Pharmacokinetic interaction between high-dose methotrexate and oxacillin
Karine Titier1, Fabrice Lagrange, Fabienne Péhourcq
1Department of Clinical Pharmacology and Toxicology, Pellegrin Hospital and University Victor Ségalen, Bordeaux, France.
Abstract:
An 18-year-old man received two high-dose methotrexate cycles for the treatment of an osteosarcoma. Fifteen grams of methotrexate were infused over 6 hours. During the second cycle, co-administration of oxacillin (1g/8h) resulted in prolonged and marked elevation of methotrexate plasma concentrations. The patient experienced acute toxicity with renal failure, myelosuppression, mucitis, fever, and dermatologic abnormalities. After an initial improvement with folinic acid rescue and hemodialysis, the patient died. Oxacillin may thus inhibit the elimination of methotrexate.
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