Basic Information
ID DDInter1174 and DDInter1559
Interaction Coadministration with proton pump inhibitors (PPIs) may increase the serum concentrations of methotrexate (MTX) and its potentially active 7-hydroxy metabolite. The proposed mechanism is PPI inhibition of the active tubular secretion of MTX and 7-hydroxymethotrexate via renal H+/K+ ATPase pumps. Inhibition of the breast cancer resistance protein (BCRP)-mediated transport of methotrexate and 7-hydroxymethotrexate by the proton pump inhibitors has also been suggested.
Management Proton pump inhibitor therapy should preferably be stopped several days prior to administration of methotrexate. In addition, it is not generally recommended to use proton pump inhibitors with high-dose methotrexate therapy, particularly in the presence of renal impairment. If concomitant use is necessary, clinicians should consider the potential for interaction and closely monitor methotrexate serum levels and toxicity. Use of an H2 antagonist may also be an appropriate alternative. It is not known if the interaction occurs with low, oral doses of methotrexate used to treat rheumatoid arthritis.
References [1] Cerner Multum, Inc. "Australian Product Information." O 0 [2] Beorlegui B, Aldaz A, Ortega A, Aquerreta I, Sierrasesumega L, Giraldez J "Potential interaction between methotrexate and omeprazole/." Ann Pharmacother 34 (2000): 1024-7 [3] Breedveld P, Zelcer N, Pluim D, et.al "Mechanism of the Pharmacokinetic Interaction between Methotrexate and Benzimidazoles; Potential Role for Breast Cancer Resistance Protein in Clinical Drug-Drug Interactions." Cancer Res 64 (2004): 5804-11 [4] "Product Information. Methotrexate (methotrexate)." Lederle Laboratories, Wayne, NJ. [5] Reid T, Yuen A, Catolico M, Carlson RW "Impact of omeprazole on the plasma clearance of methotrexate." Cancer Chemother Pharmacol 33 (1993): 82-4 [6] Troger U, Stotzel B, Martens-Lobenhoffer J, Gollnick H, Meyer FP "Severe myalgia from an interaction between treatments with pantoprazole and methotrexate." BMJ 324 (2002): 1497 [7] Nesher G, Mates M, Zevin S "Effect of caffeine consumption on efficacy of methotrexate in rheumatoid arthritis." Arthritis Rheum 48 (2003): 571-572
Alternative for Methotrexate L04A
Deucravacitinib Teprotumumab Antithymocyte immunoglobulin (rabbit) Ocrelizumab Tildrakizumab Natalizumab
Eculizumab Efalizumab Sarilumab Pomalidomide Belatacept
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Alternative for Rabeprazole A02B
Rifabutin Vonoprazan Bismuth subcitrate potassium Tinidazole

M01A
Glucosamine Chondroitin sulfate

M02A
Dimethyl sulfoxide Tolazoline
Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.