ORTHOVISC Brochure

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between science

and nature.

Anatural balance

ORTHOVISC®: Close to nature.

High Molecular Weight Hyaluronan

ORTHOVISC®: Closely matches healthy synovial fluid.

High concentration of HA in synovial fluid (SF) is essential for normal joint function:10

• Responsible for shock absorbing and lubricating properties of SF, which are diminished by osteoarthritis

• Reduces wear and attrition of cartilage

• Important for nutrition of cartilage

• Eliminates metabolites and unhealthy substances from joint cavity

Properties of synovial uid:

Molecular weight (million daltons) Elasticity (Pa at 2.5 Hz) Viscosity (Pa at 2.5 Hz)

0.6 1.9 1.4

OA of the knee1,2

1-2.9 60 46

ORTHOVISC®1,3

3-4 117 45

Healthy4,5

ORTHOVISC® has the highest concentration of hyaluronic

acid (HA) amongst available viscosupplements.

Hyaluronic acid concentration – mg/mL

15

8

10

ORTHOVISC®3

SYNVISC®5 SYNVISC-ONE®6

HYALGAN®7 SUPARTZ®8 EUFLEXXATM9

ORTHOVISC®: Close to nature.

High Molecular Weight Hyaluronan

High purity may minimize risk of inflammatory reactions.11,12

• ORTHOVISC® contains no additives

• Derived from bacterial cells, it can be prescribed to patients with known avian allergies

• Repeat courses may be safely administered3

Comparison of syringe contents

ORTHOVISC® 2 mL No additives

SYNVISC® 2 mL

SYNVISC-ONE® 6 mL*

HYALGAN® 2 mL

SUPARTZ® 2.5 mL

EUFLEXXATM 2 mL

Hyaluronan

30 mg

Sodium chloride

18 mg

Sodium chloride

17 mg

0.32 mg Disodium

hydrogen phosphate

0.08 mg Sodium dihydrogen

phosphate monohydrate

0.1 mg Monobasic

sodium phosphate

1.2 mg Dibasic sodium

phosphate

1.12 mg Disodium hydrogen

phosphate dodecahydrate

0.1 mg Sodium dihydrogen

phosphate dihydrate

Sodium chloride

17 mg

Sodium chloride

21.25 mg

Sodium chloride

17 mg

Sodium hyaluronate

20 mg

Sodium hyaluronate

20 mg

Sodium hyaluronate

25 mg

Hylan polymers

(hylan A + hylan B)

16 mg

1.34 mg dibasic sodium

phosphate dodecayhdrate

0.04 mg Sodium dihydrogen

phosphate dihydrate

*SYNVISC-ONE® 6 mL = 3 times content of SYNVISC® 2 mL.

Visual Depiction of content not to scale. Illustrations for presentation purposes only.

Proven efficacy across 26 weeks of randomized

controlled trials.3,13

ORTHOVISC®: Efficacy that matches expectation.

• ORTHOVISC® provided signicant improvement in WOMAC pain score versus saline at all time points

• Up to 6 months of symptom relief with 3 or 4 injections

• 58% of patients achieved 5 units or greater improvement

in mean pain score (control = 40%)13

• Twice as many achieved 7 units or greater improvement

(ORTHOVISC® 30% vs. control 17%)13

Significant improvement in WOMAC pain score

(effectiveness population†)13

*Statistically signicant difference between treatment groups (p<0.05 vs. control group).

†Patients with contralateral WOMAC knee pain score less than 12.

WOMAC Pain Score

Mean Change from Baseline

Visit Week

0 5 10 15 20 25 30

0

-1

-2

-3

-4

-5

-6

ORTHOVISC® (n = 66) Saline (n = 69)

***

*

Don’t wait until it’s too late for a non-surgical option.

ORTHOVISC®: Efficacy that matches expectation.

• Diagnose and treat early for improved results1

• ORTHOVISC® demonstrated statistically and clinically signicant symptom improvement

when used in patients with mild to moderate knee osteoarthritis13‡

• The American College of Rheumatology places

viscosupplementation early in treatment paradigm14

Pain Scale

Mild Pain Moderate Pain Severe Pain

10 2345 6 7 8 910

‡ Kellgren-Lawrence Grade II or III radiographic evidence of knee

osteoarthritis, WOMAC Osteoarthritis Index pain score of 13 or

greater (possible range, 5-25).

