Drug Interactions between azathioprine and trimethoprim

MONITOR: Even though the combination is used in clinical practice, the risk of bone marrow suppression may be increased when azathioprine or mercaptopurine is coadministered with trimethoprim or sulfamethoxazole-trimethoprim (co-trimoxazole). The risk may be increased when concurrent therapy is longer than 3 weeks. Thrombocytopenia and neutropenia have been reported; however, data have been conflicting. The mechanism is unknown, but may be related to additive myelosuppressive effects and hemodialysis-induced folate depletion.

MANAGEMENT: Close clinical and laboratory monitoring for the development of hematologic adverse effects is recommended both during and after discontinuation of therapy. Dosage adjustment of azathioprine or mercaptopurine may be considered if an interaction is suspected. Patients should be advised to promptly report symptoms such as chills, fever, malaise, sore throat, mouth sores, unusual fatigue, bruising, or bleeding.