Proton pump inhibitors Methotrexate

PROTON PUMP INHIBITORS METHOTREXATE Likely t plasma concentrations of methotrexate and t risk of toxic effects, e.g. blood dyscrasias, liver cirrhosis, pulmonaiy toxicity, renal toxicity Attributed to omeprazole 1 renal elimination of methotrexate Monitor clinically and biochemically for blood dyscrasias, liver toxicity, renal toxicity and pulmonaiy toxicity... 

Azathioprine, chloramphenicol, colchicine, cyclophosphamide, cytarabine, 5-fluorodeoxyuridine, 5-fluorouracil, hydroxyurea, mercaptopurine, metformin, methotrexate, phenobarbital, phenytoin, primidone, proton pump inhibitors, pyrimethamine, sulfasalazine, and vinblastine... 

Proton pump inhibitors may affect renal, and possibly hepatic, clearance of methotrexate by inhibition of methotrexate transporter proteins. It has been suggested that omeprazole may inhibit the activity of a hydrogen-ion dependent mechanism in the kidney, on which methotrexate depends for its excretion, so that its loss is diminished. It has also been suggested that the situation with lansoprazole may be similar, but that pantoprazole may differ since at about the pH found in the renal tubules (pH 5), pantoprazole is more slowly activated than omeprazole. However, a case of an interaction with pantoprazole has also been reported. ... 

Information seems to be limited to these few reports and with the exception of one case report, they all found that proton pump inhibitors reduced the clearance of methotrexate. Any changes in methotrexate kinetics are important in terms of the potential for increased toxicity. Further study is required. The authors of one study in which the levels of methotrexate and its active metabolite were increased during the concurrent use of omeprazole or lansoprazole advise against concurrent use. Further, the authors of one report recommend that if omeprazole is necessary for a patient about to receive methotrexate, then omeprazole should be discontinued 4 to 5 days before methotrexate administration. The situation with other proton pump inhibitors may be similar. Ranitidine was found to be a suitable alternative in two of the cases.Note that the risks would appear to be most significant with high-dose methotrexate, but the case report involving a 15 mg weekly dose of methotrexate introduces a note of caution in all patients. 

Drug-drug iuteractious Proton pump inhibitors Proton pump inhibitors have been associated with delayed elimination of high-dose methotrexate and with impaired renal function [81 ]. 

Santucci R, Leveque D, Lescoute A, Kemmel V, Herbrecht R. Delayed elimination of methotrexate associated with co-administration of proton pump inhibitors. Anticancer Res 2010 30(9) 3807-10. 

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