Do you hold Leflunomide (disease-modifying antirheumatic drug) in the setting of an infection?

Management of Leflunomide During Infection

Leflunomide should be temporarily withheld during active infection until the infection has completely resolved. 1

Rationale for Withholding Leflunomide

Leflunomide is an immunosuppressive disease-modifying antirheumatic drug (DMARD) that can increase susceptibility to infections due to its mechanism of action. The FDA drug label specifically states that "in the event that a serious infection occurs, it may be necessary to interrupt therapy with leflunomide" 1. This recommendation is based on several important considerations:

• Leflunomide has immunosuppressive properties that may make patients more susceptible to infections, including opportunistic infections
• Severe infections including sepsis, which may be fatal, have been reported in patients receiving leflunomide
• Common serious infections associated with leflunomide include pneumonia, oral candidiasis, pyelonephritis, tuberculosis, cellulitis, and disseminated herpes zoster 2

Risk Factors for Severe Infections

Patients at higher risk for developing severe infections while on leflunomide include:

• Older age
• Presence of diabetes mellitus
• Higher daily dosage of concomitant corticosteroids 2
• Combination therapy with other immunosuppressants, particularly methotrexate 3

Management Algorithm During Infection

1. For active infection:

   • Temporarily withhold leflunomide
   • Treat the infection appropriately
   • Consider cholestyramine washout for severe infections (as recommended in the FDA label) 1

2. For severe infections not responding to standard treatment:

   • Discontinue leflunomide
   • Administer cholestyramine or activated charcoal to enhance drug elimination 1
   • Early cholestyramine washout is strongly recommended as infections may rapidly progress in patients taking leflunomide 3

3. For patients receiving antibiotics:

   • Withhold leflunomide until the patient recovers and completes the antibiotic course

Restarting Leflunomide After Infection

After complete resolution of the infection:

• Restart leflunomide at the previous effective dose if the infection was uncomplicated
• Consider a lower dose if the patient had a severe infection or is at high risk for recurrent infections
• Monitor more closely for recurrent infections after restarting therapy

Special Considerations

• Drug interactions: Be aware that certain antibiotics may interact with leflunomide or other concomitant medications
• Monitoring: After restarting leflunomide, monitor complete blood count and liver function tests as leflunomide can cause bone marrow suppression and hepatotoxicity 1
• Permanent discontinuation: Consider permanent discontinuation in patients who develop opportunistic infections or recurrent severe infections despite temporary withholding

Common Pitfalls to Avoid

• Failure to recognize infection early: Infections may progress rapidly in patients on leflunomide
• Inadequate drug elimination: For severe infections, simply withholding the drug may not be sufficient due to leflunomide's long half-life (approximately 2 weeks) 4; consider cholestyramine washout
• Restarting too soon: Restarting leflunomide before complete resolution of infection may lead to prolonged or recurrent infection
• Ignoring risk factors: Patients with multiple risk factors (age, diabetes, concomitant steroids) require closer monitoring

By temporarily withholding leflunomide during active infection and ensuring complete resolution before restarting, you can minimize the risk of infection-related morbidity and mortality while maintaining long-term disease control for your patient.