Interactions between protonix(pantoprazole) and Methotrexate sodium preservative free (methotrexate)
methotrexate and pantoprazole (Moderate Drug-Drug)
MONITOR: 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. The interaction was suspected in 2 case reports involving omeprazole and high-dose MTX cycles, where elimination of MTX was significantly delayed during cycles with omeprazole but became normal during subsequent cycles after omeprazole was discontinued or substituted with ranitidine. In another case, coadministration of pantoprazole and low-dose pulse MTX (15 mg IM once a week) resulted in severe myalgia and bone pain for several days following each of five MTX injections. The symptoms subsided dramatically and eventually disappeared after pantoprazole was replaced with ranitidine. A subsequent rechallenge led to reappearance of symptoms. Although the pharmacokinetics of MTX were not affected, systemic exposure (AUC) of 7-hydroxymethotrexate was significantly increased by 70% and half-life was doubled in the presence of pantoprazole.
MANAGEMENT: Proton pump inhibitor therapy should preferably be stopped several days prior to administration of methotrexate. 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.
