Significant interaction between high-dose methotrexate and high-dose piperacillin-tazobactam causing reversible neurotoxicity and renal failure in an osteosarcoma patient

Introduction Pharmacokinetic interaction of high-dose methotrexate (MTX) and other concomitantly administered renally secreted medicinal products may lead to insufficient methotrexate serum level decrease and significant MTX toxicity. Case report We report the case of an 18-year-old male patient treated with high-dose MTX for an osteosarcoma and with high-dose piperacillin-tazobactam at the same time. MTX serum levels were severely elevated 24 hours after the MTX infusion and did not decrease in accordance with the specific calcium folinate rescue protocol. The patient experienced renal failure accompanied by neurological symptoms, most consistent with MTX-related renal and CNS toxicity. Management and outcome: After discontinuation of piperacillin-tazobactam, intensified calcium folinate rescue therapy, and IV hydration, the MTX serum levels decreased appropriately, and toxicity symptoms resolved. Discussion Severe MTX-related toxicity, caused by drug-drug interaction, suggests that the concomitant use of high-dose MTX and high-dose piperacillin-tazobactam should be avoided generally.