What are the risks of hematuria associated with leflunomide (disease-modifying antirheumatic drug)?

Risks of Hematuria Associated with Leflunomide

Leflunomide therapy carries a risk of hematuria that requires monitoring, though it is not specifically listed as a common adverse effect in FDA labeling. While hematuria is not prominently mentioned among leflunomide's primary side effects, evidence suggests it may occur as part of the drug's hematologic complications or urinary tract effects.

Hematologic and Urinary Risks of Leflunomide

Documented Hematologic Complications

• The FDA label for leflunomide warns about rare reports of pancytopenia, agranulocytosis, and thrombocytopenia 1
• These hematologic complications occur more frequently when:
  • Leflunomide is combined with methotrexate or other immunosuppressants
  • Patients have recently discontinued other immunosuppressive therapies
  • Patients have a prior history of significant hematologic abnormalities 1

Urinary System Considerations

• While hematuria is not explicitly listed as a common side effect in the FDA label, several factors may contribute to this risk:
  • The American College of Chest Physicians guidelines recommend further evaluation for patients who develop hematuria while on cyclophosphamide therapy (another immunosuppressant), suggesting similar vigilance may be appropriate for leflunomide 2
  • Immunosuppressive medications like leflunomide can mask symptoms of urinary tract infections or other conditions that may cause hematuria

Monitoring Recommendations

Laboratory Monitoring

• CBC monitoring is strongly recommended:
  • At baseline
  • Monthly for the first 6 months of therapy
  • Every 6-8 weeks thereafter 1
  • More frequent monitoring (monthly) if used with methotrexate or other immunosuppressants 1

Specific Monitoring for Juvenile Idiopathic Arthritis

• For children with JIA receiving leflunomide:
  • CBC and liver function tests are conditionally recommended within the first 1-2 months of usage
  • Continued monitoring every 3-4 months thereafter 2

Risk Factors for Hematuria with Leflunomide

Patient-Specific Risk Factors

• Concomitant use of anticoagulants or antiplatelet medications significantly increases the risk of hematuria-related complications 3
• Pre-existing renal disease or genitourinary malignancies may increase risk
• Advanced age appears to increase risk of hematologic complications 4

Drug Interactions

• Combined therapy with methotrexate increases risk of hematologic abnormalities 1, 4
• Patients on both anticoagulants and antiplatelet agents have substantially higher rates of hematuria-related complications compared to those not on these medications 3

Management of Hematuria

When to Discontinue Therapy

• If evidence of bone marrow suppression occurs (including hematuria with other hematologic abnormalities), treatment with leflunomide should be stopped 1
• Drug elimination procedure with cholestyramine or charcoal should be implemented to reduce plasma concentration of leflunomide's active metabolite 1

Evaluation of Hematuria

• Patients who develop hematuria should undergo further evaluation to rule out:
  • Urinary tract infection
  • Malignancy (patients on antithrombotic medications with hematuria have higher rates of bladder cancer diagnosis) 3
  • Other urologic conditions

Special Considerations

Caution with Concomitant Medications

• Avoid combining leflunomide with other medications that have known hematologic toxicity when possible
• If switching from leflunomide to another anti-rheumatic agent with hematologic suppression potential, monitor closely for hematologic toxicity due to overlapping systemic exposure 1

Pregnancy Considerations

• Leflunomide is teratogenic and contraindicated in pregnancy
• Women of childbearing potential must use reliable contraception during treatment and undergo drug elimination procedure before attempting conception 1