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significant drug-drug interactions have been demonstrated with aspirin, lithium, digoxin, methotrexate, cyclosporine, cholestyramine, and colestipol.

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case reports and published population pharmacokinetic studies suggest that concomitant use of some ppis, such as omeprazole, esomeprazole, and pantoprazole, with methotrexate primarily at high dose , may elevate and prolong serum levels of methotrexate and or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities.

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