Flucloxacillin Methotrexate

Reduced clearance and acute methotrexate toxicity has been attributed to the concurrent use of various penicillins (amoxicillin, benzylpenicillin, carbenicillin, dicloxacillin, flucloxacillin, mezlocillin, oxacillin, penicillin, phenoxymethylpenicillin, piperacillin, ticarcillin) in a small number of case reports. 

Low-dose regimen 7.5 mg weekly Amoxicillin 500 mg orally three times daily for 7 days from day 17, intravenous flucloxacillin 2 g every 4 hours, plus intravenous benzylpenicillin 2 million units every 4 hours Rheumatoid arthritis Neutropenia and thrombocytopenia probably as a result of reduced methotrexate clearance folinic acid given, but patient died 7... 

Herrick AL, Grennan DM, Griffen K, Aarons L, Gifford LA. Lack of interaction between flucloxacillin and methotrexate in patients with rheumatoid arthritis. Br J Clin Pharmacol mSj 41, 223-7. 

It is thought that weak acids such as the penicillins can possibly successfully compete with methotrexate in the kidney tubules for excretion so that the methotrexate is retained, thereby increasing its effects and its toxicity. However, this was not demonstrated in a study with flucloxacillin, and the mechanism has been disputed." ... 

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