Duration of Cholestyramine Treatment for Leflunomide Toxicity
For leflunomide toxicity, cholestyramine should be administered at a dose of 8 grams three times daily for 11 days to achieve adequate drug elimination. 1
Drug Elimination Protocol
- Cholestyramine 8 grams three times daily for 11 days (these days do not need to be consecutive unless rapid lowering of plasma levels is required) 1
- Plasma levels of the active metabolite (M1) should be verified to be less than 0.02 mg/L (0.02 mcg/mL) by two separate tests at least 14 days apart 1
- If plasma levels remain higher than 0.02 mg/L after the initial 11-day course, additional cholestyramine treatment should be considered 1
Monitoring During Elimination
- Monitor teriflunomide (active metabolite) blood concentration to ensure levels decrease below 0.02 mg/L 1, 2
- Monitor for resolution of toxicity symptoms as drug levels decrease 2
- Without the drug elimination procedure, it may take up to 2 years to reach safe plasma levels due to individual variation in drug clearance 1
Clinical Evidence Supporting Protocol
- In a documented case of leflunomide toxicity with severe diarrhea, teriflunomide blood concentration decreased from 156 mg/L to 6 mg/L after 11 days of cholestyramine washout therapy 2
- Complete resolution of diarrhea occurred 26 days after initiating cholestyramine treatment 2
- For severe skin reactions like toxic epidermal necrolysis, immediate discontinuation of leflunomide and prompt initiation of the washout procedure are essential 3
Special Considerations
- For patients with interstitial lung disease associated with leflunomide, activated charcoal and cholestyramine significantly decrease the half-life of the drug and should be considered in cases with acute toxicity 4
- For patients with hepatotoxicity, the same elimination protocol should be followed, with close monitoring of liver function tests 5
- For patients of reproductive potential planning pregnancy, verification of plasma levels less than 0.02 mg/L is critical before attempting conception 1
Common Pitfalls
- Failure to complete the full 11-day course of cholestyramine may result in inadequate drug elimination 1
- Not verifying plasma levels with two separate tests at least 14 days apart may lead to inaccurate assessment of drug elimination 1
- Assuming toxicity will resolve quickly without cholestyramine washout is incorrect, as the active metabolite has a long half-life (approximately 2 weeks) 6
- Not monitoring for improvement in clinical symptoms alongside decreasing drug levels may miss persistent toxicity 2