CAUTION

Federal law restricts this device to sale by or on the order of a physician (or properly licensed practitioner).

DESCRIPTION

ORTHOVISC®is a sterile, non-pyrogenic, clear, viscoelastic solution of hyaluronan contained in a single-use

syringe. ORTHOVISC®consists of high molecular weight (1.0-2.9 million daltons), ultra-pure natural hyaluronan

dissolved in physiological saline. Hyaluronan is a natural complex sugar of the glycosaminoglycan family.

ORTHOVISC®is derived from bacterial cells.

INDICATIONS

ORTHOVISC®is indicated in the treatment of pain in osteoarthritis (OA) of the knee in patients who have failed to

respond adequately to conservative nonpharmacologic therapy and to simple analgesics, e.g., acetaminophen.

CONTRAINDICATIONS

• Do not administer to patients with known hypersensitivity (allergy) to hyaluronate preparations.

• Do not administer to patients with known hypersensitivity (allergy) to gram positive bacterial proteins.

• Do not inject ORTHOVISC®in the knees of patients with infections or skin diseases in the area of the injection

site or joint.

WARNINGS

• Do not concomitantly use disinfectants containing quarternary ammonium salts for skin preparation as

hyaluronic acid can precipitate in their presence.

• Transient increases in inflammation in the injected knee following ORTHOVISC®injection have been reported

in some patients with inflammatory osteoarthritis.

PRECAUTIONS

General

• Strict aseptic injection technique should be used during the application of ORTHOVISC®.

• The safety and effectiveness of the use of ORTHOVISC®in joints other than the knee have not been demonstrated.

• The effectiveness of a single treatment cycle of less than 3 injections has not been established. Pain relief

may not be seen until after the third injection.

• The effectiveness of ORTHOVISC®has not been established for more than one course of treatment.

• STERILE CONTENTS. The pre-filled syringe is intended for single use only. The contents of the syringe should

be used immediately after opening. Discard any unused ORTHOVISC®. Do not resterilize.

• Do not use ORTHOVISC®if the package has been opened or damaged.

• Store ORTHOVISC®in its original package at room temperature (below 77°F/25°C). DO NOT FREEZE.

• Remove joint effusion, if present, before injecting ORTHOVISC®.

• Only medical professionals trained in accepted injection techniques for delivering agents into the knee joint

should inject ORTHOVISC®for the indicated use.

Information for Patients

• Transient pain or swelling may occur after the intra-articular (IA) injection.

• As with any invasive joint procedure, it is recommended that patients avoid strenuous activity or prolonged

(i.e., more than one hour) weight-bearing activities such as running or tennis within 48 hours following the

intra-articular injection.

Use in Specific Populations

• Pregnancy: The safety and effectiveness of the use of ORTHOVISC®in pregnant women has not been tested.

• Nursing Mothers: It is not known if ORTHOVISC®is excreted in human milk. The safety and effectiveness of

the use of the product in lactating women has not been tested.

• Children: The safety and effectiveness of the use of ORTHOVISC®in children has not been tested.

ADVERSE EVENTS

ORTHOVISC®was investigated in 3 randomized, controlled clinical studies conducted in the U.S. An integrated

safety analysis was conducted, pooling the ORTHOVISC®groups from the 3 studies and pooling the control

groups, which were either intra-articular saline injections or arthrocentesis. In the integrated analysis, there

were 562 patients in the groups treated with ORTHOVISC®(434 receiving 3 injections and 128 receiving 4

injections), 296 in the group treated with physiological saline, and 123 in the group treated with arthrocentesis.

Adverse events occurring at >5% of the overall integrated population included: arthralgia (12.6% in the

ORTHOVISC®group, 17.2% in the saline group, and 0.8% in the arthrocentesis group); back pain (6.9% in the

ORTHOVISC®group, 12.2% in the saline group, and 4.9% in the arthrocentesis group); and headache NOS

(12.1% in the ORTHOVISC®group, 16.6% in the saline group, and 17.9% in the arthrocentesis group). Injection

site adverse events (including erythema, edema, pain and reaction NOS) occurred at rates of 0.4%, 0.9%, 2.5%

and 0.2%, respectively, in the ORTHOVISC®group, compared to 0.0%, 0.3%, 2.0%, and 0.7% in the saline

group and 0.0%, 0.0%, 0.8% and 0.8% in the arthrocentesis group. Local adverse events reported on a by-

patient basis for the combined ITT populations of the three studies are presented in Table 1.

