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Uses

Rheumatoid Arthritis in Adults

Used to manage the signs and symptoms of rheumatoid arthritis, to improve physical function, and to retard structural damage associated with the disease. Efficacy comparable to that of methotrexate or sulfasalazine.

Has been used with methotrexate in a limited number of adults. Used concomitantly with aspirin, NSAIAs, or low dosages of oral corticosteroids (e.g., prednisone 10 mg daily) in clinical studies.

Solid Organ Transplantation

Has been used for the prevention of acute and chronic rejection† in recipients of solid organ transplants (designated an orphan drug by FDA for this use). Evaluated in a limited number of renal or hepatic transplant recipients.

Dosage and Administration

General

Drug Elimination Procedures Following Leflunomide Discontinuance

• Plasma concentration of the active metabolite of leflunomide (A77 1726) may be detectable in plasma for up to 2 years following discontinuance of the drug. Manufacturer recommends use of a drug elimination procedure whenever more rapid elimination is indicated or desirable.
• An 11-day cholestyramine regimen is recommended whenever leflunomide is discontinued in women of childbearing potential and should be considered in men who wish to father a child after discontinuing the drug; this regimen reduces plasma concentrations of A77 1726 to undetectable levels.
• A shorter regimen of cholestyramine or activated charcoal (≥1 day) can be used to hasten elimination of A77 1726 in other patients (see Prolonged Leflunomide Exposure following Discontinuance under Cautions). In patients who discontinued leflunomide because of hypersensitivity reaction, a more prolonged regimen may be necessary to achieve rapid and sufficient clearance of A77 1726.

11-Day Cholestyramine Drug-Elimination Procedure

• Cholestyramine 8 g orally 3 times daily for 11 days; the 11 days do not need to be consecutive unless plasma concentrations need to be reduced rapidly.
• Following completion of regimen, determine plasma concentrations of A77 1726 twice (≥14 days apart) to verify that concentrations are undetectable. If plasma concentrations exceed 0.02 mcg/mL, administer additional cholestyramine.

Shorter Cholestyramine or Activated Charcoal Regimen

• Cholestyramine (8 g 3 times daily) given orally for 24 hours reduces plasma concentrations of A77 1726 by approximately 40% in 24 hours and 49–65% in 48 hours.
• Alternatively, suspension of activated charcoal (50 g every 6 hours) given for 24 hours either orally or via nasogastric tube reduces plasma concentrations of A77 1726 by approximately 37% in 24 hours and 48% in 48 hours.
• Repeat the elimination procedure if clinically necessary.

Administration

Oral Administration

Usually administered orally as a single daily dose, without regard to meals.

Dosage

Adults

Rheumatoid Arthritis in Adults

Oral

100 mg once daily for 3 days, then 20 mg once daily. If this dosage is not tolerated, decrease to 10 mg once daily. Dosage adjustment or discontinuance may be required in patients who experience hepatotoxicity. (See Hepatic Effects under Cautions.)

Eliminating the 3-day loading dose may decrease the risk of adverse effects (see Plasma Concentrations under Pharmacokinetics). Elimination of loading dose may be especially important for patients at increased risk of hematologic or hepatic toxicity.

Solid Organ Transplantation

Renal or Hepatic Transplant Recipients

Oral

Initial loading dosage of 1.2–1.4 g (administered in divided doses over 5–7 days), then 10–120 mg daily.†

Prescribing Limits

Adults

Rheumatoid Arthritis in Adults

Oral

Maintenance therapy: Maximum 20 mg daily. Dosages of 25 mg daily associated with higher incidence of alopecia, weight loss, and increases in serum liver enzyme concentrations.

Special Populations

Dosage in Hepatic Impairment

Not recommended in patients with substantial hepatic impairment or those who are seropositive for hepatitis B or C. (See Hepatic Impairment and also Hepatic Effects, under Cautions.)