Pantoprazole Methotrexate

The excretion of methotrexate is reported to have been reduced in twelve patients given omeprazole and three patients given lansoprazole. However, similar elevations in methotrexate levels in another patient were independent of omeprazole use. One patient had myalgia and elevated 7-hydroxymethotrexate levels when given methotrexate with pantoprazole. 

Severe generalised myalgia occurred in a man taking pantoprazole 20 mg daily afler he received intramuscular methotrexate 15 mg weekly. The symptoms subsided and eventually disappeared when the pantoprazole was replaced with ranitidine. The symptoms reappeared in response to rechallenge with pantoprazole, and the AUC of 7-hydroxymethotrexate was found to be increased by about 70%, although the AUC of methotrexate was unchanged. ... 

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. ... 

Troger U, Stotzel B, Martens-Lobenhoffer J, Gollnick H, Meyer FP, Severe myalgia from an interaction between treatments with pantoprazole and methotrexate, 5A4l/(2002) 324, 1497,... 

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