﬁ cient numbers

of elderly patients to determine whether they respond differently from younger patients,

although other reported clinical experience has not identiﬁ ed differences in responses

between the elderly and younger patients. Metformin is known to be substantially

excreted by the kidney and because the risk of serious adverse reactions to the drug is

greater in patients with impaired renal function, metformin should only be used in

patients with normal renal function (see CONTRAINDICATIONS, WARNINGS, and CLINICAL

PHARMACOLOGY: Pharmacokinetics in full prescribing information). Because aging is

associated with reduced renal function, metformin should be used with caution as age

increases. Care should be taken in dose selection and should be based on careful and

regular monitoring of renal function. Generally, elderly patients should not be titrated to

the maximum dose of metformin (see also WARNINGS and DOSAGE AND ADMINISTRATION

in full prescribing information).

ADVERSE REACTIONS: In a U.S. double-blind clinical study of metformin in patients with

type 2 diabetes, a total of 141 patients received metformin therapy (up to 2550 mg per

day) and 145 patients received placebo. Adverse reactions reported in greater than 5% of

the metformin patients, and that were more common in metformin- than placebo-treated

patients, are listed in Table 1.

Table 1. Most Common Adverse Reactions (> 5%) in a

Placebo-Controlled Clinical Study of Metformin Monotherapy*

Adverse Reaction

Metformin Monotherapy

(n = 141)

Placebo

(n = 145)

% of Patients

Diarrhea 53.2 11.7

Nausea/Vomiting 25.5 8.3

Flatulence 12.1 5.5

Asthenia 9.2 5.5

Indigestion 7.1 4.1

Abdominal Discomfort 6.4 4.8

Headache 5.7 4.8

* Reactions that were more common in metformin- than placebo-treated patients.

Diarrhea led to discontinuation of study medication in 6% of patients treated with

metformin. Additionally, the following adverse reactions were reported in ≥ 1 to ≤ 5%

of metformin patients and were more commonly reported with metformin than placebo:

abnormal stools, hypoglycemia, myalgia, lightheaded, dyspnea, nail disorder, rash, sweating

increased, taste disorder, chest discomfort, chills, ﬂ u syndrome, ﬂ ushing, palpitation.

Pediatric Patients: In clinical trials with metformin in pediatric patients with type 2

diabetes, the proﬁ le of adverse reactions was similar to that observed in adults.

OVERDOSAGE: Overdose of metformin hydrochloride has occurred, including ingestion

of amounts greater than 50 grams. Hypoglycemia was reported in approximately 10%

of cases, but no causal association with metformin hydrochloride has been established.

Lactic acidosis has been reported in approximately 32% of metformin overdose cases

(see WARNINGS). Metformin is dialyzable with a clearance of up to 170 mL/min under

good hemodynamic conditions. Therefore, hemodialysis may be useful for removal of

accumulated drug from patients in whom metformin overdosage is suspected.

Manufactured in India by:

Matrix Laboratories Limited

Secunderabad — 500 003, India

Code No.: MH/DRUGS/25/NKD/89

Manufactured for:

MYLAN®

Mylan Pharmaceuticals Inc.

Morgantown, WV 26505 U.S.A.

REVISED JANUARY 2010

BS:MX:METB:R1ppt

Page 2 of 2

CONTENTS

DIGITAL EDITION

WWW.DRUGTOPICS.COM

DRUG TOPICS

December 2010

Vol. 154 No. 12

December 2010

COUNTER POINTS

9 GUEST EDITORIAL

The MTM challenge:

Grab those crayons

and get on with it

10 LETTERS

Sometimes a

placebo can be a

real lifesaver

13 JP AT LARGE

The 200th column:

Images from a

lifetime in pharmacy

52 VIEWPOINT

“It’s our profession”:

A conversation with JP

ISSUES & TRENDS

14 UPFRONT

New tools for chronic

pain patients and

healthcare providers

16 UPFRONT IN DEPTH

REMS update: Risk

management gets

its third checkup

CHAINS & BUSINESS

21 PROFESSIONAL

The war over

counterfeit drugs

rages on

CLINICAL

29 PACE-MI TRIAL

It’s time to revisit

beta blocker dosage

for MI patients

REGULATORY & LEGAL

42 FDA IN COURT

The deaths of 27

polo ponies touch off

a struggle over the

legal deﬁ nition of

compounding

PRODUCT UPDATES

47 DIGESTIVES

Some resources for

those who dine not

wisely but too well

48 NEW PRODUCTS

Pradaxa: The ﬁ rst new

oral anticoagulant

approved in the United

States in 50 years

CONTINUING

EDUCATION

30 C. DIFFICILE UPDATE

Common risk factors;

treatments and

therapies; interactions

and adverse events;

control and prevention

Drug Topics (ISSN# 0012-6616) is published monthly

and Drug Topics Digital Edition (ISSN# 1937-8157) is

issued every week by Advanstar Communications, Inc.,

131 West First St., Duluth, MN 55806-2065. One-

year subscription rates: $61 in the United States &

Possessions; $109 in Canada and Mexico; all other

countries, $109. Single copies (prepaid only) $10 in

the United States; $10 in Canada and Mexico; all other

countries, $15. Include $6 per copy for U.S. postage

and handling. Periodicals postage paid at Duluth, MN

55806 and additional mailing ofﬁ ces. POSTMASTER:

Please send address changes to Drug Topics, P.O.

Box 6079, Duluth, MN 55806-6079. Canadian G.S.T.

number: R-124213133RT001. Publications Mail

Agreement Number 40017597. Printed in the U.S.A.

Subscription inquiries/address changes: toll-free (888)

No part of this publication may be reproduced or

transmitted in any form or by any means, electronic

or mechanical including by photocopy, recording, or

information storage and retrieval without permission in

writing from the publisher. Authorization to photocopy

items for internal/educational or personal use, or

the internal/educational or personal use of speciﬁ c

clients is granted by Advanstar Communications Inc. for

libraries and other users registered with the Copyright

Clearance Center, 222 Rosewood Dr. Danvers, MA

01923, 978-750-8400 fax 978-646-8700. For uses

beyond those listed above, please direct your written

request to Permission Dept. fax 440-891-2650 or email:

bgilbert@advanstar.com. Microﬁ lm or microﬁ che copies

of issues are available through Advanstar Marketing

Services, (800) 225-4569, Ext. 839. Unsolicited

manuscripts, photographs, art, and other material will

not be returned. Publisher assumes no responsibility

for unsolicited manuscripts, photographs, art, and other

material. Advanstar Communications provides certain

customer contact data (such as customers’ names,

addresses, phone numbers, and e-mail addresses) to

third parties who wish to promote relevant products,

services, and other opportunities that may be of interest

to you. If you do not want Advanstar Communications to

make your contact information available to third parties

for marketing purposes, simply call toll-free (888) 527-

7008 between the hours of 7:30 am and 5 pm CT and

a customer service representative will assist you in

removing your name from Advanstar’s lists. Outside the

U.S., please phone (218) 740-6477.

DRUG TOPICS does not verify any claims or other

information appearing in any of the advertisements

contained in the publication, and cannot take

responsibility for any losses or other damages

incurred by readers in reliance on such content. DRUG

TOPICS welcomes unsolicited articles, manuscripts,

photographs and other materials but cannot be held

responsible for their safekeeping or return.

GETTY IMAGES/COMSTOCK IMAGES

Subscribe to the monthly digital

edition of Drug Topics and receive the

journal electronically with live links.

Go to

http://drugtopics.com/digital

77% 23%

STEADY SAILING FOR NOW

Drug Topics’ 2011 business

outlook survey shows us which way the

wind is blowing as pharmacists plan to

chart their course for the coming year.

WWW.DRUGTOPICS.COM

■ Visit the Drug Topics blog: A new forum for pharmacist voices

(http://drugtopics.com/blog)

■ FDA hears testimony on approval pathway for biosimilars

(http://drugtopics.com/biosimilars)

■ The future of genetics and genomics

(http://drugtopics.com/genomics)

■ Ohio becomes a hub for prescription monitoring

(http://drugtopics.com/hub)

DOES REIMBURSEMENT HAVE YOU

DOWN?

FLU SEASON HAVE YOU OUT IN THE

COLD?

OR DO YOU JUST NEED TO BE

HEARD?

E-mail Associate Editor

Christina Phillis at

cphillis@advanstar.com, or

visit the blog on our homepage

(www.drugtopics.com).

Voice your opinions

on Drug Topics’ new blog!

Voice your opinions

on Drug Topics’ new blog!

The

Mylan

CLONIDINE TRANSDERMAL SYSTEM is much smaller than the Par

Generic Clonidine patch—closer in size to the brand.1,2 It contains no metal so

it doesn’t need to be removed during an MRI to avoid potential skin burns;1,2

and it has an easy-open tab so there’s no need to cut the pouch open

with scissors like the Par patch.1

The

Mylan

CLONIDINE TRANSDERMAL SYSTEM is designed with patients in mind.

Patch Appeal

Actual Size Actual Size

INDICATION: Clonidine Transdermal System is indicated in the treatment of hypertension. It may be employed alone or concomitantly

with other antihypertensive agents.

IMPORTANT SAFETY INFORMATION: Patients should be instructed not to discontinue therapy without consulting their physician.

Sudden cessation of clonidine treatment has resulted in symptoms such as nervousness, agitation, headache, and confusion accompanied

or followed by a rapid rise in blood pressure and elevated catecholamine plasma concentrations. Such reactions appear to be associated

with higher doses or continuation of concomitant beta-blocker treatment and special caution is therefore advised in these situations.

Rare instances of hypertensive encephalopathy, cerebrovascular accidents and death have been reported after clonidine withdrawal.

When discontinuing therapy with Clonidine, the physician should reduce the dose gradually over 2 to 4 days to avoid withdrawal

symptomatology.

The most frequent adverse reactions to Clonidine are dermatological, including erythema and/or pruritus. Systemic adverse reactions

with transdermal clonidine were mild and included dry mouth, drowsiness, fatigue, headache, and lethargy and sedation.

Please see adjacent Brief Summary of Prescribing Information.

800.RX.MYLAN • www.mylanpharms.com

Small size. No metal. Easy-open packaging.

References: 1. Par Clonidine Transdermal System Prescribing Information. 2. Catapres-TTS Prescribing Information.

CLONIDINE

TRANSDERMAL SYSTEM, USP

BRIEF SUMMARY: Please see package insert for full prescribing information.

INDICATIONS AND USAGE: CLONIDINE TRANSDERMAL SYSTEM, USP is

indicated in the treatment of hypertension. It may be employed alone or

concomitantly with other antihypertensive agents.

CONTRAINDICATIONS: CLONIDINE TRANSDERMAL SYSTEM should not be

used in patients with known hypersensitivity to clonidine or to any other

component of the therapeutic system.

WARNINGS: Withdrawal: Patients should be instructed not to discontinue

therapy without consulting their physician. Sudden cessation of clonidine treat -

ment has, in some cases, resulted in symptoms such as nervousness, agitation,

headache, and confusion accompanied or followed by a rapid rise in blood

pressure and elevated catecholamine concentrations in the plasma. The likelihood

of such reactions to discontinuation of clonidine therapy appears to be greater

after administration of higher doses or continuation of concomitant beta-blocker

treatment and special caution is therefore advised in these situations. Rare

instances of hypertensive encephalopathy, cerebrovascular accidents and death

have been reported after clonidine withdrawal. When discontinuing therapy with

CLONIDINE TRANSDERMAL SYSTEM, the physician should reduce the dose

gradually over 2 to 4 days to avoid withdrawal symptomatology.

An excessive rise in blood pressure following discontinuation of CLONIDINE

TRANSDERMAL SYSTEM therapy can be reversed by administration of oral

clonidine hydrochloride or by intravenous phentolamine. If therapy is to be

discontinued in patients receiving a beta-blocker and clonidine concurrently, the

beta-blocker should be withdrawn several days before the gradual discontinu-

ation of CLONIDINE TRANSDERMAL SYSTEM.

ADVERSE REACTIONS: Clinical trial experience with CLONIDINE TRANSDERMAL

SYSTEM: Most systemic adverse effects during CLONIDINE TRANSDERMAL

SYSTEM therapy have been mild and have tended to diminish with continued

therapy. In a 3-month multiclinic trial of CLONIDINE TRANSDERMAL SYSTEM in

101 hypertensive patients, the systemic adverse reactions were, dry mouth (25

patients) and drowsiness (12), fatigue (6), headache (5), lethargy and sedation (3

each), insomnia, dizziness, impotence/sexual dysfunction, dry throat (2 each) and

constipation, nausea, change in taste and nervousness (1 each).

In the above mentioned 3-month controlled clinical trial, as well as other

uncontrolled clinical trials, the most frequent adverse reactions were dermato-

logical and are described below.

In the 3-month trial, 51 of the 101 patients had localized skin reactions such

as erythema (26 patients) and/or pruritus, particularly after using an adhesive

cover throughout the 7-day dosage interval. Allergic contact sensitization to

CLONIDINE TRANSDERMAL SYSTEM was observed in 5 patients. Other skin

reactions were localized vesiculation (7 patients), hyperpigmentation (5), edema

(3), excoriation (3), burning (3), papules (1), throbbing (1), blanching (1), and a

generalized macular rash (1).

In additional clinical experience, contact dermatitis resulting in treatment discon-

tinuation was observed in 128 of 673 patients (about 19 in 100) after a mean

duration of treatment of 37 weeks. The incidence of contact dermatitis was about

34 in 100 among white women, about 18 in 100 in white men, about 14 in 100 in

black women, and approximately 8 in 100 in black men. Analysis of skin reaction

data showed that the risk of having to discontinue CLONIDINE TRANSDERMAL

SYSTEM treatment because of contact dermatitis was greatest between treatment

weeks 6 and 26, although sensitivity may develop either earlier or later in treatment.

In a large-scale clinical acceptability and safety study by 451 physicians in a

total of 3,539 patients, other allergic reactions were recorded for which a causal

relationship to CLONIDINE TRANSDERMAL SYSTEM was not established:

maculopapular rash (10 cases); urticaria (2 cases); and angioedema of the face

(2 cases), which also affected the tongue in one of the patients.

Marketing Experience with CLONIDINE TRANSDERMAL SYSTEM: The following

adverse reactions have been identified during post-approval use of CLONIDINE

TRANSDERMAL SYSTEM. Because these reactions are reported voluntarily

from a population of uncertain size, it is not always possible to estimate

reliably their frequency or establish a causal relationship to drug exposure.

Decisions to include these reactions in labeling are typically based on one or

more of the following factors: (1) seriousness of the reaction, (2) frequency of

reporting, or (3) strength of causal connection to CLONIDINE TRANSDERMAL

SYSTEM.

Body as a Whole: Fever; malaise; weakness; pallor; and withdrawal syndrome.

Cardiovascular: Congestive heart failure; cerebrovascular accident; electrocar-

diographic abnormalities (i.e., bradycardia, sick sinus syndrome disturbances

and arrhythmias); chest pain; orthostatic symptoms; syncope; increases in

blood pressure; sinus bradycardia and atrioventricular (AV) block with and

without the use of concomitant digitalis; Raynaud’s phenomenon; tachycardia;

bradycardia; and palpitations.

Central and Peripheral Nervous System/Psychiatric: Delirium; mental de -

pression; hallucinations (including visual and auditory); localized numbness;

vivid dreams or nightmares; restlessness; anxiety; agitation; irritability; other

behavioral changes; and drowsiness.

Dermatological: Angioneurotic edema; localized or generalized rash; hives; urticaria;

contact dermatitis; pruritus; alopecia; and localized hypo or hyper pigmentation.

Gastrointestinal: Anorexia and vomiting.

Genitourinary: Difficult micturition; loss of libido; and decreased sexual activity.

Metabolic: Gynecomastia or breast enlargement and weight gain.

Musculoskeletal: Muscle or joint pain; and leg cramps.

Ophthalmological: Blurred vision; burning of the eyes and dryness of the eyes.

Adverse Events Associated with Oral Clonidine Therapy: Most adverse effects

are mild and tend to diminish with continued therapy. The most frequent (which

appear to be dose-related) are dry mouth, occurring in about 40 of 100 patients;

drowsiness, about 33 in 100; dizziness, about 16 in 100; constipation and

sedation, each about 10 in 100. The following less frequent adverse experiences

have also been reported in patients receiving clonidine hydrochloride, USP

tablets, but in many cases patients were receiving concomitant medication and

a causal relationship has not been established.

Body as a Whole: Fatigue, fever, headache, pallor, weakness, and withdrawal

syndrome. Also reported were a weakly positive Coombs’ test and increased

sensitivity to alcohol.

Cardiovascular: Bradycardia, congestive heart failure, electrocardiographic

abnormalities (i.e., sinus node arrest, junctional bradycardia, high degree AV

block and arrhythmias), orthostatic symptoms, palpitations, Raynaud’s

phenomenon, syncope, and tachycardia. Cases of sinus bradycardia and AV

block have been reported, both with and without the use of concomitant digitalis.

Central Nervous System: Agitation, anxiety, delirium, delusional perception,

hallucinations (including visual and auditory), insomnia, mental depression,

nervousness, other behavioral changes, paresthesia, restlessness, sleep disorder,

and vivid dreams or nightmares.

Dermatological: Alopecia, angioneurotic edema, hives, pruritus, rash, and urticaria.

Gastrointestinal: Abdominal pain, anorexia, constipation, hepatitis, malaise, mild

transient abnormalities in liver function tests, nausea, parotitis, pseudo-obstruction

(including colonic pseudo-obstruction), salivary gland pain, and vomiting.

Genitourinary: Decreased sexual activity, difficulty in micturition, erectile

dysfunction, loss of libido, nocturia, and urinary retention.

Hematologic: Thrombocytopenia.

Metabolic: Gynecomastia, transient elevation of blood glucose or serum creatine

phosphokinase, and weight gain.

Musculoskeletal: Leg cramps and muscle or joint pain.

Oro-otolaryngeal: Dryness of the nasal mucosa.

Ophthalmological: Accommodation disorder, blurred vision, burning of the eyes,

decreased lacrimation, and dryness of the eyes.

OVERDOSAGE: Hypertension may develop early and may be followed by

hypo tension, bradycardia, respiratory depression, hypothermia, drowsiness,

de creased or absent reflexes, weakness, irritability and miosis. The frequency of

CNS depression may be higher in children than adults. Large overdoses may

result in reversible cardiac conduction defects or dysrhythmias, apnea, coma

and seizures. Signs and symptoms of overdose generally occur within 30

minutes to 2 hours after exposure. As little as 0.1 mg of clonidine has produced

signs of toxicity in children.

If symptoms of poisoning occur following dermal exposure, remove all

CLONIDINE TRANSDERMAL SYSTEMS. After their removal, the plasma

clonidine levels will persist for about 8 hours, then decline slowly over a period

of several days. Rare cases of CLONIDINE TRANSDERMAL SYSTEM poisoning

due to accidental or deliberate mouthing or ingestion of the patch have been

reported, many of them involving children.

There is no specific antidote for clonidine overdosage. Ipecac syrup-induced

vomiting and gastric lavage would not be expected to remove significant

amounts of clonidine following dermal exposure. If the patch is ingested, whole

bowel irrigation may be considered and the administration of activated charcoal

and/or cathartic may be beneficial. Supportive care may include atropine sulfate

for bradycardia, intravenous fluids and/or vasopressor agents for hypotension

and vasodilators for hypertension. Naloxone may be a useful adjunct for the

management of clonidine-induced respiratory depression, hypotension and/or

coma; blood pressure should be monitored since the administration of naloxone

has occasionally resulted in paradoxical hyper tension. Tolazoline administration

has yielded inconsistent results and is not recommended as first-line therapy.

Dialysis is not likely to significantly en hance the elimination of clonidine.

The largest overdose reported to date, involved a 28-year old male who

ingested 100 mg of clonidine hydrochloride powder. This patient developed hyper-

tension followed by hypotension, bradycardia, apnea, hallucinations, semicoma,

and premature ventricular contractions. The patient fully recovered after intensive

treatment. Plasma clonidine levels were 60 ng/mL after 1 hour, 190 ng/mL after

1.5 hours, 370 ng/mL after 2 hours, and 120 ng/mL after 5.5 and 6.5 hours. In

mice and rats, the oral LD50 of clonidine is 206 and 465 mg/kg, respectively.

MYLAN®

Mylan Pharmaceuticals Inc.

Morgantown, WV 26505

REVISED NOVEMBER 2009

BS:CTS:R9

WWW.DRUGTOPICS.COM

December 2010

DRUG TOPICS

DISPENSED AS WRITTEN

Counter Points

I continually receive surveys from pharmacy orga-

nizations, pharmacy practice residents, university

faculty, and others, asking for my opinion on medi-

cation therapy management (MTM). The frustrating thing is

that these surveys focus mainly on barriers.

There is usually a section instructing me to checkmark

all the barriers to providing MTM that I perceive. Then the

survey asks me to rank the barriers according to some or-

der of magnitude. Next I’m asked how I feel about certain

barriers (e.g., “On a scale of 1 to 10, how does the lack of

patient awareness affect the number of MTM services you

provide?”). By the time I get to the last section (which, by

the way, is a blank box asking me to list any other barri-

ers that I may know of, so that they can undoubtedly add

more items to their previous sections), I just want to shout,

“ENOUGH, ALREADY!”

Yes, barriers to providing MTM do exist for pharmacists.

I’m not about to say that providing MTM is as easy (or as

comfortable) as verifying prescriptions, counseling a patient,

or scribbling down a reﬁ ll authorization. But we all have to

ﬁ gure out a way to do it — we should feel an obligation to

do it.

Many community pharmacists are providing MTM in one

form or another, although not enough. The literature is full

of examples of pharmacists successfully implementing MTM

and providing high-level patient care in Asheville Project-

type programs.

• The Pharmacy Society of Wisconsin created an MTM

program that reimburses pharmacists in the state for both

acute interventions and more comprehensive care.

• The federal government recognized the importance of

MTM when it created Medicare Part D.

• Even the medical profession is claiming that pharmacists

are underutilized and need to be part of the team.

Yet it seems to me as if provision of MTM by pharmacists is

more of a niche than the norm right now. This has to change.

If you are a pharmacist in an independent community

pharmacy that is not currently providing MTM, start! If you

don’t know how, pick up the phone and call one of the

thousands who have ﬁ gured it out.

If you are in an upper-level management position in a

chain pharmacy organization that is not allowing pharmacists

time to provide MTM, ﬁ gure out a way! Make it a priority.

The pharmacists working under you need your support. Start

with paying them to be out of the workﬂ ow 1 hour a week.

Offer them an incentive to provide MTM, and hold them

accountable. Create new ways to make use of technicians.

Think of it as an investment in the future … an advancement

of the profession.

Let’s stop focusing on barriers and listing reasons why we

cannot provide MTM. Years ago (when what is now referred

to as MTM was called pharmaceutical care) a pharmacy pro-

fessor for whom I have a great deal of respect would from time

to time be confronted by a pharmacist or student who was

skeptical about providing high-level patient care. When said

skeptic would rattle off the typical laundry list of issues (lack of

time, lack of tools, lack of space, etc.) that stood in the way, the

professor’s response was “You can provide pharmaceutical care

with a blank sheet of paper and a big fat crayon. Just do it.”

I think it’s time for all of us to start coloring.

Marvin Moore, PharmD, is a community pharmacist in Two

Rivers, Wis., and a Drug Topics board member. He can be

reached at marvmoore4@hotmail.com.

The opinions expressed by guest editorial writers are their own and

do not necessarily represent the views of Drug Topics’ staff or the

staff of Advanstar Communications.

As part of our ongoing initiative to encourage dialogue between

pharmacists working in different environments, each month Drug

Topics presents an editorial by a guest columnist writing on a sub-

ject of his or her choice. Send us your feedback; we look forward to

sharing it in an upcoming issue.

Time to get out the big fat crayon

Marvin Moore, PharmD

Guest editorial

WWW.DRUGTOPICS.COM

Counter Points

DRUG TOPICS

December 2010

Context is everything

During my 31 years of pharmacy prac-

tice, I have been asked to ﬁ ll capsules for

the placebo effect. Each time, I did fill

the prescription with the placebo, after I

evaluated the patient’s usage and abuse to

determine that the physician’s choice for

placebo was the correct therapy and in the

best interests of the patient. Most of these

patients were abusing their prescription

drugs. It worked every time, and I never

had a problem with patient or family.

As a Christian pharmacist, I do not

think that deception or a lie is OK unless it

is in the best interests of patient care. I did

not lie to the patients when counseling, as

most of these prescriptions were for reﬁ lls.

Students have not seen this type of

patient in a practical setting and lack the

ﬁ rst-hand knowledge to make this call.

Believe me, when they see the patients

who need this therapy, they will quickly

change their minds.

Mark Barclay, RPh

VENICE, FLA.

Score 1 for placebo ... make that 2

In 1957, I was a brand-new pharmacist

in a New York hospital. An elderly female

patient of the arthritis clinic adjacent to my

pharmacy had no clinical disease in real-

ity but constantly sought treatment. The

rheumatologist, the director, and I con-

ferred and decided to give her a 2-month

supply of saccharin tablets with ad lib re-

ﬁ lls to be taken 1 tid.

This went well for several months, with

the patient reporting good results, until she

came to my window one day, shouting,

and accused us of giving her substandard

medication. The previous night she had

tried to commit suicide by taking the entire

supply — “And look at me: I’m standing

right here in front of you, and I’m alive!”

We sent her for a psych consult. I

didn’t know whether to laugh or to cry.

Irving Gerber, RPh

FAIR LAWN, N.J.

Correction: The Web Exclusive article

“Propofol shortage leads to allergy warnings

about European product” noted in the Table

of Contents of the November 2010 issue stated

that Fresenius Propoven (propofol) 1% con-

tained peanut oil. It does not. The statement

was taken from an inaccurate press release.

The label of the European product contains

the following statement: “...the product con-

tains soybean oil and there are reports of cross

allergies between soybean and peanut oil.”

Drug Topics regrets the error.

Letters

Placebos and healing

Re: “When to Lie?”

[Regulatory & Legal,

November 2010]: ...Daniel

Moerman, a medical anthro-

pologist and author of dozens

of peer-reviewed articles on

the placebo effect, warns that

to withhold the prescription of

placebos could be considered

unethical in one sense, as they

can be powerfully therapeutic.

He particularly warns against

prohibiting the use of placebos

in clinical trials, in which re-

searchers face the same ethical dilemma as every doctor

and pharmacist.

Robert Speers, MA

BOULDER, COLO.

For more from Robert Speers, including details of a groundbreaking

study mixing placebo prescriptions with prescriptions for speciﬁ c thera-

peutic agents, go to the new DT Blog at www.drugtopics.com.

Printed and e-mailed letters should be brief

and include the writer’s name, address,

daytime phone number, and date of the

issue you are referencing: Editor,

Drug Topics, 24950 Country Club Blvd., Suite

200, North Olmsted, OH 44070-5351.

E-mail address: drugtopics@advanstar.com.

Letters may be edited for length, style,

content, and clarity at our discretion.

We want to hear from you

WWW.DRUGTOPICS.COM

DRUG TOPICS

November 2010

Regulatory & Legal

Iteach a course in ethics at Midwest-

ern University College of Pharmacy

in Glendale, Ariz. Recently I present-

ed my students with an ethical problem,

asking them to decide on a correct course

of action. Their answers surprised me so

much that I presented the same problem

to some practicing pharmacists over the

next week. In every case, the answers giv-

en by the students were different from the

responses of the practicing pharmacists.

The problem I set was this. The stu-

dent, now a graduate pharmacist, is

directed by the boss, the pharmacist-

in-charge (PIC), to ﬁ ll a prescription by

emptying the contents of a C III sedative

capsule and replacing them with lactose.

The PIC explains that the doctor is pre-

scribing a placebo and that over the past

few months the pharmacist and physi-

cian have been slowly replacing active

ingredient with inactive ingredient, until

now the capsules contain only lactose.

The new capsules are working as well as

the regular medication worked, and the

patient reports that she is sleeping well

throughout the night.

The PIC then tells the student/pharma-

cist to label the prescription with the name

of the regular C III sedative and to stress,

in counseling the patient, the strength of

the drug and the importance of avoiding

an overdose. In other words, the student

is told to lie to the patient. Then the PIC

departs; he will not return until his regular

shift the following day.

The class assignment was to work

through a decision-tree algorithm

leading to the ultimate decision: What

would the student/pharmacist do when

the patient arrives?

Not one of the students was willing

to ﬁ ll the prescription or counsel the pa-

tient if it meant lying. They came to this

conclusion in spite of the fact that they

had been assigned to watch 2 videos ex-

tolling the necessity and use of placebos.

Intellectually, the students understood

the value of the placebo effect, but some-

how the situation was different when it

became a question of what the students

were willing to do to make the patient

believe in the placebo.

If a pharmacist believes that he or she

cannot participate in a deception, what

are the alternatives?

In this instance, the student/phar-

macist could tell the patient that she will

have to wait to pick up her prescription

until the PIC is on duty.

Would the answer ever be to tell the

patient the truth? In that case, the pa-

tient would learn that her doctor and her

regular pharmacist had been lying to her.

When the same question was pre-

sented to 6 pharmacists who had been

practicing for several years, they gave

the opposite answer. Every one of them

would ﬁ ll the prescription by replacing

the active ingredients with an inert sub-

stance. In addition, all of them would

counsel the patient as if she were receiv-

ing the drug named on the label.

They all understood that the label was

technically wrong and that there was a

risk that the patient would someday dis-

cover the deception. However, all were

strongly motivated to provide the patient

with the full effect of the prescribed med-

ication, even though it was the placebo

effect that had actually been prescribed.

The practicing pharmacists saw no

ethical problem in the concept that some-

times it is okay to lie, that issues are not

always black and white, but can be gray,

and that choices may depend on the con-

squences of the act.

