FDA seeks Arava label change
Arava was approved by the U.S. Food and Drug Administration on September 11, 1998 for the treatment of active rheumatoid arthritis in adults. It is manufactured by Aventis pharmaceuticals. Rheumatoid arthritis is a chronic autoimmune disease. In this disease patient can suffer deformity or permanent disability. Most of rheumatoid arthritis patients are women.
Arava is brand name for leflunomide. It is used for treatment of rheumatoid arthritis. It reduces damage on bone joints and improves physical functioning. It reduces signs and symptoms of rheumatoid arthritis. It also improves physical function and prevents the development of structural damage to the joints. It blocks the certain enzymes, which cause abnormal tissue development or growth. Through this it checks arthritis.
In clinical trials it proved effective in treatment of tender and swollen joints, and functional and disability problems due to arthritis. It also proved effective in reducing intensity of pain. It is prescribed in both, early or advance stages of rheumatoid arthritis. The label of drug included special warnings against using Arava for pregnant women, pre-menopausal women not using effective birth control, and for people with significant liver disease. The label warned that pregnancy must be excluded before the start of treatment with Arava as it can have contraindications in pregnant women, or women in their childbearing age. It also warned against severe liver injury such as liver failure, which can result due to use of Arava. Thus patients having acute or chronic liver disease, or serum alanine aminotransferase should not use Arava.
The information regarding prescription of Arava was updated by Aventis Pharmaceuticals and FDA both in 2003. Arava has shown severe side effects such as serious hepatic injury. Some cases even resulted in death. Other side effects reported were severe infections, including sepsis.
In July 2010 FDA added information on severe liver injury through the Boxed Warning on label of Arava. Previously black box warning was regarding contraindication in pregnant women, or women of childbearing potential who were not using reliable contraception. This was a result of a review by FDA regarding adverse effects of Arava. This review included 14 cases of fatal liver failure, between August 2002 and May 2009. This review revealed that patients using Arava were at greater risk of developing liver diseases compared to those who are not using this medicine.
FDA asked following information to be added in the Black Box warning
- Patients having liver disease must not use Arava.
- Patients who have an elevated level of liver enzymes or ALT should not use this medicine.
- It should be taken care of whether patient is using other liver damaging medicine along with Arava.
- There should be regular monitoring of liver enzymes on monthly basis for at least three months while using Arava and after every three months after stopping its use.
- In case of ALT being more than two times the upper limit of normal use of Arava must be stopped and cholestyramine washout should be undertaken to remove Arava from the body till ALT becomes normal.