Hepatotoxicity, Risk of Teratogenicity & Embryofetal Toxicity

Hepatotoxicity

• Severe liver injury, including fatal liver failure has been reported in patients treated with leflunomide, which is indicated for rheumatoid arthritis. A similar risk would be expected for teriflunomide because recommended doses of teriflunomide and leflunomide result in a similar range of plasma concentrations of teriflunomide.
• Concomitant use of teriflunomide and other potentially hepatotoxic drugs may increase the risk of severe liver injury.
• Obtain transaminase and bilirubin levels within 6 months before initiation of teriflunomide therapy. Monitor ALT levels at least monthly for 6 months after starting teriflunomide.
• If drug induced liver injury is suspected, discontinue teriflunomide and start an accelerated elimination procedure with cholestyramine or charcoal.
• Teriflunomide is contraindicated in patients with severe hepatic impairment. Patients with pre-existing liver disease may be at increased risk of developing elevated serum transminases when taking teriflunomide.

Teratogenicity

• Based on animal data, teriflunomide may cause major birth defects if used during pregnancy.
• Pregnancy must be excluded before starting therapy with this agent.
• Teriflunomide is contrainidcated in pregnant women or women of childbearing potential who are not using reliable contraception.
• Pregnancy must be avoided during teriflunomide treatment or prior to the completion of an accelerated elimination procedure after teriflunomide treatment.

Embryofetal Toxicity

• AUBAGIO is contraindicated for use in pregnant women and in females of reproductive potential who are not using effective contraception because of the potential for fetal harm. Teratogenicity and embryolethality occurred in animals at plasma teriflunomide exposures lower than that in humans. Exclude pregnancy before the start of treatment with AUBAGIO in females of reproductive potential. Advise females of reproductive potential to use effective contraception during AUBAGIO treatment and during an accelerated drug elimination procedure after AUBAGIO treatment. Stop AUBAGIO and use an accelerated drug elimination procedure if the patient becomes pregnant.

Pancreatitis in Pediatric Patients

• AUBAGIO is not approved for use in pediatric patients. In the pediatric clinical trial, cases of pancreatitis were observed in 1.8% (2/109) of patients receiving AUBAGIO; one of these cases was serious. If pancreatitis is suspected, discontinue teriflunomide and start an accelerated elimination procedure.