Sanofi Announces Launch of Authorized Generic Version of Arava^® (Leflunomide) Tablets

PR Newswire, Bridgewater, NJ – October 1, 2015 — Sanofi US announced today the availability of an authorized generic version of Arava^®, Leflunomide tablets through Winthrop, the company’s US generics division. For people living with rheumatoid arthritis (RA), Leflunomide blocks autoimmune antibodies that reduce inflammation with the aim of improving mobility. Sanofi’s authorized generic version is the same formulation as the original drug, Arava, for which the company holds the original patent.

Rheumatoid arthritis is a chronic disease for which signs and symptoms can be lessened with treatment. Because joint damage is irreversible, early diagnosis and treatment are recommended.¹ Disease-modifying anti-rheumatic drugs (DMARDs) such as Arava help to reduce signs and symptoms, inhibit structural damage as evidenced by X-Ray erosions and joint space narrowing and improve physical function. Since treatment is highly individualized based on patient response, Arava provides the ability to be used either alone or in combination with other DMARDs or biologics.

The authorized generic version of Arava has the identical chemical makeup as the original Arava first approved by the FDA in 1998. Authorized generics possess the identical active ingredients as the original medications. Generic medications often include a variety of different inactive ingredients than brand-name medications. These may include fillers, dyes or other ingredients that may cause adverse events for people with allergies or sensitivities.

Winthrop delivers affordable solutions to the healthcare community by transforming Sanofi’s branded products into authorized generics and is devoted to supplying high quality products to its customers with excellent service.

Important Safety Information for Leflunomide Tablets:

Females of childbearing potential:
There are no adequate and well-controlled studies evaluating Leflunomide in pregnant women. Thus, do not start Leflunomide until the following steps are completed:

•       Pregnancy is excluded
•       Confirm that reliable contraception is being used
•       Fully counsel patients on the potential for serious risk to the fetus

Suspicion of Pregnancy
The patient must be advised that if there is any delay in onset of menses or any other reasons to suspect pregnancy, they must stop Leflunomide and notify the physician immediately for pregnancy testing and if positive, the physician and patient must discuss the risk of pregnancy. It is possible that rapidly lowering the blood level of the active metabolite by instituting the drug elimination procedure described below at the first delay of menses may decrease the risk to the fetus from Leflunomide.

Females on Leflunomide who wish to become pregnant:

• Must discontinue Leflunomide and undergo the drug elimination procedure
• Human plasma levels of the active metabolite less than 0.02 mg/L (0.02 µg/mL) are expected to have minimal risk based on available animal data

Drug elimination procedure for females

1. Administer cholestyramine 8 grams 3 times daily for 11 days. (The 11 days do not need to be consecutive unless there is a need to lower the plasma level rapidly.)
2. Verify plasma levels less than 0.02 mg/L (0.02 µg/mL) by 2 separate tests at least 14 days apart. If plasma levels are higher than 0.02 mg/L, additional cholestyramine treatment should be considered.

Without the drug elimination procedure, it may take up to 2 years for the active metabolite of Leflunomide to reach plasma levels less than 0.02 mg/L due to individual variation in drug clearance.

Information for males
Available information does not suggest that Leflunomide would be associated with an increased risk of male-mediated fetal toxicity. To minimize any possible risk, men wishing to father a child should consider discontinuing use of Leflunomide and taking cholestyramine 8 grams 3 times daily for 11 days.

Additional safety information

• Leflunomide is contraindicated in patients with known hypersensitivity to Leflunomide, teriflunomide, or any of the other components of Leflunomide.
• Severe liver injury, including fatal liver failure, has been reported in some patients treated with Leflunomide. Patients with pre-existing acute or chronic liver disease, or those with serum ALT > 2 X ULN before initiating treatment, should not be treated with Leflunomide.
• Leflunomide is not recommended for patients with severe immunodeficiency, bone marrow dysplasia, or severe, uncontrolled infections. Severe infections including sepsis, which may be fatal, have been reported. Rarely, interstitial lung disease, which may be fatal, has been reported
• Rare reports of pancytopenia, agranulocytosis, thrombocytopenia, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and peripheral neuropathy have been reported in post marketing experience. In these or any other serious toxicities, Leflunomide should be stopped and a drug elimination procedure (eg, cholestyramine 8 g TID x 11 days) should be used to reduce the drug concentration more rapidly
• It would be prudent to monitor for hematologic toxicity when switching from Leflunomide to another antirheumatic agent with a known potential for hematologic suppression
• Adverse reactions associated with the use of Leflunomide in clinical trials at 1 year (n=1339) included diarrhea (17%), respiratory infection (15%), alopecia (10%), hypertension (10%), rash (10%), and elevated liver enzymes (ALT and AST) (5%)
• Co-administration of teriflunomide with Leflunomide is not recommended, as Leflunomide is the parent compound of teriflunomide
• Prior to initiating immunomodulatory therapies, including Leflunomide, all patients should be screened for active and inactive (²latent²) tuberculosis infection as per commonly used diagnostic tests. Leflunomide has not been studied in patients with a positive tuberculosis screen, and the safety of Leflunomide in individuals with latent tuberculosis infection is unknown. Patients with a history of tuberculosis should be carefully monitored because of the possibility of reactivation of the infection. Patients testing positive in tuberculosis screening should be treated by standard medical practice prior to therapy with Leflunomide.

Laboratory tests

• At minimum, ALT (SGPT) must be performed at baseline and at least monthly for six months after starting Leflunomide, and thereafter every 6 to 8 weeks.
• At minimum, patients taking Leflunomide should have platelet, white blood cell count, and hemoglobin or hematocrit monitored at baseline and monthly for 6 months following initiation of therapy and every 6 to 8 weeks thereafter
• If used concomitantly with immunosuppressants such as methotrexate, chronic monitoring should be monthly

Please see Full Prescribing Information, including boxed WARNING, for additional important information.

References

¹ Arthritis Foundation: http://www.arthritis.org/about-arthritis/types/rheumatoid-arthritis/what-is-rheumatoid-arthritis.php

About Sanofi
Sanofi, a global healthcare leader, discovers, develops and distributes therapeutic solutions focused on patients’ needs. Sanofi has core strengths in diabetes solutions, human vaccines, innovative drugs, consumer healthcare, emerging markets, animal health and Genzyme. Sanofi is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY).

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