Who is right? Perhaps it is heartening

to ﬁ nd that at some early stage in our ca-

reers, our ethical values are absolute: It is

never okay to lie to a patient. To students,

virtues are pure and ethics are black and

white, with little contrast.

Perhaps it is also good to find that

as we move through life the choices

become more difficult, as we discover

when we deal with real patients and ﬁ nd

that the consequences of our actions can

have a real effect. The 6 older, practicing

pharmacists have all had to make tough

choices; some have actually participated

in placebo treatment.

It would be interesting to ask today’s

students the same question in 20 years.

How would you answer?

These articles are not intended as legal ad-

vice and should not be used as such. When

a legal question arises the pharmacist should

consult with an attorney familiar with

pharmacy law in his or her state.

KEN BAKER consults in the areas of

pharmacy error reduction, communication,

and risk management. He is a pharmacist

and an attorney of counsel with the

Arizona law ﬁ rm Renaud Cook Drury

Mesaros, PA. Contact him at ken@

kenbakerconsulting.com.

ETHICAL PRACTICE

A question of ethics:

When to lie?

Kenneth R. Baker, BS Pharm, JD

The practicing pharma-

cists saw no ethical

problem in the concept

that sometimes it is

okay to lie, that issues

are not always black and

white, but can be gray ...

DOES REIMBURSEMENT HAVE YOU

DOWN?

FLU SEASON HAVE YOU OUT IN THE

COLD?

OR DO YOU JUST NEED TO BE

HEARD?

E-mail Associate Editor

Christina Phillis at

cphillis@advanstar.com, or

visit the blog on our homepage

(www.drugtopics.com).

Voice your opinions

on Drug Topics’ new blog!

Voice your opinions

on Drug Topics’ new blog!

EPIPEN and EPIPEN Jr Auto-Injectors

There is no AB-rated substitute

Help at-risk patients

prepare for a life-threatening

anaphylactic emergency…

* Data on ﬁ le. SDI Health, Physician Disease & Diagnosis Audit, Drug Uses for

Dx Code 9950-Anaphylactic Shock, 1990-2009. www.EpiPen.com

DEY® and the Dey logo are registered trademarks of Dey Pharma, L.P.

EpiPen®, EpiPen 2-Pak®, and EpiPen Jr 2-Pak® are registered trademarks of

Mylan Inc., licensed exclusively to its wholly-owned subsidiary, Dey Pharma, L.P.

YEARS

MORE THAN

Convenient 2-PAK contains

2 Auto-Injectors and a trainer.

• The FDA has not determined a therapeutic equivalent to BX-rated EPIPEN Auto-Injector

• No absolute contraindications to use in life-threatening situations

• EPIPEN Auto-Injector delivers epinephrine with speed and simplicity

• Only EPIPEN Auto-Injector has a unique, user-friendly design with

the added safety of automatic needle protection before and after use

Indications

EpiPen and EpiPen Jr Auto-Injectors (0.3 and 0.15 mg epinephrine) are indicated in the emergency

treatment of type 1 allergic reactions, including anaphylaxis, to allergens, idiopathic and exercise-

induced anaphylaxis, and in patients with a history or increased risk of anaphylactic reactions.

Selection of the appropriate dosage strength is determined according to body weight.

Important Safety Information

EpiPen Auto-Injectors should only be injected into the anterolateral aspect of the thigh. DO NOT

INJECT INTO BUTTOCK, OR INTRAVENOUSLY.

Epinephrine should be used with caution in patients with certain heart diseases, and in patients who

are on drugs that may sensitize the heart to arrhythmias, because it may precipitate or aggravate

angina pectoris and produce ventricular arrhythmias. Adverse reactions include transient moderate

anxiety, apprehensiveness, restlessness, tremor, weakness, dizziness, sweating, palpitations, pallor,

nausea and vomiting, headache, and/or respiratory difficulties.

EpiPen and EpiPen Jr Auto-Injectors are intended for immediate self-administration as emergency

supportive therapy only and are not intended as a substitute for immediate medical or hospital care.

Please see Brief Summary of Prescribing Information on the adjacent page.

EPIPEN carton NDC 49502-500-01

EPIPEN 2-PAK NDC 49502-500-02

EPIPEN Jr carton NDC 49502-501-01

EPIPEN Jr 2-PAK NDC 49502-501-02

EPIPEN® 0.3 mg EPINEPHRINE AUTO-INJECTOR

EPIPEN® Jr 0.15 mg EPINEPHRINE AUTO-INJECTOR

BRIEF SUMMARY. See package insert for full Prescribing Information.

DO NOT REMOVE ACTIVATION CAP UNTIL READY FOR USE.

THIS UNIT CONTAINS NO LATEX.

INDICATIONS AND USAGE: EpiPen® and EpiPen® Jr Auto-Injectors are indicated in the emergency treatment of

allergic reactions (Type I) including anaphylaxis to stinging insects (e.g., order Hymenoptera, which include bees,

wasps, hornets, yellow jackets and ﬁre ants) and biting insects (e.g., triatoma, mosquitos), allergen immunotherapy,

foods, drugs, diagnostic testing substances (e.g., radiocontrast media) and other allergens, as well as idiopathic

anaphylaxis or exercise-induced anaphylaxis. EpiPen® and EpiPen® Jr Auto-Injectors are intended for immediate

administration in patients, who are determined to be at increased risk for anaphylaxis, including individuals

with a history of anaphylactic reactions. Selection of the appropriate dosage strength is determined according to

patient body weight (See DOSAGE AND ADMINISTRATION section of the full Prescribing Information).

Such reactions may occur within minutes after exposure and consist of ﬂushing, apprehension, syncope,

tachycardia, thready or unobtainable pulse associated with a fall in blood pressure, convulsions, vomiting,

diarrhea and abdominal cramps, involuntary voiding, wheezing, dyspnea due to laryngeal spasm, pruritus, rashes,

urticaria or angioedema.

EpiPen® and EpiPen® Jr Auto-Injectors are intended for immediate self-administration as emergency supportive

therapy only and are not a substitute for immediate medical care.

CONTRAINDICATIONS: There are no absolute contraindications to the use of epinephrine in a life-threatening

situation.

WARNINGS: EpiPen® and EpiPen® Jr Auto-Injectors should only be injected into the anterolateral aspect of the

thigh. DO NOT INJECT INTO BUTTOCK. Injection into the buttock may not provide effective treatment of anaphylaxis.

Advise the patient to go immediately to the nearest emergency room for further treatment of anaphylaxis.

Since epinephrine is a strong vasoconstrictor, accidental injection into the digits, hands or feet may

result in loss of blood ﬂow to the affected area. Treatment should be directed at vasodilation in addition to

further treatment of anaphylaxis. (see ADVERSE REACTIONS). Advise the patient to go immediately to the nearest

emergency room and to inform the healthcare provider in the emergency room of the location of the

accidental injection.

DO NOT INJECT INTRAVENOUSLY. Large doses or accidental intravenous injection of epinephrine may

result in cerebral hemorrhage due to sharp rise in blood pressure. Rapidly acting vasodilators can counteract

the marked pressor effects of epinephrine if there is such inadvertent administration.

Epinephrine is the preferred treatment for serious allergic reactions or other emergency situations even though this

product contains sodium metabisulﬁte, a sulﬁte that may, in other products, cause allergic-type reactions including

anaphylactic symptoms or life-threatening or less severe asthmatic episodes in certain susceptible persons.

The alternatives to using epinephrine in a life-threatening situation may not be satisfactory. The presence of a sulﬁte

in this product should not deter administration of the drug for treatment of serious allergic or other emergency

situations even if the patient is sulﬁte-sensitive.

Epinephrine should be administered with caution in patients who have heart disease, including patients with cardiac

arrhythmias, coronary artery or organic heart disease, or hypertension. In such patients, or in patients who are on

drugs that may sensitize the heart to arrhythmias, e.g., digitalis, diuretics, or anti-arrhythmics, epinephrine may

precipitate or aggravate angina pectoris as well as produce ventricular arrhythmias. It should be recognized that

the presence of these conditions is not a contraindication to epinephrine administration in an acute, life-threatening

situation.

Epinephrine is light sensitive and should be stored in the carrier tube provided. Store at 25°C (77°F); excursions

permitted to 15°C-30°C (59°F-86°F) (See USP Controlled Room Temperature). Do not refrigerate. Before using,

check to make sure the solution in the auto-injector is not discolored. Replace the auto-injector if the solution is

discolored or contains a precipitate.

PRECAUTIONS:

(1) General

EpiPen® and EpiPen® Jr Auto-Injectors are not intended as a substitute for immediate medical care. In conjunction

with the administration of epinephrine, the patient should seek immediate medical or hospital care. More than two

sequential doses of epinephrine should only be administered under direct medical supervision.

Epinephrine is essential for the treatment of anaphylaxis. Patients with a history of severe allergic reactions

(anaphylaxis) to insect stings or bites, foods, drugs, and other allergens as well as idiopathic and exercise-induced

anaphylaxis should be carefully instructed about the circumstances under which epinephrine should be used.

It must be clearly determined that the patient is at risk of future anaphylaxis, since the following risks may

be associated with epinephrine administration (see DOSAGE and ADMINISTRATION section of the full

Prescribing Information).

Epinephrine should be used with caution in patients who have cardiac arrhythmias, coronary artery or

organic heart disease, hypertension, or in patients who are on drugs that may sensitize the heart to

arrhythmias, e.g., digitalis, diuretics, quinidine, or other anti-arrhythmics. In such patients, epinephrine may

precipitate or aggravate angina pectoris as well as produce ventricular arrhythmias. The effects of epinephrine may

be potentiated by tricyclic antidepressants and monoamine oxidase inhibitors.

Some patients may be at greater risk of developing adverse reactions after epinephrine administration. These

include: hyperthyroid individuals, individuals with cardiovascular disease, hypertension, or diabetes, elderly

individuals, pregnant women, pediatric patients under 30 kg (66 lbs.) body weight using EpiPen® Auto-Injector, and

pediatric patients under 15 kg (33 lbs.) body weight using EpiPen® Jr Auto-Injector.

Despite these concerns, epinephrine is essential for the treatment of anaphylaxis. Therefore, patients with these

conditions, and/or any other person who might be in a position to administer EpiPen® or EpiPen® Jr Auto-Injector

to a patient experiencing anaphylaxis should be carefully instructed in regard to the circumstances under which

epinephrine should be used.

(2) Information for Patients

Complete patient information, including dosage, direction for proper administration and precautions can be found

inside each EpiPen®/EpiPen® Jr Auto-Injector carton.

Epinephrine may produce symptoms and signs that include an increase in heart rate, the sensation of a more

forceful heartbeat, palpitations, sweating, nausea and vomiting, difﬁculty breathing, pallor, dizziness, weakness or

shakiness, headache, apprehension, nervousness, or anxiety. These symptoms and signs usually subside rapidly,

especially with rest, quiet and recumbency. Patients with hypertension or hyperthyroidism may develop more severe

or persistent effects, and patients with coronary artery disease could experience angina. Patients with diabetes may

develop increased blood glucose levels following epinephrine administration. Patients with Parkinson’s disease may

notice a temporary worsening of symptoms.

In case of accidental injection, the patient should be advised to immediately go to the emergency room for

treatment. Since the epinephrine in the EpiPen® Auto-Injector is a strong vasoconstrictor when injected into the digits,

hands or feet, treatment should be directed at vasodilation if there is such an inadvertent administration to these areas.

(see ADVERSE REACTIONS).

(3) Drug Interactions

Patients who receive epinephrine while concomitantly taking cardiac glycosides or diuretics should be observed carefully

for the development of cardiac arrhythmias.

The effects of epinephrine may be potentiated by tricyclic antidepressants, monoamine oxidase inhibitors, levothyroxine

sodium, and certain antihistamines, notably chlorpheniramine, tripelennamine and diphenhydramine.

The cardiostimulating and bronchodilating effects of epinephrine are antagonized by beta-adrenergic blocking

drugs, such as propranolol. The vasoconstricting and hypertensive effects of epinephrine are antagonized by alpha-

adrenergic blocking drugs, such as phentoloamine. Ergot alkaloids may also reverse the pressor effects of

epinephrine.

(4) Carcinogenesis, Mutagenesis, Impairment of Fertility

Epinephrine and other catecholamines have been shown to have mutagenic potential in vitro and to be an oxidative

mutagen in a WP2 bacterial reverse mutation assay. Epinephrine had a moderate degree of mutagenicity, and was

positive in the DNA Repair test with B. subtilis (REC) assay, but was not mutagenic in the Salmonella bacterial reverse

mutation assay. Studies of epinephrine after repeated exposure in animals to evaluate the carcinogenic and mutagenic

potential or the effect on fertility have not been conducted. This should not prevent the use of epinephrine under the

conditions noted under INDICATIONS AND USAGE.

(5) Usage in Pregnancy

Pregnancy Category C: There is no study on the acute effect of epinephrine on pregnancy. Epinephrine has been shown

to have developmental effects when administered subcutaneously in rabbits at a dose of 1.2 mg/kg daily for two to

three days (approximately 30 times the maximum recommended daily subcutaneous or intramuscular dose on a

mg/m2 basis), in mice at a subcutaneous dose of 1 mg/kg daily for 10 days (approximately 7 times the maximum daily

subcutaneous or intramuscular dose on a mg/m2 basis) and in hamsters at a subcutaneous dose of 0.5 mg/kg daily for

4 days (approximately 5 times the maximum recommended daily subcutaneous or intramuscular dose on a mg/m2

basis). These effects were not seen in mice at a subcutaneous dose of 0.5 mg/kg daily for 10 days (approximately

3 times the maximum recommended daily subcutaneous or intramuscular dose on a mg/m2 basis). Although, there

are no adequate and well-controlled studies in pregnant women, epinephrine should be used in pregnancy only if the

potential beneﬁt justiﬁes the potential risk to the fetus.

ADVERSE REACTIONS: Adverse reactions to epinephrine include transient, moderate anxiety; apprehensiveness;

restlessness; tremor; weakness; dizziness; sweating; palpitations; pallor; nausea and vomiting; headache; and/

or respiratory difﬁculties. These symptoms occur in some persons receiving therapeutic doses of epinephrine, but

are more likely to occur in patients with hypertension or hyperthyroidism. Arrhythmias, including fatal ventricular

ﬁbrillation, have been reported in patients with underlying cardiac disease or certain drugs [see PRECAUTIONS,

Drug Interactions]. Rapid rises in blood pressure have produced cerebral hemorrhage, particularly in elderly

patients with cardiovascular disease. Angina may occur in patients with coronary artery disease. The potential for

epinephrine to produce these types of adverse reactions does not contraindicate its use in an acute life-threatening

allergic reaction.

Accidental injection into the digits, hands or feet may result in loss of blood ﬂow to the affected area (see

WARNINGS). Adverse events experienced as a result of accidental injections may include increased heart rate, local

reactions including injection site pallor, coldness and hypoaesthesia or injury at the injection site resulting in bruising,

bleeding, discoloration, erythema or skeletal injury.

OVERDOSAGE: Epinephrine is rapidly inactivated in the body and treatment following overdose with epinephrine

is primarily supportive. If necessary, pressor effects may be counteracted by rapidly acting vasodilators or alpha-ad-

renergic blocking drugs. If prolonged hypotension follows such measure, it may be necessary to administer another

pressor drug.

Overdosage of epinephrine may produce extremely elevated arterial pressure, which may result in cerebrovascular

hemorrhage, particularly in elderly patients.

Overdosage may also result in pulmonary edema because of peripheral vascular constriction together with cardiac

stimulation. Treatment consists of a rapidly acting alpha-adrenergic blocking drug and/or respiratory support.

Epinephrine overdosage can also cause transient bradycardia followed by tachycardia and these may be

accompanied by potentially fatal cardiac arrhythmias. Premature ventricular contractions may appear within one

minute after injection and may be followed by multifocal ventricular tachycardia (preﬁbrillation rhythm). Subsidence of

the ventricular effects may be followed by atrial tachycardia and occasionally by atrioventricular block. Treatment of

arrhythmias consists of administration of a beta-blocking drug such as propranolol.

Overdosage sometimes results in extreme pallor and coldness of the skin, metabolic acidosis and kidney failure. Suitable

corrective measures must be taken in such situations.

HOW SUPPLIED: EpiPen® Auto-Injectors (epinephrine injections, USP, 1:1000, 0.3 mL) are available in individual

cartons, NDC 49502-500-01, and as EpiPen 2-Pak®

, NDC 49502-500-02, a pack that contains two EpiPen® Auto-Injectors

(epinephrine injections, USP, 1:1000, 0.3 mL) and one EpiPen® Auto-Injector trainer device.

EpiPen® Jr Auto-Injectors (epinephrine injection, USP, 1:2000, 0.3 mL) are available in individual cartons,

NDC 49502-501-01, and as EpiPen Jr 2-Pak®, NDC 49502-501-02, a pack that contains two EpiPen® Jr Auto-Injectors

(epinephrine injections, USP, 1:2000, 0.3 mL) and one EpiPen® Auto-Injector trainer device.

EpiPen 2-Pak® and EpiPen Jr 2-Pak® also includes an S-clip to clip two cases together.

Store at 25°C (77°F); excursions permitted to 15°C-30°C (59°F-86°F) (See USP Controlled Room Temperature).

Contains no latex. Protect from light.

Rx only.

MANUFACTURED FOR Dey, L.P.,

NAPA, CALIFORNIA, 94558, U.S.A.

by Meridian Medical Technologies, Inc.,

a subsidiary of King Pharmaceuticals®, Inc.,

Columbia, MD 21046, U.S.A.

EpiPen®, EpiPen® Jr, EpiPen 2-Pak®, and EpiPen Jr 2-Pak® are registered trademarks of Mylan, Inc,

licensed exclusively to its wholly-owned afﬁliate, Dey, L.P. of Napa, California, USA.

03-500-03 (BRS) March 2009

Counter Points

WWW.DRUGTOPICS.COM December 2010

DRUG TOPICS

Twenty-plus years and 200 columns

and I am still standing. Pharmacists

have asked for my help, told me their

stories, and lambasted me. So many

moments stand out in memory. Here

are just a few.

January 23, 1989. Publication date

of the ﬁ rst “JP at Large.” My stomach

did ﬂ ips when a woman who suffered

from bipolar disorder told me that she

was going to jump off the Deception Pass

Bridge. Life was just too tough. I just lis-

tened. That’s all she wanted. She prom-

ised to go back on her meds.

1996. A woman asked me how she

could help her mother kill herself. I was

silent. She mentioned

the 180 clonazepam

and 240 APAP/codeine

that had come from

a mail-order outfit.

“My Mom loves mar-

tinis,” she said, giving

me a look. The drugs

plus martinis could

be a deadly cocktail. I

watched the obituaries

for weeks after that.

1990s. I thought I was a jazzman for

a time. I took my troubles down to Madame

Ruth/You know that Gypsy with the gold-

capped tooth/She’s got a shop down at 34th

and Vine/Selling little bottles of/Love Potion

Number Nine.

If you get your juju on, you can see

how that song about Madame Ruth epit-

omizes what we do. Rite-Aid’s got a shop

near a Pennsylvania mine/it sells Viagra and/

cheap red Italian wine.

1998. A store manager accused me of

being unprofessional because I refused to

reﬁ ll an Rx for his friend. I told him to get

a dictionary. I was on the professional train

for the long ride.

Mid-1990s. I did a stealth interview

with the produce manager at a local mar-

ket. I asked him if the OTC famotidine

was any good. Lettuce leaves started

ﬂ ying all over the place. “How the hell

do I know?” He was red-faced from the

cooler. “Ask a pharmacist!”

It was my first justification for a BTC

class of drugs. A month earlier, famoti-

dine had been Rx Only

and too dangerous for

self-use. All of a sudden,

it could be sold at truck

stops. Pathetic oversight

from effete regulators.

Profit rules!

1990. An elderly

man who had been

watching me work

asked, “How long you

been a registered man?”

It was the old-fashioned distinction be-

tween a registered pharmacist and an ap-

prentice. We talked and he told me about

being paid in eggs, 2 dozen every week,

by a cash-poor farm family.

“The people were the best part,” he

said. “I went to weddings and funerals.

Pharmacists don’t seem to have time for

people these days.” 1990 was 2 decades

before the Prescription Mill Red Warning

Timers of 2010.

2004. I did everything I could to shame

a young mother because she had prob-

lems understanding how to dose her baby

with the Prednisolone 15 mg/5 ml syrup.

Then I realized that she did not know

how to read. After that I did everything

I could to help her, including sending her

to the adult reading program at the local

library. Months later, there were tears on

my cheeks when she proudly showed

me the ﬁ rst book she had read by herself:

“Snuggle Piggy and the Magic Blanket.”

A retail pharmacist today

I often wrote about the absurdity of work-

ing in a modern drugstore. You know you

are a pharmacist when you are frequently

referred to as “Hey” and one of the most

common questions you are asked is “Hey,

where are the lawn chairs for $9.99?”

You know you are a pharmacist when

you get home at 10:30 p.m. and your

spouse says, “I fed the kids. You can make

your own dinner.” Your spouse likes your

money but isn’t willing to dance the dance.

Pharmacists often complain that the

profession is in the pits. I invite them to

focus more closely. It’s the job, stupid. The

profession is just ﬁ ne.

JP AT LARGE

Jim Plagakis, RPh

Pharmacy then and now

In 1989, an RPh complained that she was expected to work off the clock after her shift

had ended. I told her that she should not put up with it. I told her that she was a phar-

macist, not a high school dropout stocking shelves. The day I work off the clock will be

the day your company starts paying for a catered deli lunch every day. You’re a professional. You

always have choices. You can be passive, or you can be smart. The company will always take

what it can get.

th d

Jim Plagakis is a community pharmacist

in Galveston, Texas. You can e-mail him

at jpgakis@hotmail.com and cc us at

drugtopics@advanstar.com. You can also

check out his website at jimplagakis.com.

“The people were

the best part,” he

said. “Pharmacists

don’t seem to have

time for people

these days.”

DRUG TOPICS

December 2010 WWW.DRUGTOPICS.COM

Up front

INDUSTRY NEWS & ANALYSIS

Patients with health insurance are abandoning their prescrip-

tions at higher rates than they did a year ago and far more

frequently than they did 5 years ago, according to a recent study

from healthcare data ﬁ rm Wolters Kluwer Pharma Solutions,

Bridgewater, N.J.

From 2006 to 2010, patient abandonment rates at retail

pharmacies have soared 83.6%, according to the Wolters

Kluwers study.

• In the ﬁ rst quarter of 2006, 5% of patients failed to pick

up their brand prescriptions and 2.9% failed to pick up their

generic prescriptions.

• In the ﬁ rst quarter of 2010, 9.4% abandoned their brand

prescriptions and 5.1% abandoned their generics.

“It does seem to be tied to the economic climate right now,

but we will see if it begins to ﬂ atten out or improve [when the

economy improves],” said Mark Spiers, CEO of Wolters Kluwer

Pharma Solutions.

As the United States entered recession in the third quarter

of 2008, rates of prescription abandonment began to rise. “We

really started to see a bump in 2009, which continued into 2010,”

Spiers said.

While prescription abandonment rates stayed the same for ge-

neric medications between the ﬁ rst and second quarter of 2010,

the abandonment rates for brands rose from 9.4% to 9.6%.

Wolters Kluwer also tracks the abandonment rates by cat-

egory of medication and found that adrenergic blocking pre-

scriptions had the highest rate-of-abandonment increase from

2008 to 2009. In 2008, approximately 3% of patients abandoned

adrenergic blocking medications; in 2009, the rate had risen to

approximately 3.9%.

“We have also seen an increase in abandonment of mainte-

nance medications such as those for diabetes and hypertension.

Those are the areas that tend to become more concerning, be-

cause many of the drugs have demonstrated outcomes to prevent

heart attack, stroke, and other conditions that put a greater cost

on the healthcare system,” Spiers said.

Approximately 4.8% of patients abandoned anti-ulcerant

prescriptions in 2009, 4% abandoned diabetes prescriptions,

4.2% abandoned antidepressants, and approximately 3.7%

failed to pick up cholesterol reducers.

— Christine Blank, Contributing Editor

Website for providers, patients, focuses on chronic pain

NEW STUDY

More patients are abandoning prescriptions

Pharmacists working with chronic pain patients have a new

tool. PainSAFE (Pain Safety & Access for Everyone), an initiative

of the American Pain Foundation, has launched the website

www.painsafe.org to educate patients and practitioners about

pain-management therapies and their risks.

In Portland, Ore., at a Bi-Mart

Pharmacy that specializes in

helping patients with chronic pain,

pharmacy staff keeps files on such

patients and “watches for all the

things that go wrong, such as side

effects and errant behavior,” said

Kathy Hahn, PharmD, owner of

the pharmacy and Action Network

Leader of the American Pain

Foundation. “Some of our staff

have become advocates. It’s all

about increasing access and trying to figure how we can work on

the crisis of abusing pain medications,” Hahn said.

PainSAFE organizers agree that the pharmacist’s role

is vital. “Pharmacists play a key role in preventing misuse

and overuse of prescriptions. They are the last gate before

a patient receives their medication,” said Lynn Webster, MD,

FACPM, and an advisor to PainSAFE.

Pharmacists can help prevent misuse of pain medication

by monitoring initial drug doses. “Physicians often start patients

on too high of a dose or increase the dose too rapidly. The

pharmacist can see that and will hopefully contact the physician.

This could save thousands of lives every year,” Webster said.

Pharmacists can also help patients who switch or combine

medications. “Pharmacists need to make sure that patients

understand the higher risks of taking 2 together. There could be a

substantial reduction in deaths immediately,” Webster said.

At the website, simple tips include reminders to lock up

pain medications to prevent misuse by the young or the

elderly. “We have not been good at putting out the information

that pain medications should be locked up,” Hahn said.

— Christine Blank, Contributing Editor

Kathy Hahn

www.painsafe.org: A new tool for chronic pain patients and healthcare providers

GROWTHINNOVAT IONQUALITYAFFORDABILITYImpacting Tomorrow Right Now.

Growth

Expanding product lines

Innovation

Technically complex

products

Affordability

Accessible pharmaceuticals

for all

Quality

The highest standards

for safe and compliant

manufacturing

For more information, please visit www.roxane.com

or call 800.520.1631.

Right Now, Roxane Laboratories is – and always has been – focused on the

needs of our customers and their patients.

125 Years of Impacting

Tomorrow Right Now

years of innovation

DRUG TOPICS

December 2010 WWW.DRUGTOPICS.COM

Up front

In Depth

REMS UPDATE

Since the 1999 publication of the

Institute of Medicine (IOM) re-

port “To Err is Human: Build-

ing a Safer Health System,” both public

and private interests have made patient

safety a priority. Pharmacists can play a

critical role in patient safety by ensuring

that correct medications be dispensed

appropriately. But necessary patient

counseling, along with interaction with

physicians and payors, often goes un-

compensated. While recent FDA safety

policies give the agency more authority

to demand post-marketing accountabil-

ity from manufacturers, they present an

increasing burden for pharmacists.

Manufacturer risk reduction

Part of the 2007 FDA Amendment Act

(FDAAA) was the Risk Evaluation and

Mitigation Strategy (REMS) require-

ment for manufacturers, “to ensure

that the beneﬁ ts of a drug or biological

product outweigh its risks.”

FDA now publicly lists more than 160

REMS-approved drugs, detailing for each

product the REMS components, which

may include a medication guide, a com-

munication plan, elements to assure safe

use, and/or an implementation system.

At the Third Annual Risk Manage-

ment and Drug Safety Summit, held

October 18 and 19 in Bethesda, Md.,

attendees and presenters discussed the

latest issues related to risk and safety,

and examined

how REMS and

drug safety have

been faring since

2007.

Annette Stem-

hagen, DrPH,

FISPE, senior vice

president of safety,

epidemiology, reg-

istries, and risk management for Unit-

ed BioSource Corporation, a Summit

sponsor, said that most REMS (70%)

are “a medication-guide-only REMS.”

Pharmacist fact-checking

“The pharmacist has the responsibil-

ity of dispensing the medication guide

along with the prescription, but there’s

a bigger responsibility for the pharma-

cist when there’s a REMS communica-

tion plan,” Stemhagen said, explaining

that when FDA requires a manufac-

turer to provide a com-

munication plan, the

pharmacist will have

to conﬁ rm whether the

patient is eligible to re-

ceive a speciﬁ c product

and whether certain

tests are needed before

the patient can obtain a

drug or drug reﬁ ll, as with Accutane,

which requires a pregnancy test.

Risk management

Before REMS legislation, manufacturers

of Accutane and its generics operated

iPLEDGE, a program designed to re-

duce risk of fetal exposure. On October

22, 2010, FDA approved the iPLEDGE

program as an ofﬁ cial REMS. The pro-

gram has continued as before; the only

change was in its ofﬁ cial designation.

FDA representative Crystal Rice said

that pharmacists could help commu-

nicate with physicians who are new to

REMS and “help them complete the

needed processes for a particular prod-

uct,” but that pharmacists should not be

expected “to be the primary source of

information regarding the correct pre-

scribing choice for a physician’s patients.”

Summit keynote speaker Peter Pitts,

co-founder and president of the Cen-

ter for Medicine in the Public Interest

(CMPI) and a Summit sponsor, said

that “the REMS issue is part of the larg-

er conversation of postmarket safety.”

He added that he suspects pharmacists

are probably much more knowledgeable

about REMS than are physicians, whose

“awareness of REMS is slim to none.”

Education and technology

FDA is planning a number of projects

to help pharmacists, Rice said, including

a uniform REMS interface for prescrib-

ers, expanded pharmacy

access to REMS, CE for

pharmacists, and more.

“We are researching

the possibilities presented

by today’s technology for

using current or develop-

ing electronic systems to

implement the registra-

tion and prescribing requirements of

REMS,” Rice said.

