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TIRF FDA Memo on REMS Modification 2017 08 30 Department of Health and Human Services Food and Drug Administration
Center for Drug Evaluation and Research Office of Surveillance and Epidemiology Office of Medication Error Prevention and Risk Management
REMS MODIFICATION REVIEW
Date:
August 30, 2017
Reviewer(s):
LaShaun Washington-Batts, Pharm.D. Risk Management Analyst Division of Risk Management (DRISK)
Kate Oswell, M.A. Health Communication Specialist DRISK
Team Leader:
Selena Ready, Pharm.D. DRISK
Division Director:
Cynthia LaCivita, Pharm.D. DRISK
Subject:
REMS Modification
Therapeutic Class:
Opioid Analgesic
OND Review Division:
Division of Anesthetics, Analgesia, and Addiction Products
OSE RCM #:
2017-1183
DMF #:
027320
Drug Name, Dosage Form, NDA Number and Sponsor Name:
Reference ID: 4146711
FDA_7235
Table 1: Products included in the TIRF REMS Access Program
Drug Name
Dosage Form and Route
NDA Number
Abstral (fentanyl)
Sublingual tablet
022510
Actiq (fentanyl citrate) Oral transmucosal lozenge
020747
Fentora and Authorized Generic (fentanyl citrate)
Buccal tablet
021947
Lazanda (fentanyl)
Nasal spray
022569
Onsolis (fentanyl)
Buccal soluble film
022266
Subsys (fentanyl)
Sublingual spray
202788
Sponsor
Galenya BioPharma Cephalon, Inc.
Cephalon, Inc.
DepoMed, Inc. Meda Pharmaceuticals
Insys Therapy
fentanyl buccal fentanyl citrate fentanyl citrate
Buccal tablet
Oral transmucosal lozenge
Oral transmucosal lozenge
ANDA 079075
ANDA 078907
ANDA 077312
Watson Laboratories, Inc. Mallinckrodt, Inc.
Par Pharmaceutical, Inc.
Reference ID: 4146711
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TABLE OF CONTENTS
1. Introduction ....................................................................................................................................................................... 4 2. Background........................................................................................................................................................................ 4 3. Regulatory History .......................................................................................................................................................... 5 4. Materials Reviewed......................................................................................................................................................... 7 4.1. Submissions .................................................................................................................................................................. 7 4.2. Other Materials Informing Our Review............................................................................................................... 7 5. Rationale for the REMS Modification ...................................................................................................................... 7 6. Review of the proposed REMS Modification......................................................................................................... 7 6.1. Medication Guide........................................................................................................................................................ 7 6.2. REMS Document ........................................................................................................................................................ 8 6.3. Elements to Assure Safe Use .................................................................................................................................. 8 6.4. Implementation System............................................................................................................................................. 8 6.5. Timetable for Submission of Assessments ......................................................................................................... 8 6.6. REMS Supporting Document ................................................................................................................................. 8 7. Discussion and Conclusion........................................................................................................................................... 8 8. Recommendation ............................................................................................................................................................. 9 9. Attachments....................................................................................................................................................................... 9
Reference ID: 4146711
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1. INTRODUCTION
This review by the Division of Risk Management (DRISK) provides an evaluation of the amended proposed modification of the transmucosal immediate-release fentanyl (TIRF) risk evaluation and mitigation strategy (REMS) Access Program (TIRF REMS) received on August 29, 2017. This REMS modification is required to conform to safety labeling changes (SLC) approved on December 16, 2016 that address the addition of language related to the risks of misuse, abuse, addiction, overdose, death, and neonatal opioid withdrawal syndrome (NOWS), serotonin syndrome with concomitant use of serotonergic drugs, adrenal insufficiency, androgen deficiency, and risks of concomitant use of opioid analgesics with benzodiazepines or other central nervous system depressants to the Prescribing Information.
Thus, the primary purpose of this proposed TIRF REMS modification is to incorporate the approved safety labeling changes within the TIRF REMS document and materials.
This review is written by the DRISK in consultation with the Office of Prescription Drug Promotion (OPDP).
2. BACKGROUND
TIRF products are used for the management of breakthrough cancer pain in patients already receiving and who are tolerant to around the clock opioid therapy for their underlying persistent cancer pain.
The approved TIRF products include:
Abstral (fentanyl) sublingual tablet Actiq (fentanyl citrate) oral transmucosal lozenge Fentora (fentanyl citrate) buccal tablet Lazanda (fentanyl) nasal spray, Onsolis (fentanyl) buccal soluble film Subsys (fentanyl) sublingual spray Approved generic equivalents of these products
The TIRF products are approved under a shared system REMS and all Sponsors with approved products in the TIRF REMS are members of the TIRF REMS Industry Group (TRIG). The goals of the TIRF REMS are to mitigate the risk of misuse, abuse, addiction, overdose and serious complications due to medication errors by:
Prescribing and dispensing TIRF medicines only to appropriate patients, which includes use only in opioid-tolerant patients.
Preventing inappropriate conversion between TIRF medicines. Preventing accidental exposure to children and others for whom it was not prescribed. Educating prescribers, pharmacists, and patients on the potential for misuse, abuse, addiction, and
overdose of TIRF medicines.
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The REMS is comprised of Medication Guides (MG) for each individual TIRF medicine and the following elements to assure safe use (ETASU):
Healthcare providers who prescribe TIRF medicines for outpatient use are specially certified TIRF medicines will only be dispensed by pharmacies that are specially certified TIRF medicines will only be dispensed for outpatient use with evidence or other documentation
of safe-use conditions.
The timetable for submission of TIRF REMS assessments is at 6 and 12 months from the date of the initial REMS approval, and annually thereafter.
The TIRF REMS was approved by the Agency on December 28, 2011 and was launched on March 12, 2012. The TIRF REMS was modified June 5, 2012, November 7, 2013 and December 24, 2014.
3. REGULATORY HISTORY
The following provides the regulatory history for the TIRF REMS relevant to this review.
March 22, 2016: The Agency issued SLC notification letters to Sponsors of the TIRF product new drug applications (NDAs). The new safety information to be included in the labeling pertains to the risks of misuse, abuse, addiction, overdose, death, and neonatal opioid withdrawal syndrome; serotonin syndrome with concomitant use of serotonergic drugs; adrenal insufficiency; and androgen deficiency.
August 31, 2016: The Agency issued SLC notification letters to the Sponsors of the TIRF product NDAs. The new safety information to be included in the labeling pertains to the risks of concomitant use of opioid analgesics with benzodiazepines or other central nervous system depressants.
December 16, 2016: The Agency approved the SLCs for all TIRF products. The new safety information included the following: Updating the warning to include misuse, abuse, addiction, overdose, death, and NOWS, Serotonin Syndrome with concomitant use of serotonergic drugs, adrenal insufficiency, androgen deficiency, and risks of concomitant use of opioid analgesics with benzodiazepines or other central nervous system depressants.
June 9, 2017: The TRIG point of contact submitted the TIRF Access Program REMS Modification to the Drug Master File (DMF) 27320.
June 12, 2017: All TRIG sponsors submitted individual cover letters for the TIRF Access Program REMS Modification to their applications, referencing the DMF Submission.
July 12, 2017: The Agency emailed comments from the DRISK's review of the June 9, 2017 submission of the proposed REMS modification1, requesting amended REMS materials by July 26, 2017.
July 19, 2017: The TRIG proposed an extension to the requested July 26, 2017 submission date of the REMS Modification. After evaluating the FDA comments received on July 12, 2017, additional time was
1 Washington-Batts L. DAAAP. REMS Modification Review TIRFS. Submitted in DAARTS July 12, 2017
Reference ID: 4146711
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required to fully prepare the documents, create the updated website screenshots, accommodate required sponsor review and voting approval of the final submission, and allow for the publishing and sequence processing by our external DMF submission vendor.
The TRIG proposed to email the unformatted final version of the REMS, REMS Supporting Document, appended materials, and listing of website changes on July 31, 2017 andsubmit to the DMF the final formatted REMS, REMS Supporting Document, appended materials including updated website screenshotson August 18, 2017.
July 26, 2017: The Agency emailed the TRIG the following comments:
FDA is willing to accept the TRIG's proposal. The TRIG will submit (via email to the FDA POC) the redline and clean Word version of the REMS Document, REMS Supporting Document, appended materials, and listing of website changes on July 31, 2017. The Agency will review the emailed documents to determine if they are acceptable. If approved, the TRIG must submit the final formatted REMS document, materials including website screenshots, and REMS Supporting Document as separate files, as well as, a compiled document for posting on the FDA REMS website, to the DMF on August 18, 2017. In addition to the final submission to the DMF, on August 18, 2017, each applicant must also submit to each respective application, a cross-reference submission titled "REMS Final for approved NDA ######, Supplement S-XXX.
July 31, 2017: The TRIG emailed the unformatted final versions of the REMS Document, materials, and Supporting Document.
August 11, 2017: The Agency emailed the TRIG the following comments:
The Agency will not be able to take an action on the modification until we are able to review TRIG's submission to the DMF planned for August 18, 2017 of the final formatted REMS document, materials including website screenshots, and REMS Supporting Document.
August 18, 2017: The TRIG submitted formatted versions of the REMS Document, materials, and Supporting Document.
August 22, 2017: The Agency emailed the TRIG the following comments:
We reviewed your August 18th submission of final formatted REMS Document, Supporting Document and Materials. We note there is a discrepancy between the emailed documents and the final formatted submission. Specifically, the Dear Healthcare Provider and Pharmacy Letters that you submitted are not the original letters sent via email on July 31, 2017. You must resubmit by 8/29/2017, the final formatted REMS Document, REMS Supporting Document and appended materials with the original letters. However, please modify the original letters to include a boxed statement at the top of each letter to state the letter ceased distribution in March 2012. See the attachment for a redlined version for your reference.
August 29, 2017: The TRIG submitted the final formatted versions of the REMS Document, materials, and Supporting Document. These are the subject of this review.
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4. MATERIALS REVIEWED
4.1. SUBMISSIONS
· DMF # 027320 eCTD Sequence No. 029 TIRF Access Program REMS Modification received on
June 9, 2017.
Submission Date Product Name
June 12, 2017 June 12, 2017 June 12, 2017
Abstral (fentanyl) Actiq (fentanyl citrate) Fentora and Authorized Generic (fentanyl citrate)
Application Number NDA 022510 NDA 020747 NDA 021947
Supplement Number 17 47 27
June 12, 2017
Lazanda (fentanyl)
NDA 022569
26
June 12, 2017
Onsolis(fentanyl)
NDA 022266
19
June 12, 2017
Subsys (fentanyl)
NDA 202788
18
June 12, 2017
Fentanyl buccal tablet
ANDA 079075
13
June 12, 2017
Fentanyl citrate lozenge
ANDA 078907
16
June 12, 2017
Fentanyl citrate lozenge
ANDA 077312
9
Amended -DMF # 027320 eCTD Sequence No. 0031 TIRF Access Program REMS Modification received on August 18, 2017.
Amended - DMF # 027320 eCTD Sequence No. 0033 TIRF Access Program REMS Modification received on August 29, 2017.
4.2. OTHER MATERIALS INFORMING OUR REVIEW
TIRF REMS Modification DRISK Interim Review by L.Washington-Batts finalized in DARRTS on July 12, 2017
Email correspondence to the TRIG dated July 12, 2017 and August 22, 2017
5. RATIONALE FOR THE REMS MODIFICATION
The proposed TIRF REMS modification is in response to the SLC Approval Letter dated December 16, 2016 that included the addition of language related to the risks of misuse, abuse, addiction, overdose, death, and NOWS, serotonin syndrome with concomitant use of serotonergic drugs, adrenal insufficiency, androgen deficiency, and risks of concomitant use of opioid analgesics with benzodiazepines or other central nervous system depressants to the Prescribing Information. This REMS modification is necessary to align the TIRF REMS document and REMS materials with the SLC approved on December 16, 2016.
6. REVIEW OF THE PROPOSED REMS MODIFICATION 6.1. MEDICATION GUIDE
There were no changes proposed for this element.
Reference ID: 4146711
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6.2. REMS DOCUMENT
The TRIG submitted a revised REMS Document reflecting the Agency's comments emailed on July 12, 2017.
Reviewer Comment: The Agency agrees with the proposed REMS Document.
6.3. ELEMENTS TO ASSURE SAFE USE 6.3.1. REMS MATERIALS
The TRIG submitted revised REMS Materials and a list of website changes reflecting the Agency's comments emailed on July 12, 2017 and August 22, 2017.
Reviewer Comment: The Agency agrees with the proposed REMS Materials and list of website changes.
6.4. IMPLEMENTATION SYSTEM
There were no changes proposed for this element.
6.5. TIMETABLE FOR SUBMISSION OF ASSESSMENTS
There were no changes proposed for this element.
6.6. REMS SUPPORTING DOCUMENT
The TRIG submitted a revised REMS Supporting Document reflecting the Agency's comments emailed on July 12, 2017.
Reviewer Comment: The Agency agrees with the proposed REMS Supporting Document.
7. DISCUSSION AND CONCLUSION
DRISK reviewed the proposed REMS modification which was necessary to provide the safety information regarding the SLC for the addition of language related to the risks of misuse, abuse, addiction, overdose, death, and NOWS, serotonin syndrome with concomitant use of serotonergic drugs, adrenal insufficiency, androgen deficiency, and risks of concomitant use of opioid analgesics with benzodiazepines or other central nervous system depressants to the Prescribing Information. The REMS modification was received from the TRIG on June 9, 2017 and the final content of the modified materials were received on August 29, 2017. These materials contained the appropriate changes to the REMS as agreed upon by the Agency. Therefore, the proposed modified TIRF REMS, as appended to this review, for all products covered under the TIRF REMS program (Table 1) is acceptable to DRISK.
Reference ID: 4146711
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8. RECOMMENDATION
DRISK recommends approval of the proposed TIRF REMS modification as appended to this review.
9. ATTACHMENTS
1. REMS Document and Appended Materials
Reference ID: 4146711
FDA_7243
Initial REMS approval: 12/2011 Most recent modification: 08/2017
TRANSMUCOSAL IMMEDIATE RELEASE FENTANYL (TIRF) RISK EVALUATION AND MITIGATION STRATEGY (REMS)
Reference ID: 4146711
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I. GOALS
The goals of the TIRF REMS Access program are to mitigate the risk of misuse, abuse, addiction, overdose and serious complications due to medication errors by:
1. Prescribing and dispensing TIRF medicines only to appropriate patients, which includes use only in opioid-tolerant patients.
2. Preventing inappropriate conversion between TIRF medicines. 3. Preventing accidental exposure to children and others for whom it was not prescribed. 4. Educating prescribers, pharmacists, and patients on the potential for misuse, abuse,
addiction, and overdose of TIRF medicines.
II. REMS ELEMENTS
A. Medication Guide
The product-specific TIRF Medication Guide will be dispensed with each TIRF prescription in accordance with 21 CFR 208.24. The Medication Guides for TIRF medicines are part of the TIRF REMS Access program and will be available on the TIRF REMS Access website (www.TIRFREMSaccess.com).
B. Elements to Assure Safe Use
1. Healthcare providers who prescribe TIRF medicines for outpatient use are specially certified.
a. TIRF sponsors will ensure that healthcare providers who prescribe TIRF medicines for outpatient use are specially certified.
b. To become certified to prescribe TIRF medicines, prescribers will be required to enroll in the TIRF REMS Access program. Prescribers must complete the following requirements to be enrolled:
i. Review the TIRF REMS Access education materials (TIRF REMS Access Education Program), including the Full Prescribing Information (FPI) for each TIRF medicine,
and successfully complete the Knowledge Assessment (Knowledge Assessment).
ii. Complete and sign the Prescriber Enrollment Form. In signing the Prescriber Enrollment Form, each prescriber is required to acknowledge the following:
a) I have reviewed the TIRF REMS Access Education Program, and I have completed the Knowledge Assessment. I understand the responsible use conditions for TIRF medicines and the risks and benefits of chronic opioid therapy.
b) I understand that TIRF medicines can be abused and that this risk should be considered when prescribing or dispensing TIRF medicines in situations
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where I am concerned about an increased risk of misuse, abuse, or overdose, whether accidental or intentional.
c) I understand that TIRF medicines are indicated only for the management of breakthrough pain in cancer patients 18 years of age or older (Actiq and its generic equivalents are approved for 16 years of age and older), who are already receiving, and who are tolerant to, around-the-clock opioid therapy for their underlying persistent cancer pain.
d) I understand that TIRF medicines are contraindicated for use in opioid nontolerant patients, and know that fatal overdose can occur at any dose.
e) I understand that TIRF medicines must not be used to treat acute or postoperative pain, including headache/migraine, dental pain, or acute pain in the emergency department.
f) I understand that converting patients from one TIRF medicine to a different TIRF medicine must not be done on a microgram-per-microgram basis. I understand that TIRF medicines are not interchangeable with each other, regardless of route of administration, and that conversion may result in fatal overdose, unless conversion is done in accordance with labeled productspecific conversion recommendations (refer to the list of currently approved TIRF products located on the TIRF REMS Access website at www.TIRFREMSaccess.com/TirfUI/rems/products.action. Note, a branded TIRF medicine and its specific generic product(s) are interchangeable.
g) I understand that the initial starting dose for TIRF medicines for all patients is the lowest dose, unless individual product labels provide product-specific conversion recommendations, and I understand that patients must be titrated individually.
h) I will provide a Medication Guide for the TIRF medicine that I intend to prescribe to my patient or their caregiver and review it with them. If I convert my patient to a different TIRF medicine, the Medication Guide for the new TIRF medicine will be provided to, and reviewed with, my patient or their caregiver.
i) I will complete and sign a TIRF REMS Access Patient-Prescriber Agreement Form with each new patient, before writing the patient's first prescription for a TIRF medicine, and renew the agreement every two (2) years.
j) I will provide a completed, signed copy of the Patient-Prescriber Agreement Form to the patient and retain a copy for my records. I will also provide a completed, signed copy to the TIRF REMS Access program (through the TIRF REMS Access website or by fax) within ten (10) working days.
k) At all follow-up visits, I agree to assess the patient for appropriateness of the dose of the TIRF medicine, and for signs of misuse and abuse.
l) I understand that TIRF medicines are only available through the TIRF REMS Access program. I understand and agree to comply with the TIRF REMS
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Access program requirements for prescribers.
m) I understand that I must re-enroll in the TIRF REMS Access program and successfully complete the enrollment requirements every two (2) years.
In signing the Patient-Prescriber Agreement Form, the prescriber documents the following:
1) I understand that TIRF medicines are indicated only for the management of breakthrough pain in cancer patients 18 years of age or older (Actiq and its generic equivalents are approved for 16 years of age and older), who are already receiving, and who are tolerant to, around-the-clock opioid therapy for their underlying persistent cancer pain.
2) I understand that TIRF medicines are contraindicated for use in opioid non-tolerant patients, and know that fatal overdose can occur at any dose.
3) I understand that TIRF medicines are not for use in the management of acute or postoperative pain, including headache/migraine, dental pain, or acute pain in the emergency department.
4) I understand that patients considered opioid-tolerant are those who are taking, for one week or longer, at least: 60 mg oral morphine/day; 25 micrograms transdermal fentanyl/hour; 30 mg oral oxycodone/day; 8 mg oral hydromorphone/day; 25 mg oral oxymorphone/day; 60 mg oral hydrocodone/day; or an equianalgesic dose of another opioid daily.
5) I have provided to, and reviewed with, my patient or their caregiver the Medication Guide for the TIRF medicine I intend to prescribe.
6) If I change my patient to a different TIRF medicine, I will provide the Medication Guide for the new TIRF medicine to my patient or my patient's caregiver, and I will review it with them.
7) I understand that if I change my patient to a different TIRF medicine, the initial dose of that TIRF medicine for all patients is the lowest dose, unless individual product labels provide product-specific conversion recommendations.
8) I have counseled my patient or their caregiver about the risks, benefits, and appropriate use of TIRF medicines including communication of the following safety messages:
A. If you stop taking your around-the-clock pain medicine, you must stop taking your TIRF medicine.
B. NEVER share your TIRF medicine.
C. Giving a TIRF medicine to someone for whom it has not
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been prescribed can result in a fatal overdose.
D. TIRF medicines can be fatal to a child; used and unused dosage units must be safely stored out of the reach of children living in or likely to visit the home and disposed of in accordance with the specific disposal instructions detailed in the product's Medication Guide.
I will ensure that the patient and/or caregiver understand that, in signing the Patient-Prescriber Agreement Form, they document the following:
1) My prescriber has given me a copy of the Medication Guide for the TIRF medicine I have been prescribed, and has reviewed it with me.
2) I understand that TIRF medicines should only be taken by patients who are regularly using another opioid, around-the-clock, for constant pain. If I am not taking around-the-clock opioid pain medicine, my prescriber and I have discussed the risks of only taking TIRF medicines.
3) I understand that if I stop taking another opioid pain medicine that I have been taking regularly, around-the-clock, for my constant pain, then I must also stop taking my TIRF medicine.
4) I understand how I should take this TIRF medicine, including how much I can take, and how often I can take it. If my prescriber prescribes a different TIRF medicine for me, I will ensure I understand how to take the new TIRF medicine.
5) I understand that any TIRF medicine can cause serious side effects, including life-threatening breathing problems which can lead to death, especially if I do not take my TIRF medicine exactly as my prescriber has directed me to take it.
6) I agree to contact my prescriber if my TIRF medicine does not relieve my pain. I will not change the dose of my TIRF medicine myself or take it more often than my prescriber has directed.
7) I agree that I will never give my TIRF medicine to anyone else, even if they have the same symptoms, since it may harm them or even cause death.
8) I will store my TIRF medicine in a safe place, out of reach of children and teenagers because accidental use by a child, or anyone for whom it was not prescribed, is a medical emergency and can cause death.
9) I have been instructed on how to properly dispose of my partially used or unneeded TIRF medicine remaining from my prescription, and will dispose of my TIRF medicine as soon as I no longer need it.
10) I understand that selling or giving away my TIRF medicine is against the law.
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11) I have asked my prescriber all the questions I have about my TIRF medicine. If I have any additional questions or concerns in the future about my treatment with my TIRF medicine, I will contact my prescriber.
12) I have reviewed the "Patient Privacy Notice for the TIRF REMS Access Program" and I agree to its terms and conditions which allow my healthcare providers to share my health information, as defined in that document, with the makers of TIRF medicines (TIRF Sponsors) and their agents and contractors for the limited purpose of managing the TIRF REMS Access program.
c. Prescribers are required to re-enroll every two (2) years. Additionally, prescribers must re-counsel their patients and complete a new Patient-Prescriber Agreement Form every two (2) years.
d. TIRF Sponsors will:
i. Ensure that prescriber enrollment can successfully be completed via the TIRF REMS Access website, or by mailing or faxing the forms.
ii. Ensure that, as part of the enrollment process, the following materials that are part of the TIRF REMS Access program are available to prescribers. These materials are appended:
· TIRF REMS Access Prescriber Program Overview
· TIRF REMS Access Education Program
· Knowledge Assessment
· Prescriber Enrollment Form
· Patient-Prescriber Agreement Form
· TIRF REMS Access Patient and Caregiver Overview
· Frequently Asked Questions (FAQs)
· TIRF REMS Access Website
iii. Ensure that prescribers have successfully completed the Knowledge Assessment, and ensure that enrollment forms are complete before activating a prescriber's enrollment in the TIRF REMS Access program.
iv. Ensure that prescribers are notified when they are successfully enrolled in the TIRF REMS Access program, and therefore, are certified to prescribe TIRF medicines.
v. Monitor education and enrollment requirements for prescribers and may inactivate non-compliant prescribers. Upon initial activation, prescribers remain active until inactivation occurs or expiration of the enrollment period.
vi. Ensure that prior to the first availability of the TIRF REMS Access program/website, Dear Healthcare Provider Letters will be sent. The target audience for the letters will include pain management specialists (comprised of anesthesiologists, physical medicine and rehabilitation physicians), primary care
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physicians, oncologists, oncology nurse practitioners who treat breakthrough pain in patients with cancer, and other appropriately licensed healthcare professionals who prescribe TIRF medicines. The letter will include information on the risks associated with the use of TIRF medicines and will explain to healthcare providers that if they wish to treat patients using TIRF medicines, they must enroll in the TIRF REMS Access program. The letters will be available on the TIRF REMS Access website for 1 year from the date of the mailing.
The Dear Healthcare Provider Letter is part of the TIRF REMS Access program and is appended.
2. TIRF medicines will only be dispensed by pharmacies that are specially certified.
a. TIRF Sponsors will ensure that TIRF medicines will only be dispensed by certified pharmacies. To become certified to dispense TIRF medicines, each pharmacy must be enrolled in the TIRF REMS Access program.
b. Each pharmacy will be required to designate an authorized pharmacy representative (chain and closed system outpatient pharmacies) or authorized pharmacist (independent outpatient and inpatient pharmacies) to complete enrollment on behalf of the pharmacy(s).
c. For the purposes of this REMS, there are different requirements for :
· Outpatient Pharmacies
i. Chain Outpatient Pharmacy: Retail, mail order or institutional outpatient
pharmacies having a chain headquarters that is responsible for ensuring enrollment and training of the pharmacy staff of all associated outpatient pharmacies. The chain headquarters will enroll multiple locations (i.e., chain stores) in the TIRF REMS Access program.
ii. Independent Outpatient Pharmacy: Retail, mail order, or institutional
outpatient pharmacies having an authorized pharmacy representative that is responsible for ensuring enrollment and training of the pharmacy staff within an individual outpatient pharmacy. Each store will individually enroll in the TIRF REMS Access program as a single pharmacy location.
iii. Closed System Outpatient Pharmacy: Institutional or mail order outpatient
pharmacies that use a pharmacy management system that does not support the process of electronically transmitting the validation and claim information currently required by the TIRF REMS Access program.
· Inpatient pharmacies (e.g., hospitals, in-hospital hospices, and long-term care facilities that dispense for inpatient use)
d. Chain and Independent Outpatient Pharmacy(s):
The authorized pharmacist/pharmacy representative must complete the following requirements to enroll their chain or independent outpatient pharmacy:
i. Review the TIRF REMS Access Education Program (TIRF REMS Access Education Program) and successfully complete the Knowledge Assessment.
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ii. Ensure the pharmacy enables its pharmacy management system to support communication with the TIRF REMS Access program system, using established telecommunication standards, and runs the standardized validation test transaction to validate the system enhancements.
iii. Complete and sign the Independent Outpatient Pharmacy Enrollment Form or the Chain Outpatient Pharmacy Enrollment Form for groups of associated pharmacies. In signing the Independent Outpatient Pharmacy Enrollment Form or Chain Outpatient Pharmacy Enrollment Form, the authorized pharmacist is required to acknowledge the following:
a) I have reviewed the TIRF REMS Access Education Program, and I have completed the Knowledge Assessment. I understand the risks and benefits associated with TIRF medicines and the requirements of the TIRF REMS Access program for pharmacies.
b) I will ensure that all pharmacy staff who participate in dispensing TIRF medicines are educated on the risks associated with TIRF medicines and the requirements of the TIRF REMS Access program, as described in the TIRF REMS Access Education Program. This training should be documented and is subject to audit.
c) I understand that converting patients from one TIRF medicine to a different TIRF
medicine must not be done on a microgram-per-microgram basis. I understand
that TIRF medicines are not interchangeable with each other, regardless of route
of administration, and that conversion may result in fatal overdose, unless
conversion is done in accordance with labeled product-specific conversion
recommendations (refer to the list of currently approved TIRF products located
on
the
TIRF
REMS
Access
website
at
www.TIRFREMSaccess.com/TirfUI/rems/products.action. Note, a branded TIRF
medicine and its specific generic product(s) are interchangeable.
d) I understand that TIRF medicines are contraindicated for use in opioid nontolerant patients.
e) I understand that the initial starting dose of TIRF medicines for all patients is the lowest dose, unless individual product labels provide product-specific conversion recommendations, and I understand that patients must be titrated individually.
f) I understand the importance of discussing the risks and benefits of TIRF medicines with patients and their caregivers, and in particular the importance of taking the drug as prescribed, not sharing with others, and proper disposal.
g) I understand that the product-specific Medication Guide must be given to the patient or their caregiver each time a TIRF medicine is dispensed.
h) I understand that TIRF medicines will not be dispensed without verifying through our pharmacy management system that the prescriber and pharmacy are enrolled and active, and that the patient has not been inactivated in the program.
i) I understand that ALL TIRF medicine prescriptions, regardless of the method
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of payment, must be processed through our pharmacy management system.
j) I understand that all dispensing locations must be enrolled in the TIRF REMS Access program to dispense TIRF medicines.
k) I understand that TIRF medicines can only be obtained from wholesalers/distributors that are enrolled in the TIRF REMS Access program.
l) I understand that our pharmacy will not sell, loan or transfer any TIRF medicine inventory to any other pharmacy, institution, distributor, or prescriber.
m) I understand that our pharmacy must re-enroll in the TIRF REMS Access program and successfully complete the enrollment requirements every two (2) years.
n) I understand that TIRF medicines are only available through the TIRF REMS Access program. I understand that the pharmacy must comply with the TIRF REMS Access program requirements for outpatient pharmacies.
o) I understand that differences in pharmacy software may affect automation
capabilities for adjudicating prescriptions through the TIRF REMS Access program without an insurance claim (i.e.: cash claim). If insurance is not used, pharmacy staff must manually enter the REMS Cash BIN #014780 or the designated chain pharmacy cash bin in order for the transaction to be properly adjudicated through the TIRF REMS Access program.
