Can leflunomide or hydroxychloroquine cause pancytopenia?

Leflunomide and Hydroxychloroquine Can Both Cause Pancytopenia

Yes, both leflunomide and hydroxychloroquine can cause pancytopenia, with leflunomide posing a higher risk, particularly when combined with other immunosuppressive medications. 1, 2

Leflunomide-Associated Pancytopenia

Risk Profile

• Rare but serious reports of pancytopenia, agranulocytosis, and thrombocytopenia have been documented in patients receiving leflunomide 3
• The risk is significantly higher when leflunomide is combined with methotrexate or other immunosuppressive agents 1, 4
• Estimated incidence ranges from 1 in 3698 to 1 in 4582 patients when taking leflunomide alone, but increases to 1 in 575 to 1 in 822 patients when combined with methotrexate 4

Timing and Presentation

• Time to onset of pancytopenia is variable, ranging from 11 days to 4 years (median 4 months) after starting treatment 5
• Pancytopenia can be severe, requiring hospitalization, drug discontinuation, and intensive supportive care 5, 6
• Fatal outcomes have been reported, particularly in older patients and those on combination therapy 5

Monitoring Recommendations

• Complete blood count (CBC) should be performed at baseline and monitored monthly for the first 6 months of therapy 3, 7
• After 6 months, if stable, monitoring can be reduced to every 6-8 weeks 3, 1
• More frequent monitoring may be necessary for patients on combination therapy with other immunosuppressants 1

Hydroxychloroquine-Associated Pancytopenia

Risk Profile

• Hydroxychloroquine may cause myelosuppression including aplastic anemia, agranulocytosis, leukopenia, and thrombocytopenia, though this occurs less frequently than with leflunomide 2
• Isolated thrombocytopenia has been reported in patients with systemic lupus erythematosus taking hydroxychloroquine 8

Monitoring Recommendations

• CBC monitoring is recommended annually for patients on prolonged hydroxychloroquine therapy 3, 2
• More frequent monitoring may be warranted in patients with additional risk factors or those taking other medications that may cause bone marrow suppression 2

Management of Drug-Induced Pancytopenia

Immediate Actions

• If pancytopenia is suspected or confirmed, discontinue the offending medication immediately 1, 2
• For leflunomide, consider accelerated drug elimination with cholestyramine or activated charcoal to reduce plasma concentration of the active metabolite 3, 1
• Provide supportive care as needed, including treatment of neutropenic sepsis if present 5

Risk Factors to Consider

• Older age appears to increase risk of pancytopenia with both medications 5
• Concomitant use of other immunosuppressive medications significantly increases risk 1, 5
• Changes in baseline health status, particularly acute renal failure or dehydration, may trigger pancytopenia in previously stable patients 5

Clinical Pearls and Pitfalls

• Pitfall: Assuming stable blood counts mean continued safety - pancytopenia can develop even after years of stable therapy 5
• Pitfall: Failing to recognize that acute illness (especially renal failure) can precipitate pancytopenia in previously stable patients on these medications 5
• Pearl: When switching between immunosuppressive agents, be aware of potential overlapping toxicity during the transition period 1
• Pearl: G6PD deficiency increases risk of hemolysis with hydroxychloroquine and should be ruled out before treatment 3, 2