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If you review medication interactions for methotrexate, the list appears long, but in fact, is not entirely accurate. There are many medications listed that you should not take with methotrexate, but most of them are only theoretical, whereas we have years of experience knowing these combinations are in fact safe.

It is very common to use methotrexate and sulfasalazine together, and it is considered safe. Similarly, some texts suggest methotrexate should not be used with anti-inflammatories (NSAIDs) or stomach protector medications called proton pump inhibitors (PPIs). Again, these combinations are used frequently. In fact, it is not uncommon that some arthritis patients are on methotrexate, sulfasalazine, ibuprofen and omeprazole (a PPI) all at the same time.

We do recommend holding methotrexate if you require a sulfa-based or penicillin-based antibiotic, but these are really the only interactions we watch for.