FDA is also “very involved in ongo-

ing education for pharmacists and other

stakeholders,” Rice said, “to decrease

the burden of the REMS process.”

In her plenary remarks, Summit

presenter Janet Woodcock, MD, Direc-

tor of FDA’s Center for Drug Evaluation

and Research (CDER) said that “CDER

promotes and protects public health by

ensuring that safe and effective drugs

are available to Americans, but ‘safe’

does not mean risk-free, and ‘effective’

does not mean equally for all.”

In other words, Pitts said, the REMS

program “doesn’t tell physicians how to

practice medicine, and it gives the FDA

the route to keep higher-risk drugs on

the market.”

Barbara Hesselgrave is a freelance writer

based in Virginia.

BARBARA HESSELGRAVE

Safety summit: Risk management gets its third checkup

Annette Stemhagen

FDA now

publicly lists

more than 160

REMS-approved

drugs.

WWW.DRUGTOPICS.COM

December 2010

DRUG TOPICS

Professional

COUNTERFEIT DRUGS

Gren spoke in October in Washing-

ton, D.C., at Interchange 2010, a con-

ference sponsored by the Partnership

for Safe Medicines, a coalition of indi-

viduals and groups working to protect

consumers from counterfeit or contra-

band medications.

Along with counterfeit medications,

substandard medications are also al-

ways on the rise. These are deﬁ ned as

products made primarily by manufac-

turers who do not comply with regu-

latory standards or U.S. Pharmacopeia

requirements.

Although counterfeit drugs can

contain anything from powdered dry-

wall to highway paint, Gren said, he

believes more counterfeit drugs include

some actual ingredients, making them

effective enough to bring the counter-

feiters repeat business. He called this

one of the most frightening potentials.

Although the counterfeit drug issue

has received more government funding

and attention in recent years, it has not

received nearly enough, Gren told the

meeting, which included the group’s

members, pharmaceutical profession-

als, government ofﬁ cials, and others.

Foreign drugs

According to FDA, Gren said, 80% of

active pharmaceutical ingredients (API)

in drugs consumed in the United States

come from other countries, mostly from

nations that don’t have sophisticated reg-

ulatory regimes. An API, he said, “may

come from China, it may be packaged in

the Middle East, it may be sent through

Brazil; ultimately it makes it to the United

States or other parts of the world,” mak-

ing the problem difﬁ cult to solve.

Diplomatic efforts to address the issue

include dialogues with countries such

as China, India, and Brazil, and include

Department of Commerce initiatives

originated by the U.S.-China Joint Com-

mission on Commerce and Trade. Also,

a series of seminars and other projects

continues under the aegis of Asia-Paciﬁ c

Economic Cooperation, a forum for the

Paciﬁ c Rim nations, Gren said.

A growing problem

Another speaker at the Interchange meet-

ing, Nancy Kennedy, senior operations

manager of drug investigations in FDA’s

Ofﬁ ce of Criminal Investigations, said that

some years ago imported, unapproved,

and counterfeit drugs came into the Unit-

ed States addressed to individuals or pack-

aged in small quantities. Then quantities

increased, and counterfeits started going

to drop-shippers and distributors working

from online pharmacy operations.

“Now we see quantities of these drugs

coming in and going directly to doctors,

clinics, brick-and-mortar-pharmacies—

and these are for use and distribution

directly to patients,” Kennedy said.

A question of resources

Asked at the meeting about resources

allocated to the counterfeit drug prob-

lem, Kennedy said that for some time

Congress and others have been saying,

“Show us the bodies.” But there may

not be many bodies at one time, she

said, unless an event occurs such as the

mass poisonings that have happened in

other countries.

Currently, she added, counterfeit

drugs are more likely either to cause

injuries or to cause patients to receive

inappropriate doses of prescribed drugs

without their realizing it.

Targeted enforcement

In another session at the partnership’s

forum, FDA Commissioner Margaret

Hamburg said that her agency has now

ranked more than 1,000 active pharma-

ceutical ingredients according to their

vulnerability to economically motivated

adulteration, so that enforcement can be

better targeted.

To jump-start efforts to deal with sup-

ply-chain threats that include counterfeit-

ing, economically motivated adulteration,

diversion, and cargo thefts, Hamburg said,

the agency is creating a new Drug Integ-

rity and Security Program within the Of-

ﬁ ce of Compliance of the FDA’s Center for

Drug Evaluation and Research.

Hamburg also said that FDA is devel-

oping standards for track-and-trace and

authentication systems that would enable

the identiﬁ cation of substandard prescrip-

tion drugs as they move along the supply

chain. The agency will help in efforts to

recall these drugs.

However, asked when the require-

ment that drugs carry a pedigree will

be enforced, as mandated by the 1987

Prescription Drug Marketing Act, Ham-

burg said she could not give a speciﬁ c

answer. That requirement, calling for

wholesale distributors (or others not

deﬁ ned as “authorized distributors”) to

provide a statement of each prior sale,

trade, or purchase of a prescription drug,

has been held up by regulatory and legal

wrangling for 2 decades.

CHAINS & BUSINESS

Kathryn Foxhall

The counterfeiters are winning the global counterfeit drug war, with counterfeit medi-

cations more abundant than ever before, according to Jeffrey Gren, director of the

Ofﬁ ce of Health and Consumer Goods in the U.S. Department of Commerce.

Kathryn Foxhall is a healthcare journalist

based in the Washington, D.C., area.

Counterfeit drug war continues,

threatens supply chain

WWW.DRUGTOPICS.COM

DRUG TOPICS

December 2010

While the economy in many industries has yet to re-

bound, the pharmacy industry has remained strong

and most pharmacists are hopeful about 2011. How-

ever, optimism isn’t running as high as it was last year, and the

pharmacy community is concerned about how competition,

reimbursement, and healthcare reform will affect the industry.

These are just a few of the conclusions drawn from Drug

Topics’ annual business outlook survey, an online survey con-

ducted in October that received more than 400 responses from

community, hospital, and long-term-care (LTC) pharmacists.

Overall, respondents believe that the business climate

looks positive for 2011. Of the 305 community pharmacists

who responded to the survey, 77% believe that 2010 will

be an excellent, very good, or good business year, and 68%

predict that the trend will continue in 2011.

In addition, of the 96 hospital and LTC pharmacists who

responded, 84% anticipate that 2010 will be an excellent,

very good, or good business year, and 73% believe that will

also be the case in 2011.

“I think there are a lot of very posi-

tive things going on in pharmacy, and

so I think [pharmacists’] optimism is

warranted, but it isn’t going to get any

easier,” said Thomas Menighan, executive

vice president and chief executive ofﬁ cer

of the American Pharmacists Associa-

tion (APhA). “Margins are not going to

get larger. People are going to have to be

more efﬁ cient. They are going to have to

ﬁ nd ways to make the services that pharmacists can provide

pay off rather than relying on buy low, sell high.”

Community pharmacists’ ﬁ nancial outlook

Pharmacists’ ﬁ nancial expectations for 2011 are generally

positive, but they aren’t without their concerns.

Nearly half (45%) of community pharmacists surveyed

believe that sales will increase in 2011. For those who antici-

pate rising sales ﬁ gures, the average increase expected is 4.5%.

However, not everyone sees predicted sales in such a

positive light. Survey ﬁ ndings indicate that 11% believe

sales will decrease, and they predict an average decrease

in 2011 of 2.3%.

In addition, 56% anticipate an increase to operating ex-

penses, while 6% expect a decrease. For those who believe

there will be an increase, the average expected increase is

4.1%. For those who anticipate a decrease, the average ex-

pected decrease is 1.2%.

About a third, or 35%, expect net proﬁ ts to increase in

2011 by an average of 2.6%.

Half of community pharmacists believe that in their

pharmacies, pharmacist salaries will increase in 2011, while

40% do not expect an increase. For the 50% who expect an

increase, the average expected increase is 3.6%.

Steady sailing

for now

Drug Topics’ 2011 business outlook survey

Cover Story

Jill Sederstrom

2010: Overall Business View

84%

16%

77% 23%

68% 32% 73% 27%

2011: Overall Business View

Community Pharmacists Hospital/LTC Pharmacists

ommunity Pharmacist

50%

40%

10%

2011: Salary Expectations

armac

sts

42%

47%

11%

Positive View Negative View

Salary Increase No Increase

Undecided

Half of community pharmacists expect salaries to increase next year. More than 40%

of hospital and LTC pharmacists believe their salaries will climb in 2011.

Thomas Menighan

WWW.DRUGTOPICS.COM December 2010

DRUG TOPICS

Cover Story

BUSINESS OUTLOOK SURVEY

Hospital pharmacists’ ﬁ nancial outlook

Hospital and LTC pharmacists are less optimistic about sales

expectations than are their counterparts in community

pharmacy. According to the results, just 30% of hospital

pharmacists expect an increase in sales in the coming year;

the average increase they anticipate is 3.9%. However, only

6% predict a decrease in sales. For those who expected a

decrease, the average expected decrease was 2.1%.

Most hospital pharmacists surveyed (51%) expect op-

erating expenses to increase in the new year; they predict

an average increase of 5.4%. On the other side of the spec-

trum, 6% of those surveyed believe operating expenses will

decrease and expect an average decrease in 2011 of 0.6%.

Nearly a quarter, or 23%, of hospital pharmacists expect

net proﬁ ts to increase in 2011 by an average increase of 2.5%.

A signiﬁ cant percentage of hospital pharmacists do not be-

lieve a raise is in their future in 2011. According to the survey

results, 47% do not expect a salary increase. However, 42%

do believe that their pharmacies will be giving pharmacists a

raise in 2011. The average increase anticipated is 3%.

Anna Garrett, PharmD, BCPS, man-

ager of outpatient clinical pharmacy

services for Mission Hospital in Ashe-

ville, N.C., believes that if pharmacists

are expecting salary increases now,

those increases will be more in line

with cost-of-living adjustments, rather

than being signiﬁ cant jumps in pay.

“It looks like the days when ev-

erybody is getting the huge raises are

over,” said Garrett, who is joining Drug Topics’ editorial ad-

visory board next month.

Challenges and opportunities

In any given year, the pharmacy industry will face chal-

lenges and opportunities, and 2011 is no exception. In one

section of the survey, pharmacists identiﬁ ed the top 3 posi-

tive and top 3 negative factors that they believe will inﬂ u-

ence the industry in the coming year.

The most frequently cited positive factors expected to

affect business are major brand-name drugs going off patent

(cited by 62% of respondents), an increase of e-prescriptions

(cited by 37% of respondents), and immunization certiﬁ ca-

tion (cited by 36% of respondents).

The most frequently mentioned negative factors affecting

business for 2011 are expected to be the recession (cited by

77% of respondents), low reimbursement from third parties

(cited by 66% of respondents), and mail-order programs

(cited by 63% of respondents).

Charlie Mollien, PharmD, a staff

pharmacist with Meijer Pharmacy, Jen-

ison, Mich., and a Drug Topics Frontline

editorial advisory board member, said

that he is optimistic about the future

of pharmacy, although he does see

some hurdles. While he believes that

pharmacy utilization will continue to

increase, he added that low reimburse-

ment could translate into pharmacists

ﬁ lling more prescriptions for less proﬁ t.

To combat the problem, and to make up proﬁ ts, Mollien

said, pharmacists may need to look into other areas, such

as adopting education programs for smoking cessation or

chronic disease management. For the programs to be suc-

cessful, however, pharmacists would need to be given the

time, staff, and leadership support to run them.

The biggest challenges pharmacists will face in 2011 are

said to be competition from chains offering generics at low

or no cost (cited by 51% of respondents), competition from

mail-order pharmacies (cited by 59%), and state Medicaid

rates and Maximum Allowable Cost (MAC) and Federal

Upper Limit (FUL) programs (cited by 53% of respondents).

To get ahead in the industry, Menighan believes, phar-

macists will need to think creatively and reach out to the

medical community to discuss new changes to healthcare.

“There are opportunities to partner with medicine in col-

laborative ways that are going to beneﬁ t everybody,” he said.

One area that is not expected to be a challenge this year is

the number of pharmacists in the market. While last year more

than half of respondents believed that their states had a short-

age of pharmacists, this year 74% of community pharmacists

and 64% of hospital and LTC pharmacists said that they don’t

believe there is a pharmacist shortage in their states.

Cristina Medina, PharmD, manager

of professional and college relations for

CVS Caremark and a new member of

Drug Topics’ editorial advisory board, said

that although the demand for pharma-

cists varies based on geographic region,

most of the markets are now well staffed.

Medina attributes this change to an

increase in pharmacy programs in the

country and to the struggling economy.

The additional competition in the job market has not

been lost on pharmacy students. Most students realize now

that they may have to spend more time looking for a job,

although Medina doesn’t believe that

the industry has become too diluted.

Anna Garrett

Charlie Mollien

Cristina Medina

Continued on pg. 24

WWW.DRUGTOPICS.COM

DRUG TOPICS

December 2010

Cover Story

BUSINESS OUTLOOK SURVEY

“I think there are deﬁ nitely positions. I just think that

in the major metropolitan areas students have to drive out

further or go into different markets, but I think that supply

is right with demand,” she said.

Grading the associations

Pharmacy associations were established to serve the best

interests of pharmacists, but how well they perform can be

a matter of opinion. On the basis of responses to the Drug

Topics survey, it appears that more than 40% of community,

hospital, and LTC pharmacists are satisﬁ ed with the repre-

sentation they’ve received.

According to the results, 43% of community pharmacists

said they were satisﬁ ed with their pharmacy associations this

year, while 27% were not and 30% did not know. Similarly,

42% of hospital and LTC pharmacists are satisﬁ ed with the

way their associations have represented them, while 22%

were not and 37% were not sure.

Mollien, who serves on both the Michigan Pharmacists

Association and the APhA board, believes that associations

can advocate for change that individual pharmacists may

not have the time or power to effect on their own.

“One voice can be lost in a crowd,” he said. “An associa-

tion voice is more likely to be heard.”

Edith Rosato, senior vice president

of pharmacy affairs for the National

Association of Chain Drug Stores

(NACDS) and president of the NACDS

Foundation, credited pharmacy asso-

ciations with ushering in new industry

changes, including the power phar-

macists now have to administer im-

munizations in all 50 states, but, she

said, not all pharmacists are sufﬁ ciently

aware of the accomplishments achieved by associations.

“It’s a fact that a lot of pharmacists out there really don’t

know who their associations are,” she said.

Government programs

Medicare Part D received mixed reviews from community,

hospital, and LTC pharmacists, although community phar-

macists seemed to be more supportive overall of the pro-

gram. According to the survey results, 43% of community

pharmacists said that they believe Medicare Part D has had

a positive impact on their pharmacy, while 23% believe it

has had a negative impact. On the other hand, only 10%

of hospital and LTC pharmacists cited a positive impact on

their pharmacies, while 19% cited a negative impact, and

71% did not know.

Robert J. Greenwood, RPh, is an

independent pharmacy owner in Water-

loo, Iowa, and president of the National

Community Pharmacists Association

(NCPA). When asked about Medicare

Part D, he said that although prescrip-

tion drug plans often offer recipients an

economic incentive to use mail-order

pharmacies, which can present its own

set of challenges, overall he sees the

Medicare Part D program as a positive aspect of business.

“The Medicare D program levels the playing ﬁ eld, [and]

price is not part of the equation anymore,” he said.

Pharmacists also had conﬂ icting feelings about MTM ser-

vices under Medicare Part D.

Drug Topics found that 38% of community pharmacists

reported providing MTM services under Medicare Part D in

2010 and 26% of those who responded to the survey were

paid an average of $1,536.90 for these services.

Furthermore, 17% of hospital and LTC pharmacists

provided MTM services under Medicare Part D, and 6% of

those survey respondents received an average of $1,791.70.

Garrett, who has had success with MTM services, said

that she is able to provide additional counseling to Medi-

care surgical patients during preoperative visits for elective

surgery. The hospital environment gives her more time to

interact with patients and identify possible issues they may

have before surgery.

One reason that MTM services have not been fully em-

braced by pharmacists may be the program’s slow begin-

ning, according to Rosato. She said that when the program

began in 2003, many Medicare participants weren’t eligible

for it. Now, eligibility has increased and, Rosato believes,

MTM services will gain momentum — possibly even be-

yond Medicare.

“One of the things that we’re looking at as a profes-

sion is why not provide MTM services to patients who have

chronic diseases?” she said.

While it’s still unclear what effect the new Affordable

Care Act will have on the industry, Greenwood said, he

thinks the act will give pharmacists greater opportunities to

demonstrate their value in the healthcare arena.

“Patients are going to be seen in a more ambulatory way

than currently, and I see pharmacists being an extension

of primary care delivery from the physician,” he said.

Jill Sederstrom is a freelance journalist based in Overland Park,

Kansas.

Edith Rosato

Robert Greenwood

Continued from pg. 23

For additional information,

visit www.PRADAXAPRO.com

or call 1-866-395-1764.

PRADAXA® is a registered trademark of Boehringer Ingelheim Pharma GmbH & Co. KG and used under license.

NOW APPROVED

As part of Eli Lilly and Company’s ongoing commitment,

we provide healthcare facilities with a choice of vial sizes.

Humalog® (insulin lispro injection [rDNA origin]),

Humulin® R U-100 (regular insulin human injection, USP

[rDNA origin]), and Humulin® N (NPH human insulin [rDNA

origin] isophane suspension) are available in a smaller vial size.*

The smaller vials are designed to give healthcare facilities

ﬂ exibility when evaluating insulin storage and distribution

(ﬂ oor stock vs individual patient supply), in addition to the

10 mL vial and Humalog® KwikPen™.

• Humalog NDC Number - 0002-7510-17

• Humulin R U-100 NDC Number - 0002-8215-17

• Humulin N NDC Number - 0002-8315-17

* Smaller vials contain 3 mL of insulin in a 5 mL vial.

Humalog Indication

Humalog (insulin lispro injection [rDNA origin]) is for

use in patients with diabetes mellitus for the control of

hyperglycemia. Humalog should be used with longer-

acting insulin, except when used in combination with

sulfonylureas in patients with type 2 diabetes.

Humalog Important Safety Information

Contraindications

Humalog is contraindicated during episodes of hypoglycemia

and in patients sensitive to Humalog or one of its excipients.

Warnings

Humalog differs from regular human insulin by its rapid onset

of action as well as a shorter duration of action. Therefore,

when used as a mealtime insulin, Humalog should be given

within 15 minutes before or immediately after a meal.

Due to the short duration of action of Humalog, patients

with type 1 diabetes also require a longer-acting insulin

to maintain glucose control (except when using an

insulin pump).

Glucose monitoring is recommended for all patients

with diabetes.

The safety and effectiveness of Humalog in patients less

than 3 years of age have not been established. There are

no adequate and well-controlled clinical studies of the use

of Humalog in pregnant or nursing women.

Step up to a range of

insulin delivery options.

Humalog Important Safety Information, continued

Warnings, continued

Starting or changing insulin therapy should be done

cautiously and only under medical supervision.

Hypoglycemia

Hypoglycemia is the most common adverse effect associated

with insulins, including Humalog. Hypoglycemia can happen

suddenly, and symptoms may be different for each person

and may change from time to time. Severe hypoglycemia

can cause seizures and may be life-threatening.

Other Side Effects

Other potential side effects associated with the use of

insulins include: hypokalemia, weight gain, lipodystrophy,

and hypersensitivity. Systemic allergy is less common,

but may be life-threatening. Because of the difference

Humalog Important Safety Information, continued

Other Side Effects, continued

in action of Humalog, care should be taken in patients

in whom hypoglycemia or hypokalemia may be clinically

relevant (eg, those who are fasting, have autonomic

neuropathy or renal impairment, are using potassium-

lowering drugs, or taking drugs sensitive to serum

potassium level).

Please see reverse side for Brief Summary of full

Prescribing Information.

Please see full user manual that accompanies the pen.

Humalog® and Humalog® KwikPen™ are registered trademarks of Eli Lilly

and Company and are available by prescription only.

Humulin® is a registered trademark of Eli Lilly and Company.

HUMALOG®

INSULIN LISPRO INJECTION (rDNA ORIGIN)

BRIEF SUMMARY: Consult package insert for complete prescribing information.

INDICATIONS AND USAGE: Humalog is an insulin analog that is indicated in the treatment of patients with

diabetes mellitus for the control of hyperglycemia. Humalog has a more rapid onset and a shorter duration of

action than regular human insulin. Therefore, in patients with type 1 diabetes, Humalog should be used in

regimens that include a longer-acting insulin. However, in patients with type 2 diabetes, Humalog may be used

without a longer-acting insulin when used in combination therapy with sulfonylurea agents.

Humalog may be used in an external insulin pump, but should not be diluted or mixed with any other

insulin when used in the pump. Humalog administration in insulin pumps has not been studied in patients

with type 2 diabetes.

CONTRAINDICATIONS: Humalog is contraindicated during episodes of hypoglycemia and in patients sensitive to

Humalog or any of its excipients.

WARNINGS: This human insulin analog differs from regular human insulin by its rapid onset of action as well

as a shorter duration of activity. When used as a mealtime insulin, the dose of Humalog should be given

within 15 minutes before or immediately after the meal. Because of the short duration of action of Humalog,

patients with type 1 diabetes also require a longer-acting insulin to maintain glucose control (except when

using an external insulin pump).

External Insulin Pumps: When used in an external insulin pump, Humalog should not be diluted or mixed

with any other insulin. Patients should carefully read and follow the external insulin pump manufacturer’s

instructions and the “PATIENT INFORMATION” leaﬂet before using Humalog.

Physicians should carefully evaluate information on external insulin pump use in the Humalog physician

package insert and in the external insulin pump manufacturer’s instructions. If unexplained hyperglycemia or

ketosis occurs during external insulin pump use, prompt identiﬁcation and correction of the cause is necessary.

The patient may require interim therapy with subcutaneous insulin injections (see PRECAUTIONS, For Patients

Using External Insulin Pumps, and DOSAGE AND ADMINISTRATION).

Hypoglycemia is the most common adverse effect associated with the use of insulins, including Humalog.

As with all insulins, the timing of hypoglycemia may differ among various insulin formulations. Glucose

monitoring is recommended for all patients with diabetes and is particularly important for patients using an

external insulin pump.

Any change of insulin should be made cautiously and only under medical supervision. Changes in insulin

strength, manufacturer, type (eg, regular, NPH, analog), species, or method of manufacture may result in the

need for a change in dosage.

PRECAUTIONS: General—Hypoglycemia and hypokalemia are among the potential clinical adverse effects

associated with the use of all insulins. Because of differences in the action of Humalog and other insulins, care

should be taken in patients in whom such potential side effects might be clinically relevant (eg, patients who are

fasting, have autonomic neuropathy, or are using potassium-lowering drugs or patients taking drugs sensitive to

serum potassium level). Lipodystrophy and hypersensitivity are among other potential clinical adverse effects

associated with the use of all insulins.

As with all insulin preparations, the time course of Humalog action may vary in different individuals or at

different times in the same individual and is dependent on site of injection, blood supply, temperature, and

physical activity.

Adjustment of dosage of any insulin may be necessary if patients change their physical activity or their usual

meal plan. Insulin requirements may be altered during illness, emotional disturbances, or other stress.

Hypoglycemia—As with all insulin preparations, hypoglycemic reactions may be associated with the

administration of Humalog. Rapid changes in serum glucose concentrations may induce symptoms of

hypoglycemia in persons with diabetes, regardless of the glucose value. Early warning symptoms of

hypoglycemia may be different or less pronounced under certain conditions, such as long duration of diabetes,

diabetic nerve disease, use of medications such as beta-blockers, or intensiﬁed diabetes control.

Renal Impairment—The requirements for insulin may be reduced in patients with renal impairment.

Hepatic Impairment—Although impaired hepatic function does not affect the absorption or disposition of

Humalog, careful glucose monitoring and dose adjustments of insulin, including Humalog, may be necessary.

Allergy—Local Allergy—As with any insulin therapy, patients may experience redness, swelling, or itching

at the site of injection. These minor reactions usually resolve in a few days to a few weeks. In some instances,

these reactions may be related to factors other than insulin, such as irritants in a skin cleansing agent or poor

injection technique.

Systemic Allergy—Less common, but potentially more serious, is generalized allergy to insulin, which may

cause rash (including pruritus) over the whole body, shortness of breath, wheezing, reduction in blood pressure,

rapid pulse, or sweating. Severe cases of generalized allergy, including anaphylactic reaction, may be life-

threatening. Localized reactions and generalized myalgias have been reported with the use of cresol as an

injectable excipient. In Humalog-controlled clinical trials, pruritus (with or without rash) was seen in 17 patients

receiving Humulin R® (N=2969) and 30 patients receiving Humalog (N=2944) (P=.053).

Antibody Production—In large clinical trials, antibodies that cross-react with human insulin and insulin lispro

were observed in both Humulin R- and Humalog-treatment groups. As expected, the largest increase in the

antibody levels during the 12-month clinical trials was observed with patients new to insulin therapy.

Usage of Humalog in External Insulin Pumps—The infusion set (reservoir syringe, tubing, and catheter),

Disetronic® D-TRON®2,3 or D-TRONplus®2,3 cartridge adapter, and Humalog in the external insulin pump

reservoir should be replaced and a new infusion site selected every 48 hours or less. Humalog in the external

insulin pump should not be exposed to temperatures above 37°C (98.6°F).

In the D-TRON®2,3 or D-TRONplus®2,3 pump, Humalog 3 mL cartridges may be used for up to 7 days. However,

as with other external insulin pumps, the infusion set should be replaced and a new infusion site should be

selected every 48 hours or less.

When used in an external insulin pump, Humalog should not be diluted or mixed with any other insulin (see

INDICATIONS AND USAGE, WARNINGS, PRECAUTIONS, For Patients Using External Insulin Pumps, Mixing of

Insulins, DOSAGE AND ADMINISTRATION, and Storage).

Information for Patients—Patients should be informed of the potential risks and advantages of Humalog and

alternative therapies. Patients should also be informed about the importance of proper insulin storage, injection

technique, timing of dosage, adherence to meal planning, regular physical activity, regular blood glucose

monitoring, periodic hemoglobin A1C testing, recognition and management of hypoglycemia and hyperglycemia,

and periodic assessment for diabetes complications.

Patients should be advised to inform their physician if they are pregnant or intend to become pregnant.

Refer patients to the “PATIENT INFORMATION” leaﬂet for timing of Humalog dosing (<_15 minutes before or

immediately after a meal), storing insulin, and common adverse effects.

For Patients Using Insulin Pen Delivery Devices: Before starting therapy, patients should read the “PATIENT

INFORMATION” leaﬂet that accompanies the drug product and the User Manual that accompanies the delivery

device. They should also reread these materials each time the prescription is renewed. Patients should be

instructed on how to properly use the delivery device, prime the Pen to a stream of insulin, and properly dispose

of needles. Patients should be advised not to share their Pens with others.

For Patients Using External Insulin Pumps: Patients using an external infusion pump should be trained in

intensive insulin therapy and in the function of their external insulin pump and pump accessories. Humalog was

tested in the MiniMed®1 Models 506, 507, and 508 insulin pumps using MiniMed®1 Polyﬁn®1 infusion sets.

Humalog was also tested in the Disetronic®2 H-TRONplus® V100 insulin pump (with plastic 3.15 mL insulin

reservoir), and the Disetronic D-TRON®2,3 and D-TRONplus®2,3 insulin pumps (with Humalog 3 mL cartridges)

using Disetronic Rapid®2 infusion sets.

The infusion set (reservoir syringe, tubing, catheter), D-TRON®2,3 or D-TRONplus®2,3 cartridge adapter,

and Humalog in the external insulin pump reservoir should be replaced, and a new infusion site selected

every 48 hours or less. Humalog in the external pump should not be exposed to temperatures above

37°C (98.6°F).

A Humalog 3 mL cartridge used in the D-TRON®2,3 or D-TRONplus®2,3 pump should be discarded after 7 days,

even if it still contains Humalog. Infusion sites that are erythematous, pruritic, or thickened should be reported to

medical personnel, and a new site selected.

Humalog should not be diluted or mixed with any other insulin when used in an external insulin pump.

Laboratory Tests—As with all insulins, the therapeutic response to Humalog should be monitored by periodic

blood glucose tests. Periodic measurement of hemoglobin A1C is recommended for the monitoring of long-term

glycemic control.

Drug Interactions—Insulin requirements may be increased by medications with hyperglycemic activity, such

as corticosteroids, isoniazid, certain lipid-lowering drugs (eg, niacin), estrogens, oral contraceptives,

phenothiazines, and thyroid replacement therapy (see CLINICAL PHARMACOLOGY).

Insulin requirements may be decreased in the presence of drugs that increase insulin sensitivity or have

hypoglycemic activity, such as oral antidiabetic agents, salicylates, sulfa antibiotics, certain antidepressants

(monoamine oxidase inhibitors), angiotensin-converting-enzyme inhibitors, angiotensin II receptor blocking

agents, beta-adrenergic blockers, inhibitors of pancreatic function (eg, octreotide), and alcohol. Beta-adrenergic

blockers may mask the symptoms of hypoglycemia in some patients.

Mixing of Insulins—Care should be taken when mixing all insulins as a change in peak action may occur.

The American Diabetes Association warns in its Position Statement on Insulin Administration, “On mixing,

physiochemical changes in the mixture may occur (either immediately or over time). As a result, the physiological

response to the insulin mixture may differ from that of the injection of the insulins separately.” Mixing Humalog

with Humulin® N or Humulin® U does not decrease the absorption rate or the total bioavailability of Humalog.

Given alone or mixed with Humulin N, Humalog results in a more rapid absorption and glucose-lowering effect

compared with regular human insulin.