Table 1

Local individual adverse events reported on a by-patient

basis for the combined ITT populations of the three studies.

Adverse Event ORTHOVISC Saline Arthrocentesis

N = 562 N = 296 N = 123

Any Adverse Event 349 (62.1%) 204 (68.9%) 65 (52.8%)

Injection site erythema 2 (0.4%) 0 (0%) 0 (0%)

Injection site edema 5 (0.9%) 1 (0.3%) 0 (0%)

Injection site pain 14 (2.5%) 6 (2.0%) 1 (0.8%)

Injection site reaction NOS11 (0.2%) 2 (0.7%) 1 (0.8%)

Pain NOS114 (2.5%) 11 (3.7%) 1 (0.8%)

Arthralgia 71 (12.6%) 51 (17.2%) 1 (0.8%)

Arthritis NOS14 (0.7%) 5 (1.7%) 0 (0%)

Arthropathy NOS15 (0.9%) 3 (1.0%) 0 (0%)

Baker’s cyst 2 (0.4%) 2 (0.7%) 0 (0%)

Bursitis 6 (1.1%) 6 (2.0%) 2 (1.6%)

Joint disorder NOS12 (0.4%) 0 (0%) 0 (0%)

Joint effusion 2 (0.4%) 1 (0.3%) 1 (0.8%)

Joint stiffness 3 (0.5%) 2 (0.7%) 0 (0%)

Joint swelling 4 (0.7%) 2 (0.7%) 1 (0.8%)

Localized osteoarthritis 5 (0.9%) 1 (0.3%) 1 (0.8%)

Aggravated osteoarthritis 2 (0.4%) 0 (0%) 1 (0.8%)

Knee arthroplasty 3 (0.5%) 2 (0.7%) 0 (0%)

Notes: 1NOS = Not otherwise specified.

Additional adverse event information was obtained from an open label study (OAK0101). The objective of the

open label study was to evaluate the safety of a repeat course of intra-articular ORTHOVISC®. The patients

enrolled in the open label study were previously enrolled in one of the randomized studies (OAK2001). Patients

who completed OAK2001 and had persistent pain in the index knee received 3 weekly injections of

ORTHOVISC®six months following the first treatment course and were followed for 6 weeks. Of 190 eligible

patients, 127 had been assigned to either 4 injections of ORTHOVISC®or to 3 injections of ORTHOVISC®plus

one arthrocentesis in OAK2001 and therefore underwent two courses of ORTHOVISC®treatment between the

two studies. In OAK0101, adverse event profiles (type, frequency and severity of adverse events) were

comparable among the three treatment groups (those who had undergone a previous series of 3 or 4

ORTHOVISC®injections and those who received only arthrocentesis in OAK2001) and were similar to those

seen in the OAK2001 study and the integrated safety analysis. Table 2 compares adverse event data for

patients receiving ORTHOVISC®among the integrated safety analysis (“Single Treatment”), the OAK2001

randomized study (“Single Treatment”) and the OAK0101 retreatment study (“Repeat Treatment”).

Table 2

Comparison of local individual adverse events reported on a

by-patient basis between single and repeat treatment.

Adverse Event ORTHOVISC ORTHOVISC ORTHOVISC

Single Treatment Single Treatment Repeat Treatment

N = 562 N = 247 N = 127

Any Adverse Event 349 (62.1%) 136 (55.1%) 39 (30.7%)

Injection site erythema 2 (0.4%) 2 (0.8%) 0 (0%)

Injection site edema 5 (0.9%) 1 (0.4%) 0 (0%)

Injection site pain 14 (2.5%) 3 (1.2%) 3 (2.4%)

Injection site reaction NOS11 (0.2%) 0 (0%) 4 (3.1%)

Pain NOS114 (2.5%) 3 (1.2%) 0 (0%)

Arthralgia 71 (12.6%) 20 (8.1%) 8 (6.3%)

Arthritis NOS14 (0.7%) 1 (0.4%) 0 (0%)

Arthropathy NOS15 (0.9%) 0 (0%) 0 (0%)

Baker’s cyst 2 (0.4%) 0 (0%) 0 (0%)

