Pharmacokinetic interaction between high-dose methotrexate and oxacillin.
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.
Titier
Karine
K
Department of Clinical Pharmacology and Toxicology, Pellegrin Hospital and University Victor Ségalen, Bordeaux, France.
Lagrange
Fabrice
F
Péhourcq
Fabienne
F
Moore
Nicholas
N
Molimard
Mathieu
M
D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000506:poisoning / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics* / Q000506:poisoning / Q000627:therapeutic use; D004347:Drug Interactions; D017809:Fatal Outcome; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008297:Male; D008727:Methotrexate / Q000493:pharmacokinetics* / Q000506:poisoning / Q000627:therapeutic use; D012516:Osteosarcoma / Q000188:drug therapy / Q000473:pathology; D010068:Oxacillin / Q000494:pharmacology* / Q000627:therapeutic use; D013207:Staphylococcal Skin Infections / Q000188:drug therapy
D000900:Anti-Bacterial Agents; D000964:Antimetabolites, Antineoplastic; D010068:Oxacillin; D008727:Methotrexate