Note: The `or the designated chain pharmacy cash bin' language will not be included in the attestation on the Independent Outpatient Pharmacy Enrollment Form
e. Closed System Outpatient Pharmacies:
The authorized pharmacist/pharmacy representative must complete the following requirements to enroll their closed system outpatient pharmacy:
i. Review the TIRF REMS Access Education Program (TIRF REMS Access Education Program) and successfully complete the Knowledge Assessment.
ii. Complete and sign the Closed System Outpatient Pharmacy Enrollment Form. In signing the Closed System Outpatient Pharmacy Enrollment Form, the authorized closed system outpatient pharmacy representative is required to acknowledge the following:
a) I have reviewed the TIRF REMS Access Education Program, and I have completed the Knowledge Assessment. I understand the risks and benefits associated with TIRF medicines and the requirements of the TIRF REMS Access program for pharmacies.
b) I will ensure that all pharmacy staff who participate in dispensing TIRF medicines are educated on the risks associated with TIRF medicines and the requirements of the TIRF REMS Access program, as described in the TIRF REMS Access Education Program. This training should be documented and is subject to audit.
Reference ID: 4146711
FDA_7252
c) I understand that converting patients from one TIRF medicine to a different TIRF
medicine must not be done on a microgram-per-microgram basis. I understand
that TIRF medicines are not interchangeable with each other, regardless of route
of administration, and that conversion may result in fatal overdose, unless
conversion is done in accordance with labeled product-specific conversion
recommendations (refer to the list of currently approved TIRF products located
on
the
TIRF
REMS
Access
website
at
www.TIRFREMSaccess.com/TirfUI/rems/products.action. Note, a branded TIRF
medicine and its specific generic product(s) are interchangeable.
d) I understand that TIRF medicines are contraindicated for use in opioid nontolerant patients.
e) I understand that the initial starting dose for TIRF medicines for all patients is the lowest dose, unless individual product labels provide product-specific conversion recommendations, and I understand that patients must be titrated individually.
f) I understand the importance of discussing the risks and benefits of TIRF medicines with patients and their caregivers, and in particular the importance of taking the drug as prescribed, not sharing with others, and proper disposal.
g) I understand that the product-specific Medication Guide must be given to the patient or their caregiver each time a TIRF medicine is dispensed.
h) I understand that a TIRF medicine will not be dispensed without obtaining a TIRF REMS Access prescription authorization number issued by the TIRF REMS Access program prior to dispensing the prescription. A TIRF REMS Access prescription authorization number verifies that the prescriber and pharmacy are enrolled and active, and that the patient has not been inactivated from the program.
i) I understand that all dispensing locations must be enrolled in the TIRF REMS Access program to dispense TIRF medicines
j) I understand that TIRF medicines can only be obtained from wholesalers/distributors that are enrolled in the TIRF REMS Access program.
k) I understand that our pharmacy will not sell, loan or transfer any TIRF inventory to any other pharmacy, institution, distributor, or prescriber.
l) I understand that our pharmacy must re-enroll in the TIRF REMS Access program every two (2) years.
m) I understand that TIRF medicines are only available through the TIRF REMS Access program. I understand that the pharmacy must comply with the TIRF REMS Access program requirements for outpatient closed system pharmacies.
f. Inpatient Pharmacies:
Reference ID: 4146711
FDA_7253
The authorized pharmacist must complete the following requirements to successfully enroll their inpatient pharmacy:
i. Review the TIRF REMS Access Education Program (TIRF REMS Access Education Program) and successfully complete the pharmacy Knowledge Assessment.
ii. Complete and sign the Inpatient Pharmacy Enrollment Form. In signing the Inpatient Pharmacy Enrollment Form, the authorized pharmacist is required to acknowledge the following:
a) I have reviewed the TIRF REMS Access Education Program, and I have completed the Knowledge Assessment. I understand the benefits and risks associated with TIRF medicines and the requirements of the TIRF REMS Access program for pharmacies.
b) I will ensure that our inpatient pharmacists are educated on the risks associated with TIRF medicines and the requirements of the TIRF REMS Access program, as described in the TIRF REMS Access Education Program.
c) I understand that converting patients from one TIRF medicine to a different TIRF
medicine must not be done on a microgram-per-microgram basis. I understand
that TIRF medicines are not interchangeable with each other, regardless of route
of administration, and that conversion may result in fatal overdose, unless
conversion is done in accordance with labeled product-specific conversion
recommendations (refer to the list of currently approved TIRF products located
on
the
TIRF
REMS
Access
website
at
www.TIRFREMSaccess.com/TirfUI/rems/products.action). Note, a branded TIRF
medicine and its specific generic product(s) are interchangeable.
d) I understand that TIRF medicines are contraindicated for use in opioid nontolerant patients.
e) I understand that the initial starting dose for TIRF medicines for all patients is the lowest dose, unless individual product labels provide product-specific conversion recommendations, and I understand that patients must be titrated individually.
f) I understand that pharmacies within or associated with the healthcare facility that dispense to outpatients must be separately enrolled in and comply with the TIRF REMS Access program to dispense TIRF medicines to outpatients, as described in section B.2.d, above.
g) I understand that our inpatient pharmacy must not dispense TIRF medicines for outpatient use.
h) I understand that a prescriber who wants to discharge a patient with a TIRF medicine prescription, intended to be dispensed by an outpatient pharmacy, will be required to enroll in the TIRF REMS Access program, as described in section B.1 of this REMS.
Reference ID: 4146711
FDA_7254
i) I will establish, or oversee the establishment of, a system, order sets, protocols and/or other measures to help ensure appropriate patient selection and compliance with the requirements of the TIRF REMS Access program.
j) I understand that our pharmacy will not sell, loan or transfer any TIRF inventory to any other pharmacy, institution, distributor, or prescriber.
k) I understand that TIRF medicines can only be obtained from wholesalers/distributors that are enrolled in the TIRF REMS Access program.
l) I understand that our pharmacy must re-enroll in the TIRF REMS Access program every two (2) years.
m) I understand that TIRF medicines are available only through the TIRF REMS Access program. I understand and agree to comply with the TIRF REMS Access program requirements for inpatient pharmacies.
g. Pharmacies (authorized pharmacist) are required to re-enroll every two (2) years.
h. TIRF Sponsors will:
i. Ensure that pharmacy enrollment can successfully be completed via the TIRF REMS Access website, by mailing or faxing the forms.
ii. Ensure that, as part of the enrollment process, the following materials that are part of the TIRF REMS Access program are available to pharmacies. These materials are appended:
· The TIRF REMS Access Program Overview (Independent Outpatient Pharmacy, Chain Outpatient Pharmacy, Closed System Outpatient Pharmacy or Inpatient Pharmacy, as applicable)
· TIRF REMS Access Education Program
· Knowledge Assessment
· Pharmacy Enrollment Form (Independent Outpatient, Chain Outpatient, Closed System Outpatient, or Inpatient, as applicable)
· Frequently Asked Questions (FAQs)
· TIRF REMS Access Website
iii. Ensure that all enrollment forms are complete, and that the authorized pharmacist has successfully completed the Knowledge Assessment before activating a pharmacy's enrollment in the TIRF REMS Access program.
iv. For chain and independent outpatient pharmacies only, TIRF Sponsors will also ensure that the configurations to the pharmacy management system have been validated before enrolling a pharmacy in the TIRF REMS Access program.
v. For closed system outpatient pharmacies only, TIRF Sponsors will ensure that, prior to authorizing a pharmacy's enrollment as a closed system outpatient pharmacy, the pharmacy meets the requirements of being deemed a closed system outpatient pharmacy (see II.B.2.c)
Reference ID: 4146711
FDA_7255
vi. Ensure that pharmacies are notified when they are successfully enrolled in the TIRF REMS Access program, and therefore, certified to dispense TIRF medicines.
vii. Monitor education and enrollment requirements for pharmacies and inactivate noncompliant pharmacies. Upon initial activation of enrollment, pharmacies remain active until a corrective action of inactivation occurs or expiration of the enrollment period.
viii. Ensure that prior to first availability of the TIRF REMS Access program/website, Dear Pharmacy Letters will be sent (one for inpatient pharmacies and one for outpatient pharmacies). The target audience for the letter will include outpatient and inpatient pharmacies that dispense Schedule II drugs and may be involved in dispensing TIRF medicines. The letter will include information on the risks associated with the use of TIRF medicines and the requirements of the TIRF REMS Access program. The letter will be available on the TIRF REMS Access website for 1 year from the date of the mailing.
The Dear Pharmacy Letters (Outpatient and Inpatient) are part of the TIRF REMS Access program. These materials are appended.
3. TIRF medicines will only be dispensed for outpatient use with evidence or other documentation of safe-use conditions.
a. TIRF Sponsors will ensure that TIRF medicines will only be dispensed for outpatient use if there is documentation in the TIRF REMS Access program system that the dispensing pharmacy and prescriber are enrolled and active, and the patient is not inactive in the TIRF REMS Access program.
b. Patients are passively enrolled in the TIRF REMS Access program when their first TIRF medicine prescription is processed at the pharmacy. Patients may continue to receive TIRF medicines while passively enrolled, for up to ten working days, as described in section II.C.5. Prescribers and outpatient pharmacies (including closed system outpatient pharmacies) are enrolled, as previously described in sections B.1 and B.2, respectively.
c. For chain and independent outpatient pharmacies: Prior to dispensing TIRF medicines, enrolled outpatient pharmacies will electronically verify documentation of the required enrollments by processing the TIRF prescription through their pharmacy management system.
i. If the required enrollments are verified, a unique authorization code will be issued to allow processing and dispensing of the prescription to the patient.
ii. If one or more of the required enrollments cannot be verified, the TIRF REMS Access program system will reject the prescription (prior to a claim being forwarded to the payer) and the pharmacy will receive a rejection notice.
d. For closed system outpatient pharmacies: prior to dispensing TIRF medicines, enrolled closed system outpatient pharmacies will verify documentation of the required enrollments by contacting the TIRF REMS Access program at 1-866-822-1483, or via fax, and providing the required information from the TIRF prescription.
i. If the required enrollments are verified, the TIRF REMS Access program will provide a unique authorization code to allow processing and dispensing of the prescription to the patient.
Reference ID: 4146711
FDA_7256
ii. If one or more of the required enrollments cannot be verified, a rejection reason, and information regarding how to resolve the rejection, will be provided.
e. Following initial activation, patient PPAFs remain active until a trigger for inactivation occurs. Triggers for PPAF inactivation include:
i. The patient has not filled a prescription for more than six (6) months.
ii. The PPAF has expired.
iii. The patient is deceased.
iv. The patient chooses to no longer participate in the TIRF REMS Access program.
f. If an active patient transfers from an enrolled prescriber to a non-enrolled or inactive prescriber, the TIRF REMS Access program cannot fill the prescription for TIRF medicines until the new prescriber is active in the TIRF REMS Access program.
g. A patient may have more than one current prescriber (e.g., pain management specialist, primary care physician) provided that prescriptions for TIRF medicines are not for the same or overlapping period of treatment.
h. Documentation and verification of safe-use conditions are not required for prescriptions ordered within an inpatient healthcare setting and given to an inpatient.
C. Implementation System
1. TIRF Sponsors will ensure that wholesalers/distributors who distribute TIRF medicines are enrolled in the TIRF REMS Access program and comply with the program requirements for wholesale distributors.
2. The wholesaler/distributor enrollment process is comprised of the following steps that must be completed by the distributor's authorized representative, prior to receiving TIRF medicine inventory for distribution:
a. Review the distributor TIRF REMS Access program materials
b. Complete and sign the Distributor Enrollment Form and send it to the TIRF Sponsors (by fax or mail). In signing the Distributor Enrollment Form, each wholesaler/distributor is required to indicate they understand that TIRF medicines are available only through the TIRF REMS Access program and acknowledges that they must comply with the following program requirements:
i. The Wholesaler/Distributor will ensure that relevant staff are trained on the TIRF REMS Access program procedures and will follow the requirements of the TIRF REMS Access program.
ii. The Wholesaler/Distributor will ensure that TIRF medicines are only distributed to pharmacies whose enrollment has been validated in the TIRF REMS Access program.
iii. The Wholesaler/Distributor will provide complete, unblinded and unblocked data (i.e., EDI 867 transmission) to the TIRF REMS Access program including information on shipments to enrolled pharmacies.
iv. The Wholesaler/Distributor will cooperate with periodic audits or non-compliance
Reference ID: 4146711
FDA_7257
investigations to ensure that TIRF medicines are distributed in accordance with the program requirements.
c. TIRF Sponsors will ensure that all forms are complete prior to enrolling a distributor in the TIRF REMS Access program.
d. TIRF Sponsors will notify distributors when they are enrolled in the TIRF REMS Access program and, therefore, able to distribute TIRF medicines.
e. Upon initial activation, distributors remain active until an action of inactivation occurs, expiration of the enrollment period, or failure to comply with the pharmacy enrollment verification obligations. If a previously active distributor becomes inactive, the distributor may become active again by completing the distributor enrollment process in its entirety.
f. Distributors will be re-educated and re-enrolled in the TIRF REMS Access program every two (2) years.
g. The following distributor materials are part of the TIRF REMS Access program. These materials are appended:
· Dear Distributor Letter · Distributor Enrollment Form · Frequently Asked Questions
3. TIRF Sponsors will maintain a database of all enrolled entities (prescribers, pharmacies, patients, and distributors) and their status (i.e., active or inactive), and will monitor and evaluate implementation of the TIRF REMS Access program requirements.
4. For chain and independent outpatient pharmacies, TIRF Sponsors will develop a TIRF REMS Access program system that uses existing pharmacy management systems that allow for the transmission of TIRF REMS Access information using established telecommunication standards. The TIRF REMS Access program system will incorporate an open framework that allows a variety of distributors, systems vendors, pharmacies, and prescribers to participate, and that is flexible enough to support the expansion or modification of the TIRF REMS Access program requirements, if deemed necessary in the future.
5. For closed system outpatient pharmacies, TIRF Sponsors will develop a system to allow enrollment and verification of safe use conditions through a telephone system and/or fax. TIRF Sponsors will monitor distribution data and prescription data to ensure that only actively enrolled distributors are distributing, actively enrolled pharmacies are dispensing, and actively enrolled prescribers for outpatient use are prescribing TIRF medicines. Additionally, TIRF Sponsors will monitor to ensure that, when dispensing in an outpatient setting, TIRF medicines are only being dispensed to actively enrolled patients of actively enrolled prescribers. Corrective action or inactivation will be instituted by TIRF Sponsors if non-compliance is found.
6. TIRF Sponsors will monitor prescribers' compliance with the requirement to complete a Patient-Prescriber Agreement Form with each TIRF patient, and to submit it to the TIRF REMS Access program within ten (10) working days. A maximum of three prescriptions are allowed within 10 working days from when the patient has their first prescription filled. No further prescriptions will be dispensed after the 10 working day window until a completed Patient-Prescriber Agreement Form is received. This will be accomplished by reconciling the Patient-Prescriber Agreements submitted to the TIRF REMS Access
Reference ID: 4146711
FDA_7258
program with patient enrollment data captured through the pharmacy management system for chain and independent outpatient pharmacies or through the call center for closed system outpatient pharmacies.
7. TIRF Sponsors will monitor and evaluate all enrolled outpatient pharmacies (including closed system outpatient pharmacies), distributors, and the TIRF REMS Access program vendors to validate the necessary system upgrades and ensure the program is implemented as directed.
8. TIRF Sponsors will evaluate enrolled inpatient pharmacies' compliance with the TIRF REMS Access program requirements through surveys.
9. TIRF Sponsors will maintain a call center to support patients, prescribers, pharmacies, and distributors in interfacing with the TIRF REMS Access program.
10. TIRF Sponsors will ensure that all materials listed in or appended to the TIRF REMS Access program will be available through the TIRF REMS Access program website www.TIRFREMSaccess.com or by calling the TIRF REMS Access call center at 1-866822-1483.
11. TIRF Sponsors will notify pharmacies, prescribers, and distributors of forthcoming enrollment expiration and the need to re-enroll in the TIRF REMS Access program. Notifications for patients will be sent to the patient's prescriber.
12. If there are substantive changes to the TIRF REMS Access program, TIRF Sponsors will update all affected materials and notify pharmacies, prescribers, and distributors of the changes, as applicable. Notifications for patients will be sent to the patient's prescriber. Substantive changes to the TIRF REMS Access program are defined as:
a. Significant changes to the operation of the TIRF REMS Access program.
b. Changes to the Prescribing Information and Medication Guide that affect the riskbenefit profile of TIRF medicines.
13. Based on monitoring and evaluation of the REMS Elements to Assure Safe Use, TIRF Sponsors will take reasonable steps to improve implementation of these elements and to maintain compliance with the TIRF REMS Access program requirements, as applicable.
III. TIMETABLE FOR SUBMISSION OF ASSESSMENTS
TIRF NDA Sponsors will submit REMS Assessments to the FDA at 6 and 12 months from the date of the initial REMS approval, and annually thereafter. To facilitate inclusion of as much information as possible, while allowing reasonable time to prepare the submission, the reporting interval covered by each assessment should conclude no earlier than 60 days before the submission date for that assessment. TIRF NDA Sponsors will submit each assessment so that it will be received by the FDA on or before the due date.
Reference ID: 4146711
FDA_7259
The Transmucosal Immediate Release Fentanyl (TIRF) REMS Access Program
An Overview for Prescribers
To prescribe TIRF medicines for outpatient use, Prescribers must enroll in the TIRF REMS Access program.
What is the TIRF REMS Access Program? The TIRF REMS (Risk Evaluation and Mitigation Strategy) Access program is designed to ensure informed risk-benefit decisions before initiating treatment and, while patients are on treatment to ensure appropriate use of TIRF medicines. TIRF medicines are available only through a restricted distribution program required by the Food and Drug Administration (FDA), because of the risk for misuse, abuse, addiction, overdose, and serious complications due to medication errors. A list of TIRF medicines available through the TIRF REMS Access program is located on the TIRF Products web page at www.TIRFREMSaccess.com/TirfUI/rems/products.action.
How does the TIRF REMS Access program work? The TIRF REMS Access program requires pharmacies, prescribers, patients and wholesalers to enroll in the program in order to utilize TIRF medications. The supply of TIRF medicines to pharmacies is controlled by enrolled distributors, who will verify the current enrollment status of the pharmacy prior to shipment of TIRF medicines. Pharmacies are required to verify the prescriber and the patient are enrolled in the TIRF REMS Access program before dispensing any TIRF medication.
NOTE: There are different requirements for inpatient prescribers that only prescribe TIRF medicines for inpatient use. For inpatient administration (e.g. hospitals, inhospital hospices, and long-term care facilities that prescribe for inpatient use), of TIRF medicines, patient and prescriber enrollment in the TIRF REMS Access program is not required. Only the inpatient pharmacy and distributors are required to be enrolled to be able to order and dispense TIRF medicines for inpatient use. Inpatient pharmacies may not dispense TIRF medicines for outpatient use.
Reference ID: 4146711
FDA_7260
Overview of the TIRF REMS Access Program for Prescribing to Outpatients: Steps for Enrollment and Program Requirements
Prescriber Education & Enrollment (Outpatient Use)
All enrollment activities can be completed at www.TIRFREMSaccess.com
If I have previously enrolled in an individual TIRF REMS program do I need to enroll in the shared TIRF REMS Access Program?
All prescriber enrollment information was transferred from the individual TIRF REMS to the TIRF REMS Access program on March 12, 2012.
You will be required to re-enroll in the shared TIRF REMS two (2) years after your last enrollment in an individual REMS program if you wish to continue dispensing these products. You will be notified by the TIRF REMS Access program in advance of the need to re-enroll.
The following three sections provide detailed information on the Enrollment Process (Section 1), the Patient Program Requirements (Section 2), and the Prescribing Process (Section 3) for outpatient prescribing of TIRF medicines.
Section 1: Enrollment Process
Summary of Enrollment Process
1. Create an account and complete registration at www.TIRFREMSaccess.com. 2. Complete the TIRF REMS Access Education Program and Knowledge
Assessment. 3. Complete and submit a Prescriber Enrollment form.
Detailed Enrollment Process
Step 1: Create an account and complete registration at www.TIRFREMSaccess.com
· Create an account and complete registration at www.TIRFREMSaccess.com.
How do I create an account and complete the TIRF REMS Access registration on-line? · Select the `Create My Account' button on the home page · Complete the Create Account Information section · Select `No' if you have not submitted an enrollment form via fax at the
`Already enrolled via Fax and have an enrollment ID?' question · Create User ID and Password and select `Create My Account' · Select `Prescriber' as the option to best describe you and select `Continue'
Reference ID: 4146711
FDA_7261
· Complete required fields on the Prescriber Registration page and select `Submit' to continue
· Complete required fields in the `Site Information' section by adding your site and select `Submit'
Step 2: Complete the TIRF REMS Access Education Program and Knowledge Assessment
How do I complete the TIRF REMS Access Education Program by fax?
· Review the TIRF REMS Access Education Program. A printable version of the TIRF REMS Access Education Program is available online at www.TIRFREMSaccess.com or by contacting the TIRF REMS Access call center at 1-866-822-1483.
· Once you have reviewed the Education Program complete the Knowledge Assessment and submit by fax to 1-866-822-1487.
· The TIRF REMS Access program will notify you of the status of your Knowledge Assessment via your indicated preferred method of communication (fax or e-mail).
How do I complete the TIRF REMS Access Education Program online?
· Select the `Start the TIRF REMS Access Education Program' to proceed to the training upon completion of registration
· Select `Go To Knowledge Assessment', complete the Knowledge Assessment, and select `Submit Assessment'
· A Knowledge Assessment Confirmation Code will be provided once the assessment is completed successfully
· Select `Complete Enrollment' to continue
Step 3: Complete and submit Prescriber Enrollment
· To finalize enrollment in the TIRF REMS Access program complete Prescriber Enrollment.
· If you are unable to enroll online, please call the TIRF REMS Access program call center at 1-866-822-1483 for further assistance.
How do I complete the TIRF REMS Access Enrollment on-line?
· Upon successful completion of the TIRF REMS Access Education Program and Knowledge Assessment, you will be prompted to review the demographic information previously submitted, read the TIRF REMS Access attestation and enter your electronic signature, today's date, and check the attestation box before clicking `Submit'.
NOTE: You are required to re-enroll every two (2) years. You will be notified by the TIRF REMS Access program in advance of the need to re-enroll.
Reference ID: 4146711
FDA_7262
Section 2: Patient Program Requirements
Summary of Patient Program Requirements
1. Identify appropriate patients 2. Counsel patients 3. Complete and submit the TIRF REMS Access Program Patient-Prescriber
Agreement Form
Detailed Patient Program Requirements Process
Step 1: Identify appropriate patients
· Identify appropriate patients based on the guidance provided in the TIRF REMS Access Education Program and the product-specific Full Prescribing Information. Full Prescribing Information is available on-line at www.TIRFREMSaccess.com or by contacting the TIRF REMS Access call center at 1-866-822-1483.
Step 2: Counsel Patients
· Counsel the patient about the benefits and risks of TIRF medicines and together review the appropriate product-specific Medication Guide. A Patient and Caregiver Overview is available online at www.TIRFREMSaccess.com or by contacting the TIRF REMS Access call center at 1-866-822-1483.
Step 3: Complete and submit the TIRF REMS Access Patient-Prescriber Agreement Form
· Complete the TIRF REMS Access Program Patient-Prescriber Agreement Form, for each new patient, which must be signed by both you and your patient (not required for inpatients).
NOTE: A prescriber must be enrolled in the TIRF REMS Access program to submit a Patient-Prescriber Agreement Form for a patient.
How do I complete the TIRF REMS Access Patient-Prescriber Agreement Form by fax?
· Obtain a TIRF REMS Access Patient-Prescriber Agreement Form. A printable version of the Patient-Prescriber Agreement Form is available on-line at www.TIRFREMSaccess.com or by contacting the TIRF REMS Access call center at 1-866-822-1483.
· Review the TIRF REMS Access Patient-Prescriber Agreement Form with your patient.
· Complete Prescriber required fields. · Have the patient or caregiver complete the patient required fields. · Submit Patient-Prescriber Agreement Form by fax to 1-866-822-1487.
Reference ID: 4146711
FDA_7263
How do I complete the TIRF REMS Access Patient-Prescriber Agreement Form online?
· Log in to the TIRF REMS Access program from the home page by entering in your User ID and Password
· Select the heading labeled `My Account' · Select the `PPAF' link · Review the TIRF REMS Access Patient-Prescriber Agreement Form · Enter your electronic signature, today's date, and check the attestation box · Enter the required patient information · Have the patient enter their electronic signature, today's date, and check the
attestation box o (NOTE: If applicable, a Patient Representative can enter in their information in the required section on behalf of the patient)
· Print off two copies of the form by selecting the `Print' button · Provide one copy to the patient and keep one for your records · Select the `Submit' button to submit the PPAF for the patient · You can print the confirmation by selecting the `Print Confirmation' button
Section 3: Summary of Prescribing Process
1. Write TIRF medicine prescription. 2. Help patient find an enrolled pharmacy.
Detailed Prescribing Process
Step 1: Write TIRF medicine prescription
· Write a prescription for the appropriate TIRF medicine.
Step 2: Help patient find an enrolled pharmacy
· Help each patient find pharmacies which are enrolled in the TIRF REMS Access program. A list of enrolled pharmacies can be found on www.TIRFREMSaccess.com, or by calling 1-866-822-1483.
· Inform patients that they can also find a participating pharmacy by calling the TIRF REMS Access program at 1-866-822-1483.
Reporting Adverse Events and Monitoring
To report any adverse events including the misuse, abuse, addiction, or overdose of TIRF medication contact:
· TIRF REMS Access program at 1-866-822-1483 and/or
Reference ID: 4146711
FDA_7264
· FDA MedWatch program by phone at 1-800-FDA-1088 or online at www.fda.gov/medwatch/report.htm
If you have any questions, need additional information, or need additional copies of any TIRF REMS Access documents, please visit www.TIRFREMSaccess.com, or call the TIRF REMS Access program at 1866-822-1483.