Pregnancy—Teratogenic Effects—Pregnancy Category B—Reproduction studies with insulin lispro have

been performed in pregnant rats and rabbits at parenteral doses up to 4 and 0.3 times, respectively, the average

human dose (40 units/day) based on body surface area. The results have revealed no evidence of impaired

fertility or harm to the fetus due to Humalog. There are, however, no adequate and well-controlled studies with

Humalog in pregnant women. Because animal reproduction studies are not always predictive of human response,

this drug should be used during pregnancy only if clearly needed.

Although there are limited clinical studies of the use of Humalog in pregnancy, published studies with human

insulins suggest that optimizing overall glycemic control, including postprandial control, before conception and

during pregnancy improves fetal outcome. Although the fetal complications of maternal hyperglycemia have been

well documented, fetal toxicity also has been reported with maternal hypoglycemia. Insulin requirements usually

fall during the ﬁrst trimester and increase during the second and third trimesters. Careful monitoring of the

patient is required throughout pregnancy. During the perinatal period, careful monitoring of infants born to

mothers with diabetes is warranted.

Nursing Mothers—It is unknown whether Humalog is excreted in signiﬁcant amounts in human milk. Many

drugs, including human insulin, are excreted in human milk. For this reason, caution should be exercised when

Humalog is administered to a nursing woman. Patients with diabetes who are lactating may require adjustments

in Humalog dose, meal plan, or both.

Pediatric Use—In a 9-month, crossover study of prepubescent children (n= 60), aged 3 to 11 years,

comparable glycemic control as measured by A1C was achieved regardless of treatment group: regular human

insulin 30 minutes before meals 8.4%, Humalog immediately before meals 8.4%, and Humalog immediately

after meals 8.5%. In an 8-month, crossover study of adolescents (n=463), aged 9 to 19 years, comparable

glycemic control as measured by A1C was achieved regardless of treatment group: regular human insulin 30 to

45 minutes before meals 8.7% and Humalog immediately before meals 8.7%. The incidence of hypoglycemia

was similar for all 3 treatment regimens. Adjustment of basal insulin may be required. To improve accuracy in

dosing in pediatric patients, a diluent may be used. If the diluent is added directly to the Humalog vial, the shelf

life may be reduced (see DOSAGE AND ADMINISTRATION).

Geriatric Use—Of the total number of subjects (n=2834) in 8 clinical studies of Humalog, 12% (n=338) were

65 years of age or over. The majority of these were patients with type 2 diabetes. A1C values and hypoglycemia

rates did not differ by age. Pharmacokinetic/pharmacodynamic studies to assess the effect of age on the onset

of Humalog action have not been performed.

ADVERSE REACTIONS: Clinical studies comparing Humalog with regular human insulin did not demonstrate a

difference in frequency of adverse events between the 2 treatments.

Adverse events commonly associated with human insulin therapy include the following:

Body as a Whole—allergic reactions (see PRECAUTIONS).

Skin and Appendages—injection site reaction, lipodystrophy, pruritus, rash.

Other—hypoglycemia (see WARNINGS and PRECAUTIONS).

OVERDOSAGE: Hypoglycemia may occur as a result of an excess of insulin relative to food intake, energy

expenditure, or both. Mild episodes of hypoglycemia usually can be treated with oral glucose. Adjustments in

drug dosage, meal patterns, or exercise may be needed. More severe episodes with coma, seizure, or neurologic

impairment may be treated with intramuscular/subcutaneous glucagon or concentrated intravenous glucose.

Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after

apparent clinical recovery.

DOSAGE AND ADMINISTRATION: Humalog is intended for subcutaneous administration, including use in select

external insulin pumps (see DOSAGE AND ADMINISTRATION, External Insulin Pumps). Dosage regimens of

Humalog will vary among patients and should be determined by the healthcare provider familiar with the

patient’s metabolic needs, eating habits, and other lifestyle variables. Pharmacokinetic and pharmacodynamic

studies showed Humalog to be equipotent to regular human insulin (ie, one unit of Humalog has the same

glucose-lowering effect as one unit of regular human insulin), but with more rapid activity. The quicker glucose-

lowering effect of Humalog is related to the more rapid absorption rate from subcutaneous tissue. An adjustment

of dose or schedule of basal insulin may be needed when a patient changes from other insulins to Humalog,

particularly to prevent premeal hyperglycemia.

When used as a mealtime insulin, Humalog should be given within 15 minutes before or immediately after a

meal. Regular human insulin is best given 30 to 60 minutes before a meal. To achieve optimal glucose control,

the amount of longer-acting insulin being given may need to be adjusted when using Humalog.

The rate of insulin absorption and consequently the onset of activity are known to be affected by the site of

injection, exercise, and other variables. Humalog was absorbed at a consistently faster rate than regular human

insulin in healthy male volunteers given 0.2 U/kg regular human insulin or Humalog at abdominal, deltoid, or

femoral sites, the 3 sites often used by patients with diabetes. When not mixed in the same syringe with other

insulins, Humalog maintains its rapid onset of action and has less variability in its onset of action among injection

sites compared with regular human insulin (see PRECAUTIONS). After abdominal administration, Humalog

concentrations are higher than those following deltoid or thigh injections. Also, the duration of action of Humalog

is slightly shorter following abdominal injection, compared with deltoid and femoral injections. As with all insulin

preparations, the time course of action of Humalog may vary considerably in different individuals or within the

same individual. Patients must be educated to use proper injection techniques.

Humalog in a vial may be diluted with STERILE DILUENT for Humalog, Humulin N, Humulin R, Humulin 70/30,

and Humulin® R U-500 to a concentration of 1:10 (equivalent to U-10) or 1:2 (equivalent to U-50). Diluted

Humalog may remain in patient use for 28 days when stored at 5°C (41°F) and for 14 days when stored at 30°C

(86°F). Do not dilute Humalog contained in a cartridge or Humalog used in an external insulin pump.

Parenteral drug products should be inspected visually before use whenever the solution and the container

permit. If the solution is cloudy, contains particulate matter, is thickened, or is discolored, the contents must not

be injected. Humalog should not be used after its expiration date. The cartridge containing Humalog is not

designed to allow any other insulin to be mixed in the cartridge or for the cartridge to be reﬁlled with insulin.

External Insulin Pumps—Humalog was tested in MiniMed®1 Models 506, 507, and 508 insulin pumps using

MiniMed®1 Polyﬁn®1 infusion sets. Humalog was also tested in the Disetronic®2 H-TRONplus® V100 insulin

pump (with plastic 3.15 mL insulin reservoir) and the Disetronic D-TRON®2,3 and D-TRONplus®2,3 pumps (with

Humalog 3 mL cartridges) using Disetronic Rapid®2 infusion sets. Humalog should not be diluted or mixed with

any other insulin when used in an external insulin pump.

HOW SUPPLIED:

Humalog (insulin lispro injection, USP [rDNA origin]) is available in the following package sizes (with each

presentation containing 100 units insulin lispro per mL [U-100]):

10 mL vials NDC 0002-7510-01 (VL-7510)

3 mL vials NDC 0002-7510-17 (VL-7533)

5 x 3 mL cartridges3 NDC 0002-7516-59 (VL-7516)

5 x 3 mL preﬁlled insulin delivery devices (Pen) NDC 0002-8725-59 (HP-8725)

5 x 3 mL preﬁlled insulin delivery devices (Humalog® KwikPen™) NDC 0002-8799-59 (HP-8799)

1 MiniMed® and Polyﬁn® are registered trademarks of MiniMed, Inc.

Disetronic®, H-TRONplus®, D-TRON®, and Rapid® are registered trademarks of Roche Diagnostics GMBH.

3 3 mL cartridge is for use in Eli Lilly and Company’s HumaPen® MEMOIR™ and HumaPen® LUXURA™ HD insulin

delivery devices, Owen Mumford, Ltd.’s Autopen® 3 mL insulin delivery device, and Disetronic D-TRON® and

D-TRONplus® pumps. Autopen® is a registered trademark of Owen Mumford, Ltd. HumaPen®,

HumaPen® MEMOIR™ and HumaPen® LUXURA™ HD are trademarks of Eli Lilly and Company.

Other product and company names may be the trademarks of their respective owners.

Storage —Unopened Humalog should be stored in a refrigerator (2° to 8°C [36° to 46°F]), but not in the

freezer. Do not use Humalog if it has been frozen. Unrefrigerated (below 30°C [86°F]) 12 vials, cartridges, Pens,

and KwikPens must be used within 28 days or be discarded, even if they still contain Humalog. Protect from

direct heat and light.

Use in an External Insulin Pump—A Humalog 3mL cartridge used in the D-TRON®2,3 or D-TRONplus®2,3

should be discarded after 7 days, even if it still contains Humalog. Infusion sets, D-TRON®2,3 and D-TRONplus®2,3

cartridge adapters, and Humalog in the external insulin pump reservoir should be discarded every 48 hours

or less.

Literature revised December 7, 2009

KwikPens manufactured by Eli Lilly and Company, Indianapolis, IN 46285, USA.

Pens manufactured by Eli Lilly and Company, Indianapolis, IN 46285, USA or Lilly France,

F-67640 Fegersheim, France.

Vials manufactured by Eli Lilly and Company, Indianapolis, IN 46285, USA or Hospira, Inc.,

Lake Forest, IL 60045, USA or Lilly France, F-67640 Fegersheim, France.

Cartridges manufactured by Lilly France, F-67640 Fegersheim, France for Eli Lilly and Company,

Indianapolis, IN 46285, USA.

www.humalog.com

WWW.DRUGTOPICS.COM December 2010

DRUG TOPICS

Clinical

PACE-MI TRIAL

“Beta blocker use is better than 93%

at discharge,” said Jeffrey Goldberger, MD,

professor of medicine, Northwestern Uni-

versity Feinberg School of Medicine, Chi-

cago. “We can attribute that to beta block-

ers post-MI becoming a quality measure.

What we’re not doing is ensuring that

they are used at appropriate doses.”

Pace-MI Trial

Dr. Goldberger is lead author of an analysis

of data from the PACE-MI Trial, evaluat-

ing the survival impact of pacemaker-

facilitated beta blocker therapy after MI

in patients who have bradycardia con-

traindications to beta blockers. The study

included a prospective registry of 1,971

consecutive MI patients across 19 centers

admitted with MI between August 2007

and July 2008.

Registry data included beta blocker

dose at discharge, Dr. Goldberger said.

Physicians were queried 3 weeks after dis-

charge for the current beta blocker dose.

Researchers found that while 93.2% of

patients were discharged on a beta blocker,

only 17% of patients were receiving more

than 50% of the recommended dose of

metoprolol (Lopressor, Novartis), carve-

dilol (Coreg, GlaxoSmithKline), atenolol

(Tenormin, AstraZeneca), propranolol (In-

deral, Wyeth), or some other beta blocker.

The right dose

“The question shouldn’t be is the patient

getting a beta blocker or not,” Dr. Gold-

berger told Drug Topics. “The question

should be is the patient getting the right

dose of a beta blocker. For the majority of

patients, the current answer is no.”

Beta blocker dosing is a sticky issue,

said Joseph Saseen, PharmD, FCCP, BCPS,

CLS, professor of

Clinical Pharmacy,

University of Colo-

rado Denver School

of Pharmacy. Much

of the data on ap-

propriate dosing

comes from heart-

failure patients.

Many MI patients

progress to heart

failure, but not all do so. Up-titrating beta

blocker doses may be less important in pa-

tients who do not progress to heart failure.

Older patients may also do well on

lower doses of beta blockers. If the resting

heart rate is about 60, Saseen noted, and

does not spike dramatically during mild

exercise such as walking, the patient is

probably on an appropriate dose.

“This study is a good snapshot of beta

blocker use post-MI, not the full picture,”

he said. “And there is good support for the

notion that the beta blocker dose 3 weeks

after discharge is a good indicator of dos-

age over the next year.”

Short stays, less titration

Patients are traditionally started on a

low dose of beta blocker and titrated

up in the hospital, Dr. Goldberger said.

But with shorter hospital stays, there is

less time for managing dose titration. In

many cases, it simply doesn’t happen.

“Once you take a patient out of the

post-MI setting, people tend to focus on

absolutes like blood pressure and patient

symptoms,” he said. “They just don’t think

about beta blocker dosage. You don’t need

a physician to up the dose. You could just

as easily use a pharmacist to follow up.”

Quality systems

Tweaking existing quality systems can

help, said Mary Andrawis, PharmD,

MPH, director, clinical guidelines and

quality improvement, American So-

ciety of Health-System Pharmacists.

Most health systems evaluate beta

blocker compliance with a simple yes/

no question. Because dosing data are

already captured, it should be possible

to reﬁ ne the qual-

ity measure to ap-

propriate dose, not

just any dose.

“Beta blockers

will be one of the

first and easiest of

these measures to

take,” she said. “Re-

ﬁ ning and evolving

our quality mea-

sures is something we could implement

in lipid dosing, anticoagulation therapy,

and other areas.”

Pharmacy could also play a role in

discharge counseling, Andrawis said. In-

cluding beta blocker dosing as part of the

medication reconciliation process when

patients move into the community is a

reasonable extension of care.

“Part of the discharge process is ensur-

ing that the patient is seen again for ap-

propriate follow-up,” she said. “Checking

a beta blocker dose is exactly what a phar-

macist should be looking for.”

Post-MI beta blocker doses too low

Care for patients with myocardial infarction (MI) may not be as good as quality mea-

sures suggest. New data show that while nearly all MI patients receive beta blockers,

most patients receive suboptimal doses that are never increased.

RX CARE

Fred Gebhart, Contributing Editor

Joseph Saseen

Mary Andrawis

If the resting heart rate

is about 60 and does

not spike dramatically

during mild exercise

such as walking, the

patient is probably on

an appropriate dose.

DRUG TOPICS

December 2010 WWW.DRUGTOPICS.COM

Clostridium difﬁ cile is an anaerobic, gram-positive spore-

forming rod that exists in both a vegetative form

and a resilient spore form. It was recognized as the

cause of antibiotic-associated pseudomembranous colitis in

1978, and it remains the most common cause of healthcare-

associated infectious diarrhea.1,2

C. difﬁ cile infection (CDI) refers to the presence in patients

of clinical symptoms of disease (usually manifested as diar-

rhea) and either a stool test positive for the presence of C.

difﬁ cile toxins or ﬁ ndings that reveal pseudomembranous

colitis. CDI ranges in severity from asymptomatic coloniza-

tion to fulminant disease characterized by severe diarrhea

with intestinal complications. CDI is now recognized as a

worldwide public health concern, as it is increasing in inci-

dence, severity of disease, and associated mortality.

Clinical practice guidelines for treating CDI in adults have

recently been updated through a collaboration of the Society

for Healthcare Epidemiology of America (SHEA) and the

Infectious Diseases Society of America (IDSA).3 This article

focuses on these guidelines and reviews the current termi-

nology, etiology, pathogenesis, and treatment recommenda-

tions for CDI.

Epidemiology

Between 1% and 3% of healthy adults and up to 50% of

patients residing in hospitals and nursing homes are colo-

nized with and asymptomatically carry C. difﬁ cile in their

stool. Interestingly, the rates of colonization are higher in

neonates, with reported ranges between 5% and 70%, al-

though this population is less likely to develop the disease

than adults. It is believed that the lower rates of disease in

neonates are due to the immaturity of their intestinal cells,

which lack receptors for one of the organism’s disease-pro-

ducing toxins.4 C. difﬁ

cile is currently recognized as the most

common cause of nosocomial infectious diarrhea in nursing

homes, and overall mortality associated with CDI is esti-

mated to be more than 17% in the older adult population.5

CDI occurs in up to 8% of hospitalized patients and

results in an estimated $1.3 billion annually in healthcare

costs in the United States.6,7 As previously mentioned, CDI

is increasing in frequency and severity of disease. During the

1990s, the incidence of CDI in U.S. hospitals was approxi-

mately 30 to 40 cases per 100,000 persons; this number

increased to 84 per 100,000 in 2005. The number of fatal

CDI cases has also increased over this time.

A new strain of C. difﬁ cile, which has caused disease out-

breaks in the United States, Canada, Europe, and Asia, was

reported by the Centers for Disease Control and Prevention

(CDC) in 2004.8 This hypervirulent strain produces toxins

A and B in quantities 16-fold to 20-fold higher than seen in

other strains, and produces an additional third toxin, as well.

This strain has been referred to by several different names:

“North American pulsed-ﬁ eld gel electrophoresis type 1

(NAP-1)”; “restriction endonuclease pattern BI”; or “PCR

ribotype 027.” It is now commonly referred to as “NAP1/

BI/027.” Overall, the NAP1/BI/027 strain is considered to

be easier to transmit, more virulent, and more difﬁ cult to

treat than previously identiﬁ ed strains.9

Transmission

Transmission of C. difﬁ cile occurs via the fecal-oral route,

through ingestion of either the vegetative form or the spore

form of the microorganism. The spore form of C. difﬁ cile may

survive on inanimate surfaces and is resistant to alcohol

and routine disinfectants.10 Transmission of the microorgan-

ism occurs in healthcare facilities via the fecal-oral route

either directly from person to person (particularly from the

spore-contaminated hands of healthcare workers) or from

a contaminated environment, especially in institutions with

improper hygiene practices, isolation precautions, or envi-

ronmental cleaning practices.11

Pathogenesis

Disease pathogenesis of CDI involves the following factors:

disruption of normal enteric ﬂ ora; colonization with C. dif-

ﬁ cile; production by the microorganism of toxins A and B;

and mucosal injury and inﬂ ammation. In general, disease

progresses from a patient in an uncolonized state becom-

ing colonized with C. difficile to the organism producing

its toxins, ultimately resulting in CDI. The host’s immune

AN ONGOING CE PROGRAM OF THE UNIVERSITY OF FLORIDA

COLLEGE OF PHARMACY AND DRUG TOPICS

Elias B. Chahine, PharmD, BCPS

ASSISTANT PROFESSOR OF PHARMACY PRACTICE

LLOYD L. GREGORY SCHOOL OF PHARMACY

PALM BEACH ATLANTIC UNIVERSITY

WEST PALM BEACH, FLORIDA

Allana J. Sucher, PharmD, BCPS

ASSOCIATE PROFESSOR OF PHARMACY PRACTICE

REGIS UNIVERSITY SCHOOL OF PHARMACY

DENVER, COLORADO

An update on Clostridium

difﬁ cile infection

GETTY IMAGES/ROB LEWINE

Continuing Education

WWW.DRUGTOPICS.COM Month 2010

DRUG TOPICS

EDUCATIONAL OBJECTIVES

EARN CE CREDIT FOR THIS ACTIVITY AT WWW.DRUGTOPICS.COM

CREDIT: 2.0

Goal: To provide pharmacists with the knowledge nec-

essary to appropriately treat and prevent Clostridium

difﬁ cile infection.

After participating in this activity, pharmacists

should be able to:

● Identify the most common risk factors for

Clostridium difﬁ cile infection.

● Recommend the most appropriate

therapeutic regimen, including

pharmacologic and nonpharmacologic

agents, for the prevention and treatment of

C. difﬁ cile infection.

● List common adverse effects and drug

interactions of medications used to treat

C. difﬁ cile infection.

● Discuss infection-control strategies to

prevent the spread of C. difﬁ cile.

For questions concerning PRINT CEs, call 352-273-6275.

For questions concerning ONLINE CEs, call 877-252-7711.

To obtain immediate CE credit, take the test online at

www.drugtopics.com. Click on the “Continuing Educa-

tion” box on the Drug Topics home page, which will take

you to the CE site. Log in, find and click on this lesson,

and follow the three simple steps. Test results will be

displayed immediately and you can print the certificate

showing your earned CE credits.

The University of Florida College of Pharmacy is accredited

by the Accreditation Council for Pharmacy Education

as a provider of continuing pharmacy education

ACPE # 0012-9999-10-106-H01-P (K)

This lesson is not valid for CE credit after 12/31/2012.

WWW.DRUGTOPICS.COM

DRUG TOPICS

December 2010

Continuing Education

UPDATE: C. DIFFICILE

system helps protect an individual from the progression of

colonization to symptomatic disease. Those who are unable

to produce antitoxin antibodies are more likely to develop

severe disease and experience disease recurrence.1

The spore form of C. difﬁ cile is resistant to stomach acid

and, once ingested, is able to survive passage through the

stomach into the intestine, where it changes into its active

vegetative form. If normal enteric ﬂ ora are disrupted (as

may occur in the presence of antimicrobial agents), the veg-

etative form can reproduce within intestinal crypts. The bac-

teria then release toxins key to the development of disease.

Toxin A has proinﬂ ammatory activity, attracting neutrophils

and monocytes, and has enterotoxic activity, loosening tight

junctions between cells that line the colon. This allows the

cytotoxic toxin B to enter into and degrade epithelial cells

of the colon. The effect of both toxins causes colitis and may

cause the formation of pseudomembranes on the intestinal

wall that impair the normal process of reabsorption, ulti-

mately producing watery diarrhea.4

NAP1/BI/027 strains of C. difﬁ cile have an altered repres-

sor gene, which normally inhibits toxin production. These

isolates produce 16 to 20 times more quantities of toxins A

and B than other strains and also produce a unique third

toxin, referred to as binary toxin, which acts synergisti-

cally with toxins A and B to produce more severe forms

of disease.4

Risk factors

The most important modiﬁ able risk factor for acquiring CDI

is receipt of an antimicrobial agent. Although longer expo-

sure, exposure to multiple agents, or exposure to broader-

spectrum agents may increase a patient’s risk, even a single

dose of an antimicrobial agent increases the risk for C. difﬁ cile

colonization and symptomatic disease. In addition to use of

antimicrobial agents, there are several other risk factors for

CDI as indicated in Table 1.1,3,7,9,12,13 It is not clear whether

the use of acid-suppressing medications such as histamine-2

blockers or proton pump inhibitors increase a patient’s risk

for CDI; some studies have shown an epidemiologic associa-

tion, but others have found that the association is due to

confounding factors such as severity of illness and duration

of hospitalization. In addition to previously established risk

factors for disease, an increased incidence of CDI has been

reported in otherwise healthy individuals (“community-as-

sociated” infection) and in women during the peripartum

period.1,3,7,9,12,13

Clinical presentation

Although the median incubation period between the in-

gestion of C. difﬁ cile and the development of CDI is 2 to 3

days, this varies greatly among individuals. Patients may

become symptomatic soon after starting antimicrobial

therapy or several weeks after completion of an antimi-

crobial regimen.1,13

Clinical manifestations of CDI range from asymptom-

atic carriage of the organism to mildly or moderately acute

watery diarrhea, to severe disease characterized by pseudo-

membranous colitis. About 50% of patients will also have

fever, cramping, lower abdominal pain, and leukocytosis.

Complications of severe colitis include sepsis, toxic megaco-

lon (characterized by colonic dilation >6 cm), colonic ileus,

or bowel perforation. Patients who develop toxic megacolon

or an ileus usually have abdominal pain and distension but

may not develop diarrhea.1,12

The updated guidelines include proposed criteria for

the deﬁ nitions of mild or moderate, severe, and compli-

cated CDI. The 3 main criteria that are recommended for

consideration when choosing treatment include age (older

patients may have a decreased immune response to C. dif-

ﬁ cile toxins); peak white blood cell (WBC) count (this may

reﬂ ect the severity of colonic inﬂ ammation and potential

for complications); and elevated serum creatinine level

(this may indicate dehydration or inadequate renal perfu-

sion from severe diarrhea). These criteria for severity of CDI,

based on expert opinion, are included in Table 2.3 Because

treatment recommendations vary according to the patient’s

severity of illness, the clinician should be familiar with these

deﬁ nitions. However, the guidelines acknowledge that these

Risk factors associated with CDI

TABLE 1

Exposure risk factors Host risk factors

Exposure to antimicrobial agents

Duration of hospitalization

GI procedures (including feeding

tubes)

Proximity to patients with CDI

Advanced age

Comorbidities

Compromised immune system

(cancer chemotherapy, other im-

munosuppressive agents, HIV)

Abbreviations: CDI, Clostridium diﬃ cile infection; GI, gastrointestinal;

HIV, human immunode ciency virus

Source: Refs 1,3,7,9,12,13

Criteria for determining severity of illness

resulting from CDI

TABLE 2

De nition Supportive data

Mild or moderate infection WBC count ≤15,000 cells/μL and

SCr <1.5 times the level prior to

illness

Severe infection WBC count ≥15,000 cells/μL and

SCr >1.5 times the level prior to

illness

Severe, complicated infection Hypotension or shock, ileus,

megacolon

Abbreviations: CDI, Clostridium diﬃ cile infection; SCr, serum creatinine;

WBC, white blood cell

Source: Ref 3

WWW.DRUGTOPICS.COM December 2010

DRUG TOPICS

CONTINUING EDUCATION

criteria may need to be adjusted in the future as further data

become available.

Recurrent CDI is common, with some sources estimating

that up to 50% of patients experience recurrent infection

within 2 weeks after completion of therapy. Mechanisms

of recurrence include relapse of infection from the original

strain of C. difﬁ cile or re-infection with a new bacterial strain.

Identiﬁ ed risk factors for recurrent CDI include exposure to

antimicrobials during or after initial treatment for CDI and

an impaired immune response against C. difﬁ cile toxins. A

recently identiﬁ ed potential risk factor for recurrence may be

the use of metronidazole as treatment for CDI, particularly

in patients aged ≥65 years.

Diagnosis

Unless the clinician suspects that a patient has an ileus

due to CDI, it is recommended that only patients with

diarrhea (deﬁ ned as 3 or more unformed stools in ≤24 hr)

be tested for the presence of C. difﬁ cile. This is because of

the high rate of persons with asymptomatic colonization

with C. difﬁ cile. As previously stated, the diagnosis of CDI

includes both clinical symptoms of diarrhea and either a

positive stool test for C. difﬁ cile toxins or the presence of

pseudomembranous colitis.1

In the United States, the most commonly used method

for diagnosis of CDI is an enzyme immunoassay (EIA) test-

ing for C. difﬁ cile toxins A and B. EIA testing is relatively

easy to use and is associated with low labor costs. In addi-

tion, it has a rapid turnaround time of within 1 day, a high

speciﬁ city, and an estimated sensitivity of 63% to 94%.3

Other testing methods that are more sensitive for detec-

tion of C. difﬁ cile but are less commonly used, due to higher

cost and slower turnaround time, include a cell cytotoxin

assay (to detect toxin activity in stools) and stool culture.

It is recommended that stool cultures be performed for

molecular typing of strains for the purpose of epidemio-

logic studies. Another testing strategy recently studied is a

2-step testing method that uses EIA detection of glutamate

dehydrogenase (GDH), an enzyme produced by C. difﬁ cile,

as an initial screening tool. A negative result is considered

negative, while a positive assay requires additional testing

to determine whether the strain of C. difﬁ cile is toxin-pro-

ducing. This additional testing is performed with the cell

cytotoxin assay or stool culture. The 2-step GDH testing

method has a sensitivity of 85% to 95% and a speciﬁ city

of 89% to 99%.3

Direct visualization of pseudomembranes on the colonic

mucosa via endoscopy or histopathologic examination de-

ﬁ nitively establishes the diagnosis of pseudomembranous

colitis. However, because of its cost, the potential risk of

colonic perforation, and the availability of other tests for

diagnosis, it is usually reserved for times when a rapid

diagnosis is needed, as in the case of a patient with severe

disease, or when other tests are insensitive or the results

are delayed.3,13

Treatment

The goals of treatment for CDI are to stop the production

of toxins, eradicate the microorganism, attenuate signs and

symptoms of the disease, decrease disease recurrence, and

prevent associated morbidity and mortality.

The newly released guidelines recommend treating CDI

on the basis of disease severity.3 In cases of mild CDI, early

discontinuation of a precipitating antimicrobial will resolve

symptoms in 15% to 23% of patients. Most cases, however,

will require antimicrobial therapy directed against C. difﬁ cile

in addition to routine ﬂ uid and electrolyte replacement as

needed. Deﬁ nitions of disease severity are included in Table

2 (page 32), and adult dosages of antimicrobial agents used

for the treatment of CDI are listed in Table 3.3,14

First episode of CDI. For mild-to-moderate cases of

CDI, metronidazole 500 mg orally 3 times daily for 10 to 14

days is recommended. If the patient has a comorbidity or

drug interaction that prohibits the use of metronidazole, oral

vancomycin may be used instead. For severe cases of CDI,

vancomycin 125 mg orally 4 times daily for 10 to 14 days

is recommended. For severe, complicated cases, vancomy-

cin 500 mg orally or by nasogastric tube in a liquid form 4

times daily plus metronidazole 500 mg intravenously every

8 hours is recommended for 10 to 14 days at the discretion

Abbreviations: CDI, Clostridium diﬃ cile infection; IV, intravenous;

PO, by mouth; q, every

a Widely used

b No data support its use as monotherapy

c Dosages are for patients with normal renal and hepatic function

Source: Ref 14

Antibiotics Usual dosing regimenc

Vancomycina125 mg PO q 6 hra

250 mg – 500 mg PO q 6 hr

500 mg dissolved in 100 mL nor-

mal saline via retention enemab

q 6 hr

Metronidazolea250 mg PO q 6 hr

500 mg PO q 8 hra

500 mg IV q 8 hr

Nitazoxanide 500 mg PO q 12 hr

Bacitracin 25,000 U PO q 6 hr

Rifaximin 400 mg PO q 12 hr

200 mg PO q 8 hr

Rifampinb300 mg – 600 mg PO q 12 hr

Tigecycline 100 mg IV loading dose, followed

by 50 mg IV q 12 hr

Antimicrobial dosing recommendations

for treatment of CDI

TABLE 3

WWW.DRUGTOPICS.COM

DRUG TOPICS

December 2010

Continuing Education

UPDATE: C. DIFFICILE

of the clinician. No evidence supports the routine use of

oral metronidazole and oral vancomycin in combination.

