The incidence of pancytopenia in patients taking leflunomide alone or with methotrexate.
OBJECTIVE
To estimate the incidence of pancytopenia in patients taking leflunomide with or without methotrexate in Australia.


METHODS
Review of spontaneous reports to the Australian Adverse Drug Reactions Advisory Committee (ADRAC); estimation of incidence using national prescription reimbursement data; concomitant exposure to methotrexate was estimated using three sources of information.


RESULTS
ADRAC received 11 reports of pancytopenia (meeting predefined criteria) associated with the use of leflunomide during its first 31 months of marketing. In nine reports, the patients were also taking methotrexate. Estimates of incidence in patients taking leflunomide alone ranged from 1 in 3698 to 1 in 4582 patients exposed; for patients also taking methotrexate the estimates ranged from 1 in 575 to 1 in 822.


CONCLUSIONS
Use of methotrexate with leflunomide increases the risk of pancytopenia compared with use of leflunomide alone. The haematological toxicity of the combination requires further study.
McEwen
John
J
Department of Executive Office, Therapeutic Goods Administration, Woden, Australian Capital Territory, Australia. mclaudj@webone.com.au
Purcell
Patrick M
PM
Hill
Richard L
RL
Calcino
Lisa J
LJ
Riley
Cathy G
CG
D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data*; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced / Q000453:epidemiology; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001315:Australia / Q000453:epidemiology; D002220:Carbamazepine / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D004359:Drug Therapy, Combination; D017723:Drug Utilization Review / Q000379:methods / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D015994:Incidence; D007555:Isoxazoles / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use; D000077339:Leflunomide; D008297:Male; D008727:Methotrexate / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000453:epidemiology; D050607:Organogold Compounds / Q000008:administration & dosage / Q000009:adverse effects; D010198:Pancytopenia / Q000139:chemically induced / Q000453:epidemiology*; D013921:Thrombocytopenia / Q000139:chemically induced / Q000453:epidemiology
D018501:Antirheumatic Agents; D007555:Isoxazoles; D050607:Organogold Compounds; D002220:Carbamazepine; D000077339:Leflunomide; D008727:Methotrexate