Reference ID: 4146711
FDA_7265
Transmucosal Immediate Release Fentanyl (TIRF) Products
Risk Evaluation and Mitigation Strategy (REMS)
TIRF REMS Access Program Education Program for Prescribers
and Pharmacists
Reference ID: 4146711
FDA_7266
Products Covered Under this Program:
· Abstral® (fentanyl) sublingual tablets · Actiq® (fentanyl citrate) oral transmucosal lozenge · Fentora® (fentanyl buccal tablet) · Lazanda® (fentanyl) nasal spray · Onsolis® (fentanyl buccal soluble film) · Subsys ® (fentanyl sublingual spray) · Approved generic equivalents of these products are also covered under this
program
Reference ID: 4146711
FDA_7267
TIRF REMS Access Education Program:
· Before you can enroll in the TIRF REMS Access program, you must review the Education Program, successfully complete the Knowledge Assessment, and sign the acknowledgement statements on the enrollment form.
· The Education Program and enrollment can be completed online at www.TIRFREMSaccess.com. The enrollment form may also be downloaded from the website on the Resources tab, completed and faxed into the program at 1-866-822-1487.
· Renewal of enrollment is required every 2 years. You will receive a reminder to renew your enrollment at the appropriate time.
· Prescribers writing prescriptions for inpatient use only do not need to enroll in the TIRF REMS Access program.
Reference ID: 4146711
FDA_7268
TIRF REMS Access Program Goals:
The goals of the TIRF REMS Access program are to mitigate the risk of misuse, abuse, addiction, overdose, and serious complications due to medication errors by: 1. Prescribing and dispensing TIRF medicines only to appropriate patients, which
includes use only in opioid-tolerant patients. 2. Preventing inappropriate conversion between fentanyl products. 3. Preventing accidental exposure to children and others for whom it was not
prescribed. 4. Educating prescribers, pharmacists, and patients on the potential for misuse,
abuse, addiction, and overdose.
Reference ID: 4146711
FDA_7269
TIRF REMS Access Education Program
Overview
· This Education Program contains key safety information critical for minimizing the risks associated with TIRF medicines.
· The program will address:
o Appropriate patient selection
o Understanding each patient's risk factors for misuse, abuse, addiction, and overdose
o Dosage and administration
o Patient counseling
o Effective patient management and follow-up
Reference ID: 4146711
FDA_7270
TIRF REMS Access Education Program
Overview (cont.)
· Information on the TIRF REMS Access program requirements and operations is provided in the TIRF REMS Access program overviews for prescribers and pharmacies, which can be accessed at www.TIRFREMSaccess.com.
· This Education Program is NOT a substitute for reading the Full Prescribing Information for each TIRF medicine.
· Please also review the Full Prescribing Information and familiarize yourself with the contents of the Medication Guide for each product prescribed.
Reference ID: 4146711
FDA_7271
Appropriate Patient Selection
Indication:
· TIRF medicines are indicated only for the management of breakthrough pain in cancer patients 18 years of age and older who are already receiving and who are tolerant to around-the-clock opioid therapy for underlying persistent cancer pain. The only exception is for Actiq, and its generic equivalents, which are approved for cancer patients 16 years and older.
Reference ID: 4146711
FDA_7272
Appropriate Patient Selection (cont.)
Definition of Opioid Tolerance:
· Patients considered opioid-tolerant are those who are taking, for one week or longer, at least: o 60 mg oral morphine/day o 25 mcg transdermal fentanyl/hour o 30 mg oral oxycodone/day o 8 mg oral hydromorphone/day o 25 mg oral oxymorphone/day o 60 mg oral hydrocodone/day o OR an equianalgesic dose of another oral opioid daily
· Patients must remain on around-the-clock opioids when taking a TIRF medicine.
Reference ID: 4146711
FDA_7273
Appropriate Patient Selection (cont.)
· TIRF medicines are intended to be used only in the care of opioid-tolerant patients with cancer and only by healthcare professionals who are knowledgeable of, and skilled in, the use of Schedule II opioids to treat cancer pain.
Contraindications:
· TIRF medicines must not be used in opioid non-tolerant patients or in
· the management of acute or postoperative pain including headache/migraine, dental pain, or acute pain in the emergency department,
· acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment,
· known or suspected gastrointestinal obstruction, including paralytic ileus,
· known hypersensitivity to fentanyl, or components of the TIRF medicine.
Reference ID: 4146711
FDA_7274
Appropriate Patient Selection (cont.)
Please see each TIRF medicine's Full Prescribing Information for a full list of specific situations in which TIRF medicines are not indicated or are contraindicated.
Life-threatening respiratory depression could occur at any dose in opioid non-tolerant patients. Deaths have occurred in opioid non-tolerant patients treated with fentanyl products.
Reference ID: 4146711
FDA_7275
Determine Patient-Specific Risk Factors
1. Risk of Misuse, Abuse, Addiction, and Overdose
· TIRF medicines contain fentanyl, an opioid agonist and Schedule II controlled substance. TIRF medicines contain fentanyl, which has a high potential for abuse similar to other opioids. TIRF medicines can be abused and are subject to misuse, addiction, and criminal diversion.
· These risks should be considered when prescribing or dispensing TIRF medicines in situations where the prescriber or pharmacist is concerned about an increased risk of misuse, abuse, addiction, or overdose.
· Risk factors for opioid abuse include: o A history of past or current alcohol or drug abuse o A history of psychiatric illness o A family history of illicit drug use or alcohol abuse
· Drug seeking tactics include: o emergency calls or visits near the end of office hours o refusal to undergo appropriate examination, testing, or referral o repeated loss of prescriptions o tampering with prescriptions
Reference ID: 4146711
FDA_7276
Determine Patient-Specific Risk Factors
1. Risk of Misuse, Abuse, Addiction, and Overdose (cont.)
o reluctance to provide prior medical records or contact information for other treating healthcare providers
o "doctor shopping" (visiting multiple prescribers to obtain additional prescriptions) is common among drug abusers and people suffering from untreated addiction
· Concerns about abuse and addiction should not prevent the proper management of pain.
· All patients treated with opioids require careful monitoring for signs of abuse and addiction because use of opioid analgesic products carries the risk of addiction even under appropriate medical use
Reference ID: 4146711
FDA_7277
Determine Patient-Specific Risk Factors
1. Risk of Misuse, Abuse, Addiction, and Overdose (cont.)
· Measures to help limit abuse of opioid products: o Proper assessment of patients o Safe prescribing practices o Periodic re-evaluation of therapy o Proper dispensing and storage o Keeping detailed records of prescribing information o Keeping a signed TIRF REMS Access Patient-Prescriber Agreement Form o Informing patients/caregivers to protect against theft and misuse of TIRF medicines
· TIRF medicines, like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests as required by state and federal law, is strongly advised.
Reference ID: 4146711
FDA_7278
Determine Patient-Specific Risk Factors
2. Accidental Ingestion or Exposure
· TIRF medicines contain fentanyl in an amount which can be fatal in: o children,
o individuals for whom it is not prescribed, and
o those who are not opioid-tolerant
· Inform patients that these products have a rapid onset of action.
· Instruct patients to take steps to store TIRF medicines in a safe place out of reach of children.
· Prescribers and pharmacists must specifically question patients or their caregivers about the presence of children in the home (on a full time or visiting basis) and counsel them regarding the dangers to children from inadvertent exposure.
Reference ID: 4146711
FDA_7279
Determine Patient-Specific Risk Factors
2. Accidental Ingestion or Exposure (cont.)
· Any accidental ingestion or exposure, especially in children, may result in respiratory depression or death. Talk with your patients about safe and appropriate storage and disposal of TIRF medicines.
Reference ID: 4146711
FDA_7280
Determine Patient-Specific Risk Factors
3. Drug Interactions
· Fentanyl is metabolized mainly via the human cytochrome P450 (CYP3A4) isoenzyme system; therefore, potential drug interactions may occur when TIRF medicines are given concurrently with agents that affect CPY3A4 activity.
· Concomitant use of TIRF medicines with CYP3A4 inhibitors (e.g., certain protease inhibitors, ketoconazole, fluconazole, diltiazem, erythromycin, verapamil) may increaseplasma concentrations of fentanyl and prolong opioid adverse reactions which may cause potentially fatal respiratory depression.
· Patients receiving TIRF medicines who begin therapy with, or increase the dose of, CYP3A4 inhibitors are to be carefully monitored for signs of opioid toxicity over an extended period of time. Dosage increases should be done conservatively.
· Due to the additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, increases the risk of respiratory depression, profound sedation, coma, and death.
Reference ID: 4146711
FDA_7281
Determine Patient-Specific Risk Factors
3. Drug Interactions (cont.)
· The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
· Monoamine Oxidase Inhibitors (MAOIs) interactions with opioids may manifest as serotonin syndrome.
· Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics may reduce the analgesic effect of TIRF medicines and/or precipitate withdrawal symptoms.
· Fentanyl may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.
· Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
· The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Reference ID: 4146711
FDA_7282
Determine Patient-Specific Risk Factors
4. Pregnancy
· Prolonged use of TIRF medicines during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts.
· If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
Reference ID: 4146711
FDA_7283
Dosage and Administration General
Patients beginning treatment with a TIRF medicine MUST begin with titration from the lowest dose available for that specific product, even if they have taken another TIRF medicine. Carefully consult the initial dosing instructions in each product's specific Full Prescribing Information.
Appropriate Conversion
· TIRF medicines are not interchangeable with each other, regardless of route of administration. Differences exist in the pharmacokinetics of TIRF medicines resulting in clinically important differences in the amount of fentanyl absorbed.
· TIRF medicines are not equivalent to any other fentanyl product, including another TIRF medicine, on a microgram-per-microgram basis. The only exception is for substitution of a generic equivalent for a branded TIRF medicine.
· Substantial differences exist in the pharmacokinetic profiles of different fentanyl products that result in clinically important differences in the extent of absorption of fentanyl that could result in a fatal overdose.
Reference ID: 4146711
FDA_7284
Dosage and Administration General
Appropriate Conversion (cont.)
· As a result of these differences, the conversion of a TIRF medicine for any other TIRF medicine may result in fatal overdose.
· Converting from one TIRF medicine to a different TIRF medicine must not be done on a microgram-per-microgram basis and, must be titrated according to the labeled dosing instructions each time a patient begins use of a new TIRF medicine.
· The only exception is for substitutions between a branded TIRF medicine and its generic equivalents.
· For patients being converted specifically from Actiq to Fentora, Actiq to Subsys, and Actiq to Abstral, you must refer to the Full Prescribing Information for detailed instructions.
Reference ID: 4146711
FDA_7285
Maintenance/Dose Adjustments for all TIRF Medicines
· Once a dose that provides adequate analgesia and minimizes adverse reactions is found, that dose should be prescribed for each subsequent episode of breakthrough cancer pain.
· Patients must wait at least 2 or 4 hours before treating another episode of breakthrough pain with their TIRF medicines. Please refer to the TIRF medicine's Full Prescribing Information to determine the time between doses.
· Limit the use of TIRF medicines to 4 or fewer doses per day.
· If the prescribed dose no longer adequately manages the breakthrough cancer pain for several consecutive episodes, increase the dose as described in the titration section of the prescribing information.
· Pharmacists: Instruct patients to consult with their prescriber.
· Consider increasing the dose of the around-the-clock opioid medicine used for persistent cancer pain in patients experiencing more than 4 breakthrough cancer pain episodes per day.
Reference ID: 4146711
FDA_7286
Patient Counseling
Before initiating treatment with a TIRF medicine, review the productspecific Medication Guide with patients and caregivers, and counsel them on TIRF medicine risks and safe use.
Inform patients of the risk of life-threatening respiratory depression, including information that the risk is greatest when starting the TIRF medicine or when the dosage is increased, and that it can occur even at recommended dosages.
· Tell patients exactly how to take the TIRF medicine. Instruct them to take the TIRF medicine strictly as prescribed, with special regard to dosage, dose titration, administration and proper disposal of partially used or unneeded TIRF medicine.
Tell the patient:
· You must be regularly using another opioid pain medicine, around-the-clock, for your constant pain.
· If you stop taking your around-the-clock opioid pain medicine for your constant pain, you must stop taking your TIRF medicine.
Reference ID: 4146711
FDA_7290
Patient Counseling
Tell the patient (cont.):
· Note: Patients have had difficulty comprehending this concept; please emphasize it to your patients.
· TIRF medicines can cause serious side effects, including life-threatening breathing problems which can lead to death. You must take TIRF medicines exactly as prescribed.
· Contact me or my office if your TIRF medicine does not relieve your pain. Do not change your dose of the TIRF medicine or take the TIRF medicine more often than I have directed.
· Accidental ingestion or exposure, especially in children, may result in respiratory depression or death. Always store your TIRF medicine in a safe place away from children and teenagers because accidental use by a child, or anyone for whom it was not prescribed, is a medical emergency and can cause death. Use the child safety kit if one is provided with your TIRF medicine.
Reference ID: 4146711
FDA_7291
Patient Counseling
Tell the patient (cont.):
· Potentially fatal additive effects may occur if the TIRF medicine is used with benzodiazepines or other CNS depressants, including alcohol, and not to use these concomitantly unless supervised by a healthcare provider.
· The use of the TIRF medicine, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose and death.
· Opioids could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs.
· Avoid taking their TIRF medicine while using any drugs that inhibit monoamine oxidase.
· Opioids could cause adrenal insufficiency, a potentially life-threatening condition.
· Their TIRF medicine may cause orthostatic hypotension and syncope.
Reference ID: 4146711
FDA_7292
Patient Counseling
Tell the patient (cont.):
· Properly dispose of partially used or unneeded TIRF medicine remaining from a prescription. Refer to the Full Prescribing Information and Medication Guide for each product for specific instructions for disposal.
· Prolonged use of TIRF medicines during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life threatening if not recognized and treated.
· Never give your TIRF medicine to anyone else, even if they have the same symptoms, because it may harm them or even cause death.
· Never sell or give away your TIRF medicine. Doing so is against the law.
Reference ID: 4146711
FDA_7293
Effective Patient Management & Follow-up
All patients treated with opioids require careful monitoring. At follow-up visits:
· Assess appropriateness of dose, and make any necessary dose adjustments to the TIRF medicine or of their around-the-clock opioid medicine.
· Assess for signs of misuse, abuse, or addiction.
· Be aware that abuse and addiction are separate and distinct from physical dependence and tolerance.
o Abuse of opioids can occur in the absence of addiction, and is characterized by misuse for non-medical purposes, often in combination with other psychoactive substances.
o The possibility of physical and/or psychological dependence should be considered when a pattern of inappropriate behavior is observed.
Reference ID: 4146711
FDA_7294
Effective Patient Management & Follow-up
All patients treated with opioids require careful monitoring. At follow-up visits (cont.):
· TIRF medicines, like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests as required by state and federal law, is strongly advised.
Reference ID: 4146711
FDA_7295
Transmucosal Immediate Release Fentanyl (TIRF) REMS Knowledge Assessment
For real-time processing of this Knowledge Assessment, please go to www.TIRFREMSaccess.com.
To submit this form via fax, please answer all questions below, fill in the fields at the bottom of the form, and fax all pages to 1-866-822-1487. You will receive enrollment confirmation via email or fax.
Question 1 The patients described are all experiencing breakthrough pain, but ONE is not an appropriate patient for a TIRF medicine. Which patient should not receive a TIRF medicine? Select one option
A. 12-year-old sarcoma patient, using transdermal fentanyl for her underlying persistent cancer pain.
B. Adult female with advanced breast cancer; on 60 mg of oral morphine daily for the past 4 weeks.
C. Adult male with advanced lung cancer, his underlying persistent pain is managed with 25 mcg/hour transdermal fentanyl patches for the past 3 months.
D. Adult male with multiple myeloma who has bone pain currently managed with 50 mg oral oxymorphone daily for the last 2 weeks.
Question 2 The patients described are experiencing breakthrough pain. A TIRF medicine is NOT appropriate for one of them. Which patient should not receive a TIRF medicine? Select one option.
A. Adult male with advanced lung cancer; underlying persistent cancer pain managed with 25 mcg/hour transdermal fentanyl patches for the past 2 months.
B. Adult female with localized breast cancer; just completed a mastectomy and reconstructive surgery; persistent cancer pain managed with 30 mg oral morphine daily for the past 6 weeks.
C. Adult male patient with advanced prostate cancer who, over the last 2 weeks, has been prescribed 100 mg oral morphine daily for pain due to bone metastasis.
D. Adult female with advanced sarcoma who has been taking a daily dose of 12 mg oral hydromorphone for the last 3 weeks.
DEA Number or Chain ID:________________________
Reference ID: 4146711
FDA_7296
Question 3 Certain factors may increase the risk of abuse and/or diversion of opioid medications. Which of the following is most accurate? Select one option.
A. A history of alcohol abuse with the patient or close family members. B. The patient has a household member with a street drug abuse problem. C. The patient has a history of prescription drug misuse. D. All of the above.
Question 4 A patient is already taking a TIRF medicine but wants to change their medicine. His/her doctor decides to prescribe a different TIRF medicine (that is not a bioequivalent generic version of a branded product) in its place. How should the prescriber proceed? Select one option.
A. The prescriber can safely convert to the equivalent dosage of the new TIRF medicine as it has the same effect as other TIRF medicines.
B. The prescriber must not convert from the equivalent TIRF medicine dose to another TIRF medicine because they have different absorption properties and this could result in a fentanyl overdose.
C. Convert from the other TIRF medicine to the new TIRF medicine at half of the dose. D. The prescriber should base the starting dose of the newly prescribed TIRF medicine on
the dose of the opioid medicine used for their underlying persistent cancer pain.
Question 5 A patient is starting titration with a TIRF medicine. What dose must they start with? Select one option.
A. An appropriate dose based on the dose of the opioid medicine used for underlying persistent cancer pain.
B. The dose that the prescriber believes is appropriate based on their clinical experience. C. The lowest available dose, unless individual product Full Prescribing Information
provides product-specific guidance. D. The median available dose.
Question 6 A prescriber has started titrating a patient with the lowest dose of a TIRF medicine. However, after 30 minutes, the breakthrough pain has not been sufficiently relieved. What should they advise the patient to do? Select one option.
A. Take another (identical) dose of the TIRF medicine immediately. B. Take a dose of an alternative rescue medicine. C. Provide guidance based on the product-specific Medication Guide because the
instructions are not the same for all TIRF medicines. D. Double the dose and take immediately.
DEA Number or Chain ID:________________________
Reference ID: 4146711
FDA_7297
Question 7 A patient is taking a TIRF medicine and the doctor would like to prescribe erythromycin, a CYP3A4 inhibitor. Which of the following statements is true? Select one option.
A. The patient can't be prescribed erythromycin, because using it at the same time as a TIRF medicine could be fatal.
B. Use of a TIRF medicine with a CYP3A4 inhibitor may require dosage adjustment; carefully monitor the patient for opioid toxicity, otherwise such use may cause potentially fatal respiratory depression.
C. There is no possible drug interaction between CYP3A4 inhibitors and TIRF medicines. D. The dose of the TIRF medicine must be reduced by one half if a CYP3A4 inhibitor is
prescribed in the same patient.
Question 8 Before initiating treatment with a TIRF medicine, prescribers must review the Medication Guide with the patient. Which of the following counseling statements is not correct? Select one option.
A. TIRF medicines contain fentanyl in an amount that could be fatal to children of all ages, in individuals for whom they were not prescribed, and in those who are not opioid tolerant.
B. Inform patients that TIRF medicines must not be used to treat acute or postoperative pain, including headache/migraine, dental pain or acute pain in the emergency department.
C. Instruct patients that, if they stop taking their around -the-clock opioid medicine, they can continue to take their TIRF medicine.
D. Instruct patients to never share their TIRF medicine with anyone else, even if that person has the same symptoms.
Question 9 There is a risk of fatal overdose with inappropriate use of TIRF medicines. Which one of the following answers is most accurate? Select one option.
A. TIRF medicines can be fatal if taken by children. B. TIRF medicines can be fatal if taken by anyone for whom it is not prescribed. C. TIRF medicines can be fatal if taken by anyone who is not opioid-tolerant. D. All of the above.
Question 10 Which one of the following statements is most accurate regarding the safe storage and disposal of TIRF medicines? Select one option.
A. TIRF medicines should be kept in a safe place and out of the reach of children. B. TIRF medicines should be protected from theft. C. Dispose of partially used or unneeded TIRF medicine by following the TIRF medicine-
specific procedure specified in the Medication Guide. D. All of the above.
Reference ID: 4146711
FDA_7298
DEA Number or Chain ID:________________________ Question 11 Conversion between specific TIRF medicines has been established and is described in the Prescribing Information for which products? Select one option.
A. Actiq to Abstral B. Actiq to Fentora C. Actiq to Subsys D. All of the above
Prescriber / Authorized Pharmacy Representative ________________________________________
DEA Number _______________________________________________________________________
Chain ID (if applicable) _______________________________________________________________
DEA Number or Chain ID:________________________
Reference ID: 4146711
FDA_7299
The Transmucosal Immediate Release Fentanyl (TIRF) REMS Access Program Prescriber Enrollment Form
For real-time processing of enrollment, please go to www.TIRFREMSaccess.com.
To submit this form via fax, please complete all required fields below and fax pages 1, 2 and 3 to 1-866-822-1487. Please note, you must review the TIRF REMS Access Education Program and successfully complete the Knowledge Assessment to complete enrollment. If you have not completed the Knowledge Assessment online, please include it with this enrollment form. You will receive enrollment confirmation via email or fax.
I understand that TIRF medicines are only available through the TIRF REMS (Risk Evaluation and Mitigation Strategy) Access program and that I must comply with the program requirements. In addition, I acknowledge that:
1. I have reviewed the TIRF REMS Access Education Program, including the Full Prescribing Information for each TIRF medicine, and I have completed the Knowledge Assessment. I understand the responsible use conditions for TIRF medicines and the risks and benefits of chronic opioid therapy.
2. I understand that TIRF medicines can be abused and that this risk should be considered when prescribing or dispensing TIRF medicines in situations where I am concerned about an increased risk of misuse, abuse, or overdose, whether accidental or intentional.
3. I understand that TIRF medicines are indicated only for the management of breakthrough pain in cancer patients 18 years of age or older (Actiq and its generic equivalents are approved for 16 years of age and older), who are already receiving and who are tolerant to, around-the-clock opioid therapy for their underlying persistent cancer pain.
4. I understand that TIRF medicines are contraindicated for use in opioid non-tolerant patients, and know that fatal overdose can occur at any dose.
5. I understand that TIRF medicines must not be used to treat acute or postoperative pain, including headache/migraine, dental pain, or acute pain in the emergency department.
6. I understand that converting patients from one TIRF medicine to a different TIRF medicine must not be done on a microgram-per-microgram basis. I understand that TIRF medicines are not interchangeable with each other, regardless of route of administration, and that conversion may result in fatal overdose, unless conversion is done in accordance with labeled product-specific conversion recommendations (refer to the list of currently approved TIRF products located on the TIRF REMS Access website at www.TIRFREMSaccess.com/TirfUI/rems/products.action. Note, a branded TIRF medicine and its specific generic product(s) are interchangeable.
7. I understand that the initial starting dose for TIRF medicines for all patients is the lowest dose, unless individual product labels provide product-specific conversion recommendations, and I understand that patients must be titrated individually.
8. I will provide a Medication Guide for the TIRF medicine I intend to prescribe to my patient or their caregiver and review it with them. If I convert my patient to a different TIRF medicine, the Medication Guide for the new TIRF medicine will be provided to, and reviewed with my patient or their caregiver.
9. I will complete and sign a TIRF REMS Access Patient-Prescriber Agreement (PPAF) with each new patient, before writing the patient's first prescription for a TIRF medicine, and renew the agreement every two (2) years.
10. I will provide a completed, signed copy of the Patient-Prescriber Agreement (PPAF) to the patient and retain a copy for my records. I will also provide a completed, signed copy to the TIRF REMS Access program (through the TIRF REMS Access website or by fax) within ten (10) working days.
Prescriber Name* (please print):
Reference ID: 4146711
FDA_7300
11. At all follow-up visits, I agree to assess the patient for appropriateness of the dose of the TIRF medicine, and for signs of misuse and abuse.
12. I understand that TIRF medicines are only available through the TIRF REMS Access program. I understand and agree to comply with the TIRF REMS Access program requirements for prescribers.
13. I understand that I must re-enroll in the TIRF REMS Access program and successfully complete the enrollment requirements every two (2) years.
Prescriber Information:
Prescriber Signature* ________________________________________________ Date* ______________
First Name* _____________________________
Site Name* ______________________________ Address* _______________________________ City* ___________________________________ State* _____________ ZIP* ______________ Phone Number* __________________________ Fax Number* ____________________________ Email* __________________________________
Last Name* _________________ Credentials ________ State License Number* ___________________________ State Issued* ___________________________________ DEA Number* ___________________________________ National Provider Identifier (NPI)* __________________
*Required Fields
Preferred Method of Communication (please select one):
Fax
Email
If you have additional practice sites, state licenses or DEA numbers that you may use when prescribing TIRF medicines, please provide the information requested below.
Prescriber Name* (please print):_____________________________
Reference ID: 4146711
FDA_7301
Additional Prescriber Information (All Fields Required)
Site Name* ______________________________ Address* ________________________________ City* ___________________________________ State* _____________ ZIP* ______________ Phone Number* __________________________ Fax Number* ____________________________
*Required Fields
Site Name* ______________________________ Address* ________________________________ City* ___________________________________ State* _____________ ZIP* ______________ Phone Number* __________________________ Fax Number* ____________________________
*Required Fields
Site Name* ______________________________ Address* ________________________________ City* ___________________________________ State* _____________ ZIP* ______________ Phone Number* __________________________ Fax Number* ____________________________
*Required Fields
State License Number*___________________________ State Issued* ___________________________________ DEA Number* __________________________________
State License Number*___________________________ State Issued* DEA Number*
State License Number*___________________________ State Issued* DEA Number*
If you have any questions or require additional information or further copies of any TIRF REMS Access documents, please visit either www.TIRFREMSaccess.com, or call the TIRF REMS Access program at 1-866-822-1483.
Prescriber Name* (please print):_____________________________
Reference ID: 4146711
FDA_7302
The Transmucosal Immediate Release Fentanyl (TIRF) REMS Access Program Patient-Prescriber Agreement Form
For real-time processing of the Patient Prescriber Agreement Form go to www.TIRFREMSaccess.com.
To submit this form via fax, please complete all required fields below and fax all pages to 1-866-8221487.
As the prescriber of any TIRF medicine in this TIRF REMS (Risk Evaluation and Mitigation Strategy) Access program, I acknowledge that:
1. I understand that TIRF medicines are indicated only 7. I understand that if I change my patient to a different
for the management of breakthrough pain in cancer
TIRF medicine, the initial dose of that TIRF medicine for
patients 18 years of age and older (Actiq and its
all patients is the lowest dose, unless individual product
generic equivalents are approved for 16 years of age
labels
provide
product-specific
conversion
and older), who are already receiving, and who are
recommendations.
tolerant to, around-the-clock opioid therapy for their 8. I have counseled my patient or their caregiver about the
underlying persistent cancer pain.
risks, benefits, and appropriate use of the TIRF medicine
2. I understand that TIRF medicines are contraindicated
including communication of the following safety
for use in opioid non-tolerant patients, and know that
messages:
fatal overdose can occur at any dose. 3. I understand that TIRF medicines are not for use in
the management of acute or postoperative pain, including headache/migraine, dental pain, or acute pain in the emergency department. 4. I understand that patients considered opioid-tolerant are those who are taking, for one week or longer, at least: 60 mg oral morphine/day; 25 micrograms transdermal fentanyl/hour; 30 mg oral oxycodone/day; 8 mg oral hydromorphone/day; 25 mg oral oxymorphone/day; 60 mg oral hydrocodone/day; or an equianalgesic dose of another opioid daily.
a. If you stop taking your around-the-clock pain medicine, you must stop taking your TIRF medicine.
b. NEVER share your TIRF medicine. c. Giving a TIRF medicine to someone for whom it has
not been prescribed can result in a fatal overdose. d. TIRF medicines can be fatal to a child; used and
unused dosage units must be safely stored out of the reach of children living in or likely to visit the home and disposed of in accordance with the specific disposal instructions detailed in the product's Medication Guide.