Bursitis 6 (1.1%) 2 (0.8%) 0 (0%)

Joint disorder NOS12 (0.4%) 0 (0%) 0 (0%)

Joint effusion 2 (0.4%) 2 (0.8%) 1 (0.8%)

Joint stiffness 3 (0.5%) 0 (0%) 0 (0%)

Joint swelling 4 (0.7%) 2 (0.8%) 2 (1.6%)

Localized osteoarthritis 5 (0.9%) 3 (1.2%) 1 (0.8%)

Aggravated osteoarthritis 2 (0.4%) 2 (0.8%) 0 (0%)

Knee arthroplasty 3 (0.5%) 0 (0%) 0 (0%)

CLINICAL STUDIES

The effectiveness of ORTHOVISC®for the treatment of osteoarthritis of the knee was evaluated in three main

studies; two randomized, controlled, double-blind multicenter studies (OAK9501 and OAK2001) that involved

unilateral treatment, and one study (OAK9801) that involved bilateral treatment. Because bilateral treatment

confounded the assessment of effectiveness of the OAK9801 study, the effectiveness data are summarized for

the OAK9501 and OAK2001 studies. Safety data for all three studies are reported in “Adverse Events.”

Study Design/Analysis

The objective of the randomized studies was to assess the effectiveness of ORTHOVISC®for the treatment of

joint pain of patients with idiopathic osteoarthritis of the knee. The OAK9501 study randomized patients to 3

weekly injections of either ORTHOVISC®(O3) or saline. The OAK2001 study randomized patients to one of three

treatments: 4 ORTHOVISC®injections (O4), 3 ORTHOVISC®injections + 1 arthrocentesis (O3A1) procedure, or

4 arthrocentesis (A4) procedures. Follow-up occurred at weeks 7/8, 11/12, 15/16 and 21/22, with final follow-

up at week 27/28. When each study was analyzed individually, the primary analyses for each study did not

show statistical significance. A combined analysis was additionally performed. The combined data consisted

of data obtained from a subgroup of patients from each of the studies (the “ITT Subgroup” from OAK9501 and

the “Evaluable Subgroup” from OAK2001) who had Kellgren-Lawrence radiographic grades of II or III at

baseline and WOMAC pain in the contralateral knee of <175 mm (out of 500) and is referred to as the

effectiveness subgroup population. For the effectiveness subgroup population, the primary effectiveness

analysis performed was to determine the proportion of patients achieving a 20% improvement from baseline

in the WOMAC Pain Score in conjunction with a minimum absolute improvement of 50 mm from baseline in

the WOMAC Pain Score, and a 40% and 50% improvement from baseline in WOMAC Pain Score at four

assessment points between Weeks 7/8 to 21/22 for the index knee.

Study Population

OAK9501 included 226 patients at 10 centers, and OAK2001 involved 373 patients at 24 centers. Within the

individual studies, baseline and demographic variables were similar among groups. Table 3 below summarizes

the baseline and patient demographic characteristics for the combined effectiveness subgroup.

Table 3

Baseline and patient demographics summary—effectiveness subgroup.1

Characteristic O3 Saline x 3 O4 O3A1 A4

N = 83 N = 81 N = 104 N = 90 N = 100

No. (%) female 51 49 46 59 50

(61.4%) (60.5%) (44.2%) (65.5%) (50.0%)

Mean ± SD age (years) 65 ± 8 68 ± 9 59 ± 9 59 ± 9 59 ± 8

Mean ± SD BMI (kg/m2) 32 ± 7 30 ± 6 29 ± 4 30 ± 4 30 ± 4

Mean ± SD WOMAC Pain 274 ± 65 268 ± 70 288 ± 60 290 ± 50 293 ± 59

(0-500 mm) Study Knee

Mean ± SD WOMAC Pain 83 ± 57 87 ± 54 69 ± 47 70 ± 47 68 ± 48

(0-500 mm) Contralateral

Mean ± SD Investigator 53 ± 19 51 ± 19 59 ± 14 58 ± 14 58 ± 15

Global (0-100 mm)

Mean ± SD Patient Global 56 ± 20 53 ± 22 67 ± 15 62 ± 17 64 ± 15

(0-100 mm)

Notes: 1Patients with Kellgren-Lawrence radiographic grades of II or III at baseline and WOMAC pain in the

contralateral knee of <175mm (out of 500).