If a patient has a complete ileus, adding vancomycin 500

mg in 100 mL of normal saline administered per rectum

as a retention enema may be considered. For critically ill

patients, colectomy may be considered.3 Vancomycin may

be administered as capsule, or the reconstituted intravenous

formulation may be administered orally after dilution in 1

ounce of water. The intravenous formulation may also be

used to prepare an enema.

Recurrent CDI. The updated guidelines recommend

treating the ﬁ rst recurrence of CDI with the same antibiotic

used for the initial episode as long as the recurrence occurs

at the severity level of the initial episode. The guidelines

recommend against the use of metronidazole beyond the

ﬁ rst recurrence of CDI, because of increased potential for

cumulative neurotoxicity and because stool concentration of

metronidazole tends to wane during recovery. For patients

with a second recurrence of infection, vancomycin should

be given via a tapered or pulsed regimen, such as the fol-

lowing example: at the end of the traditional vancomycin

regimen, continue with vancomycin 125 mg twice daily for

a week, then 125 mg once daily for a week, and 125 mg

every 2 to 3 days for 2 to 8 weeks.3

A closer look at antibiotic treatment options

Vancomycin. Vancomycin is currently the only antibiotic

that has been approved by FDA for the treatment of CDI.

Oral vancomycin achieves high concentrations in the intes-

tinal lumen and has little systemic absorption, which may

explain the rapid response to its use. The administration of 2

g of oral vancomycin daily results in a mean fecal concentra-

tion of 3,100 μg/g of stool, which far exceeds the minimum

inhibitory concentration (MIC) needed to inhibit 90% of

strains of C. difﬁ cile (MIC90 0.75 – 2 μg/mL).15 Intravenous

vancomycin should never be used for the treatment of CDI,

as subtherapeutic levels reach the gastrointestinal (GI) tract

when given via this route of administration. Higher dosing

of vancomycin is recommended for cases complicated by an

ileus to ensure that adequate therapeutic concentrations of

drug are reached within the lumen of the colon.16

Due to concerns regarding the emergence of vancomy-

cin-resistant enterococci (VRE), the use of vancomycin has

historically been limited to patients with multiple episodes

of CDI, patients intolerant to metronidazole, patients who

had not responded to 2 to 5 days of treatment with metro-

nidazole, or patients who were pregnant or breastfeeding.

The recent emergence of the more toxic epidemic NAP1/

BI/027 strain of C. difﬁ cile has caused a marked increase in

the use of vancomycin as a ﬁ rst-line antibiotic.

In addition, a recent prospective, randomized, double-

blind, placebo-controlled trial comparing vancomycin to

metronidazole in the treatment of 172 patients with CDI

stratiﬁ ed by disease severity showed that vancomycin was

superior to metronidazole for severe cases.17 The clinical

cure rate was 97% with vancomycin and 76% with met-

ronidazole (P=.02). Severe CDI was deﬁ ned as endoscopic

evidence of pseudomembranous colitis, treatment in the

intensive care unit (ICU), or the presence of 2 or more of

the following conditions within 48 hours of enrollment into

the study: patient aged >60 years; temperature >38.3°C; al-

bumin level <2.5 mg/dL; or WBC count >15,000 cells/mm3.

Factors associated with treatment failure of metronida-

zole in patients with severe disease included a low albumin

level, pseudomembranous colitis, or admission to the ICU. It

is hypothesized that superiority of vancomycin over metro-

nidazole for the treatment of severe disease may be due not

to drug resistance but to decreased blood ﬂ ow to the colon,

and therefore lower local concentrations of metronidazole in

patients with severe disease. For patients who meet criteria

for severe CDI, use of vancomycin for treatment of a ﬁ rst

episode or for disease recurrence is recommended.

Metronidazole. Metronidazole, although not FDA-ap-

proved for treatment of CDI, is widely used for that purpose.

Both oral and intravenous metronidazole achieve sufﬁ cient

concentrations in watery or semiformed stools. The admin-

istration of 1.2 g of oral metronidazole daily results in a

mean fecal concentration of 0.4 to 14.9 μg/g of stool, and

the administration of 1.5 g of intravenous metronidazole

per day results in a mean fecal concentration of 5.1 to 24.2

μg/g of stool. This exceeds the MIC needed to inhibit 90%

of existing strains of C. difﬁ cile (MIC90 0.2 – 2 μg/mL).

Historically, metronidazole has been preferred to vanco-

mycin because it is less expensive, it is less likely to induce

the development of VRE, and it can be given by IV to patients

who are unable to tolerate oral medications or to those with

an ileus.18,19 Even though a recent study questioned its efﬁ cacy,

oral metronidazole has been proven to be as efﬁ cacious as oral

vancomycin in patients with mild-to-moderate CDI.20

In a recent prospective, randomized, double-blind, pla-

cebo-controlled trial comparing vancomycin to metronida-

zole in the treatment of 172 patients with CDI stratiﬁ ed by

disease severity, the clinical cure rate was 90% with met-

ronidazole and 98% with vancomycin (P=.36).17 However,

when compared to vancomycin, metronidazole is associ-

ated with a slightly delayed response. It is also important for

the clinician to be aware that the NAP1/BI/027 strain of C.

difﬁ cile may not respond well to metronidazole therapy. In

addition, vancomycin is preferred over metronidazole in pa-

tients with severe episodes of CDI, patients with complicated

courses of CDI, patients with more than one recurrence of

CDI, and patients who are pregnant or breastfeeding.

Nitazoxanide. Nitazoxanide is an antiparasitic agent that

has been shown to be active against C. difﬁ cile. In a small

prospective, double-blind, randomized controlled trial com-

paring nitazoxanide with vancomycin for the treatment of

50 patients with CDI, the initial response rates were 77%

with nitazoxanide and 74% with vancomycin (95% conﬁ -

dence interval [CI], -24% to 28%) and the sustained response

rates were 89% with nitazoxanide and 78% with vancomy-

WWW.DRUGTOPICS.COM December 2010

DRUG TOPICS

CONTINUING EDUCATION

cin (95% CI, -18% to 35%).21 Although results of this small

study suggest that nitazoxanide may be as effective as van-

comycin for the treatment of patients with CDI, the authors

acknowledge that larger studies are needed before deﬁ nitive

conclusions about its place in therapy can be drawn.

In a prospective, randomized, double-blind study com-

paring nitazoxanide with metronidazole for the treatment

of 110 patients with CDI, the initial response rates were

89.5% with nitazoxanide and 82.4% with metronidazole

(95% CI, -7.1% to 25.5%) and the sustained response rates

were 65.8% with nitazoxanide given for 7 days, 74.3% with

nitazoxanide given for 10 days, and 57.6% with metroni-

dazole for 10 days (P=.34).22 The authors concluded that

nitazoxanide is at least as effective as metronidazole in the

treatment of patients with CDI.

In an open-label study, nitazoxanide was also shown to

be effective in 26 (74%) of 35 patients who did not re-

spond to treatment with metronidazole for CDI; however,

7 patients later had recurrent disease yielding an estimated

overall cure rate of 54%.23 Although it is not currently

recommended in the updated guidelines for routine use,

nitazoxanide may represent an alternative option for the

treatment of initial and recurrent CDI.

Bacitracin. Bacitracin, a commonly used topical antibi-

otic for the treatment of staphylococcal infections, has been

shown to be active against C. difﬁ cile when given in an oral

formulation.24 The injection formulation is extemporaneously

prepared and ﬂ avored to improve palatability. Although par-

enteral bacitracin therapy is associated with renal failure, oral

administration achieves low, nontoxic serum concentrations.

Studies conducted in the 1980s showed that oral bacitracin

was as effective as oral vancomycin in resolving the symp-

toms of CDI, but that it was less effective in eradicating C.

difﬁ cile and its toxin from the stools of patients.24,25 The fact

that some patients still had detectable toxins in stools did not

affect the number of clinical recurrences in one study.

Rifaximin. Rifaximin, a rifamycin antibiotic with limited

oral bioavailability, is approved by FDA for the treatment of

travelers’ diarrhea and for prophylaxis against hepatic encepha-

lopathy. As it is active in vitro against C. difﬁ cile and achieves a

high concentration in the colon, rifaximin is currently under

investigation for the treatment of CDI. In a recent uncontrolled

case series, 4 of 6 patients with multiple recurrences of CDI

responded to rifaximin therapy immediately after completing

their last course of vancomycin therapy.26

In another uncontrolled case series, 8 women who each

experienced 4 to 8 episodes of diarrhea due to C. difﬁ cile were

given a 2-week course of rifaximin therapy immediately

after completing their last course of vancomycin therapy.

Seven of the 8 patients experienced no further recurrence

of diarrhea. However, resistance of C. difﬁ cile to this agent has

already been reported, so its use is not recommended until

further clinical trials have been performed.27,28

Rifampin. Rifampin has been used as adjunctive ther-

apy with either vancomycin or metronidazole for the treat-

ment of CDI, as it has been shown to have potent in vitro

activity against C. difﬁ cile and anecdotal reports have shown

success with its use.29 A small prospective, randomized, sin-

gle-blinded study was performed to compare metronidazole

monotherapy versus metronidazole plus rifampin for the

treatment of 39 patients with a primary episode of CDI.29

After 10 days of treatment, no difference was observed

between treatment groups in terms of time to symptom

improvement (6.5 days vs 9 days; P=.74), proportion of pa-

tients with relapse (38% vs 42%; P=1.0), or time to ﬁ rst

relapse (16 days vs 26 days; P=.23). The authors concluded

that rifampin does not have a role for use as routine adjunc-

tive therapy with metronidazole for the treatment of CDI.

Tigecycline. Tigecycline is a parenteral glycylcycline

antibiotic approved by FDA for the treatment of compli-

cated skin and skin-structure infections, complicated intra-

abdominal infections, and community-acquired pneumonia.

Tigecycline is active in vitro against C. difﬁ cile and has been

reported successful in the treatment of CDI in an uncon-

trolled case series of 4 patients with severe CDI, including

patients with ileus and patients refractory to vancomycin

and metronidazole.30-32 None of the tigecycline-treated pa-

tients relapsed within 3 months of therapy, which makes

tigecycline an attractive potential addition to the arsenal of

antibiotics directed against C. difﬁ cile.

Antibiotic agents available outside the U.S.

Teicoplanin. Teicoplanin, a glycopeptide similar to vancomy-

cin but not available in the United States, has been shown to

have excellent activity against C. difﬁ cile and similar efﬁ cacy to

oral vancomycin in prospective randomized studies.33-35

Fusidic acid. Fusidic acid is a commonly used topical

antibiotic in Europe and Canada for the treatment of skin

infections due to gram-positive bacteria. Although oral fu-

sidic acid is effective for the treatment of CDI, its use is as-

sociated with a higher rate of relapse when compared to

vancomycin or metronidazole.35,36

Investigational antibiotic agents

Fidaxomicin. Fidaxomicin, also known by several other

names including OPT-80 or diﬁ micin, is a novel macrocyclic

antibiotic that exhibits potent in vitro activity against C. difﬁ cile.

It has a narrow spectrum of activity and lacks activity against

Gram-negative bacteria, thus potentially limiting its effect on

GI ﬂ ora. Studies have shown that oral ﬁ daxomicin achieves

high concentrations in stool while maintaining low plasma

concentrations. Preliminary results from phase 2 and 3 clinical

trials involving patients with CDI showed favorable outcomes

for diﬁ micin when compared to oral vancomycin.37

Ramoplanin. Ramoplanin, a novel glycolipodepsipep-

tide nonabsorbable antibiotic, showed a potential beneﬁ t

against C. difﬁ cile in both in vitro studies and an in vivo ham-

ster model. One study showed that all isolates of C. difﬁ cile,

independent of their levels of susceptibility to vancomycin

or metronidazole, were susceptible to ramoplanin.38 The

WWW.DRUGTOPICS.COM

DRUG TOPICS

December 2010

Continuing Education

UPDATE: C. DIFFICILE

results of a second study suggested that ramoplanin may

be more effective than vancomycin at eradicating C. difﬁ cile

spores and preventing spore recrudescence.39 The FDA ap-

proved a Special Protocol Assessment non-inferiority trial

against vancomycin for phase 3.

Nonantibiotic treatment options

Anion-binding resins. The anion-binding resins include

cholestyramine and colestipol. Cholestyramine is theoreti-

cally useful for the treatment of CDI because it binds to the

disease-producing toxins secreted by C. difﬁ cile without alter-

ing GI ﬂ ora. However, although there are some reports of

patients with disease relapses responding to cholestyramine,

not enough clinical evidence supports its routine use for

CDI. In addition, cholestyramine may bind to an oral van-

comycin, thus potentially decreasing its effect. It is impor-

tant for the clinician to note that other medications must be

given 1 hour before or 4 to 6 hours after an anion-binding

resin to maintain therapeutic efﬁ cacy.4,14,40

One randomized, placebo-controlled trial of colestipol in

38 patients with postoperative diarrhea showed no differ-

ence in fecal excretion of C. difﬁ cile toxins as compared to

placebo. Therefore the use of colestipol for the treatment of

CDI is not justiﬁ ed.41

Toxin-binding polymer. Tolevamer is a nonantimi-

crobial toxin-binding polymer that has been studied for

the treatment of CDI. Although it showed early promise

from in vitro, animal, and phase 2 studies, a randomized,

double-blind, phase 3 clinical trial showed that tolevamer

was less effective than either vancomycin or metronidazole

for CDI.42,43 Interestingly, among patients who did achieve

clinical success with tolevamer, use of this agent was as-

sociated with signiﬁ cantly lower rates of disease recurrence.

Probiotics. Probiotics, which are live microorganisms

that confer a potential health beneﬁ t when administered

in adequate amounts, have been used in practice for the

treatment and prevention of CDI.44 Examples of probiotics

used for this purpose include Biﬁ dobacterium spp., Lactobacil-

lus rhamnosus GG, and Saccharomyces spp.45 Although some

small studies and meta-analyses have provided data sug-

gesting that prophylactic use of probiotics may decrease the

incidence of CDI, no large, prospective, randomized trials

have been designed to assess the beneﬁ ts of probiotics for

the prevention or treatment of CDI.

One small open-label trial assessing the effect of S. boular-

dii added to oral vancomycin in patients with recurrent CDI

showed that 11 of 13 patients had no further recurrences of

infection with this combination.46

In addition to a lack of data, product dosages of probi-

otics are not standardized, and there have been reports of

fungemia resulting from Saccharomyces spp. and bacteremia

resulting from Lactobacillus spp., especially in patients who

are critically ill or immunocompromised. Thus, the guide-

lines recommend against using probiotics to prevent primary

CDI until further, larger trials are conducted. The guidelines

acknowledge that adjunctive S. boulardii may be useful for

treatment of recurrent CDI, but caution against its use in

those who are immunocompromised or critically ill.

Immunomodulators. Intravenous immunoglobulin

(IVIG) has been used in the treatment of CDI with variable

success.47 IVIG is formed through pooling immunoglobulin

(containing antitoxin A and B antibodies) from donors and

providing this passive immunization to a host who is unable

to form an adequate protective immune response. Because

low levels of IgG antitoxin are associated with increased

disease severity, IVIG may compensate for this failed host

immune response to C. difﬁ cile toxins.

Although there are no prospective, randomized, con-

trolled clinical trials of IVIG, case reports and case series

suggest that it may be efﬁ cacious for patients with severe or

recurrent CDI.48 There is conﬂ icting evidence, however, as

published retrospective reviews showed no clinical beneﬁ t

with the use of IVIG in patients with severe disease. Ad-

ditional drawbacks to IVIG therapy include its unknown

optimal dose, high cost, limited supply, and adverse effect

proﬁ le. The updated guidelines refer to IVIG as a potential

option for the treatment of recurrent disease.

Recently, a phase 2 randomized, double-blind, placebo-

controlled trial of 2 human monoclonal antibodies against C.

difﬁ cile toxins A and B was performed.49 This study showed

a signiﬁ cantly decreased rate of recurrence of CDI when

the simultaneously administered monoclonal antibodies

were added to antibiotic agents. No signiﬁ cant difference

was seen in the incidence of adverse effects between the

monoclonal antibody and placebo groups. The ultimate role

of monoclonal antibodies for the treatment of CDI is yet to

be determined.

Corticosteroids. Given that C. difﬁ cile can cause diarrhea

and colitis from an inﬂ ammatory reaction to its toxins, and

that corticosteroids have been shown to be effective in in-

ﬂ ammatory bowel disease, clinicians may try these agents in

patients with refractory CDI. A preliminary report describing

the use of intravenous methylprednisolone followed by oral

prednisone in a child with severe CDI refractory to treat-

ment with metronidazole and vancomycin suggests that cor-

ticosteroids may be effective.50 The steroid dosing regimen

used in this study was IV methylprednisolone 2 mg/kg/day

in 2 divided doses for 16 days, followed by oral prednisone 2

mg/kg/day in 2 divided doses, with a gradual taper over the

course of 1 month. Further studies are necessary to conﬁ rm

this case-report observation.

Stool transplantation. Fecal bacteriotherapy is deﬁ ned

as the transfer of stool from one person to another. Also

known as fecal transplant, this process seeks to recolonize

the normal bacterial ﬂ ora of the intestines.51 In the largest

retrospective review of patients who received donor stool by

nasogastric tube for recurrent CDI, 15 of 18 patients were

cured, 1 patient experienced a single recurrence, and 2 pa-

tients died of unrelated illnesses.52 No adverse effects were

associated with stool treatment. Several other published re-

WWW.DRUGTOPICS.COM December 2010

DRUG TOPICS

CONTINUING EDUCATION

ports have attested to positive results from the use of fecal

bacteriotherapy for recurrent episodes of CDI.53 The updated

guidelines list fecal transplant as a potential option for recur-

rent CDI if the donor is properly screened for potentially

transmissible agents and if the logistical issues of collection

and administration can be adequately addressed.

Vaccines. A C. difﬁ cile vaccine containing toxoids A and

B is currently under development for prevention of infec-

tion in high-risk individuals. Preliminary results demonstrated

safety and immunogenicity in healthy volunteers as well as

in patients with recurrent CDI.54,55 These results must still be

validated in large randomized controlled trials, because there

is concern that the vaccine may not be effective in those who

are unable to develop an adequate immune response to C.

difﬁ cile toxins, as is common in patients with recurrent disease.

The vaccine manufacturer is currently recruiting U.S. patients

with CDI for a phase 2 randomized, double-blind, placebo-

controlled dose-ranging study of the vaccine.56

Antiperistaltics. Drugs that inhibit intestinal peristasis,

including loperamide, diphenoxylate, and narcotics, should

generally be avoided in patients with infectious diarrhea. These

agents may hinder the ﬂ ushing of GI bacteria such as C. difﬁ cile

and its associated toxins. It is hypothesized that these agents

may prolong the mucosal exposure to toxins, possibly predis-

posing patients to complications such as toxic megacolon.57

A recently published literature review challenges this long-

standing hypothesis.58 The authors found that all cases of CDI

treated with an antimotility agent that subsequently developed

complications also failed to receive an appropriate anti-C. dif-

ﬁ cile antimicrobial agent. This review concluded that further

controlled studies are needed to determine the role of antiperi-

staltics (because these agents may assist with faster resolution

of diarrhea) for the treatment of CDI. Until the results of a

prospective clinical trial are available, most practitioners would

withhold antiperistaltic agents from a patient with CDI.

Evaluation of therapeutic outcomes

Efﬁ cacy. When treating patients with CDI, clinicians should

closely monitor them for resolution of signs and symptoms of

infection. A patient’s temperature and WBC count should nor-

malize within 48 to 72 hours of start of effective therapy, and

diarrhea should improve within 48 hours and resolve by day

6 to day 7 of treatment. In light of the risk that infection may

recur, close follow-up of patients is warranted. If a patient’s dis-

ease progresses after the start of treatment, a complication may

be present, and additional or alternative therapeutic options,

including surgery, may need to be considered.12,13

Safety. The common side effects of antimicrobial agents

available in the United States for the treatment of CDI are

listed in Table 4.14 More serious but less commonly encoun-

tered side effects are discussed below.

Although oral vancomycin is not systemically absorbed

to a signiﬁ cant extent in patients with an intact intestinal

mucosa, there may be some systemic absorption when the

intestinal mucosa is severely altered, as is common in severe

CDI. Monitoring for nephrotoxicity is therefore recommend-

ed in patients taking oral vancomycin who have a severely

damaged intestinal mucosa.

Metronidazole carries a black-box carcinogenicity warning

based on animal data. Its prolonged use may cause neuropathy

and seizures. In addition, metronidazole inhibits CYP3A4 and

displaces warfarin from protein-binding sites, thus potentially

increasing a patient’s international normalized ratio (INR) and

risk for bleeding. Close monitoring of INR is highly recom-

mended in patients receiving both metronidazole and warfarin.

Parenteral bacitracin may cause renal failure resulting from

tubular and glomerular necrosis. Although nephrotoxicity is

not expected when bacitracin is used orally, one might consider

monitoring renal function in patients with severe CDI.

Anion-binding resins. When using these as adjunctive

therapy, the clinician should take into account the fact that

these agents have been shown to bind to oral vancomycin

and have the potential to bind to other oral antibiotics and

drugs, and thus compromise their efﬁ cacy.

Tigecycline has the potential to cause permanent dis-

coloration of teeth and is not recommended in pregnant

patients and in patients aged <8 years. Rare cases of pan-

creatitis have also been reported with this agent.

Prevention. CDI often occurs after administration of

antimicrobials, so judicious and appropriate use of antimi-

crobials is extremely important to reduce the risk of CDI.

Implementation of formal antimicrobial stewardship pro-

grams targeted at reducing the frequency and duration of

antimicrobial therapy and restriction of certain high-risk an-

timicrobials such as clindamycin and broad-spectrum agents

have been shown to reduce outbreaks of C. difﬁ cile.3 Discon-

Abbreviations: CDI, Clostridium diﬃ cile infection; GI, gastrointestinal

Source: Ref 14

Antibiotics Side effects

Vancomycin Bitter taste, nausea/vomiting,

fever/chills

Metronidazole Metallic taste, GI upset, disulﬁ -

ram-like reaction with alcohol,

discoloration of urine, confusion

Nitazoxanide Abdominal pain, diarrhea, nau-

sea/vomiting, headache

Bacitracin Nausea/vomiting, hypotension

Rifaximin Headache, dizziness, peripheral

edema, hypersensitivity reactions

Rifampin Red-orange discoloration of body

μ uids, GI upset, increased liver

function tests

Tigecycline Nausea/vomiting, diarrhea,

increased liver function tests

Common side effects of antimicrobials

used to treat CDI

TABLE 4

WWW.DRUGTOPICS.COM

DRUG TOPICS

December 2010

Continuing Education

UPDATE: C. DIFFICILE

tinuation of unnecessary acid-suppressing medications may

also be helpful. Prophylactic use of anti-CDI therapy such as

metronidazole or vancomycin, also known as early preven-

tive therapy, has been used in certain patients considered

to be at high risk for the development of disease, despite

the absence of supporting literature for this routine practice.

Administration of probiotics is not recommended to prevent

primary CDI because of lack of supporting evidence and

because of increased risk of bacteremia and fungemia, par-

ticularly in severely ill and immunocompromised patients.3

Close attention to personal hygiene such as the use of a

dedicated commode for each patient, isolation precautions

such as the use of single rooms, barrier precautions such as

the use of gloves and gowns, and appropriate hygiene and

environmental cleaning are also very important in prevent-

ing transmission of healthcare-associated infections, including

CDI. Oral and particularly rectal thermometers should be re-

placed with single-use disposable thermometers to minimize

potential spread of this microorganism.

As mentioned previously, the spore form of C. difﬁ cile may

survive on inanimate surfaces for long periods of time and is

resistant to alcohol and routine disinfectants. Thus, healthcare

professionals should wash their hands using soap and water

instead of alcohol-based hand rubs. Chlorine-based solutions

such as hypochlorite and isocyanuric acid are preferred for

environmental cleaning over traditional quaternary ammo-

nium-based agents, as the latter are not sporicidal. A recent

study showed that aerosolization of C. difﬁ cile occurs in patients

with symptomatic CDI.10 Therefore the necessity for isolation

of patients in single rooms as soon as possible after the onset

of diarrhea cannot be overemphasized.

Role of the pharmacist

CDI is an emerging threat to patient safety. Pharmacists play

a vital role in managing the disease by educating patients and

healthcare professionals about risk factors for CDIs. Pharmacists

are in a key position to refer patients with symptoms consistent

with CDI to a clinician for further work-up. Pharmacists are also

well positioned to recommend appropriate antimicrobial treat-

ment regimens, as well as to monitor and counsel patients about

drug therapy to achieve optimal outcomes, while minimizing

side effects and unnecessary toxicity. Pharmacists trained in in-

fectious diseases are essential for the establishment of antimicro-

bial stewardship programs targeted at reducing outbreaks of C.

difﬁ cile. Finally, pharmacists may also serve on infection control

committees and emphasize the importance of hygiene and en-

vironmental cleaning in reducing transmission of C. difﬁ cile.

References

1. Poutanen SM, Simor AE. Clostridium difﬁ cile-associated diarrhea in

adults. CMAJ. 2004;171:51–58.

2. Vasa CV, Glatt AE. Effectiveness and appropriateness of empiric met-

ronidazole for Clostridium difﬁ cile-associated diarrhea. Am J Gastroenterol.

2003;98:354–358.

3. Cohen SH, Gerding DN, Johnson S, Kelly CP, et al; Society for

Healthcare Epidemiology of America; Infectious Disease Society of

America. Clinical practice guidelines for Clostridium difﬁ cile infection

in adults: 2010 update by the Society for Healthcare Epidemiology

of America (SHEA) and the Infectious Diseases Society of America

(IDSA). Infect Control Hosp Epidemiol. 2010;31:431–455.

4. McMaster-Baxter NL, Musher DM. Clostridium difficile: Recent

epidemiologic ﬁ ndings and advances in therapy. Pharmacotherapy.

2007;27:1029–1039.

5. Crogan NL, Evans BC. Clostridium difﬁ cile: An emerging epidemic in

nursing homes. Geriatr Nurs. 2007;28:161–164.

6. Dubberke ER, Wertheimer AI. Review of current literature on the

economic burden of Clostridium difﬁ cile infection. Infect Control Hosp Epi-

demiol. 2009;30:57–66.

7. Lefﬂ er DA, Lamont JT. Treatment of Clostridium difﬁ cile-associated

disease. Gastroenterology. 2009;136:1899–1912.

8. Centers for Disease Control and Prevention. Information about the

current epidemic strain of Clostridium difﬁ cile. http://www.cdc.gov/ncidod/

dhqp/id_CdiffFAQ_newstrain.html. Accessed November 17, 2010.

9. Kelly CP, LaMont JT. Clostridium difﬁ cile – more difﬁ cult than ever.

N Engl J Med. 2008;359:1932–1940.

10. Best EL, Fawley WN, Parnell P, Wilcox MH. The potential for air-

borne dispersal of Clostridium difﬁ cile from symptomatic patients. Clin

Infect Dis. 2010;50:1450–1457.

11. Sunenshine RH, McDonald LC. Clostridium difﬁ cile-associated dis-

ease: New challenges from an established pathogen. Cleve Clin J Med.

2006;73:187–197.

12. Stanley JD, Burns RP. Clostridium difﬁ cile and the surgeon. Am Surg.

2010;76:235–244.

13. Efron PA, Mazuski JE. Clostridium difﬁ cile colitis. Surg Clin North Am.

2009;89:483–500.

14. Lacy CF, Armstrong LL, Goldman MP, Lance LL, eds. Drug Informa-

tion Handbook 2009-2010. 18th ed. Hudson, OH: Lexi-Comp Inc; 2009.

15. Shannon-Lowe J, Matheson NJ, Cooke FJ, Aliyu SH. Preven-

tion and medical management of Clostridium difﬁ cile infection. BMJ.

2010;340:c1296.

16. Fekety R, Silva J, Kauffman C, Buggy B, Deery HG. Treatment of

antibiotic-associated Clostridium difﬁ cile colitis with oral vancomycin:

Comparison of two dosage regimens. Am J Med. 1989;86:15–19.

17. Zar FA, Bakkanagari SR, Moorthi KM, Davis MB. A comparison

of vancomycin and metronidazole for the treatment of Clostridium

difﬁ cile-associated diarrhea, stratiﬁ ed by disease severity. Clin Infect Dis.

2007;45:302–307.

18. Teasley DG, Gerding DN, Olson MM et al. Prospective randomised

trial of metronidazole versus vancomycin for Clostridium difﬁ cile-associ-

ated diarrhoea and colitis. Lancet. 1983;2:1043–1046.

19. Johnson S, Peterson LR, Gerding DN. Intravenous metronida-

zole and Clostridium difﬁ cile-associated diarrhea or colitis. J Infect Dis.

1989;160:1087–1088.

20. Johnson S, Homann SR, Bettin KM et al. Treatment of asymp-

tomatic Clostridium difﬁ cile carriers (fecal excretors) with vancomycin

or metronidazole. A randomized, placebo-controlled trial. Ann Intern

Med. 1992;117:297–302.

21. Musher DM, Logan N, Bressler AM, Johnson DP, Rossignol JF.

Nitazoxanide versus vancomycin in Clostridium difﬁ cile infection: a ran-

domized, double-blind study. Clin Infect Dis. 2009;48:e41–e46.

WWW.DRUGTOPICS.COM December 2010

DRUG TOPICS

CONTINUING EDUCATION

22. Musher DM, Logan N, Hamill RJ, et al. Nitazoxanide for the treat-

ment of Clostridium difﬁ cile colitis. Clin Infect Dis. 2006;43:421–427.

23. Musher DM, Logan N, Mehendiratta V et al. Clostridium difﬁ cile

colitis that fails conventional metronidazole therapy: Response to ni-

tazoxanide. J Antimicrob Chemother. 2007;59:705–710.