5. I have provided to, and reviewed with, my patient or
their caregiver the Medication Guide for the TIRF
medicine I intend to prescribe.
6. If I change my patient to a different TIRF medicine, I
will provide the Medication Guide for the new TIRF
medicine to my patient or my patient's caregiver, and I
will review it with them.
Prescriber (*Required Fields):
Prescriber Signature* __________________________ First Name* ___________________________________ DEA Number* _________________________________ Fax* _________________________________________
Date _________________________________________ Last Name*____________________________________ National Provider Identifier (NPI)* _________________
Reference ID: 4146711
Prescriber Name* (please print):__________________________________ FDA_7303
As the patient being prescribed a TIRF medicine, or a legally authorized representative, I acknowledge that:
1. My prescriber has given me a copy of the Medication Guide for the TIRF medicine I have been prescribed, and has reviewed it with me.
2. I understand that TIRF medicines should only be taken by patients who are regularly using another opioid, around-the-clock, for constant pain. If I am not taking around-the-clock opioid pain medicine, my prescriber and I have discussed the risks of only taking TIRF medicines.
3. I understand that if I stop taking my around-the-clock opioid pain medicine for my constant pain, I must stop taking my TIRF medicine.
4. I understand how I should take this TIRF medicine, including how much I can take, and how often I can take it. If my prescriber prescribes a different TIRF medicine for me, I will ensure I understand how to take the new TIRF medicine.
5. I understand that any TIRF medicine can cause serious side effects, including life-threatening breathing problems which can lead to death, especially if I do not take my TIRF medicine exactly as my prescriber has directed me.
6. I agree to contact my prescriber if my TIRF medicine does not relieve my pain. I will not change the dose of my TIRF medicine myself or take it more often than my prescriber has directed.
7. I agree that I will never give my TIRF medicine to anyone else, even if they have the same symptoms, since it may harm them or even cause death.
8. I will store my TIRF medicine in a safe place out of reach of children and teenagers because accidental use by a child, or anyone for whom it was not prescribed, is a medical emergency and can cause death.
9. I have been instructed on how to properly dispose of my partially used or unneeded TIRF medicine remaining from my prescription, and will dispose of my TIRF medicine properly as soon as I no longer need it.
10. I understand that selling or giving away my TIRF medicine is against the law.
11. I have asked my prescriber all the questions I have about my TIRF medicine. If I have any additional questions or concerns in the future about my treatment with my TIRF medicine, I will contact my prescriber.
12. I have reviewed the "Patient Privacy Notice for the TIRF REMS Access Program" below and I agree to its terms and conditions which allow my healthcare providers to share my health information, as defined in this document to the makers of TIRF medicines (TIRF Sponsors) and their agents and contractors for the limited purpose of managing the TIRF REMS Access program.
Patient (*Required Fields):
Signature* _______________________________________ Date* _________________________________________
First Name* ______________________________________ Last Name*____________________________________
Date of Birth (MM/DD/YYYY)* _______________________ Phone Number_________________________________
State* ________
ZIP* ______________
Patient Representative (if required):
Signature* ______________________________ First Name* _____________________________ Relationship to Patient*___________________
Date* _________________________________________ Last Name*____________________________________
Reference ID: 4146711
Prescriber Name* (please print):__________________________________ FDA_7304
Patient Privacy Notice for the TIRF REMS Access Program For the purpose of the TIRF REMS Access program, my name, address, telephone number and prescription information make up my "Health Information." My doctors, pharmacists, and healthcare providers may share my Health Information with the TIRF REMS Access program, and contractors that manage the TIRF REMS Access program. My Health Information will be kept in a secure database, and may only be used as stated below.
I allow the TIRF REMS Access program to receive, use, and share my Health Information in order to: I. Enroll me in the TIRF REMS Access program and manage my participation (including contacting me) in the
TIRF REMS Access program. II. Provide me with educational information about the TIRF REMS Access program. III. Contact my healthcare providers to collect my Health Information for the TIRF REMS Access program.
I allow the TIRF REMS Access program to receive, use, and share my Health Information, using a unique, encrypted identifier instead of my name, in order to evaluate the proper use of TIRF medicines and report to the FDA about the effectiveness of the TIRF REMS Access program.
I understand that I am not required to sign this written approval. However, if I do not sign, I will not be able to enroll in the TIRF REMS Access program and will not be able to receive TIRF medicines.
I understand that I may withdraw this written approval at any time by faxing a signed, written request to the TIRF REMS Access program at 1-866-822-1487. Upon receipt of this written request, the TIRF REMS Access program will notify my healthcare providers about my request. My healthcare providers will no longer be able to share my Health Information with the TIRF REMS Access program once they have received and processed that request. However, withdrawing this written approval will not affect the ability of the TIRF REMS Access program to use and share my Health Information that it has already received to the extent allowed by law. If I withdraw this written approval, I will no longer be able to participate in the TIRF REMS Access program and will no longer be able to receive TIRF medicines.
The sponsors of the TIRF REMS Access program agree to protect my information by using and sharing it only for the purposes described.
If you have any questions or require additional information or further copies of any TIRF REMS Access documents, please visit either www.TIRFREMSaccess.com, or call the TIRF REMS Access program at 1-866-822-1483.
Prescriber Name* (please print):__________________________________
Reference ID: 4146711
FDA_7305
The Transmucosal Immediate Release Fentanyl (TIRF) Risk Evaluation and Mitigation Strategy (REMS) Access Program or TIRF REMS Access Program
An Overview for Patients and Caregivers
What are TIRF medicines?
TIRF medicines are prescription medicines that contain the drug fentanyl. TIRF medicines are used to manage breakthrough pain in adults with cancer who are routinely taking other opioid (narcotic) pain medicines around-the-clock for cancer pain. Please refer to the list of currently approved TIRF products located on the TIRF REMS website at www.TIRFREMSaccess.com/TirfUI/rems/products.action.
What is the TIRF REMS Access Program?
A REMS, or Risk Evaluation and Mitigation Strategy, is a program to help manage known or potential serious risks of a medicine. Because TIRF medicines have a risk of misuse, abuse, addiction, and overdose, the Food and Drug Administration (FDA) has required that all TIRF medicines only be available through a restricted program called the TIRF REMS Access program. Healthcare professionals who prescribe your TIRF medicine, as well as pharmacies that fill your prescriptions for TIRF medicine, must be enrolled in the program.
Why is the TIRF REMS Access Program needed?
Your TIRF medicine contains fentanyl, which can cause life threatening breathing problems, which can lead to death. These life threatening breathing problems can occur if you take more TIRF medicine than your healthcare provider tells you to take, or if the TIRF medicine is taken by anyone other than you.
The TIRF REMS Access program provides training for prescribers and pharmacists to help them select patients for whom TIRF medicines are appropriate. The TIRF REMS Access program also helps your healthcare provider and pharmacist provide advice and guidance to you on the correct way to use your TIRF medicine, including how to store and dispose of it.
How do I participate in the program?
You or your caregiver will be required to read and sign the TIRF REMS Access PatientPrescriber Agreement Form to participate in the program. Your healthcare provider will explain the Patient-Prescriber Agreement Form for the TIRF REMS Access program, which you must read and sign before receiving your prescription. Your healthcare provider will ensure that the signed form is submitted to the program. You will be part of the program when your first prescription is filled at a participating pharmacy. Your healthcare provider can identify pharmacies in your area where you can bring your prescription. When you are part of the program, you can start treatment with the TIRF medicine that your healthcare provider has prescribed for you.
Reference ID: 4146711
FDA_7306
Overview of Steps for the TIRF REMS Access Program for Patients
Step 1 Participating in the Program
· Your healthcare provider will talk with you about the best way to use your TIRF medicine, including the risks and how to store and dispose of it correctly. Your healthcare provider will also review written information about your TIRF medicine with you. This written information is called the Medication Guide. Your healthcare provider will give you a copy of the Medication Guide - read and keep it.
· Together you and your healthcare provider will complete and sign the TIRF REMS Access Patient-Prescriber Agreement Form. The form gives you important information you need to know and understand before taking a TIRF medicine.
· You will need to complete a new Patient-Prescriber Agreement Form every two (2) years. You will be notified by your healthcare provider in advance of the need to reenroll.
· Your healthcare provider will submit a copy to the TIRF REMS Access program. · Your healthcare provider will also give you a copy and keep a copy in your medical
records.
Step 2 Getting a Prescription
· Once you have signed the Patient-Prescriber Agreement Form your healthcare provider will write you a prescription for your TIRF medicine.
· Your healthcare provider can help you find a participating pharmacy to have your prescription filled, because only pharmacies that are in the TIRF REMS Access program can dispense TIRF medicines. You can also find a participating pharmacy by calling the TIRF REMS Access program at 1-866-822-1483.
Step 3 Having your Prescription Filled
· The pharmacy will check to make sure that your healthcare provider is enrolled in the TIRF REMS Access program. Only then is the pharmacy allowed to dispense the TIRF medicine to you.
· You will be automatically enrolled in the TIRF REMS Access program when you receive your first prescription for a TIRF medicine.
· The pharmacy will remind you how to take, store and dispose of your TIRF medicine correctly.
· The pharmacy will also give you a copy of the Medication Guide. Read and keep the Medication Guide.
Additional Program Information
For more information about your TIRF medicine, you can find a copy of the Medication Guide at www.TIRFREMSaccess.com or you can call the TIRF REMS Access program at 1-866-822-1483.
Reference ID: 4146711
FDA_7307
TIRF REMS Access Program Frequently Asked Questions (FAQs)
I. ALL STAKEHOLDERS FAQs II. PATIENT FAQs III. OUTPATIENT PHARMACY FAQs IV. PRESCRIBER FAQs V. INPATIENT PHARMACY FAQs VI. DISTRIBUTOR (WHOLESALER) FAQs
Reference ID: 4146711
FDA_7308
I. ALL STAKEHOLDERS FAQs
What is a TIRF Medicine? TIRF medicines are transmucosal immediate release fentanyl prescription medicines used to manage breakthrough pain in adults with cancer who are routinely taking other opioid (narcotic)
pain medicines around-the-clock for pain. Click here to see a full list of TIRF medicines.
What is a REMS? REMS stands for "Risk Evaluation and Mitigation Strategy." A Risk Evaluation and Mitigation Strategy (REMS) is a risk management program required by the FDA to ensure that the benefits of a drug outweigh the risks. FDA has determined that a REMS is necessary for all marketed TIRF medicines.
What are the goals of the TIRF REMS Access Program? The goals of the TIRF REMS Access program are to mitigate the risk of misuse, abuse, addiction, overdose and serious complications due to medication errors by:
1. Prescribing and dispensing TIRF medicines only to appropriate patients, which includes use only in opioid-tolerant patients.
2. Preventing inappropriate conversion between fentanyl products. 3. Preventing accidental exposure to children and others for whom it was not prescribed. 4. Educating prescribers, pharmacists, and patients on the potential for misuse, abuse,
addiction, and overdose.
What are the components of the TIRF REMS Access program? Because of the risk for misuse, abuse, addiction, and overdose, TIRF medicines are available only through a restricted program called the TIRF REMS Access program.
An overview of the requirements for prescribers, patients, pharmacies, and distributors is included below:
· Healthcare providers who prescribe TIRF medicines for outpatient use must review the prescriber educational materials, enroll in the REMS program, and commit to comply with the REMS requirements.
· Patients who are prescribed TIRF medicines in an outpatient setting, must understand the risks and benefits of the drug and sign a Patient-Prescriber Agreement Form with their healthcare provider to receive TIRF medicines. These patients will be enrolled by the pharmacy at the time their first prescription is filled.
· Outpatient pharmacies that dispense TIRF medicines for outpatient use must enroll in the program, train their pharmacy staff on the REMS requirements, and agree to comply with the REMS requirements. Pharmacy staff can register online to access the Education Program and take the Knowledge Assessment for training purposes.
· Inpatient pharmacies that dispense TIRF medicines for inpatient use must enroll in the Program, train their pharmacy staff on the REMS requirements, and agree to comply with the REMS requirements. Pharmacy staff can register online to access the Education Program and take the Knowledge Assessment for training purposes.
· Wholesalers and distributors that distribute TIRF medicines must enroll in the program and commit to distributing only to authorized enrolled pharmacies.
Reference ID: 4146711
FDA_7309
The educational materials referenced above will be available to prescribers and pharmacies through the TIRF REMS Access program. In an outpatient setting, FDA-approved Medication Guides will be provided to patients by prescribers and pharmacists during counseling about the proper use of TIRF medicines.
Inpatient Use Only- Prescribers who prescribe TIRF medicines that will only be used in an inpatient setting (e.g., hospitals, hospices, or long-term care facilities) are not required to enroll in the TIRF REMS Access program. Similarly, patients who receive TIRF medicines in an inpatient setting are not required to enroll in the TIRF REMS Access program. Long term care and hospice patients who obtain their medications from outpatient pharmacies must be enrolled.
Why does the TIRF REMS Access program require prescriber enrollment for outpatient prescribing? Prescriber enrollment is required to help ensure that prescribers receive education on the risks and safe use of TIRF medicines, and can demonstrate their understanding of how to mitigate the risks. Additionally, the educational materials will help them understand the requirements of the TIRF REMS Access program.
To become enrolled, prescribers must review the TIRF REMS Access Education Program including the Full Prescribing Information and successfully complete the Knowledge Assessment.
Are there requirements for prescribers for inpatient use in the TIRF REMS Access program? No. Healthcare providers who prescribe TIRF medicines for inpatient use only are not required to enroll in the TIRF REMS Access program.
Why does the TIRF REMS Access program require pharmacy enrollment? Pharmacy enrollment is required to help ensure that pharmacists receive education on the risks and safe use of TIRF medicines. Additionally, the educational materials will help them understand the requirements of the TIRF REMS Access program.
Only enrolled pharmacies are eligible to receive shipments of TIRF medicines and/or to dispense prescriptions written by enrolled prescribers for outpatients. A designated authorized pharmacist must review the Education Program and successfully complete the Knowledge Assessment. Only then can the authorized pharmacist complete enrollment on behalf of the pharmacy. The authorized pharmacist will train other staff within the pharmacy in the appropriate dispensing of TIRF medicines according to the TIRF REMS Access program.
Prescriptions for outpatient use written by prescribers who are not enrolled in the REMS will not be authorized by the TIRF REMS Access program and TIRF medicines will not be dispensed to an outpatient who is not enrolled.
Why does the TIRF REMS Access program require a Patient-Prescriber Agreement Form? The TIRF REMS Access program requires all prescribers to complete and sign a TIRF REMS Access Patient-Prescriber Agreement Form with each new patient, before writing the patient's first TIRF prescription. The Patient-Prescriber Agreement Form helps to ensure that each patient for whom the TIRF medicine has been prescribed is appropriately counselled on the safe use and storage of the TIRF medicine. The prescriber must keep a copy of the signed Patient-
Reference ID: 4146711
FDA_7310
Prescriber Agreement Form in the patient's chart, give a copy to the patient and submit a copy to the TIRF REMS Access program within 10 working days.
A Patient-Prescriber Agreement Form is not required for inpatient use of TIRF medicines.
Where do I find a list of local pharmacies that participate in the TIRF REMS Access program? The TIRF REMS Access homepage contains a feature called "Pharmacy Lookup" that is available for prescribers, and distributors, to look up and find enrolled pharmacies. This information can also be obtained by calling the TIRF REMS Access call center at 1-866-822-1483.
How can I obtain TIRF REMS Access program materials? All TIRF REMS Access education materials and forms are available and can be downloaded from www.TIRFREMSaccess.com using Adobe Acrobat Reader. Enrollment Forms and the Patient-Prescriber Agreement Forms can be completed online at www.TIRFREMSaccess.com after reviewing the Education Program and successfully completing the Knowledge Assessment. Materials are also available by calling the TIRF REMS Access call center at 1-866-822-1483 for assistance.
How do I contact the TIRF REMS Access program? You can contact the TIRF REMS Access program by calling the TIRF REMS Access call center at 1-866-822-1483 or by written correspondence to: TIRF REMS Access, PO Box 29036, Phoenix, AZ 85038
How can I report Adverse Events? Promptly report suspected adverse events associated with the use of a TIRF medicines including misuse, abuse, and overdose directly to the TIRF REMS Access program at 1-866-822-1483. You also may report adverse event information to the FDA MedWatch Reporting System by telephone at (800) FDA-1088 or by mail using Form 3500, available at www.fda.gov/medwatch.
Reference ID: 4146711
FDA_7311
II. PATIENT FAQs
As a patient, how do I participate with the TIRF REMS Access program? You must sign a Patient-Prescriber Agreement with your prescriber and take your prescription for a TIRF medicine to an `enrolled' pharmacy. The pharmacy will enroll you in the TIRF REMS Access program. Your prescriber will go over important information you need to know before you take the TIRF medicine.
Patients in an inpatient setting are not required to participate in the TIRF REMS Access program in order to be prescribed and dispensed TIRF medicines for inpatient use only. However, if your prescriber gives you a prescription for a TIRF medicine to take at home once you leave the inpatient facility, you must sign a Patient-Prescriber Agreement Form with your prescriber to participate in the TIRF REMS Access program.
Where do I find a list of local pharmacies that participate in the TIRF REMS Access program? Only pharmacies that are enrolled in the TIRF REMS Access program can dispense TIRF medicines. Your prescriber can help you find a participating pharmacy. You can also get this information by calling the TIRF REMS Access program at 1-866-822-1483.
Reference ID: 4146711
FDA_7312
III. OUTPATIENT PHARMACY FAQs
What type of Outpatient Pharmacy is my pharmacy?There are 3 types of outpatient pharmacies. They are all required to be enrolled in the TIRF REMS Access program, complete the TIRF REMS Education Program, and verify patient and prescriber enrollment when processing prescriptions. The difference is in how these pharmacies enroll in the program.
Independent Outpatient Pharmacy: Retail, mail order or institutional outpatient pharmacies having an authorized pharmacy representative that is responsible for ensuring enrollment and training of the pharmacy staff within an individual outpatient pharmacy. Each store will individually enroll in the TIRF REMS Access program as a single pharmacy location.
Chain Outpatient Pharmacy: Retail, mail or institutional outpatient pharmacy having a chain headquarters that is responsible for ensuring enrollment and training of the pharmacy staff of all associated outpatient pharmacies. The chain headquarters will enroll multiple pharmacy locations (i.e.: chain stores) in the TIRF REMS Access program.
Closed System Outpatient Pharmacy: Institutional or mail order outpatient pharmacies that uses a pharmacy management system that does not support the process of electronically transmitting the validation and claim information currently required by the TIRF REMS Access program. If you believe you are a closed system outpatient pharmacy, call the TIRF REMS Access program call center at 1-866-822-1483 to discuss enrollment.
How does an Independent Outpatient Pharmacy enroll in the TIRF REMS Access program? The authorized pharmacist must review the Education Program, successfully complete the Knowledge Assessment and complete the Independent Outpatient Pharmacy Enrollment Form through the website or complete and fax the signed Enrollment Form and Knowledge Assessment to the TIRF REMS Access program at 1-866-822-1487.
The authorized pharmacist must ensure the pharmacy enables their pharmacy management system to support communication with the TIRF REMS Access system, using established telecommunication standards, and run the standardized validation test transactions.
Before a pharmacy is able to dispense prescriptions to outpatients, an enrollment form must be received either via the website by faxing or mailing it to the TIRF REMS Access program for each pharmacy requesting enrollment in the program. (See information on chain outpatient pharmacy enrollment below.)
How does a Chain Outpatient Pharmacy enroll in the TIRF REMS Access program? An authorized chain outpatient pharmacy representative completes the TIRF REMS Access training, Knowledge Assessment and enrollment on behalf of all the pharmacies within the chain and then documents and manages training of all pharmacy staff by the chains' internal processes. Pharmacy staff can register online to access the Education Program and take the Knowledge Assessment for training purposes.
As part of enrollment, a chain outpatient pharmacy must enable the pharmacy management system to support communication with the TIRF REMS Access system, using established telecommunication standards, and must run the standardized validation test transactions. For further information or to enroll, access the TIRF REMS Access website at
Reference ID: 4146711
FDA_7313
www.TIRFREMSaccess.com or call the TIRF REMS Access program call center at 1-866822-1483 for further assistance.
How does a Closed System Outpatient Pharmacy enroll in the TIRF REMS Access program? If you believe you are a closed system outpatient pharmacy, call the TIRF REMS Access program call center at 1-866-822-1483 to discuss enrollment.
How long is my enrollment effective in TIRF REMS Access? Your enrollment is effective for two (2) years. You will be required to re-enroll in the TIRF REMS Access program every two (2) years if you wish to continue dispensing these products. You will be notified by the TIRF REMS Access program in advance of the need to re-enroll.
Independent outpatient pharmacies and chain outpatient pharmacies may re-enroll online or by fax. Closed system outpatient pharmacies may re-enroll by fax only.
For re-enrollment online, go to the "Enrollment Activity" tab on the TIRF REMS Access program website (www.TIRFREMSaccess.com). The "Enrollment Activity" tab allows you to:
· Add to, update, or delete your registration information on file. · Review the TIRF REMS Access Education Program. · Take the TIRF REMS Access Knowledge Assessment. · Submit your enrollment form by providing your attestation and signature.
For re-enrollment by fax, review the TIRF REMS Access program Education Materials and submit a new TIRF REMS Access Enrollment Form and Knowledge Assessment to the TIRF REMS Access program at 1-866-822-1487. All TIRF REMS Access Education Materials and Enrollment Forms are available and can be downloaded from www.TIRFREMSaccess.com using Adobe Acrobat Reader or by calling the TIRF REMS Access call center at 1-866-822-1483.
If the patient's prescription is denied, will the TIRF REMS Access system explain the reason? All TIRF prescriptions (excluding inpatient use), must go through an electronic verification system via the pharmacy management system. When a prescription is denied, an appropriately coded message will be displayed on the pharmacy management system. For assistance, please call the TIRF REMS Access call center at 1-866-822-1483 for any information related to your denial.
How does a pharmacy obtain TIRF Medicines from a distributor? Only enrolled distributors are allowed to distribute TIRF medicines to enrolled pharmacies. The TIRF REMS Access program provides frequently updated lists of all pharmacies that are currently enrolled in the program that distributors can use to verify enrollment before distributing TIRF medicines to a pharmacy.
Reference ID: 4146711
FDA_7314
Chain and Independent Outpatient Pharmacy CASH Claim FAQs
What is the definition of a TIRF REMS CASH Claim? The definition of a TIRF REMS CASH Claim is any claim for a TIRF medicine that is not electronically transmitted to a Third Party Insurance BIN using the pharmacy management system and established telecommunication standards. This includes claims for patients without prescription coverage or any paper claims submitted to a program for payment.
Does a TIRF REMS CASH claim need to be submitted to the TIRF REMS Access Program? Yes, all TIRF prescriptions, including CASH claims and other claims (i.e., workers comp), must be submitted to the TIRF REMS Access program to validate the enrollment status of the prescriber, patient and pharmacy prior to dispensing TIRF medicine to the patient.
How do I submit a TIRF REMS CASH claim to the TIRF REMS Access Program? Prior to dispensing TIRF medicines, transmit using the REMS CASH BIN 014780,to submit a CASH claim to the TIRF REMS Access program.
Reference ID: 4146711
FDA_7315
IV. PRESCRIBER FAQs
What is the enrollment process? The prescriber must review the Education Program, successfully complete the Knowledge Assessment and complete an enrollment form through the website at www.TIRFREMSaccess.com, or complete and fax the signed Enrollment Form and Knowledge Assessment to the TIRF REMS Access program at 1-866-822-1487.
A prescriber may obtain an enrollment form online from the TIRF REMS Access website (www.TIRFREMSaccess.com) or by calling 1-866-822-1483.
The program requires that a signed enrollment form and Knowledge Assessment be received by the TIRF REMS Access program for each prescriber who requests enrollment. Only healthcare providers who will prescribe TIRF medicines for outpatient use are required to be enrolled in the TIRF REMS Access program.
How long is my enrollment effective in TIRF REMS Access? Your enrollment is effective for two (2) years. You will be required to re-enroll in the TIRF REMS Access program every two (2) years if you wish to continue dispensing these products. You will be notified by the TIRF REMS Access program in advance of the need to re-enroll.
You may re-enroll via your "Enrollment Activity" tab on the TIRF REMS Access program website (www.TIRFREMSaccess.com). The "Enrollment Activity" tab allows you to:
· Add to, update, or delete your registration information on file. · Review the TIRF REMS Access Education Program. · Take the TIRF REMS Access Knowledge Assessment. · Submit your enrollment form by providing your attestation and signature.
Alternatively, you may also complete re-enrollment via fax by reviewing the TIRF REMS Access program Education Materials and submitting a new TIRF REMS Access Enrollment Form and Knowledge Assessment into the TIRF REMS Access program at 1-866-822-1487. All TIRF REMS Access Education Materials and Enrollment Forms are available and can be downloaded from www.TIRFREMSaccess.com using Adobe Acrobat Reader or by calling the TIRF REMS Access call center at 1-866-822-1483.
Where do I find a list of local pharmacies that participate in the TIRF REMS Access program? A list of participating pharmacies can be found on the TIRF REMS Access website
(www.TIRFREMSaccess.com) homepage under the link "Pharmacy Lookup". You may also call
1-866-822-1483.
Patients can find a participating pharmacy by calling the TIRF REMS Access program at 1-866-822-1483.
Reference ID: 4146711
FDA_7316
Can I write an order for TIRF Medicines for inpatient use? Yes, prescribers can write orders for TIRF medicines for inpatient use without the prescriber or the patient being enrolled in the TIRF REMS Access program. However, the inpatient pharmacy needs to be enrolled in the TIRF REMS Access program to receive and dispense TIRF medicines to inpatients in the healthcare facility.
If a prescriber is discharging a patient with a TIRF medicine prescription, intended to be filled by an outpatient pharmacy, then the prescriber must be enrolled in the TIRF REMS Access program and complete a Patient-Prescriber Agreement Form. The prescription for outpatient use can only be filled through an enrolled outpatient pharmacy.
Additional information on the TIRF REMS Access Education Program and enrollment can be obtained through the TIRF REMS Access program (www.TIRFREMSaccess.com) or by calling 1-866-822-1483.
Reference ID: 4146711
FDA_7317
V. INPATIENT PHARMACY FAQs
How do I enroll as an inpatient pharmacy? To enroll, the inpatient pharmacy must designate an authorized pharmacist who will review the required Education Program and successfully complete the Knowledge Assessment for the TIRF REMS Access program. Upon successful completion of the Knowledge Assessment, the authorized pharmacist will complete and sign the Inpatient Pharmacy Enrollment Form through the website (www.TIRFREMSaccess.com). The Knowledge Assessment and Enrollment Form may also be completed, signed, and faxed to the TIRF REMS Access program at 1-866-822-1487.
Additional information about the TIRF REMS Access Education Program and enrollment can be obtained through the TIRF REMS Access program (www.TIRFREMSaccess.com) or by calling 1-866-822-1483.
How long is my enrollment effective in TIRF REMS Access? Your enrollment is effective for two (2) years. You will be required to re-enroll in the TIRF REMS Access program every two (2) years if you wish to continue dispensing these products. You will be notified by the TIRF REMS Access program in advance of the need to re-enroll.
You may re-enroll via your "Enrollment Activity" tab on the TIRF REMS Access program website (www.TIRFREMSaccess.com). The "Enrollment Activity" tab allows you to:
· Add to, update, or delete your registration information on file. · Review the TIRF REMS Access Education Program. · Take the TIRF REMS Access Knowledge Assessment. · Submit your enrollment form by providing your attestation and signature.
