Generic Name

Leflunomide

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Classification

FDA Approved Indications

• Rheumatoid arthritis

Mechanism of Action

Inhibits pyrimidine synthesis by irreversibly blocking dihydroorotate dehydrogenase, leading to suppression of T-cell proliferation and reduction of inflammatory responses.

Dosage and Administration

Adult: Initially 100 mg once daily for 3 days, then 20 mg once daily.

Pediatric: Not approved for pediatric use.

Geriatric: Adjust dose based on renal and hepatic function; start at lower doses if necessary.

Renal Impairment: Use with caution; dosage adjustments may be necessary.

Hepatic Impairment: Use with caution; contraindicated if severe hepatic impairment.

Pharmacokinetics

Absorption: Well absorbed orally.

Distribution: Widely distributed, protein bound (about 99%).

Metabolism: Primarily hepatic via CYP enzymes.

Excretion: Fecal excretion predominantly; minimal renal excretion.

Half Life: Approximate half-life is 14-18 days, leading to accumulation.

Contraindications

• Pregnancy, women of childbearing potential not using contraception
• Severe hepatic impairment

Precautions

• Liver function should be monitored periodically.
• Patients should use reliable contraception during and for 2 years after therapy due to teratogenicity.
• Immunosuppressive effects; increased infection risk.
• Risk of lymphoma and other malignancies.

Adverse Reactions - Common

• Diarrhea (Frequent)
• Transaminitis (elevated liver enzymes) (Common)
• Alopecia (Common)
• Nausea (Common)

Adverse Reactions - Serious

• Hepatotoxicity (Less common but serious)
• Myelosuppression (neutropenia, thrombocytopenia, anemia) (Less common)
• Severe infections (Less common)
• Interstitial lung disease (Rare)

Drug-Drug Interactions

• Methotrexate (increased risk of hepatotoxicity and myelosuppression)
• Chloramphenicol (risk of bone marrow suppression)

Drug-Food Interactions

N/A

Drug-Herb Interactions

N/A

Nursing Implications

Patient/Family Teaching

• Do not become pregnant during therapy and for 2 years after discontinuation.
• Report signs of infection, unusual bleeding, or jaundice.
• Avoid live vaccines during therapy.
• Take medication exactly as prescribed, even if feeling well.

Special Considerations

Black Box Warnings:

• Embryo-fetal toxicity; contraindicated during pregnancy and for women trying to conceive.
• Severe liver injury.

Genetic Factors: Some populations may have differences in metabolism affecting drug levels.

Lab Test Interference: May cause elevated liver enzymes, which should be interpreted carefully.

Overdose Management

Signs/Symptoms: Gastrointestinal symptoms, leukopenia, elevated liver enzymes.

Treatment: Supportive care; activated charcoal if ingestion is recent; possibly administering cholestyramine to reduce absorption.

Storage and Handling

Storage: Store at room temperature, away from moisture and light.

Stability: Stable for the duration of the shelf life as indicated by manufacturer.