24. Dudley MN, McLaughlin JC, Carrington G, et al. Oral bacitracin vs

vancomycin therapy for Clostridium difﬁ cile-induced diarrhea. A random-

ized double-blind trial. Arch Intern Med. 1986;146:1101–1104.

25. Young GP, Ward PB, Bayley N, et al. Antibiotic-associated colitis

due to Clostridium difﬁ cile: Double-blind comparison of vancomycin with

bacitracin. Gastroenterology. 1985;89:1038–1045.

26. Johnson S, Schriever C, Patel U, et al. Rifaximin redux: Treatment of

recurrent Clostridium difﬁ cile infections with rifaximin immediately post-

vancomycin treatment. Anaerobe. 2009;15:290–291.

27. Johnson S, Schriever C, Galang M, Kelly CP, Gerding DN. Interrup-

tion of recurrent Clostridium difﬁ cile-associated diarrhea episodes by serial

therapy with vancomycin and rifaximin. Clin Infect Dis. 2007;44:846–848.

28. O’Connor JR, Galang MA, Sambol SP, et al. Rifampin and rifaximin

resistance in clinical isolates of Clostridium difﬁ cile. Antimicrob Agents Che-

mother. 2008;52:2813–2817.

29. Lagrotteria D, Holmes S, Smieja M, Smaill F, Lee C. Prospective,

randomized inpatient study of oral metronidazole versus oral metro-

nidazole and rifampin for treatment of primary episode of Clostridium

difﬁ cile-associated diarrhea. Clin Infect Dis. 2006;43:547–552.

30. Herpers BL, Vlaminckx B, Burkhardt O, et al. Intravenous tigecycline

as adjunctive or alternative therapy for severe refractory Clostridium dif-

ﬁ cile infection. Clin Infect Dis. 2009;48:1732–1735.

31. Lu CL, Liu CY, Liao CH, et al. Severe and refractory Clostridium difﬁ cile

infection successfully treated with tigecycline and metronidazole. Int J

Antimicrob Agents. 2010;35:311–312.

32. Hawser SP. Activity of tigecycline against recent European clinical

isolates of Clostridium difﬁ cile. Int J Antimicrob Agents. 2010;35:97–98.

33. Nelson R. Antibiotic treatment for Clostridium difﬁ cile-associated diar-

rhea in adults. Cochrane Database Syst Rev. 2007;(3):CD004610.

34. de Lalla F, Nicolin R, Rinaldi E, et al. Prospective study of oral teico-

planin versus oral vancomycin for therapy of pseudomembranous colitis

and Clostridium difﬁ cile-associated diarrhea. Antimicrob Agents Chemother.

1992;36:2192–2196.

35. Wenisch C, Parschalk B, Hasenhündl M, Hirschl AM, Graninger

W. Comparison of vancomycin, teicoplanin, metronidazole, and fusidic

acid for the treatment of Clostridium difﬁ cile-associated diarrhea. Clin Infect

Dis. 1996;22:813–818.

36. Wullt M, Odenholt I. A double-blind randomized controlled

trial of fusidic acid and metronidazole for treatment of an initial epi-

sode of Clostridium difﬁ

cile-associated diarrhea. J Antimicrob Chemother.

2004;54:211–216.

37. Sullivan KM, Spooner LM. Fidaxomicin: A macrocyclic antibiotic

for the management of Clostridium difﬁ cile infection. Ann Pharmacother.

2010;44:352–359.

38. Peláez T, Alcalá L, Alonso R, et al. In vitro activity of ramoplanin

against Clostridium difﬁ cile, including strains with reduced susceptibility

to vancomycin or with resistance to metronidazole. Antimicrob Agents

Chemother. 2005;49:1157–1159.

39. Freeman J, Baines SD, Jabes D, Wilcox MH. Comparison of the

efﬁ cacy of ramoplanin and vancomycin in both in vitro and in vivo

models of clindamycin-induced Clostridium difﬁ cile infection. J Antimicrob

Chemother. 2005;56:717–725.

40. Parmar M. Treating C. difﬁ cile (author reply). CMAJ. 2005;172:448.

41. Mogg GA, George RH, Youngs D, et al. Randomized controlled trial

of colestipol in antibiotic-associated colitis. Br J Surg. 1982;69:137–139.

42. Baines SD, Freeman J, Wilcox MH. Tolevamer is not efﬁ cacious in

the neutralization of cytotoxin in a human gut model of Clostridium dif-

ﬁ cile infection. Antimicrob Agents Chemother. 2009;53:2202–2204.

43. Louie T, Gerson M, Grimard D, et al. Results of a phase III trial

comparing tolevamer, vancomycin and metronidazole in patients with

Clostridium difﬁ cile-associated diarrhea (CDAD) [abstract K-425a]. In:

Program and abstracts of the 47th Interscience Conference on Antimi-

crobial Agents and Chemotherapy (ICAAC). Washington, DC: American

Society for Microbiology; 2007:219.

44. Williams NT. Probiotics. Am J Health-Syst Pharm. 2010;67:449–458.

45. Segarra-Newnham M. Probiotics for Clostridium difﬁ cile-associated

diarrhea: Focus on Lactobacillus rhamnosus GG and Saccharomyces boulardii.

Ann Pharmacother. 2007;41:1212–1221.

46. Surawicz CM, McFarland LV, Elmer G, Chinn J. Treatment of recur-

rent Clostridium difﬁ cile colitis with vancomycin and Saccharomyces boular-

dii. Am J Gastroenterol. 1989;84:1285–1287.

47. Juang P, Skledar SJ, Zgheib NK, et al. Clinical outcomes of intrave-

nous immune globulin in severe Clostridium difﬁ cile-associated diarrhea.

Am J Infect Control. 2007;35:131–137.

48. Abougergi MS, Broor A, Cui W, Jaar BG. Intravenous immuno-

globulin for the treatment of severe Clostridium difﬁ cile colitis: An obser-

vational study and review of the literature. J Hosp Med. 2010;5:E1–E9.

49. Lowy I, Molrine DC, Leav BA, et al. Treatment with monoclonal an-

tibodies against Clostridium difficile toxins. N Engl J Med. 2010;362:197–205.

50. Cavagnaro C, Berezin S, Medow MS. Corticosteroid treatment of

severe, non-responsive Clostridium difﬁ cile-induced colitis. Arch Dis Child.

2003;88:342–344.

51. Bakken JS. Fecal bacteriotherapy for recurrent Clostridium difﬁ cile

infection. Anaerobe. 2009;15:285–289.

52. Aas J, Gessert CE, Bakken JS. Recurrent Clostridium difﬁ cile colitis:

Case series involving 18 patients treated with donor stool administered

via a nasogastric tube. Clin Infect Dis. 2003;36:580–585.

53. You DM, Franzos MA, Holman RP. Successful treatment of fulmi-

nant Clostridium difﬁ cile infection with fecal bacteriotherapy. Ann Intern

Med. 2008;148:632–633.

54. Sougioultzis S, Kyne L, Drudy D, et al. Clostridium difﬁ cile toxoid

vaccine in recurrent C. difficile-associated diarrhea. Gastroenterology.

2005;128:764–770.

55. Kotloff K, Wasserman SS, Losonsky GA, et al. Safety and immuno-

genicity of increasing doses of a Clostridium difﬁ cile toxoid vaccine admin-

istered to healthy adults. Infect Immun. 2001;69:988–995.

56. U.S. National Institutes of Health. Study of a Clostridium difﬁ cile toxoid

vaccine (ACAM-CDIFF™) in subjects with Clostridium difﬁ cile infection.

http://clinicaltrials.gov/ct2/show/study/NCT00772343. Accessed Sep-

tember 19, 2010.

57. Gerding D. Antimotility agents for the treatment of Clostridium difﬁ cile

infection: Is the juice worth the squeeze? Clin Infect Dis. 2009;48:606–608.

58. Koo HL, Koo DC, Musher DM, DuPont HL. Antimotility agents for

the treatment of Clostridium difﬁ cile diarrhea and colitis. Clin Infect Dis.

2009;48:598–605.

WWW.DRUGTOPICS.COM

DRUG TOPICS

December 2010

Continuing Education

TEST QUESTIONS

1. Clostridium dif cile (C. dif cile) is classi ed as an:

a. Aerobic, gram-negative coccus c. Anaerobic, gram-negative rod

b. Aerobic, gram-positive coccus d. Anaerobic, gram-positive rod

2. Which of the following statements is TRUE?

a. Roughly 70% of healthy adults asymptomatically carry C. dif cile in their stool.

b. C. dif cile is more likely to cause disease in neonates than in adults.

c. C. dif cile infections are decreasing in frequency and severity of disease.

d. The newly identi ed NAP1/BI/027 strain of C. dif cile is more virulent

than previously identi ed strains.

3. Which of the following statements correctly identi es the pathogenesis of CDI?

a. If normal enteric ﬁ ora are disrupted, the spore form of the microorganism

reproduces within the intestinal crypts and releases toxins.

b. If normal enteric ﬁ ora are disrupted, the spore form of the microorganism

reproduces within the stomach and degrades its epithelial cells.

c. If normal enteric ﬁ ora are disrupted, the vegetative form of the

microorganism reproduces within intestinal crypts and releases toxins.

d. If normal enteric ﬁ ora are disrupted, the vegetative form of the microorganism

reproduces within the stomach and degrades its epithelial cells.

4. Which of the following is a risk factor for the development of CDI?

a. Genitourinary procedure c. Receipt of cancer chemotherapy

b. Receipt of an antiplatelet agent d. Schizophrenia

5. Which of the following would be classi ed as having severe, complicated CDI?

a. 47-year-old woman with white blood cell (WBC) count = 15,000 and

serum creatinine increase from 1 mg/dL to 1.6 mg/dL

b. 48-year-old woman with WBC = 16,000, serum creatinine increase from

1 mg/dL to 1.5 mg/dL, and ileus

c. 50-year-old man with WBC = 16,000, serum creatinine increase from

1 mg/dL to 1.3 mg/dL, and diabetes mellitus

d. 55-year-old man with WBC = 20,000 and serum creatinine increase from

1 mg/dL to 2 mg/dL

6. What is the most commonly used test for the diagnosis of CDI?

a. Endoscopy to visualize pseudomembranes

b. Enzyme-linked immunoassay for C. dif cile toxins A and B

c. Presence of WBC in stool

d. Stool culture

7. What is the recommended length of treatment of metronidazole for a 58-year-

old man who was recently diagnosed with a mild  rst-time case of CDI?

a. 5 to 7 days b. 7 to 10 days c. 10 to 14 days d. 14 to 17 days

8. A 55-year-old man recently diagnosed with CDI has a medical history that includes

alcohol and cocaine abuse. He refuses to undergo alcohol detoxi cation. His pre-

infection laboratory values include: WBC 10,000 cells/μL; serum creatinine (SCr)

0.8 mg/dL; temperature (T) 37.4° C. His laboratory values after C. dif cile include:

WBC 13,500 cells/μL; SCr 1 mg/dL; T 37.6°C. Which of the following treatment

regimens is the MOST appropriate for this patient?

a. Metronidazole 500 mg PO q 8 hours c. Rifaximin 400 mg PO q 12 hours

b. Metronidazole 500 mg IV q 8 hours d. Vancomycin 125 mg PO q 6 hours

9. After receiving antibiotics for healthcare-associated pneumonia, a 73-year-old

woman is diagnosed with a severe CDI. She has no known drug allergies and can

tolerate oral medications. Which treatment regimen would be  rst-line for her?

a. Metronidazole 500 mg PO q 8 hours

b. Metronidazole 500 mg IV q 8 hours

c. Rifaximin 400 mg PO q 12 hours

d. Vancomycin 125 mg PO q 6 hours

10. A 70-year-old male patient is transferred from the medical ward to the ICU

for management of severe, complicated CDI associated with hypotension

and acute renal failure. What treatment would you recommend?

a. Metronidazole 500 mg IV q 8 hours plus metronidazole 500 mg PO every 6 hours

b. Metronidazole 500 mg IV q 8 hours plus vancomycin 500 mg PO every 6 hours

c. Rifaximin 400 mg IV q 12 hours plus vancomycin 500 mg PO every 6 hours

d. Vancomycin 1 g IV q 12 hours

11. Which of the following antibiotics has FDA approval for treatment of CDI?

a. Bacitracin b. Metronidazole c. Nitazoxanide d. Vancomycin

12. When used to treat CDI, by which route is vancomycin most commonly given?

a. Intramuscular b. Intravenous c. Oral d. Retention enema

13. Which treatment is recommended for a 30-year-old pregnant woman diagnosed

with CDI after receiving antimicrobial therapy for community-acquired pneumonia?

a. Metronidazole 250 mg PO q 6 hours

b. Metronidazole 500 mg IV q 6 hours

c. Tigecycline 100 mg IV x 1 dose, then 50 mg IV q 12 hours

d. Vancomycin 125 mg PO q 6 hours

14. Which of the following statements is CORRECT?

a. A vaccine to prevent C. dif cile is currently under development.

b. Cholestyramine may be administered at the same time as oral vancomycin.

c. Corticosteroids may be useful because they bind to disease-producing toxins.

d. Probiotics are safe for use in immunocompromised patients.

15. Which of the following agents may prolong mucosal exposure to C. dif cile’s

toxins and predispose patients to toxic megacolon?

a. Cholestyramine c. Loperamide

b. Intravenous immunoglobulin (IVIG) d. Nitazoxanide

16. When treating patients with C. difﬁ cile infection, a patient’s temperature

should normalize within __________ and diarrhea should resolve within

__________ of effective therapy.

a. 12 hours; 2 days b. 48 hours; 7 days c. 96 hours; 12 days d. 5 days; 17 days

17. Which adjunctive treatment may cause red-orange discoloration of body ﬁ uids?

a. Bacitracin b. Metronidazole c. Nitazoxanide d. Rifampin

18. A 63-year-old man with a history of atrial  brillation and diabetes mellitus

takes amiodarone 200 mg PO daily, glipizide 10 mg PO daily, and warfarin

2.5 mg PO daily. Following a recent diagnosis of CDI, he is prescribed oral

metronidazole therapy. Which of the drug interactions below may occur?

a. Metronidazole may decrease amiodarone levels and increase arrhythmia risk.

b. Metronidazole may decrease warfarin levels and increase risk of clot formation.

c. Metronidazole may increase warfarin levels and increase risk of bleeding.

d. Metronidazole does not interact with any of his medications.

19. Which of the following strategies has NOT been shown to control CDI effectively?

a. Antimicrobial stewardship programs

b. Cleaning rectal thermometers with alcohol

c. Isolation precautions

d. Restriction of high-risk antimicrobials

20. Which of the following will reduce the risk of transmission of C. dif cile in a

healthcare facility?

a. The use of alcohol-based hand rubs

b. The use of quaternary ammonium-based agents for cleaning

c. The use of rectal thermometers

d. The use of soap and water to wash hands

Write your answers on the form appearing on page 41 (photocopies of the answer form

are acceptable) or on a separate sheet of paper. Mark the most appropriate answer.

UPDATE: C. DIFFICILE

WWW.DRUGTOPICS.COM December 2010

DRUG TOPICS

ANSWER FORM

Are you employed by a chain? If so, which one?

EVALUATION OF CE

CONTINUING EDUCATION

ACPE # 0012-9999-10-106-H01-P (K)

C. Difficile CE Quiz Answers December 2010 Test questions start on page 40

1. a. b. c. d. 5. a. b. c. d. 9. a. b. c. d. 13. a. b. c. d. 17. a. b. c. d.

2. a. b. c. d. 6. a. b. c. d. 10. a. b. c. d. 14. a. b. c. d. 18. a. b. c. d.

3. a. b. c. d. 7. a. b. c. d. 11. a. b. c. d. 15. a. b. c. d. 19. a. b. c. d.

4. a. b. c. d. 8. a. b. c. d. 12. a. b. c. d. 16. a. b. c. d. 20. a. b. c. d.

Not valid for CE credit after 12/31/2012

REGISTRANT INFORMATION

Name:

(Last) (First) (M.I.) Phone

Address: E-mail address:

(Street)

City: State: ZIP:

Florida pharmacists: Please provide your license number

Amount enclosed: □ $6.00 for this lesson

□ $54.00 for any 12 lessons you take

over the next year, starting from the

date you sign up

□ Already series-enrolled for 2010

Submit your check (payable to The University of Florida) and form to:

University of Florida College of Pharmacy

P.O. Box 113195, Gainesville, FL 32611-3195

E-mail address: continuinged@cop.ufl.edu

Fees not refundable or transferable

For questions concerning PRINT CEs, call 352-273-6275.

For questions concerning ONLINE CEs, call 877-252-7711.

2010 CEU CREDIT REQUEST

To obtain immediate CE credit, take the test online at www.drugtopics.com. Just click on the “Continuing Education” box on the

Drug Topics

home page, which will take you to the CE site. Log in, find and click on this lesson, and follow the three simple steps. Test results will be displayed

immediately and you can print the certificate showing your earned CE credits. The cost of the online test for this lesson is $6.

Strongly Agree Agree Disagree Strongly Disagree

1. The objectives listed on page 31 were met.

If not, please describe:

2. The author wrote an article of value.

3. The information was clear and presented well.

4. The learning activity (quiz) was effective.

5. The article content was useful and relevant.

6. The article was educational and not promotional.

Drug Topics is conducting an evaluation of this CE article. Please check the box that best reﬂ ects your

opinion of the evaluation questions. Please keep this evaluation attached to your answer form.

WWW.DRUGTOPICS.COM

DRUG TOPICS

December 2010

Regulatory & Legal

compounding pharmacy in

Florida, Franck’s Lab, Inc.,

which engages in veterinary

compounding, has been embroiled in

a struggle with the FDA since it com-

pounded a vitamin supplement for ad-

ministration to 21 polo ponies during

the U.S. Open Polo Championships in

April 2009. When they were injected

with the compounded vitamin supple-

ment, all 21 ponies collapsed and died.

As a result, FDA sought to obtain

a preliminary injunction against the

pharmacy to prevent it from engaging

in further veterinary compounding.

FDA makes its case

The agency argued that the pharmacy was

violating a compliance policy guidance

issued by FDA in 2003 for purposes of

clarifying its interpretation of the Animal

Medicinal Drug Use Clariﬁ cation Act. FDA

asserted that any “compounding from

bulk substances,” such as the Florida phar-

macy had done, “or unapproved drugs

renders the compounded drugs unsafe

as a matter of law, and thus adulterated

in violation of 21 USC § 351(a)(5).” FDA

argued that the bulk drugs constitute new

drugs and therefore require FDA regula-

tory approvals before they may be intro-

duced in interstate commerce.

The pharmacy responds

The pharmacy responded by asserting that

FDA has no authority to ban veterinary

drug compounding from bulk product.

In its defense, the pharmacy stated that

the “use of bulk ingredients to compound

commercially unavailable preparations is a

core part of the traditional pharmacy prac-

tice” which is left for purposes of oversight

to the individual states and not to the fed-

eral government and FDA.

The pharmacy did not dispute that

FDA may have regulatory authority over

the manufacturing of veterinary pharma-

ceuticals if it can show that the pharmacy

is truly engaged in the “manufacturing”

process. But, the pharmacy pointed out,

FDA is not permitted “to override state

law and impose a blanket ban on tradi-

tional pharmacy compounding practices.”

The pharmacy also noted that the leg-

islative history of the Federal Food, Drug,

and Cosmetic Act (FDCA) proves that

Congress intentionally left regulation of

compounding to state regulatory oversight

as part of pharmacy practice, while pre-

serving regulatory oversight of manufac-

turing as a task of the federal government.

Finally, the defendant pharmacy

stated that even if the FDCA provided

FDA with the right to regulate veteri-

nary compounding, FDA would need

to promulgate regulations through for-

mal rule-making procedures that would

include a notice-and-comment period,

rather than through the issuance of an

informal compliance policy guide.

Motion denied

In summary, the judge denied FDA’s mo-

tion for preliminary injunction without

issuing an opinion. However, the court is

currently reviewing the request for per-

manent injunction.

This case illustrates the important

point that legal tension arises when phar-

macy compounding is alleged by FDA to

reach the level of manufacturing. FDA

regulates manufacturing, while state laws

and regulations govern pharmacy com-

pounding. If FDA is able to demonstrate

that a compounding pharmacy was in

fact engaged in manufacturing, then it

will be able to exercise its authority over

the pharmacy, and state regulatory over-

sight would not apply.

Other cases have analyzed this matrix,

and this body of law continues to evolve

as different parties and efforts — including

by the federal government through the

FDA; by state governments and boards

of pharmacy; and through the various

pharmacy practice acts — attempt to draw

the ﬁ ne line whereby compounding and

manufacturing are deﬁ ned.

These articles are not intended as legal ad-

vice and should not be used as such. When a

legal question arises, the pharmacist should

consult an attorney familiar with pharmacy

law in his or her state.

Ned Milenkovich is a member at McDonald

Hopkins, LLC, and chairs its Drug &

Pharmacy Practice Group. He is also a

member of the Illinois State Board of

Pharmacy. Contact him at 312-642-1480 or

at nmilenkovich@mcdonaldhopkins.com.

LEGAL COMPLIANCE

FDA loses preliminary injunction case

against vet-compounding pharmacy

Ned Milenkovich, PharmD, JD

If FDA can demonstrate

that a compounding

pharmacy was in

fact engaged in

manufacturing, then it

will be able to exercise

its authority over the

pharmacy, and state

regulatory oversight

would not apply.

Visit the LEXAPRO website at www.lexapro.com

See the effect of LEXAPRO

Proven efﬁ cacy in MDD in adolescents aged

12 to 17, and in MDD and GAD in adults1-5

In adolescents aged 12 to 17 with

Major Depressive Disorder (MDD)*1

In adults with MDD and Generalized

Anxiety Disorder (GAD)1

WARNING: SUICIDALITY AND ANTIDEPRESSANT DRUGS

Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and

young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of

Lexapro or any other antidepressant in a child, adolescent or young adult must balance this risk with the clinical need. Short-term

studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was

a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric

disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy

should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and

caregivers should be advised of the need for close observation and communication with the prescriber. Lexapro is not approved for use

in pediatric patients less than 12 years of age.

Contraindications

• Lexapro is contraindicated in patients taking monoamine oxidase inhibitors (MAOIs). There have been reports of serious, sometimes

fatal, reactions with some cases resembling neuroleptic malignant syndrome (NMS) and serotonin syndrome. Features may include

hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid ﬂ uctuations of vital signs, and mental status changes

that include extreme agitation progressing to delirium and coma. These reactions have also been reported in patients who have

recently discontinued SSRI treatment and have been started on an MAOI. Serotonin

syndrome was reported for two patients who were concomitantly receiving linezolid,

an antibiotic which has MAOI activity. Lexapro should not be used in combination with

an MAOI or within 14 days of discontinuing an MAOI. MAOIs should not be initiated within

14 days of discontinuing Lexapro.

• Lexapro is contraindicated in patients taking pimozide

or with hypersensitivity to escitalopram or citalopram.

Please see additional Important Safety Information on adjacent page.

* LEXAPRO is indicated as an integral part of a total treatment program for MDD.

Drug treatment may not be indicated for all adolescents with this syndrome.

LEXAPRO and citalopram are not the same1,6,7

• LEXAPRO is approved for MDD and GAD1;

citalopram is not approved for GAD.6

• LEXAPRO is approved for MDD in adolescents

aged 12 to 17 years1; citalopram is not.6

There is no generic available for LEXAPRO

Please see accompanying brief summary of Prescribing Information

for LEXAPRO, including Boxed Warning.

Lexapro (escitalopram oxalate) is indicated for the acute and maintenance treatment of major depressive disorder (MDD) in adults

and adolescents aged 12-17 years. Lexapro is also indicated for the acute treatment of generalized anxiety disorder (GAD) in adults.

IMPORTANT SAFETY INFORMATION

Warnings and Precautions

• All patients treated with antidepressants should be monitored appropriately and observed closely for clinical worsening,

suicidality and unusual changes in behavior, especially within the ﬁ rst few months of treatment or when changing the dose.

Consideration should be given to changing the therapeutic regimen, including discontinuing medication, in patients whose

depression is persistently worse, who are experiencing emergent suicidality or symptoms that might be precursors to worsening

depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient’s presenting

symptoms. Families and caregivers of patients treated with antidepressants should be alerted about the need to monitor patients

daily for the emergence of agitation, irritability, unusual changes in behavior, or the emergence of suicidality, and report such

symptoms immediately. Prescriptions for Lexapro should be written for the smallest quantity of tablets, consistent with good

patient management, in order to reduce the risk of overdose.

• A major depressive episode may be the initial presentation of bipolar disorder. In patients at risk for bipolar disorder, treating

such an episode with an antidepressant alone may increase the likelihood of precipitating a mixed/manic episode. Prior to

initiating treatment with an antidepressant, patients should be adequately screened to determine if they are at risk for bipolar

disorder. Lexapro should be used cautiously in patients with a history of mania or seizure disorder. Lexapro is not approved for

use in treating bipolar depression.

• The concomitant use of Lexapro with other SSRIs, SNRIs, triptans, tryptophan, antipsychotics or other dopamine antagonists

is not recommended due to potential development of life-threatening serotonin syndrome or neuroleptic malignant syndrome

(NMS)-like reactions. Reactions have been reported with SNRIs and SSRIs alone, including Lexapro, but particularly with drugs

that impair metabolism of serotonin (including MAOIs). Management of these events should include immediate discontinuation

of Lexapro and the concomitant agent and continued monitoring.

• Patients should be monitored for adverse reactions when discontinuing treatment with Lexapro. During marketing of Lexapro and

other SSRIs and SNRIs, there have been spontaneous reports of adverse events occurring upon discontinuation, including dysphoric

mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesias), anxiety, confusion, headache, lethargy, emotional

lability, insomnia and hypomania. A gradual dose reduction rather than abrupt cessation is recommended whenever possible.

• SSRIs and SNRIs have been associated with clinically signiﬁ cant hyponatremia. Elderly patients and patients taking diuretics or

who are otherwise volume-depleted appear to be at a greater risk. Discontinuation of Lexapro should be considered in patients

with symptomatic hyponatremia and appropriate medical intervention should be instituted.

• SSRIs (including Lexapro) and SNRIs may increase the risk of bleeding. Patients should be cautioned that concomitant use of

aspirin, NSAIDs, warfarin or other anticoagulants may add to the risk.

• Patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain

that Lexapro does not affect their ability to engage in such activities.

• Lexapro should be used with caution in patients with severe renal impairment or with diseases or conditions that alter metabolism

or hemodynamic responses. In subjects with hepatic impairment, clearance of racemic citalopram was decreased and plasma

concentrations were increased. The recommended dose of Lexapro in hepatically impaired patients is 10 mg/day.

• For pregnant or nursing mothers, Lexapro should be used only if the potential beneﬁ t justiﬁ es the potential risk to the fetus or child.

Adverse Reactions

• In clinical trials of MDD, the most common adverse reactions in adults treated with Lexapro (approximately 5% or greater

and at least twice the incidence of placebo) were nausea (15% vs 7%), insomnia (9% vs 4%), ejaculation disorder (9%

vs <1%), fatigue (5% vs 2%), somnolence (6% vs 2%), and increased sweating (5% vs 2%). In pediatric patients, the overall

proﬁ le of adverse reactions was similar to that seen in adults; however, the following additional adverse reactions were

reported at an incidence of at least 2% for Lexapro and greater than placebo: back pain, urinary tract infection, vomiting, and

nasal congestion.

• In clinical trials of GAD, the most common adverse reactions in adults treated with Lexapro (approximately 5% or greater and at

least twice the incidence of placebo) were nausea (18% vs 8%), ejaculation disorder (14% vs 2%), insomnia (12% vs 6%), fatigue

(8% vs 2%), decreased libido (7% vs 2%) and anorgasmia (6% vs <1%).

There is no generic available

for LEXAPRO

References: 1. LEXAPRO [package insert]. St. Louis, Mo: Forest Pharmaceuticals, Inc.; 2009. 2. Emslie GJ, Ventura D, Korotzer A,

Tourkodimitris S. Escitalopram in the treatment of adolescent depression: a randomized placebo-controlled multisite trial.

J Am Acad Child Adolesc Psychiatry. 2009;48:721-729. 3. Burke WJ, Gergel I, Bose A. Fixed-dose trial of the single isomer SSRI

escitalopram in depressed outpatients. J Clin Psychiatry. 2002;63:331-336. 4. Davidson JRT, Bose A, Korotzer A, Zheng H. Escitalopram

in the treatment of generalized anxiety disorder: double-blind, placebo controlled, ﬂ exible-dose study. Depress Anxiety. 2004;19:23 4-

240. 5. Wade A, Lemming OM, Hedegaard KB. Escitalopram 10 mg/day is effective and well tolerated in a placebo-controlled

study in depression in primary care. Int Clin Psychopharmacol. 2002;17:95-102. 6. Celexa [package insert]. St. Louis, Mo: Forest

Pharmaceuticals, Inc.; 2009. 7. Mork A, Kreilgaard M, Sanchez C. The R-enantiomer of citalopram counteracts escitalopram-induced

increase in extracellular 5-HT in the frontal cortex of freely moving rats. Neuropharmacology. 2003;45:167-173.

LEXAPRO®(escitalopram oxalate) TABLETS/ORAL SOLUTION Rx Only

Brief Summary: For complete details, please see full Prescribing Information for Lexapro.

WARNINGS: SUICIDALITY AND ANTIDEPRESSANT DRUGS

Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and

young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of

Lexapro or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term

studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was

a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric

disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on anti depressant

therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior.

Families and caregivers should be advised of the need for close observation and communication with the prescriber. Lexapro is not

approved for use in pediatric patients less than 12 years of age.

[See Warnings and Precautions: Clinical Worsening and Suicide Risk,

Patient Counseling Information: Information for Patients, and Used in Specific Populations: Pediatric Use].