Alternatively, you may also complete re-enrollment via fax by reviewing the TIRF REMS Access program Education Materials and submitting a new TIRF REMS Access Enrollment Form and Knowledge Assessment into the TIRF REMS Access program at 1-866-822-1487. All TIRF REMS Access Education Materials and Enrollment Forms are available and can be downloaded from www.TIRFREMSaccess.com using Adobe Acrobat Reader or by calling the TIRF REMS Access call center at 1-866-822-1483.
Can inpatient pharmacies obtain TIRF Medicines in a Healthcare Facility? Yes. However, the inpatient pharmacy within or associated with the healthcare facility must be enrolled in the TIRF REMS Access program before inpatient pharmacies can purchase TIRF medicines.
Additional information can be obtained from www.TIRFREMSaccess.com or by calling the TIRF REMS Access call center at 1-866-822-1483.
Reference ID: 4146711
FDA_7318
VI. DISTRIBUTOR (WHOLESALER) FAQs
Does a distributor have to enroll in the TIRF REMS Access program? Yes, distributors will need to enroll in the TIRF REMS Access program in order to be able to purchase and distribute TIRF medicines.
How long is my enrollment effective in TIRF REMS Access? Your enrollment is effective for two (2) years. You will be required to re-enroll in the TIRF REMS Access program every two (2) years if you wish to continue dispensing these products. You will be notified by the TIRF REMS Access program in advance of the need to re-enroll.
You can complete re-enrollment via fax by submitting a new TIRF REMS Access Enrollment Form into the TIRF REMS Access program at 1-866-822-1487. TIRF REMS Access Enrollment Forms are available and can be downloaded from www.TIRFREMSaccess.com using Adobe Acrobat Reader or by calling the TIRF REMS Access call center at 1-866-822-1483.
What are the TIRF REMS Access program requirements for a distributor? To enroll in the TIRF REMS Access program, a distributor will have to complete and sign the Distributor Enrollment Form. In signing the enrollment form, the distributor is required to indicate that they understand that TIRF medicines are available only through the TIRF REMS Access program and they will comply with the program requirements.
How can enrolled distributors access a list of pharmacies that participate in the TIRF REMS Access program? After enrollment, distributors can access the current list of enrolled pharmacies by: · Downloading from a secure FTP site (you will be contacted regarding the TIRF REMS
Access secure FTP site once your enrollment is complete). · Utilizing the feature "Pharmacy Look Up" on a password protected section of the TIRF
REMS Access website (www.TIRFREMSaccess.com). · Calling the TIRF REMS Access call center at 1-866-822-1483.
Reference ID: 4146711
FDA_7319
This letter ceased distribution in November 2013.
Subject:
Important Drug Warning Announcement of a single shared REMS (Risk Evaluation and Mitigation Strategy) program for all Transmucosal Immediate Release Fentanyl (TIRF) products due to the potential risk of misuse, abuse, addiction, overdose and serious complications due to medication errors
The TIRF REMS Access program is a Food and Drug Administration (FDA) required risk management program
Dear Healthcare Provider:
The purpose of this letter is to make you aware of a change from individual REMS programs to a shared REMS program (the TIRF REMS Access program) and to provide guidance on enrollment into the new shared REMS program beginning mm/dd/yyyy. The individual REMS programs are being converted to the TIRF REMS Access program to reduce the burden on the healthcare providers and the healthcare system of having multiple individual programs. The products covered under this new program include:
· Abstral® (fentanyl) sublingual tablets · Actiq® (fentanyl citrate) oral transmucosal lozenge · Fentora® (fentanyl citrate) buccal tablet · Lazanda® (fentanyl) nasal spray · Onsolis® (fentanyl buccal soluble film)
· Approved generic equivalents of these products are also covered under this program
Prescriber Action:
Option 1: If you are already enrolled in at least one individual REMS program · Your enrollment information will be automatically entered into the new shared TIRF REMS Access program. Your enrollment in the shared TIRF REMS Access program allows prescribing of all TIRF medicines that are covered under the TIRF REMS Access program. The website for the shared TIRF REMS Access program can be accessed at www.TIRFREMSaccess.com. · You can use your existing secure user ID and password from any one of your individual REMS programs to access the TIRF REMS Access website at www.TIRFREMSaccess.com and prescribe all TIRF medicines. The user ID and password you use to initially log on will become your permanent user ID and password for the shared TIRF REMS Access program. · The TIRF REMS Access Education Program is available on the shared TIRF REMS Access website or by calling 1-866-822-1483. We recommend that you review the TIRF REMS Access Education Program for information on all the products that are available under the TIRF REMS Access program. · You will be required to re-enroll in the shared TIRF REMS Access program two (2) years after your last enrollment in an individual REMS program if you wish to continue prescribing these products. You will be notified by the TIRF REMS Access program in advance of the need to re-enroll. · Patients that have already signed a Patient-Prescriber Agreement Form on file will not have to sign another form until their two year enrollment is due.
Reference ID: 4146711
FDA_7320
Option 2: If you do not have an existing enrollment in any individual REMS program · Access the TIRF REMS Access program at www.TIRFREMSaccess.com to create an account. · Review the TIRF REMS Access Education Program materials available at www.TIRFREMSaccess.com including the Full Prescribing Information for each product covered in this program, and successfully complete the Knowledge Assessment. · Enroll in the TIRF REMS Access program by completing the Prescriber Enrollment Form and re-enroll every two (2) years. You will be notified by the TIRF REMS Access program in advance of the need to re-enroll. · If you are unable to enroll online, please call the TIRF REMS program call center at 1866-822-1483 for further assistance.
The goals of the TIRF REMS Access program are to mitigate the risk of misuse, abuse, addiction, overdose and serious complications due to medication errors by:
1. Prescribing and dispensing TIRF medicines only to appropriate patients, which includes use only in opioid-tolerant patients.
2. Preventing inappropriate conversion between fentanyl products. 3. Preventing accidental exposure to children and others for whom it was not prescribed. 4. Educating prescribers, pharmacists, and patients on the potential for misuse, abuse,
addiction, and overdose of TIRF medicines.
This new shared program replaces the individual product REMS that were previously available. Any prescribers, pharmacies, patients and distributors enrolled in these programs will be automatically transitioned to the new shared TIRF REMS Access program beginning mm/dd/yyyy. If you have not enrolled in one or more of these individual REMS programs and you intend to prescribe any of these products for outpatient use you must enroll in the TIRF REMS program.
For inpatient administration (e.g. hospitals, in-patient hospices, and long-term care facilities that dispense for inpatient use) of these products, patient and prescriber enrollment in the TIRF REMS Access program is not required.
TIRF medicines are opioid analgesics indicated only for the management of breakthrough pain in cancer patients 18 years of age and older (16 years of age and older for Actiq® brand and generic equivalents) who are already receiving and who are tolerant to around-the-clock opioid therapy for their underlying persistent cancer pain, unless otherwise indicated in the product label.
Patients considered opioid-tolerant are those who are regularly taking at least 60 mg oral morphine/day, or at least 25 micrograms transdermal fentanyl/hour, or at least 30 mg of oral oxycodone/day, or at least 8 mg oral hydromorphone/day, or at least 25 mg oral oxymorphone/day or an equianalgesic dose of another opioid for one week or longer.
To help you understand the TIRF REMS Access program the following program materials are available at www.TIRFREMSaccess.com or can be ordered by calling 1-866-822-1483: · Prescriber Program Overview · TIRF REMS Access Education Program · Knowledge Assessment Form · Prescriber Enrollment Form · Frequently Asked Questions
You can also access the following patient materials at www.TIRFREMSaccess.com or
Reference ID: 4146711
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order them by calling 1-866-822-1483: · An Overview for Patients and Caregivers · Patient-Prescriber Agreement Form · Frequently Asked Questions · Full Prescribing Information and Medication Guides for each TIRF medicine
To access the above information and to enroll in the TIRF REMS Access program, visit www.TIRFREMSaccess.com or call 1-866-822-1483 to have enrollment materials sent to you.
Reference ID: 4146711
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Selected Important Safety Information
IMPORTANCE OF PROPER PATIENT SELECTION, DOSING, and POTENTIAL FOR ABUSE
TIRF medicines contain fentanyl, an opioid agonist and a Schedule II controlled substance, with an abuse liability similar to other opioid analgesics. TIRF medicines can be abused in a manner similar to other opioid agonists, legal or illicit. Consider the potential for abuse when prescribing or dispensing TIRF medicines in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse or diversion. Schedule II opioid substances which include morphine, oxycodone, hydromorphone, oxymorphone, and methadone have the highest potential for abuse and risk of fatal overdose due to respiratory depression.
Serious adverse events, including deaths, in patients treated with some oral transmucosal fentanyl medicines have been reported. Deaths occurred as a result of improper patient selection (e.g., use in opioid non-tolerant patients) and/or improper dosing. The substitution of a TIRF medicine for any other fentanyl medicine, including another TIRF medicine, may result in fatal overdose.
TIRF medicines are indicated only for the management of breakthrough pain in adult cancer patients 18 years of age and older (16 years of age and older for Actiq® brand and generic equivalents) who are already receiving and who are tolerant to around-the-clock opioid therapy for their underlying persistent cancer pain. Patients considered opioid-tolerant are those who are taking:
· at least 60 mg of oral morphine/daily · at least 25 mcg transdermal fentanyl/hour · at least 30 mg of oral oxycodone daily · at least 8 mg oral hydromorphone daily · at least 25 mg oral oxymorphone daily · or an equianalgesic dose of another opioid daily for a week or longer.
TIRF medicines are contraindicated in opioid non-tolerant patients and are contraindicated in the management of acute or postoperative pain, including headache/migraine and dental pain, or use in the emergency room. Please see the individual medicine prescribing information for a full list of specific situations in which TIRF medicines are not indicated or are contraindicated. Lifethreatening respiratory depression could occur at any dose in opioid non-tolerant patients. Deaths have occurred in opioid non-tolerant patients treated with some TIRF medicines.
When prescribing, do not convert patients on a mcg per mcg basis from another fentanyl medicine to a TIRF medicine, except for substitutions between a branded TIRF medicine and its generic equivalent. Patients beginning treatment with TIRF medicines must begin with titration from the lowest available dose for that specific medicine. Carefully consult the Initial Dosing Instructions in the TIRF medicine-specific Full Prescribing Information.
When dispensing, TIRF medicines are not interchangeable with each other, regardless of route of administration. Differences exist in the pharmacokinetics of TIRF medicines resulting in
Reference ID: 4146711
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clinically important differences in the amount of fentanyl absorbed that could cause a fatal overdose. Converting patients from one TIRF medicine to a different TIRF medicine must not be done on a microgram-per-microgram basis, and must be titrated according to the labeled dosing instructions each time they begin use of a new TIRF medicine. The only exception is for substitution between a branded TIRF medicine and its specific generic equivalent.
Special care must be used when dosing TIRF medicines. Refer to the Full Prescribing Information for the individual TIRF medicine for guidance on the maximum number of doses that can be taken per breakthrough pain episode and the time that patients must wait before treating another episode of breakthrough pain with the TIRF medicine.
TIRF medicines are intended to be used only in the care of opioid-tolerant cancer patients and only by healthcare professionals who are knowledgeable of, and skilled in, the use of Schedule II opioids to treat cancer pain.
Patients and their caregivers must be instructed that TIRF medicines contain a medicine in an amount which can be fatal in children, in individuals for whom it is not prescribed, and in those who are not opioid-tolerant. All medicines must be kept out of the reach of children.
The concomitant use of TIRF medicines with cytochrome P450 3A4 inhibitors may result in an increase in fentanyl plasma concentrations, and may cause potentially fatal respiratory depression.
Adverse Reactions The most commonly observed adverse reactions with TIRF medicines include typical opioid adverse reactions, such as nausea, vomiting, constipation, somnolence, dizziness, and headache. Refer to individual medicine prescribing information for all adverse reactions. Expect opioid side effects and manage them accordingly.
Please see the individual Full Prescribing Information for each TIRF medicine for all information including boxed warnings, and Medication Guide for important safety information for each TIRF medicine.
Adverse Event Reporting
Promptly report suspected adverse events including misuse, abuse, addiction and overdoses directly to the TIRF REMS Access program at 1-866-822-1483. You also may report adverse event information to the FDA MedWatch Reporting System by telephone at 1-800-FDA-1088 or by mail using Form 3500, available at www.fda.gov/medwatch.
Medication Guide It is important that you discuss the risks of TIRF medicines with your patients and encourage them to read the relevant Medication Guide. The Medication Guide provides important information on the safe and effective use of TIRF medicines and you will need to review the appropriate Medication Guide for the TIRF medicine you prescribe/dispense to your patient. Patients should be counseled on the need to store TIRF medicines safely out of the reach of children and other persons for whom the medicine is not prescribed.
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Provide your patient with a copy of the appropriate Medication Guide for the TIRF medicine you prescribe. Medication Guides will be provided to you by the manufacturers of individual TIRF medicines. If you require additional Medication Guides you can:
· Print copies from the TIRF REMS Access program website at www.TIRFREMSaccess.com.
· Contact the TIRF REMS Access program at 1-866-822-1483.
Sincerely,
TIRF REMS Access Industry Group
Reference ID: 4146711
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Attachment 1:
List of TIRF Medicines Available Only through the TIRF REMS Access Program
ABSTRAL® (fentanyl) sublingual tablets ACTIQ® (fentanyl citrate) oral transmucosal lozenge FENTORA® (fentanyl citrate) buccal tablet LAZANDA® (fentanyl) nasal spray ONSOLIS® (fentanyl buccal soluble film) Approved generic equivalents of these products are also covered under this
program.
Reference ID: 4146711
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Home Page
Important Safety Information (ISI) is included on the bottom of the Home Page. To reduce the space and image distortion, ISI is not shown as part of Home Page in this document.
Reference ID: 4146711
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The Transmucosal Immediate Release Fentanyl (TIRF) REMS Access Program
An Overview for Independent Outpatient Pharmacies
To dispense TIRF medicines, your Independent Outpatient Pharmacy must enroll in the TIRF REMS Access program.
What is the TIRF REMS Access Program? The TIRF REMS (Risk Evaluation and Mitigation Strategy) Access program is designed to ensure informed risk-benefit decisions before initiating treatment and, while patients are on treatment, to ensure appropriate use of TIRF medicines. TIRF medicines are available only through a restricted distribution program required by the Food and Drug Administration (FDA), because of the risk for misuse, abuse, addiction, overdose, and serious complications due to medication errors. A list of TIRF medicines available through the TIRF REMS Access program is located on the TIRF Products web page at www.TIRFREMSaccess.com/TirfUI/rems/products.action.
How does the TIRF REMS Access program work? The TIRF REMS Access program requires pharmacies, prescribers, patients and wholesalers to enroll in the program in order to utilize TIRF medications. The supply of TIRF medicines to pharmacies is controlled by enrolled distributors, who will verify the current enrollment status of the pharmacy prior to shipment of TIRF medicines. Pharmacies are required to verify the prescriber and the patient are enrolled in the TIRF REMS Access program before dispensing any TIRF medication.
Does your pharmacy qualify as an Independent Outpatient Pharmacy? For the purposes of this REMS, an independent outpatient pharmacy is defined as an outpatient pharmacy such as a retail, mail or institutional outpatient pharmacy having an authorized pharmacy representative that is responsible for ensuring enrollment and training of the pharmacy staff within an individual outpatient pharmacy. Each store will individually enroll in TIRF REMS Access as a single pharmacy location. Additionally, to qualify as an independent outpatient pharmacy, your pharmacy must use a pharmacy management system to electronically transmit the required validation and claim information to the TIRF REMS Access program using established telecommunication standards.
NOTE: There are different requirements for inpatient pharmacies that only dispense for inpatient use. Please refer to "An Overview for Inpatient Pharmacies" for more information.
Options and Requirements for the TIRF REMS Access Program for Independent Outpatient Pharmacies
Pharmacy Education, Enrollment & Pharmacy Management Systems
All enrollment activities can be completed at www.TIRFREMSaccess.com
Reference ID: 4146711
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If I have previously enrolled in an individual TIRF REMS do I need to enroll in the shared TIRF REMS Access Program?
All pharmacy enrollment information was transferred from the individual TIRF REMS to the TIRF REMS Access Program on March 12, 2012. If the authorized pharmacist or pharmacy representative logged onto the TIRF REMS Access program website and agreed to the shared program terms and conditions before September 12, 2012, your pharmacy is able to order and dispense all TIRF medications. If the authorized pharmacist or pharmacy representative has not agreed to the shared terms and conditions, your pharmacy will need to enroll in the TIRF REMS Access program (see how to enroll below).
You will be required to re-enroll in the shared TIRF REMS two (2) years after your last enrollment in an individual REMS program if you wish to continue dispensing these products. You will be notified by the TIRF REMS Access program in advance of the need to re-enroll.
The following two sections provide detailed information on the Enrollment Process (Section 1) and the Dispensing Process (Section 2) for TIRF medicines in an independent outpatient pharmacy.
Section 1: Enrollment Process
Summary of Enrollment:
1. Select an individual to be your Authorized Independent Outpatient Pharmacy Representative.
2. Create an account and complete registration at www.TIRFREMSaccess.com. 3. Complete the TIRF REMS Access Education Program and Knowledge
Assessment. 4. Complete and submit an Independent Outpatient Pharmacy Enrollment form. 5. Enable the pharmacy management system to support communication with
the TIRF REMS Access system. 6. Train pharmacy staff.
Detailed Enrollment Process
Step 1: Select an individual to be your Authorized Chain Representative
· Select an authorized pharmacy representative to establish and oversee the TIRF REMS Access program requirements.
Step 2: Create an account and complete registration at www.TIRFREMSaccess.com
Reference ID: 4146711
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· Create an account at www.TIRFREMSaccess.com and then complete registration on behalf of your pharmacy.
How do I create an account and complete the TIRF REMS Access registration on-line?
· Select the Create Account button on the home page · Complete the Create Account Information section · Select `No' if you have not submitted an enrollment form via fax at the
`Already enrolled via Fax and have an enrollment ID?' prompt · Create User ID and password and select `Create My Account' · Select `Pharmacy' as the option to best describe you and select `Continue' · Select `Independent Outpatient Authorized Pharmacist' · Review the content in the pop-up box and select `Confirm' to continue · Complete required fields on the Independent Outpatient Pharmacy
Registration page and select `Submit' to continue
Step 3: Complete the TIRF REMS Access Education Program and Knowledge Assessment
How do I complete the TIRF REMS Access Education Program by fax? · Review the TIRF REMS Access Education Program. A printable version of the TIRF REMS Access Education Program is available online at www.TIRFREMSaccess.com or by contacting the TIRF REMS Access call center at 1-866-822-1483. · Once you have reviewed the Education Program complete the Knowledge Assessment and submit by fax to 1-866-822-1487. · The TIRF REMS Access program will notify you of the status of your Knowledge Assessment via your indicated preferred method of communication (fax or e-mail).
How do I complete the TIRF REMS Access Education Program online?
· Select the `Start the TIRF REMS Access Education Program' to proceed to the training upon completion of registration
· Select `Go To Knowledge Assessment', complete the Knowledge Assessment, and select `Submit Assessment'
· A Knowledge Assessment Confirmation Code will be provided once the assessment is completed successfully
Step 4: Complete and submit Independent Outpatient Pharmacy Enrollment
· To finalize enrollment in the TIRF REMS Access program complete Independent Outpatient Pharmacy Enrollment.
· If you are unable to enroll online, please call the TIRF REMS Access program call center at 1-866-822-1483 for further assistance.
Reference ID: 4146711
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How do I complete the TIRF REMS Access Enrollment on-line?
· Upon successful completion of the TIRF REMS Access Education Program and Knowledge Assessment, you will be prompted to read the TIRF REMS Access attestation and enter your electronic signature, today's date, and check the attestation box before clicking `Submit'.
NOTE: You are required to re-enroll every two (2) years. You will be notified by the TIRF REMS Access program in advance of the need to re-enroll.
Step 5: Confirm the Pharmacy Management System supports communication with the TIRF REMS Access system
· Following completion of steps 1-4 above, you will receive instruction on how to submit test transactions to the TIRF REMS Access program. Successful submission of the test transaction confirms the pharmacy management system supports communication with the TIRF REMS Access system.
· After successful completion of the test transactions you will receive enrollment confirmation.
Step 6: Train Pharmacy Staff
· Ensure that all pharmacy staff involved in the processing and dispensing of TIRF medicines have been trained to only dispense TIRF medicines in accordance with the TIRF REMS Access program requirements. o Pharmacy staff can register online to access the Education Program and take the Knowledge Assessment for training purposes.
· Ensure that this training is documented and retained by the pharmacy. This documentation should include the pharmacist/pharmacy staff member's name, the date training was completed and the method of training as a minimum.
Section 2: Dispensing Process
Summary of Dispensing Process 1. Confirm pharmacy staff is trained. 2. Confirm patient and prescriber enrollment in TIRF REMS Access Program. 3. Dispense TIRF medication. 4. Counsel patient and provide medication guide.
Detailed Dispensing Process
Step 1: Confirm that the Pharmacy staff is trained
· Ensure all pharmacy staff involved in the processing and dispensing of TIRF medicines have been trained to specifically dispense TIRF medicines in accordance with the TIRF REMS Access program requirements available at www.TIRFREMSaccess.com. (see Section 1, Step 6: Train Pharmacy Staff).
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Step 2: Confirm prescriber and patient enrollment
· Each pharmacy site must confirm that the prescriber and patient are enrolled in the TIRF REMS Access program prior to dispensing each TIRF prescription by submitting a pharmacy billing claim via the chain pharmacy practice management system. This includes third party insurance claims, cash claims and any other claims (i.e.: workers compensation). Submitting a claim for a patient's first TIRF prescription through the pharmacy management system will automatically enroll that patient in the TIRF REMS Access program.
· To allow the TIRF REMS Access program to confirm prescriber and patient enrollment the pharmacy practice management system must populate the following fields in the pharmacy billing claim*: o Patient First Name, o Patient Last Name, o Patient Date of Birth, o Patient ZIP / Postal Zone, o Quantity Dispensed, o Days Supply, o Prescriber ID, o Prescriber Last Name *Use BIN 014780 for all cash and non-third party claims.
· If the prescriber or patient enrollment is not confirmed, or if any other rejection message is received that prevents the prescription from being filled, contact the TIRF REMS Access call center at 1-866-822-1483 for further instruction.
Step 3: Dispense TIRF Medication
· Receive approval from the TIRF REMS Access program and then prepare, label and dispense the medication.
Step 4: Counsel Patient and Provide Medication Guide
· Advise the patient on how to take, store and dispose of TIRF medicine appropriately.
· Provide a copy of the product specific Medication Guide to the patient with each prescription.
Reporting Adverse Events and Monitoring
To report any adverse events including the misuse, abuse, addiction, or overdose of TIRF medication contact:
· TIRF REMS Access program at 1-866-822-1483 and/or
Reference ID: 4146711
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· FDA MedWatch program by phone at 1-800-FDA-1088 or online at www.fda.gov/medwatch/report.htm
If you have any questions, need additional information, or need additional copies of any TIRF REMS Access documents, please visit www.TIRFREMSaccess.com, or call the TIRF REMS Access program at 1-866822-1483.
Reference ID: 4146711
FDA_7333
The Transmucosal Immediate Release Fentanyl (TIRF) REMS Access Program
An Overview for Chain Outpatient Pharmacies
To dispense TIRF medicines, your Chain Outpatient Pharmacy must enroll in the TIRF REMS Access program.
What is the TIRF REMS Access Program? The TIRF REMS (Risk Evaluation and Mitigation Strategy) Access program is designed to ensure informed risk-benefit decisions before initiating treatment and, while patients are on treatment, to ensure appropriate use of TIRF medicines. TIRF medicines are available only through a restricted distribution program required by the Food and Drug Administration (FDA), because of the risk for misuse, abuse, addiction, overdose, and serious complications due to medication errors. A list of TIRF medicines available through the TIRF REMS Access program is located on the TIRF Products web page at www.TIRFREMSaccess.com/TirfUI/rems/products.action.
How does the TIRF REMS Access program work? The TIRF REMS Access program requires pharmacies, prescribers, patients and wholesalers to enroll in the program in order to utilize TIRF medications. The supply of TIRF medicines to pharmacies is controlled by enrolled distributors, who will verify the current enrollment status of the pharmacy prior to shipment of TIRF medicines. Pharmacies are required to verify the prescriber and the patient are enrolled in the TIRF REMS Access program before dispensing any TIRF medication.
Does your pharmacy qualify as a Chain Outpatient Pharmacy? For the purposes of this REMS, a chain outpatient pharmacy is defined as an outpatient pharmacy such as a retail, mail order or institutional outpatient pharmacy having a chain headquarters that is responsible for ensuring enrollment and training of the pharmacy staff of all associated outpatient pharmacies. The chain headquarters will enroll multiple pharmacy locations (i.e.: chain stores) in the TIRF REMS Access program. Additionally, to qualify as a chain outpatient pharmacy, your pharmacy must use a pharmacy management system to electronically transmit the required validation and claim information to the TIRF REMS Access program using established telecommunication standards.
NOTE: There are different requirements for inpatient pharmacies that only dispense for inpatient use. Please refer to "An Overview for Inpatient Pharmacies" for more information.
Reference ID: 4146711
FDA_7334
Overview of the TIRF REMS Access Program for Chain Outpatient Pharmacies: Steps for Enrollment and Program Requirements
Chain Outpatient Pharmacy Education, Enrollment & Pharmacy Management Systems
All enrollment activities can be completed at www.TIRFREMSaccess.com
If I have previously enrolled in an individual TIRF REMS do I need to enroll in the shared TIRF REMS Access Program?
All pharmacy enrollment information was transferred from the individual TIRF REMS to the TIRF REMS Access program on March 12, 2012. If the authorized pharmacist or pharmacy representative logged onto the TIRF REMS Access program website, executed a TIRF REMS Access contract with their switch provider to agree to the shared program terms and conditions before September 12, 2012, your pharmacy is able to order and dispense all TIRF medications. If the authorized pharmacist or pharmacy representative has not agreed to the shared terms and conditions, your pharmacy will need to enroll in the TIRF REMS Access program (see how to enroll below).
You will be required to re-enroll in the shared TIRF REMS two (2) years after your last enrollment in an individual REMS program if you wish to continue dispensing these products. You will be notified by the TIRF REMS Access program in advance of the need to re-enroll.
The following two sections provide detailed information on the Enrollment Process (Section 1) and the Dispensing Processes (Section 2) for TIRF medicines in a chain outpatient pharmacy.
Section 1: Enrollment Process
Summary of Enrollment Process
1. Execute a TIRF REMS Access contract with your switch provider. 2. Select an individual to be your Authorized Chain Outpatient Pharmacy
Representative. 3. Create an account and complete registration at www.TIRFREMSaccess.com 4. Complete the TIRF REMS Access Education Program and Knowledge
Assessment. 5. Complete and submit a Chain Outpatient Pharmacy Enrollment form 6. Enable the pharmacy management system to support communication with
the TIRF REMS Access system. 7. Train pharmacy staff.
Reference ID: 4146711
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Detailed Enrollment Process
Step 1: Execute a TIRF REMS Access contract with your switch provider
· Call the TIRF REMS Access program at 1-866-822-1483. · The TIRF REMS program will notify your switch provider and advise that a
contract must be executed for participation in the program.
Your account executive will contact you directly and work with you to establish a contractual agreement.
Step 2: Select an individual to be your Authorized Chain Outpatient Pharmacy Representative
· Select an authorized chain outpatient pharmacy representative to establish and oversee the TIRF REMS Access program requirements.
Step 3: Create an account and complete registration at www.TIRFREMSaccess.com
· Create an account at www.TIRFREMSaccess.com and then complete registration at the corporate level on behalf of your individual pharmacies.
