Leflunomide Dosage and Treatment Protocol for Rheumatoid Arthritis
For patients with rheumatoid arthritis, leflunomide should be initiated with a loading dose of 100 mg once daily for 3 days, followed by a maintenance dose of 20 mg once daily. 1
Dosing Regimen
Initial Loading Dose
- 100 mg tablet once daily for 3 days 1
- Note: Elimination of the loading dose may be considered for patients at increased risk of hematologic or hepatic toxicity, especially those receiving concomitant treatment with methotrexate or other immunosuppressive agents 1
Maintenance Dose
- 20 mg once daily is the recommended standard dose 1
- If 20 mg daily is not well tolerated, the dose may be decreased to 10 mg daily 1
- Doses higher than 20 mg/day are not recommended due to increased incidence of side effects (alopecia, weight loss, liver enzyme elevations) 1
Efficacy and Onset of Action
- Therapeutic effect appears as early as 4 weeks after initiation 2
- Full assessment of efficacy should be made after at least 3-4 months of therapy 3
- Efficacy is maintained for durations of up to 24 months 2
- Leflunomide has shown efficacy comparable to methotrexate and sulfasalazine in clinical trials 2
Monitoring Requirements
- Monthly liver enzyme monitoring is required until stable concentrations are reached 4
- Regular monitoring for adverse effects is essential throughout treatment
Place in Treatment Algorithm
Leflunomide is recommended:
- As an alternative to methotrexate in cases of MTX contraindications or early intolerance 5
- As a second-line agent after failure of first-line DMARD therapy 6
Adverse Effects Management
Common adverse events include:
- Diarrhea (27%)
- Respiratory infections (21%)
- Nausea (13%)
- Headache (13%)
- Rash (12%)
- Elevated liver enzymes (10%)
- Alopecia (9%) 2
Management of Adverse Effects
- Dose reduction from 20 mg to 10 mg daily if side effects occur 1
- Symptomatic therapy for gastrointestinal symptoms
- Close monitoring of liver function tests
Important Considerations
- Due to the long half-life of the active metabolite (approximately 2 weeks), careful observation is needed after dose reduction 1
- Leflunomide is contraindicated in pregnant women due to risk of fetal death or teratogenic effects 4
- Male patients wishing to father a child should discontinue treatment and consider drug elimination procedures 2
Comparative Efficacy
- One study comparing loading dose (100 mg × 1 for 3 days) with fixed dose of 20 mg daily showed no differences in efficacy but better safety profile for the fixed dose 5
- A weekly dose of 50 mg showed similar benefits to a daily dose of 10 mg for mild-to-moderate early RA, though 10 mg daily is considered suboptimal 5
Leflunomide has been demonstrated to meet all three goals of disease-modifying antirheumatic drug therapy: reducing signs and symptoms, inhibiting structural damage, and improving physical function 3.