INDICATIONS AND USAGE: Major Depressive Disorder-Lexapro (escitalopram) is indicated for the acute and maintenance treatment of major

depressive disorder in adults and in adolescents 12 to 17 years of age [

see Clinical Studies

]. A major depressive episode (DSM-IV) implies a

prominent and relatively persistent (nearly every day for at least 2 weeks) depressed or dysphoric mood that usually interferes with daily func-

tioning, and includes at least five of the following nine symptoms: depressed mood, loss of interest in usual activities, significant change in weight

and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed

thinking or impaired concentration, a suicide attempt or suicidal ideation. Generalized Anxiety Disorder-Lexapro is indicated for the acute

treatment of Generalized Anxiety Disorder (GAD) in adults [

see Clinical Studies

]. Generalized Anxiety Disorder (DSM-IV) is characterized by

excessive anxiety and worry (apprehensive expectation) that is persistent for at least 6 months and which the person finds difficult to control. It

must be associated with at least 3 of the following symptoms: restlessness or feeling keyed up or on edge, being easily fatigued, difficulty

concentrating or mind going blank, irritability, muscle tension, and sleep disturbance.

CONTRAINDICATIONS: Monoamine oxidase inhibitors (MAOIs)-Concomitant use in patients taking monoamine oxidase inhibitors (MAOIs) is

contraindicated [

see Warnings and Precautions

]. Pimozide-Concomitant use in patients taking pimozide is contraindicated [

see Drug

Interactions

]. Hypersensitivity to escitalopram or citalopram-Lexapro is contraindicated in patients with a hypersensitivity to escitalopram or

citalopram or any of the inactive ingredients in Lexapro.

WARNINGS AND PRECAUTIONS: Clinical Worsening and Suicide Risk-Patients with major depressive disorder (MDD), both adult and pedi-

atric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in

behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a

known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There

has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of

suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant

drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and

young adults (ages 18-24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase

in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants com-

pared to placebo in adults aged 65 and older. The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive

compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients.

The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials

(median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among

drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of

suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs. placebo), however, were relatively

stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per

1000 patients treated) are provided in Table 1.

TABLE 1

Age Range Drug-Placebo Difference in Number of Cases

of Suicidality per 1000 Patients Treated

Increases Compared to Placebo

<18 14 additional cases

18-24 5 additional cases

Decreases Compared to Placebo

25-64 1 fewer case

65 6 fewer cases

No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclu-

sion about drug effect on suicide. It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However,

there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the

recurrence of depression. All patients being treated with antidepressants for any indication should be monitored appropriately and observed

closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy,

or at times of dose changes, either increases or decreases. The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hos-

tility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric

patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric.

Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal

impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality. Consideration should

be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently

worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially

if these symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. If the decision has been made to discon-

tinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with

certain symptoms [

see Dosage and Administration

]

Families and caregivers of patients being treated with antidepressants for major depressive

disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of

agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report

such symptoms immediately to health care providers. Such monitoring should include daily observation by families and caregivers [

see also

Patient Counseling Information

]

Prescriptions for Lexapro should be written for the smallest quantity of tablets consistent with good patient

management, in order to reduce the risk of overdose. Screening Patients for Bipolar Disorder-A major depressive episode may be the initial

presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an anti -

depressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of

the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients

with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a

detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that Lexapro is not approved

for use in treating bipolar depression. Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions-The development of a

potentially life-threatening serotonin syndrome or Neuroleptic Malignant Syndrome (NMS)-like reactions have been reported with SNRIs and

SSRIs alone, including Lexapro treatment, but particularly with concomitant use of serotonergic drugs (including triptans) with drugs which

impair metabolism of serotonin (including MAOIs), or with antipsychotics or other dopamine antagonists. Serotonin syndrome symptoms may

include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyper -

thermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).

Serotonin syndrome, in its most severe form can resemble neuroleptic malignant syndrome, which includes hyperthermia, muscle rigidity, auto-

nomic instability with possible rapid fluctuation of vital signs, and mental status changes. Patients should be monitored for the emergence of

serotonin syndrome or NMS-like signs and symptoms. The concomitant use of Lexapro with MAOIs intended to treat depression is contraindi-

cated. If concomitant treatment of Lexapro with a 5-hydroxytryptamine receptor agonist (triptan) is clinically warranted, careful observation of

the patient is advised, particularly during treatment initiation and dose increases. The concomitant use of Lexapro with serotonin precursors

(such as tryptophan) is not recommended. Treatment with Lexapro and any concomitant serotonergic or antidopaminergic agents, including

antipsychotics, should be discontinued immediately if the above events occur and supportive symptomatic treatment should be initiated.

Discontinuation of Treatment with Lexapro-During marketing of Lexapro and other SSRIs and SNRIs (serotonin and norepinephrine reuptake

inhibitors), there have been spontaneous reports of adverse events occurring upon discontinuation of these drugs, particularly when abrupt,

including the following: dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesias such as electric shock sensa-

tions), anxiety, confusion, headache, lethargy, emotional lability, insomnia, and hypomania. While these events are generally self-limiting, there

have been reports of serious discontinuation symptoms. Patients should be monitored for these symptoms when discontinuing treatment with

Lexapro. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur

following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered.

Subsequently, the physician may continue decreasing the dose but at a more gradual rate [

see Dosage and Administration

]. Seizures-Although

anticonvulsant effects of racemic citalopram have been observed in animal studies, Lexapro has not been systematically evaluated in patients

with a seizure disorder. These patients were excluded from clinical studies during the product’s premarketing testing. In clinical trials of Lexapro,

cases of convulsion have been reported in association with Lexapro treatment. Like other drugs effective in the treatment of major depressive

disorder, Lexapro should be introduced with care in patients with a history of seizure disorder. Activation of Mania/Hypomania-In placebo-

controlled trials of Lexapro in major depressive disorder, activation of mania/hypomania was reported in one (0.1%) of 715 patients treated with

Lexapro and in none of the 592 patients treated with placebo. One additional case of hypomania has been reported in association with Lexapro

treatment. Activation of mania/hypomania has also been reported in a small proportion of patients with major affective disorders treated with

racemic citalopram and other marketed drugs effective in the treatment of major depressive disorder. As with all drugs effective in the treatment

of major depressive disorder, Lexapro should be used cautiously in patients with a history of mania. Hyponatremia-Hyponatremia may occur as

a result of treatment with SSRIs and SNRIs, including Lexapro. In many cases, this hyponatremia appears to be the result of the syndrome of

inappropriate antidiuretic hormone secretion (SIADH), and was reversible when Lexapro was discontinued. Cases with serum sodium lower than

110 mmol/L have been reported. Elderly patients may be at greater risk of developing hyponatremia with SSRIs and SNRIs. Also, patients tak-

ing diuretics or who are otherwise volume depleted may be at greater risk [

see Geriatric Use

]. Discontinuation of Lexapro should be considered

in patients with symptomatic hyponatremia and appropriate medical intervention should be instituted. Signs and symptoms of hyponatremia

include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls. Signs and

symptoms associated with more severe and/or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death.

Abnormal Bleeding-SSRIs and SNRIs, including Lexapro, may increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal

anti-inflammatory drugs, warfarin, and other anticoagulants may add to the risk. Case reports and epidemiological studies (case-control and

cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastroin-

testinal bleeding. Bleeding events related to SSRIs and SNRIs use have ranged from ecchymoses, hematomas, epistaxis, and petechiae to

life-threatening hemorrhages. Patients should be cautioned about the risk of bleeding associated with the concomitant use of Lexapro and

NSAIDs, aspirin, or other drugs that affect coagulation. Interference with Cognitive and Motor Performance-In a study in normal volunteers,

Lexapro 10 mg/day did not produce impairment of intellectual function or psychomotor performance. Because any psychoactive drug may impair

judgment, thinking, or motor skills, however, patients should be cautioned about operating hazardous machinery, including automobiles, until

they are reasonably certain that Lexapro therapy does not affect their ability to engage in such activities. Use in Patients with Concomitant

Illness-Clinical experience with Lexapro in patients with certain concomitant systemic illnesses is limited. Caution is advisable in using Lexapro

in patients with diseases or conditions that produce altered metabolism or hemodynamic responses. Lexapro has not been systematically

evaluated in patients with a recent history of myocardial infarction or unstable heart disease. Patients with these diagnoses were generally exclud-

ed from clinical studies during the product’s premarketing testing. In subjects with hepatic impairment, clearance of racemic citalopram was

decreased and plasma concentrations were increased. The recommended dose of Lexapro in hepatically impaired patients is 10 mg/day [

see

Dosage and Administration

]. Because escitalopram is extensively metabolized, excretion of unchanged drug in urine is a minor route of elimina-

tion. Until adequate numbers of patients with severe renal impairment have been evaluated during chronic treatment with Lexapro, however, it

should be used with caution in such patients [

see Dosage and Administration

]. Potential for Interaction with Monoamine Oxidase Inhibitors-

In patients receiving serotonin reuptake inhibitor drugs in combination with a monoamine oxidase inhibitor (MAOI), there have been reports of

serious, sometimes fatal, reactions including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital

signs, and mental status changes that include extreme agitation progressing to delirium and coma. These reactions have also been reported in

patients who have recently discontinued SSRI treatment and have been started on an MAOI. Some cases presented with features resembling

neuroleptic malignant syndrome. Furthermore, limited animal data on the effects of combined use of SSRIs and MAOIs suggest that these drugs

may act synergistically to elevate blood pressure and evoke behavioral excitation. Therefore, it is recommended that Lexapro should not be used

in combination with an MAOI, or within 14 days of discontinuing treatment with an MAOI. Similarly, at least 14 days should be allowed after

stopping Lexapro before starting an MAOI. Serotonin syndrome has been reported in two patients who were concomitantly receiving linezolid,

an antibiotic which is a reversible non-selective MAOI.

ADVERSE REACTIONS: Clinical Trials Experience-Because clinical studies are conducted under widely varying conditions, adverse reaction

rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect

the rates observed in practice. Clinical Trial Data Sources; Pediatrics (6 -17 years)-Adverse events were collected in 576 pediatric patients

(286 Lexapro, 290 placebo) with major depressive disorder in double-blind placebo-controlled studies. Safety and effectiveness of Lexapro in

pediatric patients less than 12 years of age has not been established. Adults-Adverse events information for Lexapro was collected from 715

patients with major depressive disorder who were exposed to escitalopram and from 592 patients who were exposed to placebo in double-blind,

placebo-controlled trials. An additional 284 patients with major depressive disorder were newly exposed to escitalopram in open-label trials. The

adverse event information for Lexapro in patients with GAD was collected from 429 patients exposed to escitalopram and from 427 patients

exposed to placebo in double-blind, placebo-controlled trials. Adverse events during exposure were obtained primarily by general inquiry and

recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of

the proportion of individuals experiencing adverse events without first grouping similar types of events into a smaller number of standardized

event categories. In the tables and tabulations that follow, standard World Health Organization (WHO) terminology has been used to classify

reported adverse events. The stated frequencies of adverse reactions represent the proportion of individuals who experienced, at least once, a

treatment-emergent adverse event of the type listed. An event was considered treatment-emergent if it occurred for the first time or worsened

while receiving therapy following baseline evaluation. Adverse Events Associated with Discontinuation of Treatment; Major Depressive

Disorder; Pediatrics (6 -17 years)-Adverse events were associated with discontinuation of 3.5% of 286 patients receiving Lexapro and 1% of

290 patients receiving placebo. The most common adverse event (incidence at least 1% for Lexapro and greater than placebo) associated with

discontinuation was insomnia (1% Lexapro, 0% placebo). Adults-Among the 715 depressed patients who received Lexapro in placebo-controlled

trials, 6% discontinued treatment due to an adverse event, as compared to 2% of 592 patients receiving placebo. In two fixed-dose studies,

the rate of discontinuation for adverse events in patients receiving 10 mg/day Lexapro was not significantly different from the rate of discon -

tinuation for adverse events in patients receiving placebo. The rate of discontinuation for adverse events in patients assigned to a fixed dose of

20 mg/day Lexapro was 10%, which was significantly different from the rate of discontinuation for adverse events in patients receiving 10 mg/day

Lexapro (4%) and placebo (3%). Adverse events that were associated with the discontinuation of at least 1% of patients treated with Lexapro,

and for which the rate was at least twice that of placebo, were nausea (2%) and ejaculation disorder (2% of male patients). Generalized Anxiety

Disorder; Adults-Among the 429 GAD patients who received Lexapro 10-20 mg/day in placebo-controlled trials, 8% discontinued treatment due

to an adverse event, as compared to 4% of 427 patients receiving placebo. Adverse events that were associated with the discontinuation of at

least 1% of patients treated with Lexapro, and for which the rate was at least twice the placebo rate, were nausea (2%), insomnia (1%), and

fatigue (1%). Incidence of Adverse Reactions in Placebo-Controlled Clinical Trials; Major Depressive Disorder; Pediatrics (6 -17 years)-The

overall profile of adverse reactions in pediatric patients was generally similar to that seen in adult studies, as shown in Table 2. However, the

following adverse reactions (excluding those which appear in Table 2 and those for which the coded terms were uninformative or misleading)

were reported at an incidence of at least 2% for Lexapro and greater than placebo: back pain, urinary tract infection, vomiting, and nasal

congestion. Adults-The most commonly observed adverse reactions in Lexapro patients (incidence of approximately 5% or greater and approx-

imately twice the incidence in placebo patients) were insomnia, ejaculation disorder (primarily ejaculatory delay), nausea, sweating increased,

fatigue, and somnolence. Table 2 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse events that occurred

among 715 depressed patients who received Lexapro at doses ranging from 10 to 20 mg/day in placebo-controlled trials. Events included are

those occurring in 2% or more of patients treated with Lexapro and for which the incidence in patients treated with Lexapro was greater than

the incidence in placebo-treated patients.

TABLE 2

Treatment-Emergent Adverse Reactions Observed with a Frequency of 2%

and Greater Than Placebo for Major Depressive Disorder

Adverse Reaction Lexapro Placebo

(N=715) (N=592)

Autonomic Nervous System Disorders

Dry Mouth 6% 5%

Sweating Increased 5% 2%

Central & Peripheral Nervous System Disorders

Dizziness 5% 3%

Gastrointestinal Disorders

Nausea 15% 7%

Diarrhea 8% 5%

Constipation 3% 1%

Indigestion 3% 1%

Abdominal Pain 2% 1%

General

Influenza-like Symptoms 5% 4%

Fatigue 5% 2%

Psychiatric Disorders

Insomnia 9% 4%

Somnolence 6% 2%

Appetite Decreased 3% 1%

Libido Decreased 3% 1%

Respiratory System Disorders

Rhinitis 5% 4%

Sinusitis 3% 2%

Urogenital

Ejaculation Disorder1,2 9% <1%

Impotence23% <1%

Anorgasmia32% <1%

1Primarily ejaculatory delay.

2Denominator used was for males only (N=225 Lexapro; N=188 placebo).

3Denominator used was for females only (N=490 Lexapro; N=404 placebo).

Generalized Anxiety Disorder; Adults-The most commonly observed adverse reactions in Lexapro patients (incidence of approximately 5% or

greater and approximately twice the incidence in placebo patients) were nausea, ejaculation disorder (primarily ejaculatory delay), insomnia,

fatigue, decreased libido, and anorgasmia. Table 3 enumerates the incidence, rounded to the nearest percent of treatment-emergent adverse

events that occurred among 429 GAD patients who received Lexapro 10 to 20 mg/day in placebo-controlled trials. Events included are those

occurring in 2% or more of patients treated with Lexapro and for which the incidence in patients treated with Lexapro was greater than the

incidence in placebo-treated patients.

TABLE 3

Treatment-Emergent Adverse Reactions Observed with a Frequency of 2%

and Greater Than Placebo for Generalized Anxiety Disorder

Adverse Reactions Lexapro Placebo

(N=429) (N=427)

Autonomic Nervous System Disorders

Dry Mouth 9% 5%

Sweating Increased 4% 1%

Central & Peripheral Nervous System Disorders

Headache 24% 17%

Paresthesia 2% 1%

Gastrointestinal Disorders

Nausea 18% 8%

Diarrhea 8% 6%

Constipation 5% 4%

Indigestion 3% 2%

Vomiting 3% 1%

Abdominal Pain 2% 1%

Flatulence 2% 1%

Toothache 2% 0%

General

Fatigue 8% 2%

Influenza-like Symptoms 5% 4%

Musculoskeletal System Disorder

Neck/Shoulder Pain 3% 1%

Psychiatric Disorders

Somnolence 13% 7%

Insomnia 12% 6%

Libido Decreased 7% 2%

Dreaming Abnormal 3% 2%

Appetite Decreased 3% 1%

Lethargy 3% 1%

TABLE 3

Treatment-Emergent Adverse Reactions Observed with a Frequency of 2%

and Greater Than Placebo for Generalized Anxiety Disorder (continued)

Adverse Reactions Lexapro Placebo

(N=429) (N=427)

Respiratory System Disorders

Yawning 2% 1%

Urogenital

Ejaculation Disorder

1,2

14% 2%

Anorgasmia

6% <1%

Menstrual Disorder 2% 1%

Primarily ejaculatory delay.

Denominator used was for males only (N=182 Lexapro; N=195 placebo).

Denominator used was for females only (N=247 Lexapro; N=232 placebo).

Dose Dependency of Adverse Reactions

-The potential dose dependency of common adverse reactions (defined as an incidence rate of 5% in

either the 10 mg or 20 mg Lexapro groups) was examined on the basis of the combined incidence of adverse events in two fixed-dose trials.

The overall incidence rates of adverse events in 10 mg Lexapro-treated patients (66%) was similar to that of the placebo-treated patients (61%),

while the incidence rate in 20 mg/day Lexapro-treated patients was greater (86%). Table 4 shows common adverse reactions that occurred in

the 20 mg/day Lexapro group with an incidence that was approximately twice that of the 10 mg/day Lexapro group and approximately twice that

of the placebo group.

TABLE 4

Incidence of Common Adverse Reactions in Patients with Major

Depressive Disorder

Adverse Reaction Placebo 10 mg/day 20 mg/day

(N=311) Lexapro Lexapro

(N=310) (N=125)

Insomnia 4% 7% 14%

Diarrhea 5% 6% 14%

Dry Mouth 3% 4% 9%

Somnolence 1% 4% 9%

Dizziness 2% 4% 7%

Sweating Increased <1% 3% 8%

Constipation 1% 3% 6%

Fatigue 2% 2% 6%

Indigestion 1% 2% 6%

Male and Female Sexual Dysfunction with SSRIs

-Although changes in sexual desire, sexual performance, and sexual satisfaction often occur

as manifestations of a psychiatric disorder, they may also be a consequence of pharmacologic treatment. In particular, some evidence suggests

that SSRIs can cause such untoward sexual experiences. Reliable estimates of the incidence and severity of untoward experiences involving

sexual desire, performance, and satisfaction are difficult to obtain, however, in part because patients and physicians may be reluctant to discuss

them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in product labeling are likely to under-

estimate their actual incidence.

TABLE 5

Incidence of Sexual Side Effects in Placebo-Controlled Clinical Trials

Adverse Event Lexapro Placebo

In Males Only

(N=407) (N=383)

Ejaculation Disorder

(primarily ejaculatory delay) 12% 1%

Libido Decreased 6% 2%

Impotence 2% <1%

In Females Only

(N=737) (N=636)

Libido Decreased 3% 1%

Anorgasmia 3% <1%

There are no adequately designed studies examining sexual dysfunction with escitalopram treatment. Priapism has been reported with all SSRIs.

While it is difficult to know the precise risk of sexual dysfunction associated with the use of SSRIs, physicians should routinely inquire about

such possible side effects.

Vital Sign Changes

-Lexapro and placebo groups were compared with respect to (1) mean change from baseline in

vital signs (pulse, systolic blood pressure, and diastolic blood pressure) and (2) the incidence of patients meeting criteria for potentially clinical-

ly significant changes from baseline in these variables. These analyses did not reveal any clinically important changes in vital signs associated

with Lexapro treatment. In addition, a comparison of supine and standing vital sign measures in subjects receiving Lexapro indicated that

Lexapro treatment is not associated with orthostatic changes.

Weight Changes

-Patients treated with Lexapro in controlled trials did not differ

from placebo-treated patients with regard to clinically important change in body weight.

Laboratory Changes

-Lexapro and placebo groups were

compared with respect to (1) mean change from baseline in various serum chemistry, hematology, and urinalysis variables, and (2) the incidence

of patients meeting criteria for potentially clinically significant changes from baseline in these variables. These analyses revealed no clinically

important changes in laboratory test parameters associated with Lexapro treatment.

ECG Changes

-Electrocardiograms from Lexapro (N=625),

racemic citalopram (N=351), and placebo (N=527) groups were compared with respect to (1) mean change from baseline in various ECG

parameters and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. These

analyses revealed (1) a decrease in heart rate of 2.2 bpm for Lexapro and 2.7 bpm for racemic citalopram, compared to an increase of 0.3 bpm

for placebo and (2) an increase in QTc interval of 3.9 msec for Lexapro and 3.7 msec for racemic citalopram, compared to 0.5 msec for

placebo. Neither Lexapro nor racemic citalopram were associated with the development of clinically significant ECG abnormalities.

Other

Reactions Observed During the Premarketing Evaluation of Lexapro

-Following is a list of treatment-emergent adverse events, as defined in the

introduction to the ADVERSE REACTIONS section, reported by the 1428 patients treated with Lexapro for periods of up to one year in double-

blind or open-label clinical trials during its premarketing evaluation. The listing does not include those events already listed in Tables 2 & 3, those

events for which a drug cause was remote and at a rate less than 1% or lower than placebo, those events which were so general as to be

uninformative, and those events reported only once which did not have a substantial probability of being acutely life threatening. Events are

categorized by body system. Events of major clinical importance are described in the Warnings and Precautions section. Cardiovascular - hyper-

tension, palpitation. Central and Peripheral Nervous System Disorders - light-headed feeling, migraine. Gastrointestinal Disorders - abdominal

cramp, heartburn, gastroenteritis. General - allergy, chest pain, fever, hot flushes, pain in limb. Metabolic and Nutritional Disorders - increased

weight. Musculoskeletal System Disorders - arthralgia, myalgia jaw stiffness. Psychiatric Disorders - appetite increased, concentration impaired,

irritability. Reproductive Disorders/Female - menstrual cramps, menstrual disorder. Respiratory System Disorders - bronchitis, coughing, nasal

congestion, sinus congestion, sinus headache. Skin and Appendages Disorders - rash. Special Senses - vision blurred, tinnitus. Urinary System

Disorders - urinary frequency, urinary tract infection.

Post-Marketing Experience; Adverse Reactions Reported Subsequent to the Marketing

of Escitalopram

-The following additional adverse reactions have been identified from spontaneous reports of escitalopram received worldwide.

These adverse reactions have been chosen for inclusion because of a combination of seriousness, frequency of reporting, or potential causal

connection to escitalopram and have not been listed elsewhere in labeling. However, because these adverse reactions were reported voluntarily

from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug

exposure. These events include: Blood and Lymphatic System Disorders: anemia, agranulocytis, aplastic anemia, hemolytic anemia, idiopathic

thrombocytopenia purpura, leukopenia, thrombocytopenia. Cardiac Disorders: atrial fibrillation, bradycardia, cardiac failure, myocardial

infarction, tachycardia, torsade de pointes, ventricular arrhythmia, ventricular tachycardia. Ear and Labyrinth Disorders: vertigo Endocrine

Disorders: diabetes mellitus, hyperprolactinemia, SIADH. Eye Disorders: diplopia, glaucoma, mydriasis, visual disturbance. Gastrointestinal

Disorders: dysphagia, gastrointestinal hemorrhage, gastroesophageal reflux, pancreatitis, rectal hemorrhage. General Disorders and

Administration Site Conditions: abnormal gait, asthenia, edema, fall, feeling abnormal, malaise. Hepatobiliary Disorders: fulminant hepatitis,

hepatic failure, hepatic necrosis, hepatitis. Immune System Disorders: allergic reaction, anaphylaxis. Investigations: bilirubin increased,

decreased weight, electrocardiogram QT prolongation, hepatic enzymes increased, hypercholesterolemia, INR increased, prothrombin

decreased. Metabolism and Nutrition Disorders: hyperglycemia, hypoglycemia, hypokalemia, hyponatremia. Musculoskeletal and Connective

Tissue Disorders: muscle cramp, muscle stiffness, muscle weakness, rhabdomyolysis. Nervous System Disorders: akathisia, amnesia, ataxia,

choreoathetosis, cerebrovascular accident, dysarthria, dyskinesia, dystonia, extrapyramidal disorders, grand mal seizures (or convulsions),

hypoaesthesia, myoclonus, nystagmus, Parkinsonism, restless legs, seizures, syncope, tardive dyskinesia, tremor. Pregnancy, Puerperium and

Perinatal Conditions: spontaneous abortion. Psychiatric Disorders: acute psychosis, aggression, agitation, anger, anxiety, apathy, completed

suicide, confusion, depersonalization, depression aggravated, delirium, delusion, disorientation, feeling unreal, hallucinations (visual and

auditory), mood swings, nervousness, nightmare, panic reaction, paranoia, restlessness, self-harm or thoughts of self-harm, suicide attempt,

suicidal ideation, suicidal tendency. Renal and Urinary Disorders: acute renal failure, dysuria, urinary retention. Reproductive System and Breast

Disorders: menorrhagia, priapism. Respiratory, Thoracic and Mediastinal Disorders: dyspnea, epistaxis, pulmonary embolism, pulmonary

hypertension of the newborn. Skin and Subcutaneous Tissue Disorders: alopecia, angioedema, dermatitis, ecchymosis, erythema multiforme,

photosensitivity reaction, Stevens Johnson Syndrome, toxic epidermal necrolysis, urticaria. Vascular Disorders: deep vein thrombosis, flushing,

hypertensive crisis, hypotension, orthostatic hypotension, phlebitis, thrombosis.

DRUG INTERACTIONS: Serotonergic Drugs

-Based on the mechanism of action of SNRIs and SSRIs including Lexapro, and the potential

for serotonin syndrome, caution is advised when Lexapro is coadministered with other drugs that may affect the serotonergic neurotransmitter

systems, such as triptans, linezolid (an antibiotic which is a reversible non-selective MAOI), lithium, tramadol, or St. John’s Wort [

see Warnings

and Precautions

]. The concomitant use of Lexapro with other SSRIs, SNRIs or tryptophan is not recommended.

Triptans

-There have been rare

postmarketing reports of serotonin syndrome with use of an SSRI and a triptan. If concomitant treatment of Lexapro with a triptan is clinically

warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases [

see Warnings and

Precautions

CNS Drugs

- Given the primary CNS effects of escitalopram, caution should be used when it is taken in combination with other

centrally acting drugs.

Alcohol

-Although Lexapro did not potentiate the cognitive and motor effects of alcohol in a clinical trial, as with other

psychotropic medications, the use of alcohol by patients taking Lexapro is not recommended.

Monoamine Oxidase Inhibitors (MAOIs)

see

Contraindications and Warnings and Precautions

Drugs That Interfere With Hemostasis (NSAIDs, Aspirin, Warfarin, etc.)

-Serotonin release

by platelets plays an important role in hemostasis. Epidemiological studies of the case-control and cohort design that have demonstrated an

association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding have

also shown that concurrent use of an NSAID or aspirin may potentiate the risk of bleeding. Altered anticoagulant effects, including increased

bleeding, have been reported when SSRIs and SNRIs are coadministered with warfarin. Patients receiving warfarin therapy should be carefully

monitored when Lexapro is initiated or discontinued.

Cimetidine

-In subjects who had received 21 days of 40 mg/day racemic citalopram, com-

bined administration of 400 mg/day cimetidine for 8 days resulted in an increase in citalopram AUC and C

max

of 43% and 39%, respectively. The

clinical significance of these findings is unknown.

Digoxin

-In subjects who had received 21 days of 40 mg/day racemic citalopram, combined

administration of citalopram and digoxin (single dose of 1 mg) did not significantly affect the pharmacokinetics of either citalopram or digoxin.

Lithium

-Coadministration of racemic citalopram (40 mg/day for 10 days) and lithium (30 mmol/day for 5 days) had no significant effect on the

pharmacokinetics of citalopram or lithium. Nevertheless, plasma lithium levels should be monitored with appropriate adjustment to the lithium

dose in accordance with standard clinical practice. Because lithium may enhance the serotonergic effects of escitalopram, caution should

be exercised when Lexapro and lithium are coadministered.

Pimozide and Celexa

-In a controlled study, a single dose of pimozide 2 mg co-

administered with racemic citalopram 40 mg given once daily for 11 days was associated with a mean increase in QTc values of approximately

10 msec compared to pimozide given alone. Racemic citalopram did not alter the mean AUC or C

max

of pimozide. The mechanism of this

pharmacodynamic interaction is not known.

Sumatriptan

-There have been rare postmarketing reports describing patients with weakness,

hyperreflexia, and incoordination following the use of an SSRI and sumatriptan. If concomitant treatment with sumatriptan and an SSRI (e.g.,

fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, escitalopram) is clinically warranted, appropriate observation of the patient is advised.

Theophylline

-Combined administration of racemic citalopram (40 mg/day for 21 days) and the CYP1A2 substrate theophylline (single dose

of 300 mg) did not affect the pharmacokinetics of theophylline. The effect of theophylline on the pharmacokinetics of citalopram was not

evaluated.

Warfarin

-Administration of 40 mg/day racemic citalopram for 21 days did not affect the pharmacokinetics of warfarin, a CYP3A4 sub-

strate. Prothrombin time was increased by 5%, the clinical significance of which is unknown.