How do I create an account and complete the TIRF REMS Access registration on-line? · Select the Create Account button on the home page · Complete the Create Account Information section · Select `No' if you have not submitted an enrollment form via fax at the
`Already enrolled via Fax and have an enrollment ID?' prompt · Create User ID and password and select `Create My Account' · Select `Pharmacy' as the option to best describe you and select `Continue' · Select `Chain Outpatient Pharmacy Authorized Chain Outpatient Pharmacy
Representative' · Review the content in the pop-up box and select `Confirm' to continue · Complete required fields on the Chain Outpatient Pharmacy Registration page
and select `Submit' to continue
Step 4: Complete the TIRF REMS Access Education Program and Knowledge Assessment
How do I complete the TIRF REMS Access Education Program by fax? · Review the TIRF REMS Access Education Program. A printable version of the
TIRF REMS Access Education Program is available online at www.TIRFREMSaccess.com or by contacting the TIRF REMS Access call center at 1-866-822-1483.
Reference ID: 4146711
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· Once you have reviewed the Education Program complete the Knowledge Assessment and submit by fax to 1-866-822-1487.
· The TIRF REMS Access program will notify you of the status of your Knowledge Assessment via your indicated preferred method of communication (fax or e-mail).
How do I complete the TIRF REMS Access Education Program online? · Select the `Start the TIRF REMS Access Education Program' to proceed to the
training upon completion of registration · Select `Go To Knowledge Assessment', complete the Knowledge Assessment,
and select `Submit Assessment' · A Knowledge Assessment Confirmation Code will be provided once the
assessment is completed successfully
Step 5: Complete and submit Chain Outpatient Pharmacy Enrollment
· To finalize enrollment in the TIRF REMS Access program complete Chain Outpatient Pharmacy Enrollment.
· If you are unable to enroll online, please call the TIRF REMS Access program call center at 1-866-822-1483 for further assistance.
How do I complete the TIRF REMS Access Enrollment on-line? · Upon successful completion of the TIRF REMS Access Education Program and
Knowledge Assessment, you will be prompted to read the TIRF REMS Access attestation and enter your electronic signature, today's date, and check the attestation box before clicking `Submit'.
NOTE: You are required to re-enroll every two (2) years. You will be notified by the TIRF REMS Access program in advance of the need to re-enroll.
Step 6: Confirm the Pharmacy Management System supports communication with the TIRF REMS Access system
· A chain outpatient pharmacy is required to complete test transactions one time on behalf of all their stores. Following completion of steps 1-5 above, you will receive instruction on how to submit test transactions to the TIRF REMS Access program. Successful submission of the test transaction confirms the pharmacy management system supports communication with the TIRF REMS Access system.
· After successful completion of the test transactions you will receive enrollment confirmation.
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Step 7: Train Pharmacy Staff
· Ensure that all chain outpatient pharmacy staff involved in the processing and dispensing of TIRF medicines have been trained to only dispense TIRF medicines in accordance with the TIRF REMS Access program requirements. o Pharmacy staff can register online to access the Education Program and take the Knowledge Assessment for training purposes.
· Ensure that this training is documented and retained by the chain outpatient pharmacy in accordance to the chains' internal processes. This documentation should include the pharmacist/pharmacy staff member's name, the date training was completed and the method of training, as a minimum.
· The list of pharmacy sites that have been trained should be updated by the Authorized Chain Outpatient Pharmacy Representative on the Chain Outpatient Pharmacy Dashboard where all chain stores are listed at www.TIRFREMSaccess.com. This list should include the required Pharmacy Information for each pharmacy site.
Section 2: Dispensing Process
Summary of Dispensing Process 1. Confirm pharmacy staff is trained. 2. Confirm patient and prescriber enrollment in TIRF REMS Access Program. 3. Dispense TIRF medication. 4. Counsel patient and provide medication guide.
Detailed Dispensing Process
Step 1: Confirm that the Pharmacy staff is trained
· Ensure all pharmacy staff involved in the processing and dispensing of TIRF medicines have been trained to specifically dispense TIRF medicines in accordance with the TIRF REMS Access program requirements available at www.TIRFREMSaccess.com. (see Section 1, Step 7: Train pharmacy staff).
Step 2: Confirm prescriber and patient enrollment
· Each pharmacy site must confirm that the prescriber and patient are enrolled in the TIRF REMS Access program prior to dispensing each TIRF prescription by submitting a pharmacy billing claim via the chain outpatient pharmacy practice management system. This includes third party insurance claims, cash claims and any other claims (i.e.: workers compensation). Submitting a claim for a patient's first TIRF prescription through the pharmacy management system will automatically enroll that patient in the TIRF REMS Access program.
Reference ID: 4146711
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· To allow the TIRF REMS Access program to confirm prescriber and patient enrollment the chain outpatient pharmacy practice management system must populate the following fields in the pharmacy billing claim*: o Patient First Name, o Patient Last Name, o Patient Date of Birth, o Patient ZIP / Postal Zone, o Quantity Dispensed, o Days Supply, o Prescriber ID, o Prescriber Last Name *Use BIN 014780 for all cash and non-third party claims.
· If the prescriber or patient enrollment is not confirmed, or if any other rejection message is received that prevents the prescription from being filled, contact the TIRF REMS Access call center at 1-866-822-1483 for further instruction.
Step 3: Dispense TIRF Medication
· Receive approval from the TIRF REMS Access program and then prepare, label and dispense the medication.
Step 4: Counsel Patient and Provide Medication Guide
· Advise the patient on how to take, store and dispose of TIRF medicines appropriately.
· Provide a copy of the product specific Medication Guide to the patient with each prescription.
Reporting Adverse Events and Monitoring
To report any adverse events including the misuse, abuse, addiction, or overdose of TIRF medication contact:
· TIRF REMS Access program at 1-866-822-1483 and/or · FDA MedWatch program by phone at 1-800-FDA-1088 or online at
www.fda.gov/medwatch/report.htm
If you have any questions, need additional information, or need additional copies of any TIRF REMS Access documents, please visit www.TIRFREMSaccess.com, or call the TIRF REMS Access program at 1866-822-1483.
Reference ID: 4146711
FDA_7339
The Transmucosal Immediate Release Fentanyl (TIRF) REMS Access Program
An Overview for Closed System Outpatient Pharmacies
To dispense TIRF medicines, your Closed System Outpatient Pharmacy must enroll in the TIRF REMS Access program.
What is the TIRF REMS Access program? The TIRF REMS (Risk Evaluation and Mitigation Strategy) Access program is designed to ensure informed risk-benefit decisions before initiating treatment, while patients are on treatment, and to ensure appropriate use of TIRF medicines. TIRF medicines are available only through a required Food and Drug Administration (FDA) restricted distribution program, because of the risk for misuse, abuse, addiction, overdose, and serious complications due to medication errors. A list of TIRF medicines available through the TIRF REMS Access program is located on the TIRF Products web page at www.TIRFREMSaccess.com/TirfUI/rems/products.action.
How does the TIRF REMS Access program work? The TIRF REMS Access program requires pharmacies, prescribers, patients and wholesalers to enroll in the program in order to utilize TIRF medications. The supply of TIRF medicines to pharmacies is controlled by enrolled distributors, who will verify the current enrollment status of the pharmacy prior to shipment of TIRF medicines. Pharmacies are required to verify the prescriber and the patient are enrolled in the TIRF REMS Access program before dispensing any TIRF medication.
Does your institution qualify as a Closed System Outpatient Pharmacy? For the purposes of this REMS, a closed system outpatient pharmacy is defined as an outpatient pharmacy that uses a pharmacy management system that does not support the process of electronically transmitting the validation and claim information currently required by the TIRF REMS Access program. For example, some pharmacies that are part of integrated healthcare delivery systems may qualify as closed system outpatient pharmacies.
NOTE: There are different requirements for outpatient pharmacies that support the process of electronically transmitting claim information, and for inpatient pharmacies that only dispense for inpatient use. Please refer to "An Overview for Chain Outpatient Pharmacies", "An Overview for Independent Outpatient Pharmacies" or "An Overview for Inpatient Pharmacies" for more information. If you do not qualify as a closed system outpatient pharmacy, please refer to the requirements for the other type of pharmacies.
The following two sections provide detailed information on the Enrollment Process (Section 1) and the Dispensing Processes (Section 2) for TIRF medicines in a closed system outpatient pharmacy.
Reference ID: 4146711
FDA_7340
Section 1: Enrollment Process
Summary of Enrollment Process
1. Confirm that your facility qualifies as a closed system outpatient pharmacy. 2. Select an individual to be your Authorized Closed System Outpatient
Pharmacy Representative. 3. Complete the TIRF REMS Access Education Program and Knowledge
Assessment. 4. Complete and submit a Closed System Outpatient Pharmacy Enrollment
Form. 5. Train pharmacy staff.
Detailed Enrollment Process
Step 1: Confirm your facility qualifies as a Closed System Outpatient Pharmacy
· Notify the TIRF REMS Access program by phone at 1-866-822-1483 or by email to information@TIRFREMSaccess.com that you are a closed system outpatient pharmacy.
· When your pharmacy is validated as a closed system outpatient pharmacy, a Closed System Outpatient Pharmacy Enrollment Form will be provided.
Step 2: Select an individual to be your Authorized Closed System Outpatient Pharmacy Representative
· Select an authorized closed system outpatient pharmacy representative to establish and oversee the TIRF REMS Access program requirements.
Step 3: Complete the TIRF REMS Access Education Program
· Review the TIRF REMS Access Education Program and successfully complete the Knowledge Assessment. The TIRF REMS Access Education Program is available online at the TIRF REMS Access program website www.TIRFREMSaccess.com or by contacting the TIRF REMS Access call center at 1-866-822-1483.
· If Knowledge Assessment was completed on paper, Fax to 1-855-474-3062 or email the Knowledge Assessment to information@TIRFREMSaccess.com with enrollment form (see Step 4: Complete and submit enrollment form).
How do I complete the TIRF REMS Access Education Program online? · Select the Create Account button on the home page · Complete the Create Account Information section · `Already enrolled via Fax and have an enrollment ID?' - Select No · Create User ID and password and select the Create my Account button · Select `Pharmacy' as the option to best describe you and select `Continue' · In response to Question 2, select `Pharmacy Staff' · Review the content in the pop-up box and select `Confirm' to continue
Reference ID: 4146711
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· Complete required fields in Pharmacy Staff details · Select `Other' from the dropdown list in the Chain Pharmacy name and
populate the name of your closed system outpatient pharmacy organization in the `Other' field and submit form · Select the `Start the TIRF REMS Access Education Program' to proceed to the training · Once you have completed the Education Program, select the `Go To Knowledge Assessment' button and complete · A Knowledge Assessment Confirmation Code will be provided once the assessment is completed successfully
Step 4: Complete and Submit Enrollment Form
· Complete and return the Closed System Outpatient Pharmacy Enrollment Form by fax to 1-855-474-3062. The authorized closed system outpatient pharmacy representative will receive an Enrollment Confirmation letter and instructions for enrolling dispensing locations within the closed system outpatient pharmacy by using a standard file template provided by the TIRF REMS Access program.
· If you did not complete the Education Program online then you need to submit the Knowledge Assessment form with the Enrollment form.
· Re-enroll every two (2) years. You will be notified by the TIRF REMS Access program in advance of the need to re-enroll.
Step 5: Train Pharmacy Staff
· All closed system outpatient pharmacy staff involved in processing and dispensing of TIRF medications must be trained to dispense TIRF medicines in accordance with the TIRF REMS Access Education Program requirements available at www.TIRFREMSaccess.com.
· Ensure that this training is documented and retained by the closed system outpatient pharmacy. This documentation should include the pharmacist/pharmacy staff member's name, the date training was completed and the method of training as a minimum.
Reference ID: 4146711
FDA_7342
Section 2: Dispensing Process
Summary of Dispensing Process
1. Confirm pharmacy staff is trained. 2. Confirm patient and prescriber enrollment in TIRF REMS Access Program. 3. Dispense TIRF medication. 4. Counsel patient and provide medication guide.
Detailed Dispensing Process
Step 1: Confirm that the Pharmacy staff is trained
· Ensure all pharmacy staff involved in the processing and dispensing of TIRF medicines have been trained to specifically dispense TIRF medicines in accordance with the TIRF REMS Access program requirements available at www.TIRFREMSaccess.com. (see Section 1, Step 5: Train pharmacy staff).
Step 2: Confirm prescriber and patient enrollment:
Prior to dispensing each TIRF medicine prescription, confirm that the prescriber and patient are enrolled in the TIRF REMS Access program by contacting the TIRF REMS Access program by phone at 1-866-822-1483 or fax at 1-855-474-3062. This includes third party insurance claims, cash claims and any other claims (i.e., workers compensation).
· To confirm enrollment confirmation by phone:
o Contact the TIRF REMS Access program at 1-866-822-1483 and select option #2.
o Provide the following required data from the TIRF prescription to obtain
an authorization to dispense:
Dispensing Pharmacy DEA
Patient Date of Birth Rx Date of Service
Dispensing Pharmacy NPI
Patient First Name
Rx Number
Dispensing Pharmacy Phone # Patient Last Name
Rx NDC
Dispensing Pharmacy Fax #
Patient Zip Code
Days Supply
Prescriber DEA or NPI
Prescriber Last Name Quantity for Dispense
If validated, you will be supplied a prescription authorization number which indicates you can dispense TIRF medicine.
If not validated, you will be provided a rejection reason and information regarding how to resolve the rejection.
· To confirm enrollment confirmation by fax:
o Populate all of the required fields on the TIRF REMS Access Prescription Authorization Form and fax to 1-855-474-3062. To obtain a TIRF REMS Access Prescription Authorization Form which may be reproduced to use continually, please email information@TIRFREMSaccess.com.
Reference ID: 4146711
FDA_7343
If validated, you will be supplied a prescription authorization number via fax within one (1) business day which indicates you can dispense the TIRF medicine.
If not validated, you will be provided a rejection reason and information regarding how to resolve the rejection using the phone number provided on the request.
Step 3: Dispensing
· Receive the prescription authorization number from the TIRF REMS Access program and then prepare, label and dispense the medication.
Step 4: Counsel patient and provide Medication Guide
· Counsel the patient on the appropriate use, safe storage, and the proper disposal procedures of TIRF medicines.
· Provide a copy of the product specific Medication Guide to the patient with each prescription.
Reporting Adverse Events and Monitoring
To report any adverse events including the misuse, abuse, addiction, or overdose of TIRF medication contact:
· TIRF REMS Access program at 1-866-822-1483 and/or · FDA MedWatch program by phone at 1-800-FDA-1088 or online at
www.fda.gov/medwatch/report.htm
If you have any questions, need additional information, or need additional copies of any TIRF REMS Access documents, please visit www.TIRFREMSaccess.com, or call the TIRF REMS Access program at 1-866822-1483.
Reference ID: 4146711
FDA_7344
The Transmucosal Immediate Release Fentanyl (TIRF) REMS Access Program
An Overview for Inpatient Pharmacies (e.g. hospitals, in-hospital hospices, and long-term care facilities that dispense for inpatient use).
To dispense TIRF medicines, your Inpatient Pharmacy must enroll in the TIRF REMS Access program.
What is the TIRF REMS Access Program? The TIRF REMS (Risk Evaluation and Mitigation Strategy) Access program is designed to ensure informed risk-benefit decisions before initiating treatment and, while patients are on treatment, to ensure appropriate use of TIRF medicines. TIRF medicines are available only through a restricted distribution program required by the Food and Drug Administration (FDA), because of the risk for misuse, abuse, addiction, overdose, and serious complications due to medication errors. A list of TIRF medicines available through the TIRF REMS Access program is located on the TIRF Products web page at www.TIRFREMSaccess.com/TirfUI/rems/products.action.
How does the TIRF REMS Access program work? The TIRF REMS Access program requires pharmacies, prescribers, patients and wholesalers to enroll in the program in order to utilize TIRF medications. The supply of TIRF medicines to pharmacies is controlled by enrolled distributors, who will verify the current enrollment status of the pharmacy prior to shipment of TIRF medicines. Pharmacies are required to verify the prescriber and the patient are enrolled in the TIRF REMS Access program before dispensing any TIRF medication.
Does your pharmacy qualify as an Inpatient Pharmacy? For the purposes of this REMS, an inpatient pharmacy is defined as a pharmacy where the patient's care is coordinated on-site at a care facility and the pharmacy claims are submitted as a medical benefit.
Important Information about Outpatient Pharmacies within the Facility Outpatient pharmacies, within or associated with the healthcare facility, that provide dispensing services to outpatients must be separately enrolled in the TIRF REMS Access program and comply with the TIRF REMS Access program to dispense TIRF medicines to outpatients. Please refer to "An Overview for Outpatient Pharmacies" for more information. Additionally, any prescribers who prescribe TIRF medicines to outpatients must also be enrolled in the TIRF REMS Access program.
Overview of the TIRF REMS Access Program for Inpatient Pharmacies: Steps for Enrollment and Program Requirements
Inpatient Pharmacy Education and Enrollment
All enrollment activities can be completed at www.TIRFREMSaccess.com
Reference ID: 4146711
FDA_7345
If I have previously enrolled in an individual TIRF REMS do I need to enroll in the shared TIRF REMS Access Program? All pharmacy enrollment information was transferred from the individual TIRF REMS to the TIRF REMS Access program on March 12, 2012. Your enrollment in the shared TIRF REMS Access program allows dispensing of all TIRF medicines that are covered under the TIRF REMS Access program. The website for the shared TIRF REMS Access program can be accessed at www.TIRFREMSaccess.com.
You will be required to re-enroll in the shared TIRF REMS two (2) years after your last enrollment in an individual REMS program if you wish to continue dispensing these products. You will be notified by the TIRF REMS Access program in advance of the need to re-enroll.
The following two sections provide detailed information on the Enrollment Process (Section 1) and the Implementation Processes (Section 2) for TIRF medicines in an inpatient pharmacy.
Section 1: Enrollment Process
Summary of Enrollment
1. Select an individual to be your Authorized Inpatient Pharmacy Representative.
2. Create an account and complete registration at www.TIRFREMSaccess.com. 3. Complete the TIRF REMS Access Education Program and Knowledge
Assessment. 4. Complete and submit an Inpatient Pharmacy Enrollment form. 5. Train pharmacy staff.
Detailed Enrollment Process
Step 1: Select an individual to be your Authorized Chain Representative
· Select an authorized pharmacy representative to establish and oversee the TIRF REMS Access program requirements.
Step 2: Create an account and complete registration at www.TIRFREMSaccess.com
· Create an account at www.TIRFREMSaccess.com and then complete registration on behalf of your pharmacy.
How do I create an account and complete the TIRF REMS Access registration on-line? · Select the Create Account button on the home page · Complete the Create Account Information section · Select `No' if you have not submitted an enrollment form via fax at the
`Already enrolled via Fax and have an enrollment ID?' prompt. · Create User ID and password and select `Create My Account'
Reference ID: 4146711
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· Select `Pharmacy' as the option to best describe you and select `Continue' · Select `Inpatient Pharmacy Authorized Pharmacy Representative' · Review the content in the pop-up box and select `Confirm' to continue · Complete required fields on the Inpatient Pharmacy Registration page and
select `Submit' to continue
Step 3: Complete the TIRF REMS Access Education Program and Knowledge Assessment
How do I complete the TIRF REMS Access Education Program by fax? · Review the TIRF REMS Access Education Program. A printable version of the
TIRF REMS Access Education Program is available online at www.TIRFREMSaccess.com or by contacting the TIRF REMS Access call center at 1-866-822-1483. · Once you have reviewed the Education Program complete the Knowledge Assessment and submit by fax to 1-866-822-1487 · The TIRF REMS Access program will notify you of the status of your Knowledge Assessment via your indicated preferred method of communication (fax or e-mail)
How do I complete the TIRF REMS Access Education Program online? · Select the `Start the TIRF REMS Access Education Program' to proceed to the
training upon completion of registration · Select `Go To Knowledge Assessment' button and complete upon completion
of the Education Program · A Knowledge Assessment Confirmation Code will be provided once the
assessment is completed successfully.
Step 4: Complete and submit Inpatient Pharmacy Enrollment
· To finalize enrollment in the TIRF REMS Access program complete Inpatient Pharmacy Enrollment
· If you are unable to enroll online, please call the TIRF REMS Access program call center at 1-866-822-1483 for further assistance.
How do I complete the TIRF REMS Access Enrollment on-line? · Upon successful completion of the TIRF REMS Access Education Program and
Knowledge Assessment, you will be prompted to read the TIRF REMS Access attestation and enter your electronic signature, today's date, and check the attestation box before clicking `Submit'.
NOTE: You are required to re-enroll every two (2) years. You will be notified by the TIRF REMS Access program in advance of the need to re-enroll.
Reference ID: 4146711
FDA_7347
Section 2: Implementation Process
Summary of Implementation Process
1. Ensure appropriate patient selection and compliance with TIRF REMS Access program requirements
2. Train Pharmacy Staff
Detailed Implementation Process
Step 1: Ensure appropriate patient selection and compliance with TIRF REMS Access program requirements
· The authorized inpatient pharmacist must establish or oversee the system, order sets, protocols, and/or other measures to help ensure appropriate patient selection and compliance with the requirements of the TIRF REMS Access program.
· The authorized inpatient pharmacist must ensure the inpatient pharmacy does not sell, loan or transfer any TIRF medicines to any other pharmacy, institution, distributor, or prescriber.
· Inpatient pharmacies may not dispense TIRF medicines for outpatient use.
Step 2: Train Pharmacy Staff
· The authorized inpatient pharmacist must ensure that inpatient pharmacists and other relevant inpatient staff are educated on the risks associated with TIRF medicines and the requirements of the TIRF REMS Access program, as described in the Education Program. o Pharmacy staff can register online to access the Education Program and take the Knowledge Assessment for training purposes.
Reporting Adverse Events and Monitoring
To report any adverse events including the misuse, abuse, addiction, or overdose of TIRF medication contact:
· TIRF REMS Access program at 1-866-822-1483 and/or · FDA MedWatch program by phone at 1-800-FDA-1088 or online at
www.fda.gov/medwatch/report.htm
If you have any questions, need additional information, or need additional copies of any TIRF REMS Access documents, please visit www.TIRFREMSaccess.com, or call the TIRF REMS Access program at 1-866822-1483.
Reference ID: 4146711
FDA_7348
The Transmucosal Immediate Release Fentanyl (TIRF) REMS Access Program Independent Outpatient Pharmacy Enrollment Form
For real-time processing of enrollment, please go to www.TIRFREMSaccess.com.
To submit this form via fax, please complete all required fields below and fax pages 1, 2, 3 and 4 to 1-866-822-1487. Please note, you must review the TIRF REMS Access Education Program and successfully complete the Knowledge Assessment to complete enrollment. If you have not completed the Knowledge Assessment online, please include it with this enrollment form. You will receive enrollment confirmation via email or fax.
I understand that TIRF medicines are only available through the TIRF REMS (Risk Evaluation and Mitigation Strategy) Access program and that I must comply with the program requirements. In addition, as the designated authorized independent outpatient pharmacy representative, I acknowledge that:
1. I have reviewed the TIRF REMS Access Education Program, and I have completed the Knowledge Assessment. I understand the risks and benefits associated with TIRF medicines and the requirements of the TIRF REMS Access program for pharmacies.
2. I will ensure that all pharmacy staff who participate in dispensing TIRF medicines are educated on the risks associated with TIRF medicines and the requirements of the TIRF REMS Access program, as described in the TIRF REMS Access Education Program. This training should be documented and is subject to audit.
3. I understand that converting patients from one TIRF medicine to a different TIRF medicine must not be done on a microgram-per-microgram basis. I understand that TIRF medicines are not interchangeable with each other, regardless of route of administration, and that conversion may result in fatal overdose, unless conversion is done in accordance with labeled product-specific conversion recommendations (refer to the list of currently approved TIRF products located on the TIRF REMS Access website at www.TIRFREMSaccess.com/TirfUI/rems/products.action). Note, a branded TIRF medicine and its specific generic product(s) are interchangeable.
4. I understand that TIRF medicines are contraindicated for use in opioid non-tolerant patients. 5. I understand that the initial starting dose for TIRF medicines for all patients is the lowest dose, unless
individual product labels provide product-specific conversion recommendations, and I understand that patients must be titrated individually.
6. I understand the importance of discussing the risks and benefits of TIRF medicines with patients and their caregivers, and in particular the importance of taking the drug as prescribed, not sharing with others, and proper disposal.
7. I understand that the product-specific Medication Guide must be given to the patient or their caregiver each time a TIRF medicine is dispensed.
8. I understand that a TIRF medicine will not be dispensed without verifying through our pharmacy management system that the prescriber and pharmacy are enrolled and active, and that the patient has not been inactivated in the program.
9. I understand that ALL TIRF medicine prescriptions, regardless of the method of payment, must be processed through our pharmacy management system.
10. I understand that all dispensing locations must be enrolled in the TIRF REMS Access program to dispense TIRF medicines.
11. I understand that TIRF medicines can only be obtained from wholesalers/distributors that are enrolled in the TIRF REMS Access program.
Pharmacist Name* (please print):__________________________
Reference ID: 4146711
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12. I understand that our pharmacy will not sell, loan or transfer any TIRF medicine inventory to any other pharmacy, institution, distributor, or prescriber.
13. I understand that our pharmacy must re-enroll in the TIRF REMS Access program and successfully complete the enrollment requirements every two (2) years.
14. I understand that TIRF medicines are only available through the REMS program. I understand that the pharmacy must comply with the TIRF REMS Access program requirements for outpatient pharmacies and the terms of the agreement that follow this form.
15. I understand that differences in pharmacy software may affect automation capabilities for adjudicating prescriptions through the TIRF REMS Access program without an insurance claim (i.e.: cash claim). If insurance is not used, pharmacy staff must manually enter the REMS Cash BIN #014780 in order for the transaction to be properly adjudicated through the TIRF REMS Access program.
Please note: If you are a chain outpatient pharmacy, please complete the Chain Outpatient Pharmacy Enrollment Form which can be found on www.TIRFREMSaccess.com or call the TIRF REMS Access program at 1-866-822-1483.
Authorized Independent Outpatient Pharmacy Representative: Authorized Pharmacist Signature* _____________________________________ Date _____________
First Name* _____________________________ Phone Number* __________________________
Last Name* ___________________ Title __________ Email* ________________________________________
Independent Outpatient Pharmacy Information: Pharmacy Name*_________________________ Address* _______________________________ City* ___________________________________ State* _____________ ZIP* _______________ Phone Number* ___________________________ Fax Number* _____________________________
DEA Number* ____________________________ National Provider Identifier (NPI)* ___________ Medicaid ID _____________________________ State Issued _____________________________ NCPDP Number* _________________________
*Required Fields
Preferred Method of Communication (please select one):
Fax
Email
After submitting this form, you will receive a fax or email with instructions on how to submit test transaction(s) to the TIRF REMS Access program to ensure that your pharmacy management system has been successfully configured to allow for communication with the TIRF REMS Access program.
After successful completion of the test transaction(s) you will receive enrollment confirmation via fax or email.
For additional Medicaid IDs that you may use when dispensing TIRF medicines, please complete below:
Medicaid ID Medicaid ID Medicaid ID
State Issued State Issued State Issued Pharmacist Name* (please print):__________________________
Reference ID: 4146711
FDA_7350
If you have any questions or require additional information or further copies of any TIRF REMS Access documents, please visit either www.TIRFREMSaccess.com, or call the TIRF REMS Access program at 1-866-822-1483.
The TIRF REMS Access Program Additional Terms and Conditions Pharmacy ("Pharmacy") agrees to the following requirements, with respect to the Transmucosal Immediate Release Fentanyl (TIRF) REMS program (the "Program"), sponsored by the Transmucosal REMS Industry Group (hereinafter "TRIG" or "Program Sponsor") and supported, under the direction of TRIG by McKesson Specialty Arizona Inc and its affiliates including NDCHealth Corporation d/b/a RelayHealth ("RelayHealth") and McKesson Canada, and any other pharmacy transaction switch system (collectively, "the Providers").
