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The incidence of pancytopenia in patients taking leflunomide alone or with methotrexate

John McEwen1, Patrick M Purcell, Richard L Hill

  • 1Department of Executive Office, Therapeutic Goods Administration, Woden, Australian Capital Territory, Australia. mclaudj@webone.com.au

Pharmacoepidemiology and Drug Safety
|April 25, 2006
PubMed
Abstract

Insights

The combination of leflunomide and methotrexate significantly increases the risk of pancytopenia, a serious blood disorder. This finding highlights the need for careful monitoring when these drugs are used together.

Area of Science:

  • Pharmacovigilance
  • Clinical Pharmacology
  • Rheumatology

Background:

  • Leflunomide is a disease-modifying antirheumatic drug (DMARD) used for rheumatoid arthritis.
  • Methotrexate is commonly used alone or in combination with other DMARDs.

Purpose of the Study:

  • To determine the incidence of pancytopenia in patients using leflunomide in Australia.
  • To assess if concomitant methotrexate use alters this risk.

Main Methods:

  • Analysis of spontaneous adverse drug reaction reports to the Australian Adverse Drug Reactions Advisory Committee (ADRAC).
  • Incidence estimation using national prescription reimbursement data.
  • Assessment of methotrexate co-exposure from multiple data sources.

Main Results:

  • Eleven cases of pancytopenia linked to leflunomide were reported within 31 months.
  • Nine of these cases involved patients also taking methotrexate.
  • Estimated incidence of pancytopenia was 1 in 3698 to 1 in 4582 for leflunomide alone, versus 1 in 575 to 1 in 822 when combined with methotrexate.

Conclusions:

  • Concomitant use of methotrexate with leflunomide elevates the risk of pancytopenia.
  • The hematological toxicity of this drug combination warrants further investigation.

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