Carbamazepine

-Combined administration of

racemic citalopram (40 mg/day for 14 days) and carbamazepine (titrated to 400 mg/day for 35 days) did not significantly affect the pharmaco-

kinetics of carbamazepine, a CYP3A4 substrate. Although trough citalopram plasma levels were unaffected, given the enzyme-inducing

properties of carbamazepine, the possibility that carbamazepine might increase the clearance of escitalopram should be considered if the two

drugs are coadministered.

Triazolam

-Combined administration of racemic citalopram (titrated to 40 mg/day for 28 days) and the CYP3A4

substrate triazolam (single dose of 0.25 mg) did not significantly affect the pharmacokinetics of either citalopram or triazolam.

Ketoconazole

Combined administration of racemic citalopram (40 mg) and ketoconazole (200 mg), a potent CYP3A4 inhibitor, decreased the C

max

and AUC of

ketoconazole by 21% and 10%, respectively, and did not significantly affect the pharmacokinetics of citalopram.

Ritonavir

-Combined adminis-

tration of a single dose of ritonavir (600 mg), both a CYP3A4 substrate and a potent inhibitor of CYP3A4, and escitalopram (20 mg) did not affect

the pharmacokinetics of either ritonavir or escitalopram.

CYP3A4 and -2C19 Inhibitors

In vitro

studies indicated that CYP3A4 and -2C19 are the

primary enzymes involved in the metabolism of escitalopram. However, coadministration of escitalopram (20 mg) and ritonavir (600 mg), a

potent inhibitor of CYP3A4, did not significantly affect the pharmacokinetics of escitalopram. Because escitalopram is metabolized by multiple

enzyme systems, inhibition of a single enzyme may not appreciably decrease escitalopram clearance.

Drugs Metabolized by Cytochrome

P4502D6

In vitro

studies did not reveal an inhibitory effect of escitalopram on CYP2D6. In addition, steady state levels of racemic citalopram

were not significantly different in poor metabolizers and extensive CYP2D6 metabolizers after multiple-dose administration of citalopram,

suggesting that coadministration, with escitalopram, of a drug that inhibits CYP2D6, is unlikely to have clinically significant effects on escitalo-

pram metabolism. However, there are limited

in vivo

data suggesting a modest CYP2D6 inhibitory effect for escitalopram, i.e., coadministration

of escitalopram (20 mg/day for 21 days) with the tricyclic antidepressant desipramine (single dose of 50 mg), a substrate for CYP2D6, resulted

in a 40% increase in C

max

and a 100% increase in AUC of desipramine. The clinical significance of this finding is unknown. Nevertheless, caution

is indicated in the coadministration of escitalopram and drugs metabolized by CYP2D6.

Metoprolol

-Administration of 20 mg/day Lexapro for

21 days in healthy volunteers resulted in a 50% increase in C

max

and 82% increase in AUC of the beta-adrenergic blocker metoprolol (given in a

single dose of 100 mg). Increased metoprolol plasma levels have been associated with decreased cardioselectivity. Coadministration of Lexapro

and metoprolol had no clinically significant effects on blood pressure or heart rate.

Electroconvulsive Therapy (ECT)

-There are no clinical

studies of the combined use of ECT and escitalopram.

USE IN SPECIFIC POPULATIONS: Pregnancy;

Pregnancy Category C

In a rat embryo/fetal development study, oral administration of

escitalopram (56, 112, or 150 mg/kg/day) to pregnant animals during the period of organogenesis resulted in decreased fetal body weight and

associated delays in ossification at the two higher doses (approximately 56 times the maximum recommended human dose [MRHD] of

20 mg/day on a body surface area [mg/m

] basis). Maternal toxicity (clinical signs and decreased body weight gain and food consumption), mild

at 56 mg/kg/day, was present at all dose levels. The developmental no-effect dose of 56 mg/kg/day is approximately 28 times the MRHD on a

mg/m

basis. No teratogenicity was observed at any of the doses tested (as high as 75 times the MRHD on a mg/m

basis). When female rats

were treated with escitalopram (6, 12, 24, or 48 mg/kg/day) during pregnancy and through weaning, slightly increased offspring mortality and

growth retardation were noted at 48 mg/kg/day which is approximately 24 times the MRHD on a mg/m

basis. Slight maternal toxicity (clinical

signs and decreased body weight gain and food consumption) was seen at this dose. Slightly increased offspring mortality was also seen at

24 mg/kg/day. The no-effect dose was 12 mg/kg/day which is approximately 6 times the MRHD on a mg/m

basis. In animal reproduction

studies, racemic citalopram has been shown to have adverse effects on embryo/fetal and postnatal development, including teratogenic effects,

when administered at doses greater than human therapeutic doses. In two rat embryo/fetal development studies, oral administration of racemic

citalopram (32, 56, or 112 mg/kg/day) to pregnant animals during the period of organogenesis resulted in decreased embryo/fetal growth and

survival and an increased incidence of fetal abnormalities (including cardiovascular and skeletal defects) at the high dose. This dose was also

associated with maternal toxicity (clinical signs, decreased body weight gain). The developmental no-effect dose was 56 mg/kg/day. In a rabbit

study, no adverse effects on embryo/fetal development were observed at doses of racemic citalopram of up to 16 mg/kg/day. Thus, teratogenic

effects of racemic citalopram were observed at a maternally toxic dose in the rat and were not observed in the rabbit. When female rats were

treated with racemic citalopram (4.8, 12.8, or 32 mg/kg/day) from late gestation through weaning, increased offspring mortality during the first

4 days after birth and persistent offspring growth retardation were observed at the highest dose. The no-effect dose was 12.8 mg/kg/day. Similar

effects on offspring mortality and growth were seen when dams were treated throughout gestation and early lactation at doses 24 mg/kg/day.

A no-effect dose was not determined in that study. There are no adequate and well-controlled studies in pregnant women; therefore, escitalo-

pram should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Pregnancy-Nonteratogenic Effects

Neonates exposed to Lexapro and other SSRIs or SNRIs, late in the third trimester, have developed complications requiring prolonged hospital-

ization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included

respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia,

hyperreflexia, tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of SSRIs and SNRIs

or, possibly, a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome

[

see Warnings and Precautions

]. Infants exposed to SSRIs in late pregnancy may have an increased risk for persistent pulmonary hypertension

of the newborn (PPHN). PPHN occurs in 1-2 per 1000 live births in the general population and is associated with substantial neonatal

morbidity and mortality. In a retrospective, case-control study of 377 women whose infants were born with PPHN and 836 women whose infants

were born healthy, the risk for developing PPHN was approximately six-fold higher for infants exposed to SSRIs after the 20th week of gestation

compared to infants who had not been exposed to antidepressants during pregnancy. There is currently no corroborative evidence regarding the

risk for PPHN following exposure to SSRIs in pregnancy; this is the first study that has investigated the potential risk. The study did not include

enough cases with exposure to individual SSRIs to determine if all SSRIs posed similar levels of PPHN risk. When treating a pregnant woman

with Lexapro during the third trimester, the physician should carefully consider both the potential risks and benefits of treatment [

see Dosage

and Administration

]. Physicians should note that in a prospective longitudinal study of 201 women with a history of major depression who were

euthymic at the beginning of pregnancy, women who discontinued antidepressant medication during pregnancy were more likely to experience

a relapse of major depression than women who continued antidepressant medication.

Labor and Delivery

-The effect of Lexapro on labor and

delivery in humans is unknown.

Nursing Mothers

-Escitalopram is excreted in human breast milk. Limited data from women taking 10-20 mg

escitalopram showed that exclusively breast-fed infants receive approximately 3.9% of the maternal weight-adjusted dose of escitalopram and

1.7% of the maternal weight-adjusted dose of desmethylcitalopram. There were two reports of infants experiencing excessive somnolence,

decreased feeding, and weight loss in association with breastfeeding from a racemic citalopram-treated mother; in one case, the infant was

reported to recover completely upon discontinuation of racemic citalopram by its mother and, in the second case, no follow-up information was

available. Caution should be exercised and breastfeeding infants should be observed for adverse reactions when Lexapro is administered to a

nursing woman.

Pediatric Use

-Safety and effectiveness of Lexapro has not been established in pediatric patients (less than 12 years of age) with

Major Depressive Disorder. Safety and effectiveness of Lexapro has been established in adolescents (12 to 17 years of age) for the treatment of

major depressive disorder [

see Clinical Studies

]. Although maintenance efficacy in adolescent patients with Major Depressive Disorder has not

been systematically evaluated, maintenance efficacy can be extrapolated from adult data along with comparisons of escitalopram pharmaco -

kinetic parameters in adults and adolescent patients. Safety and effectiveness of Lexapro has not been established in pediatric patients less than

18 years of age with Generalized Anxiety Disorder.

Geriatric Use

-Approximately 6% of the 1144 patients receiving escitalopram in controlled

trials of Lexapro in major depressive disorder and GAD were 60 years of age or older; elderly patients in these trials received daily doses of

Lexapro between 10 and 20 mg. The number of elderly patients in these trials was insufficient to adequately assess for possible differential

efficacy and safety measures on the basis of age. Nevertheless, greater sensitivity of some elderly individuals to effects of Lexapro cannot

be ruled out. SSRIs and SNRIs, including Lexapro, have been associated with cases of clinically significant hyponatremia in elderly patients,

who may be at greater risk for this adverse event [see

Hyponatremia

]. In two pharmacokinetic studies, escitalopram half-life was increased by

approximately 50% in elderly subjects as compared to young subjects and C

max

was unchanged [

see Clinical Pharmacology

]. 10 mg/day is the

recommended dose for elderly patients [

see Dosage and Administration

]. Of 4422 patients in clinical studies of racemic citalopram, 1357 were

60 and over, 1034 were 65 and over, and 457 were 75 and over. No overall differences in safety or effectiveness were observed between these

subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger

patients, but again, greater sensitivity of some elderly individuals cannot be ruled out.

DRUG ABUSE AND DEPENDENCE: Abuse and Dependence;

Physical and Psychological Dependence-Animal studies suggest that the abuse

liability of racemic citalopram is low. Lexapro has not been systematically studied in humans for its potential for abuse, tolerance, or physical

dependence. The premarketing clinical experience with Lexapro did not reveal any drug-seeking behavior. However, these observations were not

systematic and it is not possible to predict on the basis of this limited experience the extent to which a CNS-active drug will be misused, divert-

ed, and/or abused once marketed. Consequently, physicians should carefully evaluate Lexapro patients for history of drug abuse and follow such

patients closely, observing them for signs of misuse or abuse (e.g., development of tolerance, incrementations of dose, drug-seeking behavior).

OVERDOSAGE: Human Experience

-In clinical trials of escitalopram, there were reports of escitalopram overdose, including overdoses of up

to 600 mg, with no associated fatalities. During the postmarketing evaluation of escitalopram, Lexapro overdoses involving overdoses of over

1000 mg have been reported. As with other SSRIs, a fatal outcome in a patient who has taken an overdose of escitalopram has been rarely

reported. Symptoms most often accompanying escitalopram overdose, alone or in combination with other drugs and/or alcohol, included

convulsions, coma, dizziness, hypotension, insomnia, nausea, vomiting, sinus tachycardia, somnolence, and ECG changes (including QT

prolongation and very rare cases of torsade de pointes). Acute renal failure has been very rarely reported accompanying overdose.

Management

of Overdose

-Establish and maintain an airway to ensure adequate ventilation and oxygenation. Gastric evacuation by lavage and use of

activated charcoal should be considered. Careful observation and cardiac and vital sign monitoring are recommended, along with general

symptomatic and supportive care. Due to the large volume of distribution of escitalopram, forced diuresis, dialysis, hemoperfusion, and exchange

transfusion are unlikely to be of benefit. There are no specific antidotes for Lexapro. In managing overdosage, consider the possibility of

multiple-drug involvement. The physician should consider contacting a poison control center for additional information on the treatment of any

overdose.

Forest Pharmaceuticals, Inc.

Subsidiary of Forest Laboratories, Inc.

St. Louis, MO 63045 USA

Licensed from H. Lundbeck A/S

LEXAPRO®(escitalopram oxalate) TABLETS/ORAL SOLUTION LEXAPRO®(escitalopram oxalate) TABLETS/ORAL SOLUTION

WWW.DRUGTOPICS.COM December 2010

DRUG TOPICS

Product Updates

DANA K. CASSELL

FEATURED THIS MONTH: DIGESTIVES

For those who dine not wisely

but too well

OTC

In this season of gustatory indulgence,

it can’t hurt to prepare for the occa-

sional upset stomach. According to re-

ports, more than 100 million Americans

are affected by some form of digestive

disorder, including gas, heartburn, indi-

gestion, vomiting, bloating, constipation,

diarrhea, and worse. Fortunately, OTC

manufacturers have been hard at work

preparing new and improved digestive

and gastrointestinal aids.

PPI

Schering-Plough HealthCare Products has

introduced Zegerid OTC, a proton pump

inhibitor (PPI), the most potent class of

acid-reducing drugs currently available.

The only nonprescription PPI prod-

uct with 2 active ingredients, Zegerid

OTC combines the PPI omeprazole with

sodium bicarbonate, which protects the

medication from being broken down by

acid in the stomach prior to absorption.

Zegerid OTC is approved for use by adults

18 and over for the treatment of frequent

heartburn (deﬁ ned as occurring 2 or more

days a week).

Fiber

Dietary fiber not only aids digestion,

it can help control weight, because it

makes one feel full faster and longer.

From GlaxoSmithKline comes an ad-

dition to its FiberChoice line: a new

strawberry-ﬂ avored Weight Manage-

ment formula containing chromium

picolinate, a naturally occurring com-

pound that aids in metabolism.

Enzymes and probiotics

When the category is digestives and gas-

trointestinal agents, increasingly popular

elements are enzymes and probiotics. En-

zymedica has combined the 2 in its new

Digest Gold + Probiotics, offering “com-

plete digestive care in a single capsule.”

Enzymedica’s Digest Gold is an

enzyme product formulated to assist in

digestion of proteins, fats, carbohydrates,

and ﬁ ber.

Digest Gold + Probiotics combines

that enzyme formula with 500 million

cultures of specially coated probiotics

that release in the alkaline pH of the

lower intestines, guaranteeing potency.

Bayer HealthCare’s Phillips’ Colon

Health now offers a larger, 60-count

package to give customers 2 months of

daily probiotic support. The product’s 3

strains of good bacteria are derived from

the 2 most common groups of good bac-

teria, Lactobacillus and Biﬁ dobacterium.

According to Bayer, “Scientiﬁ c evi-

dence demonstrates that Lactobacillus

and Biﬁ dobacterium help relieve occasion-

al gas, constipation, diarrhea, and other

common GI issues while also helping to

support a healthy immune system. Pro-

biotics work to rebalance the bacteria in

your colon to support overall digestive

health and to help defend against occa-

sional digestive symptoms.”

Dana K. Cassell, a frequent contributor to

Drug Topics, lives in North Stratford, N.H.

FiberChoice Weight

Management: The chewable

tablets offer 4g of  ber in

each 2-tablet dose.

Zegerid OTC is the only

nonprescription PPI with 2

active ingredients.

Digest Gold + Probiotics

combines digestive

enzymes and probiotics.

PHOTOS COURTESY OF SCHERING-PLOUGH HEALTHCARE PRODUCTS/GLAXO-SMITH-KLINE/ENZYMEDICA

DRUG TOPICS

December 2010

Product Updates

New drugs

FDA has approved Warner Chilcott’s

bisphosphonate Atelvia (risedronate so-

dium delayed-release tablets) for the

treatment of postmenopausal osteoporo-

sis. The product is a delayed-release for-

mulation of Actonel, which is approved

to prevent and treat postmenopausal

osteoporosis and glucocorticoid-induced

osteoporosis (in men and women), to

increase bone mass in men with osteo-

porosis, and to treat Paget’s disease of the

bone. (www.wcrx.com/800-521-8813)

Bristol-Myers Squibb’s Baraclude (en-

tecavir tablets), a nucleoside analog, is

approved for the treatment of chronic

hepatitis B (CHB) in adult patients with

decompensated liver disease. Baraclude

is already indicated for the treatment of

CHB infection in adults with evidence of

active viral replication and evidence of ei-

ther persistent elevations in serum ami-

notransferases (ALT or AST) or histologi-

cally active disease. (www.baraclude.

com/800-321-1335)

FDA has approved ISTA’s Bromday [1]

(bromfenac ophthalmic solution 0.09%),

a nonsteroidal anti-inﬂ ammatory drug

(NSAID), for the treatment of postop-

erative inﬂ ammation and reduction of

ocular pain after cataract surgery. (www.

istavision.com/949-788-6000).

Pradaxa [2] (dabigatran etexilate) cap-

sules from Boehringer Ingelheim are ap-

proved to reduce the risk of stroke and

systemic embolism in patients with non-

valvular atrial ﬁ brillation (AFib). An oral

direct thrombin inhibitor, Pradaxa is the

ﬁ rst new oral anticoagulant approved in

the United States in more than 50 years.

(www.pradaxa.com/800-542-6257)

Fera has launched a preservative-free

formulation of Garamycin (gentamicin sul-

fate ophthalmic ointment), indicated for

the treatment of susceptible ocular bacte-

rial infections, including conjunctivis, ker-

atitis, keratoconjunctivitis, corneal ulcers,

blepharitis, blepharoconjunctivitis, acute

meibomianitis, and dacryocystitis. (www.

ferapharma.com/414-434-6604)

New generics

FDA approved Teva’s ANDA to market

lansoprazole, a generic version of Takeda’s

Prevacid SoluTab. The prod-

uct, a proton pump inhibi-

tor, suppresses gastric acid

production and is often

prescribed for use in gastro-

esophageal reflux disease.

(888-838-2872)

Dr. Reddy’s Laborato-

ries will launch lansopra-

zole delayed-release cap-

sules (15 mg and 30 mg),

a bioequivalent generic

version of Prevacid De-

layed-Release Capsules, in

the U.S. market. (www.

drreddys.com)

Tris Pharma announced that FDA

has approved hydrocodone polistirex and

chlorpheniramine polistirex in extended-

release suspension, the ﬁ rst-ever generic

version of Tussionex (UCB Manufactur-

ing). (www.trispharma.com)

OTC

Chestal, a natural cough syrup free of

dextromethorphan, has been made avail-

able by Boiron. A blend of homeopathic

medicines and honey, Chestal helps loos-

en chest congestion for dry and produc-

tive coughs. (www.childrenschestal.

com/800-266-7661)

Eco Lips announces new colors in

its Eco Tints [3] line: Moonstone, Sugar

Plum, and Coralyte. With more than

90% certiﬁ ed organic ingredients, Eco

Tints are free of carmine, lead, gluten,

lanolin, petroleum, hydrogenated oils,

and nanoparticles. (www.ecolips.

com/866-326-5477)

From Smith & Nephew comes No-

Sting Skin Prep spray, a liquid dressing

that leaves a clear, waterproof, and

breathable ﬁ lm barrier for up to 4 days,

protecting skin from irritation due to

digestive secretions, exudate, adhesives,

frictional forces, and skin trauma dur-

ing tape and adhesive removal. (www.

smith-nephew.com/800-876-1261)

Vitalah has introduced Prenatal Oxylent,

a digestible effervescent vitamin formulat-

ed for needs of preconception, pregnancy,

and lactation. It is naturally sweetened

with stevia; no sugar is added and it has

no artiﬁ cial color, ﬂ avor, gluten, lactose, or

caffeine. (www.vitalah.com)

RX CARE

PHOTOS COURTESY OF ISTA/BOEHRINGER INGELHEIM/ECO LIPS

CORPORATE Amneal Pharmaceuticals 1

CLONIDINE Mylan Pharmaceuticals Inc. 7-8

CORPORATE Mylan Pharmaceuticals Inc. CV4

CORPORATE QS/1 Data Systems Inc. CV2

CORPORATE Roxane Laboratories 15

EPI-PEN Dey Pharma LP 11-12

HUMALOG Eli Lilly and Company 26-28

LEXAPRO Forest Laboratories Inc. 43-46

METFORMIN Mylan Pharmaceuticals Inc. 3-5

PRADAXA Boehringer Ingelheim Ltd. 25

RXMEDIC QS/1 Data Systems Inc. CV3

VIMOVO AstraZeneca 17-20

Advertiser Index

WHAT’S NEW

RX & OTC

New products

The Drug Topics’ team wishes you the best this holiday season

and thanks you for your continued support.

MONDAY

TUESDAY

WEDNESDAY

THURSDAY FRIDAY SATURDAY

SUNDAY

MONDAY

TUESDAY

WEDNESDAY

THURSDAY

FRIDAY

SATURDAY

SUNDAY

MARKETPLACE

Products & Services

Brokers

Books/Publications

Who should consider reading this book?

• Any licensed healthcare professional working or wanting to work a second job!

• Any licensed healthcare professional now working for a “staf ng agency” as a second job!

• Any licensed healthcare professional wanting to start their own “staf ng agency”

as a second job!

• Corporate America looking for ways to help mitigate their number one

expense...overtime and labor cost!

• Those providing insight along with integrity looking to network and join an

association to lend their expertise in the health care industry.

A Step

Ahead...

The FIRST eBook of its kind directed toward the Licensed Health Care

professionals working a SECOND JOB!

Beneﬁ ts Design Consultants/Stafﬁ ng

Making Thousands of $$$

at Your SECOND JOB and Keeping More of it

www.TIMEBANDITSRX.com

DRUG TOPICS

December 2010 WWW.DRUGTOPICS.COM

For Products and Services Advertising:

Carla Kastanis at (800) 225-4569 x2711

E-mail: ckastanis@advanstar.com

For Recruitment Advertising:

Joanna Shippoli at (800) 225-4569 x2615

E-mail: jshippoli@advanstar.com

MARKETPLACE ADVERTISING

See More Brokers on next page

Continuing Education

PHARMACY VACATION SEMINARS

ACPE ACCREDITED PROVIDER

2010

Las Vegas at Harrah’s

December 8

2011

Boca Raton, The Beach Club

January 26

Las Vegas at Harrah’s

February 23

Caribbean Cruise

March 13-20-Allure of the Seas

NEW SHIP!

Naples Grande Beach Resort, Florida

April 27

Las Vegas at Planet Hollywood

June 8

Alaska

Voyage of the Glaciers

June 11

Antlers Hilton

Colorado Springs July 27

Las Vegas at Harrah’s

September 14

Westin Maui Resort & Spa

October 26

Caribbean Cruise

November 6

Las Vegas at Harrah’s

December 7

New Drug Update DVD

Anytime

Anywhere!

1-800-940-5860

www.universitylearning.com

CALL FOR FREE BROCHURE

Kirkland, Washington

COMPOUNDING PHARMACY FOR SALE

All cash customers. No insurance plan hassles.

Also DME and cards/gifts.

No weekends. Priced for quick sale.

Contact juanitabaypharmacy@live.com

Business For Sale

How your family reacts in an emergency

can make all the difference. To make

your family disaster plan, contact your

local American Red Cross chapter or

visit www.redcross.org

Make a plan.

Reach thousands of industry professionals every month

Your message could be here!

NAPLEX

®?

www.prontopass.com

For details, please visit our website.

NAPLEX® Review

QUICKCARDS®

with Memoronics®

Need to Pass

Using Memory Techniques of:

Visual

Auditory

Repetition

Self Testing

and it’s

Do the NAPLEX®

3 Step

with

plus Posters, Audio CD,

Math Practice, Telephone quizzing,

and Patient Proﬁles.

www.prudentialcbs.com

Common Mistakes Sellers Make:

■ Not using a licensed broker specializing in pharmacies

■ Not knowing your true current market value

■ Not effectively advertising to reach enough qualiﬁed buyers

Call me before sharing information

about your pharmacy with ANY buyer.

Prudential’s proprietary selling process

will enable you to get the highest price for your pharmacy!

SELLING YOUR PHARMACY?

Call me today at 888-808-4RPH (4774)

Daniel J. Lannon, RPh, VP

Senior Pharmacy Broker Consulting Broker Services

www.prudentialcbs.com

Common Mistakes Sellers Make:

■ Not using a licensed broker specializing in pharmacies

■ Not knowing your true current market value

■ Not effectively advertising to reach enough qualiﬁed buyers

Call me before sharing information

about your pharmacy with ANY buyer.

Prudential’s proprietary selling process

will enable you to get the highest price for your pharmacy!

SELLING YOUR PHARMACY?

Call me today at 888-808-4RPH (4774)

Daniel J. Lannon, RPh, VP

Senior Pharmacy Broker Consulting Broker Services

EducationBrokers

Legal Services

Pharmacy Technicians

Financing

Pharmacy Owners:

Keep your pharmacy open!

Cash flow problems? Too much short-term debt?

We can access long-term financing and reduce your monthly

debt service. Up to $2 million available per pharmacy!

If you are looking to sell, we can also provide financing to

your buyer of up to $2 million for a terms of 10-25 years.

Visit shbconsultants.com

or call 800-603-2519

WWW.DRUGTOPICS.COM December 2010

DRUG TOPICS

ATTN:PHARMACY TECHNICIANS

DISCOVER NPTA...the largest

professional organization

specifically for pharmacy technicians.

Free CE + Advocacy + Resources

Learn more at:

www.pharmacytechnician.org/discover

MARKETPLACE

Products & Services

LEGAL PROBLEMS

With Medicare/Medicaid, Licensing Boards,

Data Bank, DEA? Impaired Status, Compliance,

Business Structuring. Whistle Blower.

Call Kenneth Haber

Over 30 years experience

Former Assistant US Attorney

Former Senior OIG Attorney

301.670.0016 • www.haberslaw.com

No Obligation

WWW.DRUGTOPICS.COM

DRUG TOPICS

December 2010

This issue is a milestone for Drug Topics, with the pub-

lication of the 200th column by Jim Plagakis to appear

under the heading “JP at Large.” In this issue (page

13), he takes us on a journey that began in 1989 with the pub-

lication of his ﬁ rst column, about a patient with bipolar disorder

who needed someone to listen. That someone was Jim.

Jim has been listening and counseling as a pharmacist for

almost 45 years. At his ﬁ rst job, in a downtown drugstore that

still had a lunch counter, patients received a coupon for a free

cup of coffee to drink while they waited for

their prescriptions. Jim would join patients

for a sip of coffee and ask whether they had

any questions about their medications. He

called it “stealth counseling in the 1960s.”

Fast-forward to 1993. Jim explained in a

column that he took “3 focused minutes”

to listen to a father’s grief for his 9-year-old

son, who was near death from brain cancer.

He wrote, “I was his sponge. He released the

poison, and I sucked it up. Not required by

law, but I think it’s part of my job, even if

the next person up for an Rx had to wait 3

extra minutes.”

Today counseling on every new prescrip-

tion is mandatory in Texas, where Jim prac-

tices. When the technician rings up the pre-

scriptions, including new ones, the whole process stops. Jim

usually asks the patient whether he has used the prescription

before. If the patient says yes, Jim asks whether he has any

questions. If there are none, Jim sends the patient on his way.

When the prescription is a new one for the patient, Jim either

sticks to the basic facts or counsels in greater depth.

“If the drug really needs extensive counseling, I move the

patient over to the counseling window and we really talk,” he

told Drug Topics. “I have serious issues with benzodiazepines,

because they are a dangerous class of drugs if used for a long

period of time. Patients hardly even know that they are taking

that stuff, because it works so well. However, for most people,

a certain part of their personality is lost to them, and it can

be the best part of their personality — the passion, the anger,

stuff that normal human beings have.”

In fact, Jim recently told one of his patients, a young medical

student who had been taking a benzodiazepine regularly for 6

months, that she was too young to continue with this drug for

so long. He warned her of the risks of terrible withdrawal and

the need to manage the stress of medical school differently.

“This is the kind of extensive counseling

that pharmacists can do, although most

don’t. Younger pharmacists don’t give

themselves permission to do that. I’m older,

so I actually can intrude like that. It helps

a lot to make eye contact and let patients

know that you are serious,” Jim said. “I

love it. It’s the best part of my job.”

Jim also believes in taking the time to

counsel patients about over-the-counter

medications. He works part-time, approx-

imately 2 to 3 days per week, as a relief

pharmacist for a national chain. While

some pharmacists direct all their attention

to the “prescription mill” behind the coun-

ter, Jim’s patients know that if they come

in on Tuesday or Friday, he is accessible and

knowledgeable about the OTC products that look so benign

on the drugstore shelves.

With the need to ﬁ ll ever-growing numbers of prescriptions,

pharmacists may be worried that technicians will take over

their jobs, Jim said. “Qualiﬁ ed technicians will be legally em-

powered to do more of the ﬁ lling tasks. The idea is to allow

the pharmacist more time for counseling and MTM, as well

as the various professional tasks that will deﬁ ne us in the 21st

century. We must, however, be ever watchful. It’s our profes-

sion. We will have it our way.”

Thank you, Jim, for sharing your perspective and insight.

A glimpse into the world of retail

pharmacy through the eyes of JP

Julia Talsma, Editor-in-Chief

)

VIEWPOINT

Final Word

“This is the kind of

extensive counsel-

ing that pharmacists

can do, although

most don’t ... It helps

a lot to make eye

contact and let

patients know that

you are serious. I

love it. It’s the best

part of my job.”

Counts

top-selling drugs, making

hand-counting a thing of the past.

The RxMedic ACS™ counting system makes pinpoint

accuracy affordable for any pharmacy. The ACS

simultaneously counts and pre-counts pills. It’s available

in four standard conﬁgurations or can be customized to ﬁt

your individual needs. The ACS includes the added safety of

digitally imaging vial contents for more complete records.

For higher-volume needs, experience fully-automated

dispensing with the RxMedic ADS™ robotic system.

Ready to count less and do more for your patients?

Visit www.rxmedic.com or call 800-882-3819.

Happy Holidays!

In the spirit of the holiday season,

we send our thanks

and best wishes for the New Year.

DT 290 Advanstar 201012

Navigation menu

Versions of this User Manual:

Views

Navigation