methotrexate and omeprazole

Pharmacokinetic interaction: omeprazole inhibits renal tubular secretion of methotrexate via organic anion transporters (OATs) and may also reduce methotrexate clearance, leading to increased plasma concentrations and potential toxicity.

Elevated methotrexate levels can increase the risk of severe toxicity, including myelosuppression, mucositis, hepatotoxicity, and renal impairment, particularly in patients receiving high-dose methotrexate or those with compromised renal function.

Avoid concurrent use of omeprazole with high-dose methotrexate. If co-administration is unavoidable, monitor methotrexate plasma levels, renal function, and full blood counts closely. Consider alternative acid-suppressive therapy such as an H2 receptor antagonist if required.

Interaction is well documented in pharmacokinetic studies and case reports, especially with high-dose methotrexate. Evidence supports a clinically significant increase in methotrexate exposure and associated toxicity; however, the magnitude varies between individuals.