Combined Study Results

In the combined analysis of OAK9501 and OAK2001, two subgroup populations (representing patients with

baseline Kellgren-Lawrence grade II or III radiographic findings and contralateral knee pain <175 mm on the

WOMAC Pain Score) were analyzed together, comprising 5 treatment groups (4 ORTHOVISC®injections [O4],

ORTHOVISC®High Molecular Weight Hyaluronan ORTHOVISC®High Molecular Weight Hyaluronan

3 ORTHOVISC®injections followed by 1 arthrocentesis [O3A1], 3 ORTHOVISC®injections [O3], 4 arthrocentesis

procedures [A4] and 3 saline injections [Saline]). For the GEE analyses, the O3A1 and O3 groups were also

pooled to form a sixth group [O3A1/O3].

The primary effectiveness analysis was performed to determine the proportion of patients achieving a 20%

improvement from baseline in the WOMAC Pain Score in conjunction with a minimum absolute improvement

of 50 mm from baseline in the WOMAC Pain Score, and a 40% and 50% improvement from baseline in WOMAC

Pain Score at four assessment points between Weeks 7/8 to 21/22 for the index knee. A significantly larger

proportion of O4 patients achieved 40% and 50% improvements from baseline in WOMAC Pain Score

compared to both A4 and Saline over 7-22 weeks (based on GEE analysis). Similarly, a significantly larger

proportion of O3 and O3A1/O3 patients achieved 40% and 50% improvements from baseline in WOMAC Pain

Score than Saline patients (based on GEE analysis) (Table 4). Table 5 presents the mean number of patients

from the effectiveness subgroup over the four follow-up visits that achieved improvement over weeks 7

through 22.

Table 4

GEE Results (P-Values) for the Effectiveness Subgroups for the Primary Endpoints

Endpoint O4 vs. A4 O4 vs. O3 vs.

Saline Saline

20% improvement from baseline and 0.0738 0.1116 0.0789

50 mm absolute improvement in

WOMAC Pain

40% improvement in WOMAC 0.0094* 0.0015* 0.0166*

Pain Score from baseline

50% improvement in WOMAC 0.0360* 0.0015* 0.0274*

Pain Score from baseline

O4 4 weekly ORTHOVISC®injections—OAK2001 Study

O3 3 weekly ORTHOVISC®injections—OAK9501 Study

A4 4 control [arthrocentesis only] procedures—OAK2001 Study

Saline 3 control [saline injection] procedures—OAK9501 Study

*Statistically significant

Table 5

Summary of mean number patients achieving primary individual patient success criteria—

effectiveness subgroups from OAK9501 and OAK2001—over weeks 7 through 22 (4 visits).

Endpoint O4 O3A1 A4 O3 Saline x 3

N=104 N=90 N=100 N=83 N=81

Mean No. (%) patients 77.5 58.3 64.5 59.3 50.8

achieving 20% improvement (74.5%) (64.7%) (64.5%) (71.4%) (62.7%)

from baseline and absolute

improvement of 50 mm in

WOMAC Pain

Mean No. (%) patients 68.0 47.0 48.8 45.8 34.3

achieving 40% improvement (65.4%) (52.2%) (48.8%) (55.1%) (42.3%)

from baseline in WOMAC Pain

Mean No. (%) patients 59.3 40.5 43.5 38.5 28.3

achieving 50% improvement (57.0%) (45.0%) (43.5%) (46.4%) (34.9%)

from baseline in WOMAC Pain

O4 4 weekly ORTHOVISC®injections—OAK2001 Study

O3A1 3 weekly ORTHOVISC®injections + 1 control [arthrocentesis only] procedure—OAK2001 Study

O3 3 weekly ORTHOVISC®injections—OAK9501 Study

A4 4 control [arthrocentesis only] procedures—OAK2001 Study

Saline 3 control [saline injection] procedures—OAK9501 Study

Summary

In summary, with respect to patients achieving 40% and 50% improvement in WOMAC Pain Score compared

to baseline, the four injection ORTHOVISC®regimen demonstrated effectiveness compared to both Saline and

Arthrocentesis control procedures, and the three-weekly injection regimen demonstrated effectiveness

compared to Saline in the indicated patient population.

DETAILED DEVICE DESCRIPTION

Hyaluronan is a high molecular weight polysaccharide composed of repeating disaccharide units of sodium

glucuronate and N-acetylglucosamine.

