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BackLeflunomide Data - Uses, Dosage, Drug class, Brand name, Warnings, etc
| Pharmacology | Leflunomide’s active metabolite (M1) inhibits dihydro-orotate dehydrogenase, thereby inhibiting pyrimidine biosynthesis. M1 exhibits immunomodulating and anti-inflammatory effects. |
|---|---|
| Administration and Adult Dosage |
For rheumatoid arthritis: - Oral (PO): 100 mg/day for 3 days, then 20 mg/day - Reduce dose to 10 mg/day if 20 mg is not tolerated |
| Special Populations - Pediatric Dosage | Safety and efficacy not established. |
| Special Populations - Geriatric Dosage | Same as adult dosage. |
| Dosage Forms | - Tablet: 10, 20, 100 mg |
| Patient Instructions |
- Do not use if pregnant or planning to become pregnant - Men should use condoms due to risk of birth defects; men planning to father children should discontinue leflunomide and consult their physician - Notify your physician of any major medical problems during therapy - Avoid alcohol to reduce the risk of liver damage - Avoid immunizations unless approved by your physician |
| Missed Doses |
- Take a missed dose as soon as remembered; if near the time for the next dose, skip the missed dose - Do not take a double dose |
| Pharmacokinetics - Fate |
- Bioavailability: 80%, with peak plasma levels in 6–12 hr - Metabolized to active metabolite (M1); parent drug rarely detectable in plasma - Metabolism occurs in hepatic cytosolic and microsomal cellular fractions - Distribution: Vdss of M1 = 0.13 L/kg; 99.3% bound to albumin - Excretion: ~45% as glucuronide and oxanilic acid metabolites in urine, 48% as M1 in feces |
| Pharmacokinetics - t¹⁄₂ | - M1: 18 ± 9 days |
| Adverse Reactions & Side Effects |
Frequent: - Diarrhea, dyspepsia, hypertension, headache, rash, alopecia, elevated liver function tests |
| Contraindications |
- Immunocompromised patients - Positive for hepatitis B or C - Pre-existing hepatic impairment - Women planning to conceive |
| Precautions & Warnings |
- Use caution in patients with renal insufficiency - Do not give live vaccines during therapy |
| Drug Interactions |
- Hepatotoxic medications (e.g., methotrexate) may increase risk of hepatotoxicity - Rifampin increases peak plasma levels of M1 - M1 inhibits CYP2C9, potentially increasing plasma-free fraction of NSAIDs and tolbutamide - Cholestyramine or activated charcoal decreases M1 levels |
| Parameters to Monitor | - Monitor ALT at baseline and monthly; if stable, monitor per clinical judgment |
| Class and Drug Brand Name |
- Class: Analgesic and Anti-Inflammatory Drugs - Brand Name: Arava |
| Notes |
- If toxicity develops or plasma levels must be decreased quickly, administer cholestyramine 8 g three times daily for 11 days; verify plasma levels are <0.02 mg/L by 2 separate tests at least 14 days apart - Without this procedure, drug elimination can take up to 2 years - Leflunomide is equally or more effective than traditional antirheumatic agents such as methotrexate, sulfasalazine, injectable gold, and cyclosporine |
References
Hand of Clinical Drug Data