Leflunomide Dosing in Rheumatoid Arthritis
The standard dosing regimen for leflunomide in rheumatoid arthritis is a loading dose of 100 mg daily for 3 days, followed by a maintenance dose of 20 mg once daily. 1
Standard Dosing Regimen
Loading Dose
- Initiate with 100 mg once daily for 3 days to achieve steady-state concentrations more rapidly due to leflunomide's long half-life (approximately 2 weeks). 1
- Elimination of the loading dose may decrease the risk of adverse events, particularly for patients at increased risk of hematologic or hepatic toxicity, such as those receiving concomitant methotrexate or other immunosuppressive agents. 1
- Avoiding the loading dose reduces nuisance side effects like nausea but delays onset of action. 2
Maintenance Dose
- 20 mg once daily is the recommended maintenance dose for treatment of rheumatoid arthritis. 1
- This dose has demonstrated similar efficacy to methotrexate and sulfasalazine in clinical trials. 3
- Doses higher than 20 mg daily are not recommended, as a cohort treated with 25 mg/day experienced greater incidence of side effects including alopecia, weight loss, and liver enzyme elevations. 1
Dose Adjustments
Dose Reduction
- If 20 mg daily is not well tolerated clinically, the dose may be decreased to 10 mg daily. 1
- However, a randomized trial comparing 10 mg versus 20 mg daily rejected the hypothesis of non-inferiority for the 10 mg dose, with the 20 mg dose showing better efficacy profile. 4
- Patients should be carefully observed after dose reduction, as it may take several weeks for metabolite levels to decline due to the prolonged half-life. 1
Alternative Dosing Approaches
Weekly Dosing
- A study of 100 mg weekly dosing (after standard loading) showed ACR20 response rates of 74% at 24 weeks, suggesting potential benefit with improved compliance and reduced cost. 5
- However, this approach lacks robust comparative data and is not part of standard FDA-approved dosing. 1
Fixed Dose vs. Loading Dose
- Studies comparing loading dose with fixed 20 mg daily dosing showed no differences in efficacy but a better safety profile for the fixed dose approach. 3
Monitoring Requirements
- Liver enzymes must be monitored and dose adjustments may be necessary. 1
- Monthly monitoring of liver enzymes is required until stable concentrations are reached. 6
Clinical Efficacy Timeline
- Therapeutic effects appear as early as 4 weeks, which is earlier than sulfasalazine or methotrexate. 7
- Efficacy is maintained for durations of up to 24 months in clinical trials. 7
Common Pitfalls to Avoid
- Do not exceed 20 mg daily maintenance dosing due to increased adverse events without additional benefit. 1
- Consider eliminating the loading dose in patients at high risk for toxicity, particularly those on concurrent immunosuppressive therapy or with recent exposure to such medications. 1
- Do not abruptly discontinue without considering the prolonged elimination time—metabolite levels take weeks to decline. 1
| Dosing Component | Recommendation |
|---|---|
| Loading Dose | 100 mg daily × 3 days (may omit in high-risk patients) [1] |
| Maintenance Dose | 20 mg once daily [1] |
| Dose Reduction | 10 mg daily if 20 mg not tolerated [1] |
| Maximum Dose | 20 mg daily (do not exceed) [1] |