Leflunomide (2 brand names, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- ARAVA
- LEFLUNOMIDE
Indications and Usage
Leflunomide Tablets are indicated for the treatment of adults with active rheumatoid arthritis (RA).
Contraindications
Leflunomide is contraindicated in: Pregnant women. Leflunomide may cause fetal harm. If a woman becomes pregnant while taking this drug, stop leflunomide, apprise the patient of the potential hazard to the fetus, and begin a drug elimination procedure [see Warnings and Precautions (5.1, 5.3) and Use in Specific Populations (8.1)]. Patients with severe hepatic impairment [see Warnings and Precautions (5.2)]. Patients with known hypersensitivity to leflunomide or any of the other components of leflunomide. Known reactions include anaphylaxis [see Adverse Reactions (6.1)]. Patients being treated with teriflunomide [see Drug Interactions (7)].
Adverse Reactions
The following serious adverse reactions are described elsewhere in the labeling: Hepatotoxicity [see Warnings and Precautions (5.2)] Immunosuppression [see Warnings and Precautions (5.4)] Bone marrow suppression [see Warnings and Precautions (5.4)] Serious infections [see Warnings and Precautions (5.4)] Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reactions with eosinophilia and systemic symptoms [see Warnings and Precautions (5.5)] Skin ulcers [see Warnings and Precautions (5.6)] Peripheral neuropathy [see Warnings and Precautions (5.8)] Interstitial lung disease [see Warnings and Precautions (5.9)]
Drug Interactions
Following oral administration, leflunomide is metabolized to an active metabolite, teriflunomide, which is responsible for essentially all of leflunomide’s in vivo activity. Drug interaction studies have been conducted with both leflunomide and with its active metabolite, teriflunomide, where the metabolite was directly administered to the test subjects.
Mechanism of Action
Leflunomide is an isoxazole immunomodulatory agent that inhibits dihydroorotate dehydrogenase (a mitochondrial enzyme involved in de novo pyrimidine synthesis) and has antiproliferative activity. Several in vivo and in vitro experimental models have demonstrated an anti-inflammatory effect.
Overdosage
There have been reports of chronic overdose in patients taking leflunomide at daily dose up to five times the recommended daily dose and reports of acute overdose in adults and children. Adverse events were consistent with the safety profile for leflunomide [see Adverse Reactions (6)]. The most frequent adverse events observed were diarrhea, abdominal pain, leukopenia, anemia, and elevated liver function tests. In the event of a significant overdose or toxicity, perform an accelerated drug elimination procedure to accelerate elimination [see Warnings and Precautions (5.3)]. Studies with both hemodialysis and CAPD (chronic ambulatory peritoneal dialysis) indicate that teriflunomide, the primary metabolite of leflunomide, is not dialyzable [see Clinical Pharmacology (12.3)].