Each syringe contains the following in a 2 mL dose sterile-filled into a syringe:

Hyaluronan 30 mg

Sodium Chloride 18 mg

Water for Injection q.s. up to 2.0 mL

ORTHOVISC®does not contain any synthetic additives.

HOW SUPPLIED

ORTHOVISC®is supplied as a sterile-filled solution, in a single-use syringe, sealed in a sterile pouch inside a

carton. The product is presented as a sterile, non-pyrogenic solution in a 3 mL syringe. Each syringe is labeled

“ORTHOVISC®” for ready identification. A rubber cap is provided on the syringe tip to prevent leakage and

protect sterility of the product. The ORTHOVISC®syringe components contain no latex.

DIRECTIONS FOR USE

ORTHOVISC®is injected into the knee joint in a series of intra-articular injections one week apart for a total of

three or four injections. Standard intra-articular injection site preparation, aseptic technique and precautions

should be used. Do not concomitantly use disinfectants containing quarternary ammonium salts for skin

preparation as hyaluronic acid can precipitate in their presence.

•After removal of the protective rubber cap on the tip of the syringe, securely attach a small gauge needle

(18-21 gauge) to the tip.

•Inject ORTHOVISC®into the knee joint using proper injection technique.

•Inject the full contents of the syringe into one knee only.

•If treatment is bilateral, a separate syringe should be used for each knee.

•If symptoms return, repeat courses of ORTHOVISC®may be administered.

ORTHOVISC®is a registered trademark of Anika Therapeutics, Inc.

Manufactured by: Distributed by:

Anika Therapeutics, Inc.

236 West Cummings Park

Woburn, MA USA 01801

DePuy Mitek, Inc.

325 Paramount Drive

Raynham, MA 02767

530-220 AML 06/05 NDC code: 59676-0360-01

Product Code: 277500

ORTHOVISC®High Molecular Weight Hyaluronan ORTHOVISC®High Molecular Weight Hyaluronan

Hyalgan is a registered trademark of sanofi-synthelabo; Supartz is a registered trademark of Seikagaku Corporation; Synvisc is a registered trademark of Genzyme Corporation;

Euflexxa is a trademark of Ferring Pharmaceuticals, Inc.

References: 1. Adams ME, Lussier AJ, Peyron JG. A risk-benefit assessment of injections of hyaluronan and its derivatives in the treatment of osteoar-

thritis of the knee. Drug Saf. 2000;23(2):115-130. 2. Mazzucco D, McKinley G, Scott RD, Spector M. Rheology of joint fluid in total knee arthroplasty

patients. J Orthop Res. 2002;20(6):1157-1163. 3. Adams ME. Viscosupplementation as articular therapy. In: Laurent TC, ed. The Chemistry, Biology and

Medical Applications of Hyaluronan and its Derivatives. London, England: Portland Press Ltd.; 1998:244-253. 4. Orthovisc® (high molecular weight

hyaluronan) manufacturer’s full prescribing information. 5. Synvisc® (hylan G-F 20) manufacturer’s full prescribing information. 6. Balazs EA, Denlinger

JL. Viscosupplementation: a new concept in the treatment of osteoarthritis. J Rheumatol. 1993;20(suppl 39):3-9. 7. Wobig M, Bach G, Beks P, et al.The

role of elastoviscosity in the efficacy of viscosupplementation for osteoarthritis of the knee: a comparison of Hylan G-F 20 and lower-molecularweight

hyaluronan. Clin Ther. 1999;21(9):1549-1561. 8. Moreland LW. Intra-articular hyaluronan (hyaluronic acid) and hylans for the treatment of osteoarthritis:

mechanisms of action. Arthritis Res Ther. 2003;5(2):54-67. 9. Hyalgan® (sodium hyaluronate) manufacturer’s full prescribing information. 10. Supartz®

(sodium hyaluronate) manufacturer’s full prescribing information. 11. Euflexxa™(1% sodium hyaluronate) manufacturer’s full prescribing information.