Pharmacy represents that (i) it shall perform its obligations under these terms and conditions in compliance with all applicable laws and regulations, (ii) Pharmacy's participation in the Program does not conflict with its obligations under any contracts or other arrangements with any third party, and (iii) Pharmacy is authorized to submit patient information to the Providers for purposes of verifying and tracking each patient's eligibility to participate in the Program and Pharmacy authorizes Providers and Program Sponsor and their respective designees and agents to use the submitted information for such purposes.
Pharmacy agrees to the following Program Requirements: (a) If applicable, enable Pharmacy's pharmacy practice management system to support the Program, including submission of required data fields and display of Program messages; (b) Respond appropriately to Program messages and alerts in order to comply with Program requirements, including contacting the call center when an exception process occurs; (c) Report all Program Drug dispensing activity for all transmucosal immediate release fentanyl Program Drug NDC #'s. This includes any future drug deemed by FDA to be included in the TIRF REMS Access Program to Providers via submission of all billing and reversal request. Please reference the following link (www.TIRFREMSaccess.com/TirfUI/rems/pdf/NDC listing.pdf) for a detailed list of products (including their NDC numbers) available through the TIRF REMS Access program. This document is available on the Resources tab (for pharmacies and distributors) on the program website at www.TIRFREMSaccess.com.
Pharmacy acknowledges that billing request for the Program Drug will not pass to the payer, or cash prescription processor, if the prescriber, pharmacy or patient registration is not verified.
Pharmacy authorizes and directs the Providers to de-identify, in accordance with the Health Insurance Portability and Accountability Act of 1996, as amended, its historical and prospective prescriptions claims data submitted to the Providers and/or their affiliates in connection with or related to the Program on behalf of Pharmacy, and to use that de-identified data for purposes of (i) analyzing, identifying, designing and/or enabling a REMS service; (ii) developing communication documentation for such services for both Program Sponsors and Pharmacy; (iii) providing the Program Sponsors with reports and information (including any fees paid, which will be aggregated), for purposes of implementing, maintaining, supporting, monitoring or improving a Program, and (iv) any other purpose required by law. These reports may contain information aggregated by NCPDP number. Further, Pharmacy authorizes Providers to deliver all of the above enumerated data and reports otherwise to be delivered to Program Sponsor to the designee or agent of Program Sponsor. In addition, Pharmacy authorizes Program Sponsor and its contracting Providers, to receive from wholesaler(s) of the Program Drug(s) distribution and purchasing data, including 867 data, with respect to the Program Drug(s).
Pharmacy acknowledges that the FDA or Program Sponsor may mandate modification, suspension or termination of a Program. The Providers reserve the right to modify, suspend or terminate any REMS service for any reason, without liability to Switch Systems.
Pharmacist Name* (please print):__________________________
Reference ID: 4146711
FDA_7351
EXCEPT FOR PROVIDER'S FRAUD OR INTENTIONAL MISCONDUCT ARISING OUT OF THE SERVICES OR THE PROGRAM, IN NO EVENT WILL THE PROGRAM SPONSOR OR PROVIDER BE LIABLE TO PHARMACY UNDER, IN CONNECTION WITH, OR RELATED TO THE PROGRAM OR THE SERVICES FOR ANY DIRECT, SPECIAL, INCIDENTAL, INDIRECT, OR CONSEQUENTIAL DAMAGES, INCLUDING, BUT NOT LIMITED TO, LOST PROFITS OR LOSS OF GOODWILL, WHETHER BASED ON BREACH OF CONTRACT, WARRANTY, TORT, PRODUCT LIABILITY, OR OTHERWISE, AND WHETHER OR NOT PROVIDERS OR PROGRAM SPONSOR HAS BEEN ADVISED OF THE POSSIBILITY OF SUCH DAMAGE.
To the extent any of these terms and conditions conflict with any other written agreement between the parties with respect to the Program, the terms and conditions of such other written agreement shall prevail.
Pharmacist Name* (please print):__________________________
Reference ID: 4146711
FDA_7352
The Transmucosal Immediate Release Fentanyl (TIRF) REMS Access Program Chain Outpatient Pharmacy Enrollment Form
For real-time processing of enrollment, please go to www.TIRFREMSaccess.com.
To submit this form via fax, please complete all required fields below and fax pages 1, 2, 3, 4 and 5 to 1-866-822-1487. Please note, you must review the TIRF REMS Access Education Program and successfully complete the Knowledge Assessment to complete enrollment. If you have not completed the Knowledge Assessment online, please include it with this enrollment form. You will receive enrollment confirmation via email or fax.
I understand that TIRF medicines are only available through the TIRF REMS (Risk Evaluation and Mitigation Strategy) Access program and that I must comply with the program requirements. In addition, as the designated authorized chain outpatient pharmacy representative, I acknowledge that:
1. I have reviewed the TIRF REMS Access Education Program, and I have completed the Knowledge Assessment. I understand the risks and benefits associated with TIRF medicines and the requirements of the TIRF REMS Access program for pharmacies.
2. I will ensure that all pharmacy staff who participate in dispensing TIRF medicines are educated on the risks associated with TIRF medicines and the requirements of the TIRF REMS Access program, as described in the Education Program. This training should be documented and is subject to audit.
3. I understand that converting patients from one TIRF medicine to a different TIRF medicine must not be done on a microgram-per-microgram basis. I understand that TIRF medicines are not interchangeable with each other, regardless of route of administration, and that conversion may result in fatal overdose, unless conversion is done in accordance with labeled product-specific conversion recommendations (refer to the list of currently approved TIRF products located on the TIRF REMS Access website at www.TIRFREMSaccess.com/TirfUI/rems/products.action). Note, a branded TIRF medicine and its specific generic product(s) are interchangeable.
4. I understand that TIRF medicines are contraindicated for use in opioid non-tolerant patients. 5. I understand that the initial starting dose for TIRF medicines for all patients is the lowest dose, unless
individual product labels provide product-specific conversion recommendations, and I understand that patients must be titrated individually.
6. I understand the importance of discussing the risks and benefits of TIRF medicines with patients and their caregivers, and in particular the importance of taking the drug as prescribed, not sharing with others, and proper disposal.
7. I understand that the product-specific Medication Guide must be given to the patient or their caregiver each time a TIRF medicine is dispensed.
8. I understand that a TIRF medicine will not be dispensed without verifying through our pharmacy management system that the prescriber and pharmacy are enrolled and active, and that the patient has not been inactivated in the program.
9. I understand that ALL TIRF medicine prescriptions, regardless of the method of payment, must be processed through our pharmacy management system.
10. I understand that all dispensing locations must be enrolled in the TIRF REMS Access program to dispense TIRF medicines.
11. I understand that TIRF medicines can only be obtained from wholesalers/distributors that are enrolled in the TIRF REMS Access program.
12. I understand that our pharmacy will not sell, loan or transfer TIRF medicine inventory to any other pharmacy, institution, distributor, or prescriber.
Chain ID*:________________________
Reference ID: 4146711
FDA_7353
13. I understand that our pharmacy must re-enroll in the TIRF REMS Access program and successfully complete the enrollment requirements every two (2) years.
14. I understand that TIRF medicines are only available through the REMS program. I understand that the pharmacy must comply with the TIRF REMS Access program requirements for outpatient pharmacies and the terms of the agreement that follow this form.
15. I understand that differences in pharmacy software may affect automation capabilities for adjudicating prescriptions through the TIRF REMS Access program without an insurance claim (i.e.: cash claim). If insurance is not used, pharmacy staff must manually enter the REMS Cash BIN #014780 or the designated chain pharmacy cash bin in order for the transaction to be properly adjudicated through the TIRF REMS Access program.
Authorized Chain Outpatient Pharmacy Representative:
Authorized Pharmacy Representative Signature* _________________________ Date _____________
First Name* _____________________________ Phone Number* __________________________
Last Name* ___________________ Title ______ Email* ____________________________________
Chain Outpatient Pharmacy Information: Pharmacy Name*_________________________ Address* _______________________________ City* ___________________________________ State* _____________ ZIP* _______________
Chain ID* ________________________________ Phone Number* __________________________ Fax Number* _____________________________
*Required Fields
Preferred Method of Communication (please select one):
Fax
Email
After submitting this form, you will receive a fax or email with instructions on how to submit test transaction(s) to the TIRF REMS Access program to ensure that your pharmacy management system has been successfully configured to allow for communication with the TIRF REMS Access program.
After successful completion of the test transaction(s) you will receive enrollment confirmation via fax or email.
Pharmacy sites that have been trained can then be updated to an enrolled status through the Chain Outpatient Pharmacy Dashboard which will list all chain stores at www.TIRFREMSaccess.com
Chain ID*:________________________
Reference ID: 4146711
FDA_7354
The following pharmacy information will need to be provided for each trained pharmacy site.
Pharmacy Information: Pharmacy Name*_________________________ Address* _______________________________ City* ___________________________________ State* _____________ ZIP ________________ Phone Number* ___________________________ Fax Number* _____________________________
DEA Number* ____________________________ National Provider Identifier (NPI)* ___________ Medicaid ID _____________________________ State Issued _____________________________ NCPDP Number* _________________________ Store Number* ___________________________
*Required Fields
Chain ID*:
If you have any questions or require additional information or further copies of any TIRF REMS Access documents, please visit either www.TIRFREMSaccess.com, or call the TIRF REMS Access program at 1-866-822-1483.
Reference ID: 4146711
Chain ID*:________________________ FDA_7355
The TIRF REMS Access Program Additional Terms and Conditions Pharmacy ("Pharmacy") agrees to the following requirements, with respect to the Transmucosal Immediate Release Fentanyl (TIRF) REMS program (the "Program"), sponsored by the Transmucosal REMS Industry Group (hereinafter "TRIG" or "Program Sponsor") and supported, under the direction of TRIG by McKesson Specialty Arizona Inc and its affiliates including NDCHealth Corporation d/b/a RelayHealth ("RelayHealth") and McKesson Canada, and any other pharmacy transaction switch system (collectively, "the Providers").
Pharmacy represents that (i) it shall perform its obligations under these terms and conditions in compliance with all applicable laws and regulations, (ii) Pharmacy's participation in the Program does not conflict with its obligations under any contracts or other arrangements with any third party, and (iii) Pharmacy is authorized to submit patient information to the Providers for purposes of verifying and tracking each patient's eligibility to participate in the Program and Pharmacy authorizes Providers and Program Sponsor and their respective designees and agents to use the submitted information for such purposes.
Pharmacy agrees to the following Program Requirements: (a) If applicable, enable Pharmacy's pharmacy practice management system to support the Program, including submission of required data fields and display of Program messages; (b) Respond appropriately to Program messages and alerts in order to comply with Program requirements, including contacting the call center when an exception process occurs; (c) Report all Program Drug dispensing activity for all transmucosal immediate release fentanyl Program Drug NDC #'s. This includes any future drug deemed by FDA to be included in the TIRF REMS Access Program to Providers via submission of all billing and reversal request. Please reference the following link (www.TIRFREMSaccess.com/TirfUI/rems/pdf/NDC listing.pdf) for a detailed list of products (including their NDC numbers) available through the TIRF REMS Access program. This document is available on the Resources tab (for pharmacies and distributors) on the program website at www.TIRFREMSaccess.com.
Pharmacy acknowledges that billing request for the Program Drug will not pass to the payer, or cash prescription processor, if the prescriber, pharmacy or patient registration is not verified.
Pharmacy authorizes and directs the Providers to de-identify, in accordance with the Health Insurance Portability and Accountability Act of 1996, as amended, its historical and prospective prescriptions claims data submitted to the Providers and/or their affiliates in connection with or related to the Program on behalf of Pharmacy, and to use that de-identified data for purposes of (i) analyzing, identifying, designing and/or enabling a REMS service; (ii) developing communication documentation for such services for both Program Sponsors and Pharmacy; (iii) providing the Program Sponsors with reports and information (including any fees paid, which will be aggregated), for purposes of implementing, maintaining, supporting, monitoring or improving a Program, and (iv) any other purpose required by law. These reports may contain information aggregated by NCPDP number. Further, Pharmacy authorizes Providers to deliver all of the above enumerated data and reports otherwise to be delivered to Program Sponsor to the designee or agent of Program Sponsor.
In addition, Pharmacy authorizes Program Sponsor and its contracting Providers, to receive from wholesaler(s) of the Program Drug(s) distribution and purchasing data, including 867 data, with respect to the Program Drug(s).
Pharmacy acknowledges that the FDA or Program Sponsor may mandate modification, suspension or termination of a Program. The Providers reserve the right to modify, suspend or terminate any REMS service for any reason, without liability to Switch Systems.
Chain ID*:________________________
Reference ID: 4146711
FDA_7356
EXCEPT FOR PROVIDER'S FRAUD OR INTENTIONAL MISCONDUCT ARISING OUT OF THE SERVICES OR THE PROGRAM, IN NO EVENT WILL THE PROGRAM SPONSOR OR PROVIDER BE LIABLE TO PHARMACY UNDER, IN CONNECTION WITH, OR RELATED TO THE PROGRAM OR THE SERVICES FOR ANY DIRECT, SPECIAL, INCIDENTAL, INDIRECT, OR CONSEQUENTIAL DAMAGES, INCLUDING, BUT NOT LIMITED TO, LOST PROFITS OR LOSS OF GOODWILL, WHETHER BASED ON BREACH OF CONTRACT, WARRANTY, TORT, PRODUCT LIABILITY, OR OTHERWISE, AND WHETHER OR NOT PROVIDERS OR PROGRAM SPONSOR HAS BEEN ADVISED OF THE POSSIBILITY OF SUCH DAMAGE.
To the extent any of these terms and conditions conflict with any other written agreement between the parties with respect to the Program, the terms and conditions of such other written agreement shall prevail.
Reference ID: 4146711
Chain ID*:________________________ FDA_7357
The Transmucosal Immediate Release Fentanyl (TIRF) REMS Access Program Closed System Outpatient Pharmacy Enrollment Form
To enroll in TIRF REMS Access, please complete all required fields below and fax pages 1 and 2 to 1-866-822-1487. You may also scan the completed form and email to: information@TIRFREMSAccess.com. Please note, you must review the TIRF REMS Access Education Program and successfully complete the Knowledge Assessment to complete enrollment. If you have not completed the Knowledge Assessment online, please include it with this enrollment form. You will receive enrollment confirmation via email or fax.
I understand that TIRF medicines are only available through the TIRF REMS (Risk Evaluation and Mitigation Strategy) Access program and that I must comply with the program requirements. In addition, as the designated authorized closed system outpatient pharmacy representative, I acknowledge that:
1. I have reviewed the TIRF REMS Access Education Program, and I have completed the Knowledge Assessment. I understand the risks and benefits associated with TIRF medicines and the requirements of the TIRF REMS Access program for pharmacies.
2. I will ensure that all pharmacy staff who participate in dispensing TIRF medicines are educated on the risks associated with TIRF medicines and the requirements of the TIRF REMS Access program, as described in the TIRF REMS Access Education Program. This training should be documented and is subject to audit.
3. I understand that converting patients from one TIRF medicine to a different TIRF medicine must not be done on a microgram-per-microgram basis. I understand that TIRF medicines are not interchangeable with each other, regardless of route of administration, and that conversion may result in fatal overdose, unless conversion is done in accordance with labeled product-specific conversion recommendations (refer to the list of currently approved TIRF products located on the TIRF REMS Access website at www.TIRFREMSaccess.com/TirfUI/rems/products.action). Note, a branded TIRF medicine and its specific generic product(s) are interchangeable.
4. I understand that TIRF medicines are contraindicated for use in opioid non-tolerant patients. 5. I understand that the initial starting dose for TIRF medicines for all patients is the lowest dose, unless
individual product labels provide product-specific conversion recommendations, and I understand that patients must be titrated individually.
6. I understand the importance of discussing the risks and benefits of TIRF medicines with patients and their caregivers, and in particular the importance of taking the drug as prescribed, not sharing with others, and proper disposal.
7. I understand that the product-specific Medication Guide must be given to the patient or their caregiver each time a TIRF medicine is dispensed.
8. I understand that a TIRF medicine will not be dispensed without obtaining a TIRF REMS Access prescription authorization number issued by the TIRF REMS Access program prior to dispensing the prescription. A TIRF REMS Access prescription authorization number verifies that the prescriber and pharmacy are enrolled and active, and that the patient has not been inactivated in the program.
9. I understand that all dispensing locations must be enrolled in the TIRF REMS Access program to dispense TIRF medicines.
10. I understand that TIRF medicines can only be obtained from wholesalers/distributors that are enrolled in the TIRF REMS Access program.
11. I understand that our pharmacy will not sell, loan or transfer TIRF medicine inventory to any other pharmacy, institution, distributor, or prescriber.
12. I understand that our pharmacy must re-enroll in the TIRF REMS Access program and successfully complete the enrollment requirements every two (2) years.
Closed System Chain ID*:
Reference ID: 4146711
FDA_7358
13. I understand that TIRF medicines are only available through the REMS program. I understand that the pharmacy must comply with the TIRF REMS Access program requirements for outpatient closed system pharmacies.
Authorized Closed System Outpatient Pharmacy Representative:
Authorized Pharmacy Representative Signature* _________________________ Date _____________
First Name* _____________________________ Phone Number* __________________________
Last Name* ___________________ Title ______ Email* ____________________________________
Closed System Outpatient Pharmacy Information:
Pharmacy Name*_________________________ Address* _______________________________ City* ___________________________________
Closed System Chain ID*___________________ Phone Number* __________________________ Fax Number* _____________________________
State* _____________ ZIP* _______________
*Required Fields
Preferred Method of Communication (please select one):
Fax
Email
After submitting this form, you will receive a fax or email with your enrollment confirmation and instructions on how your pharmacy staff can complete the training process and how your closed system outpatient pharmacy dispensing locations may obtain a TIRF REMS Access Prescription Authorization.
If you have any questions or require additional information or further copies of any TIRF REMS Access documents, please visit either www.TIRFREMSaccess.com, or call the TIRF REMS Access program at 1-866-822-1483.
Reference ID: 4146711
Closed System Chain ID*:________________________ FDA_7359
The Transmucosal Immediate Release Fentanyl (TIRF) REMS Access Program
Inpatient Pharmacy Enrollment Form (e.g. hospitals, in-hospital hospices, and long-term care facilities that dispense for inpatient use)
For real-time processing of enrollment, please go to www.TIRFREMSaccess.com.
To submit this form via fax, please complete all required fields below and fax pages 1 and 2 to 1-866-822-1487. Please note, you must review the TIRF REMS Access Education Program and successfully complete the Knowledge Assessment to complete enrollment. If you have not completed the Knowledge Assessment online, please include it with this enrollment form. You will receive enrollment confirmation via email or fax.
I understand that TIRF medicines are only available through the TIRF REMS (Risk Evaluation and Mitigation Strategy) Access program and that I must comply with the program requirements. In addition, as the designated authorized inpatient pharmacist, I acknowledge that:
1. I have reviewed the TIRF REMS Access Education Program, and I have completed the Knowledge Assessment. I understand the benefits and risks associated with TIRF medicines and the requirements of the TIRF REMS Access program for pharmacies.
2. I will ensure that our inpatient pharmacists are educated on the risks associated with TIRF medicines and the requirements of the TIRF REMS Access program, as described in the TIRF REMS Access Education Program.
3. I understand that converting patients from one TIRF medicine to a different TIRF medicine must not be done on a microgram-per-microgram basis. I understand that TIRF medicines are not interchangeable with each other, regardless of route of administration, and that conversion may result in fatal overdose, unless conversion is done in accordance with labeled product specific conversion recommendations (refer to the list of currently approved TIRF products located on the TIRF REMS Access website at www.TIRFREMSaccess.com/TirfUI/rems/products.action. Note, a branded TIRF medicine and its specific generic product(s) are interchangeable.
4. I understand that TIRF medicines are contraindicated for use in opioid non-tolerant patients. 5. I understand that the initial starting dose for TIRF medicines for all patients is the lowest dose, unless individual
product labels provide product-specific conversion recommendations, and I understand that patients must be titrated individually. 6. I understand that pharmacies within or associated with the healthcare facility that dispense to outpatients must be separately enrolled in and comply with the TIRF REMS Access program to dispense TIRF medicines to outpatients. 7. I understand that our inpatient pharmacy must not dispense TIRF medicines for outpatient use. 8. I understand that a prescriber who wants to discharge a patient with a TIRF medicine prescription, intended to be dispensed by an outpatient pharmacy, will be required to enroll in the TIRF REMS Access program. 9. I will establish, or oversee the establishment of, a system, order sets, protocols and/or other measures to help ensure appropriate patient selection and compliance with the requirements of the TIRF REMS Access program. 10. I understand that our pharmacy will not sell, loan or transfer any TIRF medicine inventory to any other pharmacy, institution, distributor, or prescriber. 11. I understand that TIRF medicines can only be obtained from wholesalers/distributors that are enrolled in the TIRF REMS Access program. 12. I understand that our pharmacy must re-enroll in the TIRF REMS Access program every two (2) years. 13. I understand that TIRF medicines are available only through the TIRF REMS Access program. I understand and agree to comply with the TIRF REMS Access program requirements for inpatient pharmacies.
Pharmacist Name* (please print):
Reference ID: 4146711
FDA_7360
Authorized Inpatient Pharmacist Signature* _______________________________ First Name* ______________________________ Phone Number* __________________________
*Required Fields
Inpatient Pharmacy Information Pharmacy Name* _________________________ Address* ________________________________ City* ____________________________________ State*______________ ZIP* ______________
*Required Fields
Date ____________________________________ Last Name* _______________ Title ________ Email* ___________________________________
DEA Number* ____________________________ Pharmacy License Number* ________________ Phone Number* ___________________________ Fax Number* _____________________________
Preferred Method of Communication (please select one):
Fax
Email
If you have any questions or require additional information or further copies of any TIRF REMS Access documents, please visit either www.TIRFREMSaccess.com, or call the TIRF REMS Access program at 1-866-822-1483.
Pharmacist Name* (please print):__________________________
Reference ID: 4146711
FDA_7361
This letter ceased distribution in November 2013.
Subject:
Important Drug Warning Announcement of a single shared REMS (Risk Evaluation and Mitigation Strategy) program for all Transmucosal Immediate Release Fentanyl (TIRF) products due to the potential risk of misuse, abuse, addiction, overdose and serious complications due to medication errors
The TIRF REMS Access program is a Food and Drug Administration (FDA) required risk management program
Dear Outpatient Pharmacy:
The purpose of this letter is to make you aware of a change from individual REMS programs to a shared REMS program (the TIRF REMS Access program) and to provide guidance on enrollment into the new shared REMS program beginning mm/dd/yyyy. The individual REMS programs are being converted to the TIRF REMS Access program to reduce the burden on the healthcare providers and the healthcare system of having multiple individual programs. The products covered under this new program include:
· Abstral® (fentanyl) sublingual tablets · Actiq® (fentanyl citrate) oral transmucosal lozenge · Fentora® (fentanyl citrate) buccal tablet · Lazanda® (fentanyl) nasal spray · Onsolis® (fentanyl buccal soluble film)
· Approved generic equivalents of these products are also covered under this program
This new shared program replaces the individual product REMS that were previously available, and any prescribers, pharmacies, patients and distributors enrolled in these programs will be automatically transitioned to the new shared REMS. Outpatient pharmacies from individual product REMS will be automatically transitioned to the new shared REMS, beginning mm/dd/yyyy, but will need to agree to shared program terms and conditions before they can order and dispense all TIRF medicines. If you have not enrolled in one or more of these individual REMS programs and, if any of these products are dispensed for outpatient use in your pharmacy, you must enroll your pharmacy in the shared TIRF REMS Access program.
Outpatient Pharmacy Action:
Option 1: If you are already enrolled in at least one individual REMS program · Your enrollment information will be automatically entered into the new shared TIRF REMS
Access program, but you will need to agree to the shared program terms and conditions before you can order and dispense all TIRF medicines. Your enrollment in the shared TIRF REMS Access program allows dispensing of all TIRF medicines that are covered under the TIRF REMS Access program. The website for the shared TIRF REMS Access program can be accessed at www.TIRFREMSaccess.com.
Once the program is available, you will have six months to agree to the shared program terms and conditions. Until you agree to the shared program terms and conditions, you will be able to dispense those TIRF medicines with an individual REMS program, in which you were previously enrolled. However, if you do not agree to the shared program terms and conditions within six months, you will no longer be able to order or dispense any TIRF medicine.
· You can use your existing secure user ID and password from any one of your individual REMS programs to access the TIRF REMS Access website at www.TIRFREMSaccess.com.
Reference ID: 4146711
FDA_7362
The user ID and password you use to initially log on will become your permanent user ID and password for the shared TIRF REMS Access program.
· Once you have logged in, review your account information and make any necessary updates. You are required to agree to the shared program terms and conditions to complete enrollment for the new shared program.
· You will be required to re-enroll in the shared TIRF REMS two (2) years after your last enrollment in an individual REMS program if you wish to continue dispensing these products. You will be notified by the TIRF REMS Access program in advance of the need to re-enroll.
Option 2: If you do not have an existing enrollment in any individual REMS program · Select an authorized pharmacy representative to establish and oversee the TIRF REMS Access program requirements. · Access the TIRF REMS Access program at www.TIRFREMSaccess.com to create an account. · Review the TIRF REMS Access Education Program materials available at www.TIRFREMSaccess.com and successfully complete the Knowledge Assessment. · Enable the pharmacy management system to support communication with the TIRF REMS Access program, using established telecommunication standards, and run the standardized validation test transactions to validate the system enhancements. · Enroll in the TIRF REMS Access program by completing the Outpatient Pharmacy Enrollment Form and re-enroll every two (2) years. You will be notified by the TIRF REMS Access program in advance of the need to re-enroll. · If you are unable to enroll online, please call the TIRF REMS Access program call center at 1-866-822-1483 for further assistance.
The goals of the TIRF REMS Access program are to mitigate the risk of misuse, abuse, addiction, overdose and serious complications due to medication errors by:
1. Prescribing and dispensing TIRF medicines only to appropriate patients, which includes use only in opioid-tolerant patients.
2. Preventing inappropriate conversion between fentanyl products. 3. Preventing accidental exposure to children and others for whom it was not prescribed. 4. Educating prescribers, pharmacists, and patients on the potential for misuse, abuse,
addiction, and overdose of TIRF medicines
TIRF medicines are opioid analgesics indicated only for the management of breakthrough pain in cancer patients 18 years of age and older (16 years of age and older for Actiq® brand and generic equivalents) who are already receiving and who are tolerant to around-the-clock opioid therapy for their underlying persistent pain.
Patients considered opioid-tolerant are those who are regularly taking at least 60 mg oral morphine/day, or at least 25 micrograms transdermal fentanyl/hour, or at least 30 mg of oral oxycodone/day, or at least 8 mg oral hydromorphone/day, or at least 25 mg oral oxymorphone/day or an equianalgesic dose of another opioid for one week or longer.
To help you understand the TIRF REMS Access program the following program materials are available at www.TIRFREMSaccess.com or can be ordered by calling 1-866-822-1483: · Overview for Outpatient Pharmacies · TIRF REMS Access Education Program · Knowledge Assessment · Frequently Asked Questions
Reference ID: 4146711
FDA_7363
· Outpatient Pharmacy Enrollment Form · Full Prescribing Information and Medication Guides for each TIRF medicine
Inpatient pharmacies have different REMS requirements. Please see the TIRF REMS Access program - An Overview for Inpatient Pharmacies available at www.TIRFREMSaccess.com.
To access the above information and to enroll in the TIRF REMS Access program, visit www.TIRFREMSaccess.com or call 1-866-822-1483 to have enrollment materials sent to you.
Reference ID: 4146711
FDA_7364
Selected Important Safety Information
IMPORTANCE OF PROPER PATIENT SELECTION, DOSING, and POTENTIAL FOR ABUSE
TIRF medicines contain fentanyl, an opioid agonist and a Schedule II controlled substance, with an abuse liability similar to other opioid analgesics. TIRF medicines can be abused in a manner similar to other opioid agonists, legal or illicit. Consider the potential for abuse when prescribing or dispensing TIRF medicines in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse or diversion. Schedule II opioid substances which include morphine, oxycodone, hydromorphone, oxymorphone, and methadone have the highest potential for abuse and risk of fatal overdose due to respiratory depression.
