How to Perform an Arava (Leflunomide) Washout
Administer cholestyramine 8 grams orally three times daily for 11 days, then verify plasma teriflunomide levels are less than 0.02 mg/L with two separate tests at least 14 days apart. 11
Washout Protocol
The FDA-approved accelerated elimination procedure follows this specific algorithm:
Primary Method: Cholestyramine
- Dose: 8 grams orally three times daily
- Duration: 11 days
- Verification: Measure plasma teriflunomide concentrations with two separate tests at least 14 days apart
- Target level: Less than 0.02 mg/L (0.02 mcg/mL)
Alternative Method: Activated Charcoal
- Dose: 50 grams of activated charcoal powder (made into suspension)
- Frequency: Every 12 hours
- Duration: 11 days
- Same verification requirements as cholestyramine 11
When to Perform Washout
Mandatory indications for accelerated elimination include:
- Pregnancy: If pregnancy occurs during treatment or is planned, washout is essential. All women of childbearing potential should undergo washout after stopping Arava 11
- Severe adverse reactions: Hepatotoxicity, serious infection, bone marrow suppression, Stevens-Johnson syndrome, toxic epidermal necrolysis, peripheral neuropathy, or interstitial lung disease 1123
- Suspected hypersensitivity reactions 11
Critical Monitoring
If initial washout fails (teriflunomide levels remain >0.02 mg/L):
- Repeat cholestyramine and/or activated charcoal treatment
- Continue monitoring until target levels achieved
- The procedure may be repeated as needed based on concentrations and clinical status 11
Important Caveats
Without washout, it may take up to 2 years to reach safe plasma concentrations naturally due to enterohepatic recirculation 11. This prolonged elimination makes the washout procedure critical in urgent situations.
Disease flare risk: The accelerated elimination may result in return of disease activity if the patient had been responding to leflunomide treatment 11. Plan for alternative disease management during and after washout.
Pregnancy planning: Recent EULAR guidelines suggest discontinuation 3.5 months before conception based on prospective pharmacovigilance data, though washout with level verification remains the definitive approach 4. The 2020 ACR guidelines strongly recommend cholestyramine washout if detectable serum levels exist prior to or when pregnancy is confirmed 5.
Clinical success: Multiple case reports demonstrate successful resolution of leflunomide-induced complications (pneumonitis, toxic epidermal necrolysis, septic shock) following cholestyramine washout 623, supporting its efficacy in urgent clinical scenarios.