Two cases of severe neutropenia in patients on low-dose methotrexate and ceftriaxone.

Purpose: There are limited data on the effect of ceftriaxone on methotrexate clearance, with results of some studies indicating altered methotrexate pharmacokinetics with the administration of ceftriaxone. We describe 2 possible cases demonstrating an interaction between methotrexate and ceftriaxone, resulting in profound neutropenia.

Summary: The decision to continue methotrexate therapy in the setting of surgery or during treatment of an active infection continues to be a topic of debate due to perceived negative effects on the healing process. Methotrexate is typically administered at a lower dose for inflammatory arthritis than for hematologic indications, thus having less immunosuppression potential. However, if methotrexate is continued during treatment of infection, drug interactions along with effects on the healing process should be considered. Ceftriaxone is commonly considered safe for long-term therapy due to its favorable adverse effect and drug interaction profile. Ceftriaxone is partially eliminated via organic anion transporters in the kidneys, leading to potential competition with methotrexate clearance in the renal tubules. Clinicians using these drugs concurrently should be aware of the potential for development of neutropenia and monitor patients receiving this combination closely.

Conclusion: Two patients receiving ceftriaxone therapy in the setting of a joint infection developed profound neutropenia after resuming oral methotrexate therapy for inflammatory arthritis.