Medication Guide — Leflunomide

Embryo-Fetal Toxicity

Leflunomide is contraindicated for use in pregnant women because of the potential for fetal harm. Teratogenicity and embryo-lethality occurred in animals administered leflunomide at doses lower than the human exposure level. Exclude pregnancy before the start of treatment with leflunomide in females of reproductive potential. Advise females of reproductive potential to use effective contraception during leflunomide treatment and during an accelerated drug elimination procedure after leflunomide treatment. Stop leflunomide tablets and use an accelerated drug elimination procedure if the patient becomes pregnant.

Hepatotoxicity

Severe liver injury, including fatal liver failure, has been reported in patients treated with leflunomide. Leflunomide is contraindicated in patients with severe hepatic impairment. Concomitant use of leflunomide with other potentially hepatotoxic drugs may increase the risk of liver injury. Patients with pre-existing acute or chronic liver disease, or those with serum alanine aminotransferase (ALT) >2xULN before initiating treatment, are at increased risk and should not be treated with leflunomide. Monitor ALT levels at least monthly for six months after starting leflunomide, and thereafter every 6 to 8 weeks. If leflunomide-induced liver injury is suspected, stop leflunomide treatment, start an accelerated drug elimination procedure, and monitor liver tests weekly until normalized.

WARNING: EMBRYO-FETAL TOXICITY and HEPATOTOXICITY

See full prescribing information for complete boxed warning.

• Teratogenicity and embryo-lethality occurred in animals administered leflunomide. ( 5.1, 8.1)
• Exclude pregnancy prior to initiating leflunomide tablets therapy. ( 5.1, 8.3)
• Advise use of effective contraception in females of reproductive potential during treatment and during a drug elimination procedure. ( 5.1, 5.3, 8.3)
• Stop leflunomide tablets and use an accelerated drug elimination procedure if the patient becomes pregnant. ( 5.1, 5.3, 8.1)

• Severe liver injury and fatal liver failure have been reported. ( 5.2)
• Avoid leflunomide use in patients with pre-existing liver disease, or those with serum alanine aminotransferase (ALT)>2xULN. ( 5.2, 8.6)
• Use caution when leflunomide is given with other potentially hepatotoxic drugs. ( 5.2)
• Monitor ALT levels. Interrupt leflunomide treatment if ALT elevation > 3 fold ULN. If likely leflunomide-induced, start accelerated drug elimination procedure and monitor liver tests weekly until normalized. ( 5.2, 5.3)