Recommended Dosage of Leflunomide for Adults with Rheumatoid Arthritis
The standard recommended dose of leflunomide for adults with rheumatoid arthritis is 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
- A loading dose is recommended to achieve steady-state concentrations more rapidly due to leflunomide's long half-life (approximately 2 weeks) 1, 2
- Standard loading dose: 100 mg once daily for 3 days 1
- The loading dose may be eliminated in patients at increased risk of hematologic or hepatic toxicity, especially those receiving concomitant treatment with methotrexate or other immunosuppressive agents 1
Maintenance Dose
- Standard maintenance dose: 20 mg once daily 1, 3
- If 20 mg daily is not well tolerated, the dose may be decreased to 10 mg daily 1
- A small cohort study (n=104) using 25 mg/day showed a greater incidence of side effects including alopecia, weight loss, and liver enzyme elevations; therefore, doses higher than 20 mg/day are not recommended 1
Efficacy Considerations
- Leflunomide has demonstrated efficacy similar to methotrexate and sulfasalazine in clinical trials 2, 4
- The therapeutic effect of leflunomide appears earlier (at 4 weeks) than that of sulfasalazine or methotrexate 2
- Leflunomide is effective in both early and late disease, regardless of whether patients have received other DMARDs previously 5
- Experts recommend observing a patient on leflunomide monotherapy for at least 3-4 months before fully assessing efficacy 5
Alternative Dosing Approaches
- A study comparing 10 mg vs 20 mg daily maintenance doses found that the 20 mg dose had better efficacy, rejecting the hypothesis of non-inferiority of the 10 mg dose 6
- One small open-label study (n=50) explored weekly dosing (100 mg once weekly after loading dose) and reported similar efficacy to daily dosing with good tolerability, but this regimen requires further validation in comparative trials 7
- A study comparing a loading dose of leflunomide (100 mg×1 for 3 days) with a fixed dose of 20 mg daily showed no differences in efficacy but a better safety profile for the fixed dose 3
Monitoring and Safety Considerations
- Liver enzyme monitoring is required during leflunomide treatment 1, 4
- Monthly monitoring of liver enzymes is recommended until stable concentrations are reached 4
- Due to the prolonged half-life of the active metabolite, patients should be carefully observed after dose reduction, as it may take several weeks for metabolite levels to decline 1
- Common adverse events include diarrhea (27%), respiratory infections (21%), nausea (13%), headache (13%), rash (12%), elevated liver enzymes (10%), dyspepsia (10%), and alopecia (9%) 2
Special Populations
- Leflunomide is contraindicated in pregnant women or women who may become pregnant due to teratogenic effects 4
- Drug treatment should be discontinued, and drug elimination procedures should be considered, in male patients wishing to father a child 2
- In patients with renal vasculitis, leflunomide has been used as a remission-maintenance therapy at a dose of 20-30 mg/day 3
Remember that leflunomide is an alternative to methotrexate in cases where methotrexate is contraindicated or not tolerated, and has shown efficacy similar to methotrexate in treating rheumatoid arthritis 3.