12. Data on file, DePuy Mitek, Inc., Raynham, MA. 13. Goldberg VM, Coutts RD. Pseudoseptic reactions to hylan viscosupplementation: diagnosis and

treatment. Clin Orthop Relat Res. 2004;419:130-137. 14. Brandt KD, Block JA, Michalski JP, Moreland LW, Caldwell JR, Lavin PT; for the ORTHOVISC

Study Group. Efficacy and safety of intraarticular sodium hyaluronate in knee osteoarthritis. Clin Orthop. 2001;385:130-143. 15. American Academy of

Orthopaedic Surgeons. Knee osteoarthritis—Phase II. http://www.aaos.org/wordhtml/research/guidelin/chart_oakn2.pdf. Accessed February 27, 2006.

16. American College of Rheumatology. Recommendations for the medical management of osteoarthritis of the hip and knee.

http://www.rheumatology.org/publications/guidelines/oa-mgmt/oa-mgmt.asp. Accessed February 27, 2006.

DePuy Mitek, Inc.

325 Paramount Drive

Raynham, MA 02767

NDC code: 59676-0360-01

Product Code: 277500

Match what exists.

It’s only natural.

• Only non-avian HA with proven efcacy across 26 weeks13

• Highest HA concentration among viscosupplements3,5,6,7,8,9

• Closely matches healthy synovial uid

• Provides signicant improvement in WOMAC pain score versus saline at all time points13

• Up to 6 months of symptom relief with 3 or 4 injections

Don’t wait, treat early.

For additional information, please call your DePuy Mitek Sales Representative at

1-800-382-4682 or visit us at www.orthoviscline.com.

References: 1. Mazzucco D, McKinley G, Scott RD, et al. Rheology of joint uid in total knee arthroplasty patients. J Orthop Res. 2002;20(6):

1157-1163. 2. Adams ME. Viscosupplementation as articular therapy. In: Laurent TC, ed. The Chemistry, Biology and Medical Applications

of Hyaluronan and its Derivatives. London, England: Portland Press Ltd.; 1998:244-253. 3. ORTHOVISC® (high molecular weight hyaluronan)

manufacturer’s full prescribing information. 4. Adams ME, Lussier AJ, Peyron JG. A risk-benet assessment of injections of hyaluronan

and it’s derivatives in the treatment of osteoarthritis of the knee. Drug Saf. 2000;23(2):114-130. 5. Synvisc® (hylan G-F 20) manufacturer’s

full prescribing information. 6. Synvisc-One® (hylan G-F 20) manufacturer’s full prescribing information. 7. Hyalgan® (sodium hyaluronate)

manufacturer’s full prescribing information. 8. Supartz® (sodium hyalronate) manufacturer’s full prescribing information. 9. EuflexxaTM

(1% sodium hyaluronate) manufacturer’s full prescribing information. 10. Ghosh Peter, Guidolin Diego. Potential Mechanism

of Action of Intra-articular Hyaluronan Therapy in Osteoarthritis: Are the Effects Molecular Weight Dependent? Seminars in Arthritis and

Rheumatism. 2002 ; 32:10-37. 11. Data on le. DePuy Mitek, Inc., Raynham, MA. 12. Goldberg VM, Coutts RD. Pseudoseptic reactions

to hylan viscosupplementation: diagnosis and treatment. Clin Orthop Relat Res. 2004;419:130-137. 13. Brandt KD, Block JA,

Michalski JP, et al. Efcacy and safety of intraarticular sodium hyaluronate in knee osteoarthritis. Clin Orthop Relat Res. 2001;385:130-143.

14. American College of Rheumatology. Recommendations for the medical management of osteoarthritis of the hip and knee.

http://www.rheumatology.org/publications/guidelines/oa-mgmt/oa-mgmt.asp. Accessed Feb 3rd, 2010.

Hyalgan is a registered trademark of Sano-Synthelabo; Supartz is a registered trademark of Seikagaku Corporation; Synvisc and

Synvisc-One are registered trademarks of Genzyme Corporation; Euexxa is a trademark of Ferring Pharmaceuticals, Inc.

ORTHOVISC is a registered trademark of Anika Therapeutics.

Manufactured by Anika Therapeutics

Anika Therapeutics, Inc.

Bedford, MA 01730 USA

DePuy Mitek, Inc.

325 Paramount Drive

Raynham, MA 02767

P/N 900878 Rev. A 4/10

© DePuy Mitek, Inc. 2010.

All rights reserved.

Printed in USA.

AN OFFICIAL HEALTH AND FITNESS PROVIDER

AN OFFICIAL HEALTH AND FITNESS PROVIDER