Serious adverse events, including deaths, in patients treated with some oral transmucosal fentanyl medicines have been reported. Deaths occurred as a result of improper patient selection (e.g., use in opioid non-tolerant patients) and/or improper dosing. The substitution of a TIRF medicine for any other fentanyl medicine, including another TIRF medicine, may result in fatal overdose.
TIRF medicines are indicated only for the management of breakthrough pain in adult cancer patients 18 years of age and older (16 years of age and older for Actiq® brand and generic equivalents) who are already receiving and who are tolerant to around-the-clock opioid therapy for their underlying persistent cancer pain. Patients considered opioid-tolerant are those who are taking:
· at least 60 mg of oral morphine/daily · at least 25 mcg transdermal fentanyl/hour · at least 30 mg of oral oxycodone daily · at least 8 mg oral hydromorphone daily · at least 25 mg oral oxymorphone daily · or an equianalgesic dose of another opioid daily for a week or longer.
TIRF medicines are contraindicated in opioid non-tolerant patients and are contraindicated in the management of acute or postoperative pain, including headache/migraine and dental pain, or use in the emergency room. Please see the individual medicine prescribing information for a full list of specific situations in which TIRF medicines are not indicated or are contraindicated. Lifethreatening respiratory depression could occur at any dose in opioid non-tolerant patients. Deaths have occurred in opioid non-tolerant patients treated with some TIRF medicines.
When prescribing, do not convert patients on a mcg per mcg basis from another fentanyl medicine to a TIRF medicine, except for substitutions between a branded TIRF medicine and its generic equivalent. Patients beginning treatment with TIRF medicines must begin with titration from the lowest available dose for that specific medicine. Carefully consult the Initial Dosing Instructions in the TIRF medicine-specific Full Prescribing Information.
When dispensing, TIRF medicines are not interchangeable with each other, regardless of route of administration. Differences exist in the pharmacokinetics of TIRF medicines resulting in
Reference ID: 4146711
FDA_7365
clinically important differences in the amount of fentanyl absorbed that could cause a fatal overdose. Converting patients from one TIRF medicine to a different TIRF medicine must not be done on a microgram-per-microgram basis, and must be titrated according to the labeled dosing instructions each time they begin use of a new TIRF medicine. The only exception is for substitution between a branded TIRF medicine and its specific generic equivalent.
Special care must be used when dosing TIRF medicines. Refer to the Full Prescribing Information for the individual TIRF medicine for guidance on the maximum number of doses that can be taken per breakthrough pain episode and the time that patients must wait before treating another episode of breakthrough pain with the TIRF medicine.
TIRF medicines are intended to be used only in the care of opioid-tolerant cancer patients and only by healthcare professionals who are knowledgeable of, and skilled in, the use of Schedule II opioids to treat cancer pain.
Patients and their caregivers must be instructed that TIRF medicines contain a medicine in an amount which can be fatal in children, in individuals for whom it is not prescribed, and in those who are not opioid-tolerant. All medicines must be kept out of the reach of children.
The concomitant use of TIRF medicines with cytochrome P450 3A4 inhibitors may result in an increase in fentanyl plasma concentrations, and may cause potentially fatal respiratory depression.
Adverse Reactions The most commonly observed adverse reactions with TIRF medicines include typical opioid adverse reactions, such as nausea, vomiting, constipation, somnolence, dizziness, and headache. Refer to individual medicine prescribing information for all adverse reactions. Expect opioid side effects and manage them accordingly.
Please see the individual Full Prescribing Information for each TIRF medicine for all information including boxed warnings, and Medication Guide for important safety information for each TIRF medicine.
Adverse Event Reporting
Promptly report suspected adverse events including misuse, abuse, addiction and overdoses directly to the TIRF REMS Access program at 1-866-822-1483. You also may report adverse event information to the FDA MedWatch Reporting System by telephone at 1-800-FDA-1088 or by mail using Form 3500, available at www.fda.gov/medwatch.
Medication Guide It is important that you discuss the risks of TIRF medicines with your patients and encourage them to read the relevant Medication Guide. The Medication Guide provides important information on the safe and effective use of TIRF medicines and you will need to review the appropriate Medication Guide for the TIRF medicine you prescribe/dispense to your patient. Patients should be counseled on the need to store TIRF medicines safely out of the reach of children and other persons for whom the medicine is not prescribed.
Reference ID: 4146711
FDA_7366
Provide your patient with a copy of the appropriate Medication Guide for the TIRF medicine you prescribe. Medication Guides will be provided to you by the manufacturers of individual TIRF medicines. If you require additional Medication Guides you can:
· Print copies from the TIRF REMS Access program website at www.TIRFREMSaccess.com.
· Contact the TIRF REMS Access program at 1-866-822-1483.
Sincerely,
TIRF REMS Access Industry Group
Reference ID: 4146711
FDA_7367
Attachment 1:
List of TIRF Medicines Available Only through the TIRF REMS Access Program
ABSTRAL® (fentanyl) sublingual tablets ACTIQ® (fentanyl citrate) oral transmucosal lozenge FENTORA® (fentanyl citrate) buccal tablet LAZANDA® (fentanyl) nasal spray ONSOLIS® (fentanyl buccal soluble film) Approved generic equivalents of these products are also covered under this program.
Reference ID: 4146711
FDA_7368
Attachment 2
Standardized validation test transaction required to validate pharmacy system enhancements
Participating pharmacies must demonstrate that their pharmacy management system can receive and display program reject codes and messages. The software certification process requires the pharmacy to submit several test transactions via their pharmacy management system.
Pharmacies will not be able to successfully process transactions for TIRF medicines through the pharmacy management system until these system changes have been implemented.
Test Transaction Flow
TEST #1 REQUIRED DATA FIELDS PHARMACY SUBMITS THE REQUIRED DATA FIELDS: ° Submits a prescription billing request to RelayHealth BIN # 014780, PCN REMS with the following data fields populated; · Patient First Name................................... TIRFREMSTEST · Patient Last Name.................................... Smithers · Date of Birth............................................. 19841105 · Patient ZIP/Postal Zone........................... 07921 · Drug Name............................................... TIRFPRODUCT 100 mcg NDC # 42747-0221-32 · Quantity Dispensed.................................. 12 · Days Supply............................................. 4 · Prescriber ID............................................. BA1111119 · Prescriber Last Name.............................. REMSTEST
· Test #1 Response ° A Successful Expected Response will look like this: ° Transaction Response Status.................. "R" (Rejected) ° Reject Code.............................................. "NN" ° Additional Message Information: *REMS* This is certification test message # 1 for TIRF REMS. Resubmit this transaction with the following value in the in the Intermediary Authorization ID or Patient ID field [NNNNNNNNNN]
° Next Step Proceed to Test #2 ° An Unsuccessful Response will look like this: ° Transaction Response Status.................. "R" (Rejected) ° Reject Code.............................................. "Will vary based upon missing/invalid required field" ° Additional Message Information: Missing/ Invalid [field]
° Next Step Call your software vendor and provide the vendor the field provided in the reject message, request the vendor to enable the submission of that field in your pharmacy management system. Once, this has been resolved Test 1 needs to be resubmitted.
Reference ID: 4146711
FDA_7369
TEST #2 RE-SUBMIT CLAIM WITH OVER-RIDE PROVIDED PHARMACY RE-SUBMITS CLAIM WITH OVERRIDE PROVIDED FROM TEST #1. ° Receives and reviews the prescription billing request reject code and message for override value ° Inputs the identified code value provided in the reject message: ° Intermediary Authorization ID, or ° Patient ID ° Resubmits the prescription billing request.
· Test #2 Response ° A Successful Expected Response will look like this: ° Transaction Response Status.................. "P" (Paid) ° Additional Message Information: *REMS* This is certification test message # 2 for TIRF REMS. Submit a reversal request for this prescription to complete TIRF REMS certification testing
° Next Step Proceed to Test #3 ° An Unsuccessful Response will look like this: ° Transaction Response Status.................. "R" (Rejected) ° Reject Code.............................................. "Will vary based upon missing/invalid required field" ° Additional Message Information: Missing/ Invalid [field]
° Next Step Call your software vendor and request the vendor enable the submission of either the Patient ID or Intermediary Authorization ID field in your pharmacy management system. TEST #3 REVERSE CLAIM- PHARMACY SUBMITS ° Receives and reviews the prescription billing request and message ° Submits the prescription reversal request for the previously approved billing request.
· Test #3 Expected Response ° A Successful Expected Response will look like this: ° Transaction Response Status = "A" (Approved) ° Additional Message Information: *REMS* This is certification test message # 3 for TIRF REMS. TIRF REMS certification testing for NCPDP Telecommunication Standard is complete.
° Next Step Vendor Verification Test complete. ° An Unsuccessful Response will look like this: ° Transaction Response Status.................. "R" (Rejected) ° Reject Code.............................................. "NN" ° Additional Message Information: "Invalid test transaction sequence"
Reference ID: 4146711
FDA_7370
This letter ceased distribution in November 2013.
Subject:
Important Drug Warning Announcement of a single shared REMS (Risk Evaluation and Mitigation Strategy) program for all Transmucosal Immediate Release Fentanyl (TIRF) products due to the potential risk of misuse, abuse, addiction, overdose and serious complications due to medication errors
The TIRF REMS Access program is a Food and Drug Administration (FDA) required risk management program
Dear Inpatient Pharmacy:
The purpose of this letter is to make you aware of a change from individual REMS programs to a shared REMS program (the TIRF REMS Access program) and to provide guidance on enrollment into the new shared REMS program beginning mm/dd/yyyy. The individual REMS programs are being converted to the TIRF REMS Access program to reduce the burden on the healthcare providers and the healthcare system of having multiple individual programs. The products covered under this new program include:
· Abstral® (fentanyl) sublingual tablets · Actiq® (fentanyl citrate) oral transmucosal lozenge · Fentora® (fentanyl citrate) buccal tablet · Lazanda® (fentanyl) nasal spray · Onsolis® (fentanyl buccal soluble film)
· Approved generic equivalents of these products are also covered under this program
This new shared program replaces the individual product REMS that were previously available. Any prescribers, pharmacies, patients and distributors enrolled in these programs will be automatically transitioned to the new shared TIRF REMS Access program beginning mm/dd/yyyy. If you have not enrolled in one or more of these individual REMS programs, and if any of these products are prescribed and dispensed in your healthcare facility (e.g., hospitals, inhospital hospices, and long-term care facilities that dispense for inpatient use), you must enroll your inpatient pharmacy in the shared TIRF REMS Access program.
For inpatient administration of these products, patient and prescriber enrollment in the TIRF REMS Access program is not required.
Inpatient Pharmacy Action:
Option 1: If you are already enrolled in at least one individual REMS program · Your enrollment information will be automatically entered into the new shared TIRF REMS Access program. Your enrollment in the shared TIRF REMS Access program allows dispensing of all TIRF medicines that are covered under the TIRF REMS Access program. The website for the shared TIRF REMS Access program can be accessed at www.TIRFREMSAccess.com. · You can use your existing secure user ID and password from any one of your individual REMS programs to access the TIRF REMS Access website at www.TIRFREMSaccess.com. The user ID and password you use to initially log on will become your permanent user ID and password for the shared TIRF REMS Access program.
Reference ID: 4146711
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· The TIRF REMS Education Program is also available on the shared TIRF REMS Access website. Alternatively, you can request this information by calling 1-866-822-1483.
· You will be required to re-enroll in the shared TIRF REMS two (2) years after your last enrollment in an individual REMS program if you wish to continue dispensing these products. You will be notified by the TIRF REMS Access program in advance of the need to re-enroll.
Option 2: If you do not have an existing enrollment in any individual REMS program · Select an authorized pharmacist to establish and oversee the TIRF REMS Access program requirements. · Access the TIRF REMS Access program at www.TIRFREMSaccess.com to create an account. · Review the TIRF REMS Access Education Program materials available at www.TIRFREMSaccess.com and successfully complete the Knowledge Assessment. · Enroll in the TIRF REMS Access program by completing the Inpatient Pharmacy Enrollment Form and re-enroll every two (2) years. You will be notified by the TIRF REMS Access program in advance of the need to re-enroll. · If you are unable to enroll online, please call the TIRF REMS Access program call center at 1-866-822-1483 for further assistance.
The goals of the TIRF REMS Access program are to mitigate the risk of misuse, abuse, addiction, overdose and serious complications due to medication errors by:
1. Prescribing and dispensing TIRF medicines only to appropriate patients, which includes use only in opioid-tolerant patients.
2. Preventing inappropriate conversion between fentanyl products. 3. Preventing accidental exposure to children and others for whom it was not prescribed. 4. Educating prescribers, pharmacists, and patients on the potential for misuse, abuse,
addiction, and overdose of TIRF medicines.
TIRF medicines are opioid analgesics indicated only for the management of breakthrough pain in cancer patients 18 years of age and older (16 years of age and older for Actiq® brand and generic equivalents) who are already receiving and who are tolerant to around-the-clock opioid therapy for their underlying persistent cancer pain, unless otherwise indicated in the product label.
Patients considered opioid-tolerant are those who are regularly taking at least 60 mg oral morphine/day, or at least 25 micrograms transdermal fentanyl/hour, or at least 30 mg of oral oxycodone/day, or at least 8 mg oral hydromorphone/day, or at least 25 mg oral oxymorphone/day or an equianalgesic dose of another opioid for one week or longer.
To help you understand the TIRF REMS Access program, the following program materials are available at www.TIRFREMSaccess.com or can be ordered by calling 1-866-822-1483: · Overview for Inpatient Pharmacies · TIRF REMS Access Education Program · Knowledge Assessment · Frequently Asked Questions · Inpatient Pharmacy Enrollment Form · Full Prescribing Information and Medication Guides for each TIRF medicine
Outpatient pharmacies within the facility providing dispensing services to discharged inpatients or outpatients have different REMS requirements. In order to dispense TIRF medicines to
Reference ID: 4146711
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outpatients, a separate enrollment in the TIRF REMS Access program is required (see the TIRF REMS Access program - An Overview for Outpatient Pharmacies available at www.TIRFREMSaccess.com).
To access the above information and to enroll in the TIRF REMS Access program, visit www.TIRFREMSaccess.com or call 1-866-822-1483 to have enrollment materials sent to you.
Reference ID: 4146711
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Selected Important Safety Information
IMPORTANCE OF PROPER PATIENT SELECTION, DOSING, and POTENTIAL FOR ABUSE
TIRF medicines contain fentanyl, an opioid agonist and a Schedule II controlled substance, with an abuse liability similar to other opioid analgesics. TIRF medicines can be abused in a manner similar to other opioid agonists, legal or illicit. Consider the potential for abuse when prescribing or dispensing TIRF medicines in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse or diversion. Schedule II opioid substances which include morphine, oxycodone, hydromorphone, oxymorphone, and methadone have the highest potential for abuse and risk of fatal overdose due to respiratory depression.
Serious adverse events, including deaths, in patients treated with some oral transmucosal fentanyl medicines have been reported. Deaths occurred as a result of improper patient selection (e.g., use in opioid non-tolerant patients) and/or improper dosing. The substitution of a TIRF medicine for any other fentanyl medicine, including another TIRF medicine, may result in fatal overdose.
TIRF medicines are indicated only for the management of breakthrough pain in adult cancer patients 18 years of age and older (16 years of age and older for Actiq® brand and generic equivalents) who are already receiving and who are tolerant to around-the-clock opioid therapy for their underlying persistent cancer pain. Patients considered opioid-tolerant are those who are taking:
· at least 60 mg of oral morphine/daily · at least 25 mcg transdermal fentanyl/hour · at least 30 mg of oral oxycodone daily · at least 8 mg oral hydromorphone daily · at least 25 mg oral oxymorphone daily · or an equianalgesic dose of another opioid daily for a week or longer.
TIRF medicines are contraindicated in opioid non-tolerant patients and are contraindicated in the management of acute or postoperative pain, including headache/migraine and dental pain, or use in the emergency room. Please see the individual medicine prescribing information for a full list of specific situations in which TIRF medicines are not indicated or are contraindicated. Lifethreatening respiratory depression could occur at any dose in opioid non-tolerant patients. Deaths have occurred in opioid non-tolerant patients treated with some TIRF medicines.
When prescribing, do not convert patients on a mcg per mcg basis from another fentanyl medicine to a TIRF medicine, except for substitutions between a branded TIRF medicine and its generic equivalent. Patients beginning treatment with TIRF medicines must begin with titration from the lowest available dose for that specific medicine. Carefully consult the Initial Dosing Instructions in the TIRF medicine-specific Full Prescribing Information.
When dispensing, TIRF medicines are not interchangeable with each other, regardless of route of administration. Differences exist in the pharmacokinetics of TIRF medicines resulting in
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clinically important differences in the amount of fentanyl absorbed that could cause a fatal overdose. Converting patients from one TIRF medicine to a different TIRF medicine must not be done on a microgram-per-microgram basis, and must be titrated according to the labeled dosing instructions each time they begin use of a new TIRF medicine. The only exception is for substitution between a branded TIRF medicine and its specific generic equivalent.
Special care must be used when dosing TIRF medicines. Refer to the Full Prescribing Information for the individual TIRF medicine for guidance on the maximum number of doses that can be taken per breakthrough pain episode and the time that patients must wait before treating another episode of breakthrough pain with the TIRF medicine.
TIRF medicines are intended to be used only in the care of opioid-tolerant cancer patients and only by healthcare professionals who are knowledgeable of, and skilled in, the use of Schedule II opioids to treat cancer pain.
Patients and their caregivers must be instructed that TIRF medicines contain a medicine in an amount which can be fatal in children, in individuals for whom it is not prescribed, and in those who are not opioid-tolerant. All medicines must be kept out of the reach of children.
The concomitant use of TIRF medicines with cytochrome P450 3A4 inhibitors may result in an increase in fentanyl plasma concentrations, and may cause potentially fatal respiratory depression.
Adverse Reactions The most commonly observed adverse reactions with TIRF medicines include typical opioid adverse reactions, such as nausea, vomiting, constipation, somnolence, dizziness, and headache. Refer to individual medicine prescribing information for all adverse reactions. Expect opioid side effects and manage them accordingly.
Please see the individual Full Prescribing Information for each TIRF medicine for all information including boxed warnings, and Medication Guide for important safety information for each TIRF medicine.
Adverse Event Reporting Promptly report suspected adverse events including misuse, abuse, addiction and overdoses directly to the TIRF REMS Access program at 1-866-822-1483. You also may report adverse event information to the FDA MedWatch Reporting System by telephone at 1-800-FDA-1088 or by mail using Form 3500, available at www.fda.gov/medwatch.
Medication Guide It is important that you discuss the risks of TIRF medicines with your patients and encourage them to read the relevant Medication Guide. The Medication Guide provides important information on the safe and effective use of TIRF medicines and you will need to review the appropriate Medication Guide for the TIRF medicine you prescribe/dispense to your patient. Patients should
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be counseled on the need to store TIRF medicines safely out of the reach of children and other persons for whom the medicine is not prescribed.
Provide your patient with a copy of the appropriate Medication Guide for the TIRF medicine you prescribe. Medication Guides will be provided to you by the manufacturers of individual TIRF medicines. If you require additional Medication Guides you can:
· Print copies from the TIRF REMS Access program website at www.TIRFREMSaccess.com.
· Contact the TIRF REMS Access program at 1-866-822-1483.
Sincerely,
TIRF REMS Access Industry Group
Reference ID: 4146711
FDA_7376
Attachment 1:
List of TIRF Medicines Available Only through the TIRF REMS Access Program
ABSTRAL® (fentanyl) sublingual tablets ACTIQ® (fentanyl citrate) oral transmucosal lozenge FENTORA® (fentanyl citrate) buccal tablet LAZANDA® (fentanyl) nasal spray ONSOLIS® (fentanyl buccal soluble film) Approved generic equivalents of these products are also covered under this
program.
Reference ID: 4146711
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This letter ceased distribution in November 2013.
Subject:
Important Drug Warning Announcement of a single shared REMS (Risk Evaluation and Mitigation Strategy) program for all Transmucosal Immediate Release Fentanyl (TIRF) products due to the potential risk of misuse, abuse, addiction, overdose and serious complications due to medication errors
The TIRF REMS Access program is a Food and Drug Administration (FDA) required risk management program
Dear Wholesaler/Distributor:
The purpose of this letter is to make you aware of a change from individual REMS programs to a shared REMS program (the TIRF REMS Access program) and to provide guidance on enrollment into the new shared REMS program beginning mm/dd/yyyy. The individual REMS programs are being converted to the TIRF REMS Access program to reduce the burden on the healthcare providers and the healthcare system of having multiple individual programs. The products covered under this new program include:
· Abstral® (fentanyl) sublingual tablets · Actiq® (fentanyl citrate) oral transmucosal lozenge · Fentora® (fentanyl citrate) buccal tablet · Lazanda® (fentanyl) nasal spray · Onsolis® (fentanyl buccal soluble film)
· Approved generic equivalents of these products are also covered under this program.
This new shared program replaces the individual product REMS that were previously available, and any prescribers, pharmacies, patients and distributors enrolled in these programs will be automatically transitioned to the new shared TIRF REMS Access program. If you have not enrolled in one or more of these individual REMS programs and you wish to purchase these products in order to fulfill orders from enrolled pharmacies, you must enroll in the TIRF REMS Access program.
Distributor Action:
Option 1: If you are already enrolled in at least one individual REMS program
· Beginning mm/dd/yyyy, your enrollment information will be automatically entered into the new shared TIRF REMS Access program. The website for the shared TIRF REMS Access program can be accessed at www.TIRFREMSaccess.com.
· You can use your existing secure user ID and password from any one of your individual REMS programs to access the TIRF REMS Access website at www.TIRFREMSaccess.com o The user ID and password you use to initially log on will become your permanent user ID and password for the shared TIRF REMS Access program.
· You will be required to re-enroll in the shared TIRF REMS within two years after your last enrollment in an individual REMS if you wish to continue distributing these products. You will be notified by the REMS program in advance of the need to re-enroll.
· By enrolling in the shared TIRF REMS Access program a distributor/wholesaler may distribute all of the TIRF medicines. However, the decision to maintain a direct selling relationship with the wholesaler/distributor is at the sole discretion of each individual TIRF manufacturer.
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Option 2: If you do not have an existing enrollment in any individual REMS program · Review and understand the requirements of the TIRF REMS Access program. · Verify that relevant staff are trained on the TIRF REMS Access program requirements and
procedures · Complete the Distributor Enrollment Form. Forms are available at
www.TIRFREMSaccess.com or by calling 1-866-822-1483. · By enrolling in the shared TIRF REMS Access program a distributor/wholesaler may
distribute all of the TIRF medicines. However, the decision to maintain a direct selling relationship with the wholesaler/distributor is at the sole discretion of each individual TIRF manufacturer.
Distributor Responsibilities in the TIRF REMS Access Program:
Verification of TIRF REMS Access program Pharmacy Enrollment Prior to Distributing TIRF medicines
· Obtain the current list of enrolled pharmacies by: o Downloading (daily) a complete electronic registry of enrolled pharmacies from a secure FTP site (you will be contacted regarding the TIRF REMS Access secure FTP site once your enrollment is complete), or o Receiving (daily) a complete electronic registry, or o Accessing the website (www.TIRFREMSaccess.com) using a user ID and password, or o Calling the TIRF REMS Access program call center at 1-866-822-1483.
· Ensure that pharmacies are enrolled in the TIRF REMS Access program before distributing TIRF medicines.
· If a pharmacy places an order for a TIRF medicine, but is not listed on the enrolled list for the TIRF REMS Access program, do not distribute TIRF medicines.
Provide periodic distribution data · Provide weekly product activity data (i.e. EDI 867 transmission) to the TIRF REMS Access program including complete (unblinded/unblocked) information to validate compliance with the TIRF REMS Access program.
Please note that a manufacturer of products included in Attachment 1 cannot ship TIRF medicines to distributors who have not completed and signed the Distributor Enrollment Form. Refer to the `List of TIRF Medicines Available only through the TIRF REMS Access program' in Attachment 1.
Adverse Event Reporting Promptly report suspected adverse events including misuse, abuse, addiction and overdoses directly to the TIRF REMS Access program at 1-866-822-1483. You also may report adverse event information to the FDA MedWatch Reporting System by telephone at 1-800-FDA-1088 or by mail using Form 3500, available at www.fda.gov/medwatch.
To access the above information and to enroll in the TIRF REMS Access program, visit www.TIRFREMSaccess.com or call 1-866-822-1483 to have enrollment materials sent to you.
Sincerely,
TIRF REMS Access Industry Group
Reference ID: 4146711
FDA_7379
Attachment 1:
List of TIRF Medicines Available Only through the TIRF REMS Access Program
ABSTRAL® (fentanyl) sublingual tablets ACTIQ® (fentanyl citrate) oral transmucosal lozenge FENTORA® (fentanyl citrate) buccal tablet LAZANDA® (fentanyl) nasal spray ONSOLIS® (fentanyl buccal soluble film) Approved generic equivalents of these products are also covered under this
program.
Reference ID: 4146711
FDA_7380
The Transmucosal Immediate Release Fentanyl (TIRF) REMS Access Program Wholesaler / Distributor Enrollment Form
To enroll in TIRF REMS Access, complete all required fields below and fax pages 1 and 2 to 1-866-822-1487. You will receive enrollment confirmation via email or fax.
TIRF medicines are available only through a FDA mandated REMS (Risk Evaluation and Mitigation Strategy), a restricted distribution program, called the TIRF REMS Access program. Under the TIRF REMS Access program, only prescribers, pharmacies, wholesalers / distributors and patients enrolled in the program are able to prescribe, dispense, distribute, purchase or receive TIRF medicines. Refer to the list of currently approved TIRF products located on the TIRF REMS Access website at www.TIRFREMSaccess.com/TirfUI/rems/products.action.
Under the TIRF REMS Access program, wholesalers / distributors must verify the current enrollment of a pharmacy in the TIRF REMS Access program prior to distributing a TIRF medicine to that pharmacy. If the pharmacy location is not enrolled, the distributor must not fill any orders for TIRF medicines until enrollment can be confirmed.
The current list of enrolled pharmacies may be accessed via: · receipt of a complete pharmacy registry daily in a mutually agreed format, · a daily download from a secure FTP site, · a password protected section of the website (www.TIRFREMSaccess.com), or · by calling 1-866-822-1483.
Your company will receive login information (unique secure user ID and password) to access the TIRF REMS Access program website and you will be contacted regarding the secure FTP site once your enrollment is complete.
The Wholesaler / Distributor understands that TIRF medicines are only available through the TIRF REMS Access program and acknowledges that they will comply with the following program requirements: 1. The Wholesaler / Distributor will ensure that relevant staff are trained on the TIRF REMS Access
program procedures and will follow the requirements of the TIRF REMS Access program. 2. The Wholesaler / Distributor will ensure that TIRF medicines are only distributed to pharmacies whose
enrollment has been verified in the TIRF REMS Access program. 3. The Wholesaler / Distributor will provide complete unblinded and unblocked data (i.e. EDI 867
transmission) to the TIRF REMS Access program, including information on shipments to enrolled pharmacies. 4. The Wholesaler / Distributor will cooperate with periodic audits or non-compliance investigations to ensure that TIRF Medicines are distributed in accordance with the program requirements.
Authorized Representative Name* (please print):__________________________
Reference ID: 4146711
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--------------------------------------------------------------------------------------------------------This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature. ---------------------------------------------------------------------------------------------------------
/s/ ----------------------------------------------------
LASHAUN WASHINGTON-BATTS 08/30/2017
JAMIE C WILKINS PARKER on behalf of CYNTHIA L LACIVITA 08/31/2017
Reference ID: 4146711
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