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Methotrexate - Interactions and Warnings

Cyclophosphamide, chlorambucil and methotrexate are contraindicated during pregnancy because of their teratogenic potential. Their use may be considered in late pregnancy if the mother has a life-threatening condition.
- Drug Saf 1998 Nov;19(5):389-410 -- Treatment of inflammatory rheumatic disorders in pregnancy: what are the safest treatment options? -- Ostensen M, Ramsey-Goldman R.

Methotrexate is a chemotherapy antimetabolite, folic acid antagonist, that inhibits the enzyme dihydrofolate reductase resulting in decreased levels of tetrahydrofolate in the cells. This in turn blocks synthesis of thymidylate, a nucleotide necessary for DNA synthesis. It is readily absorbed from the gastrointestinal tract.
- Ann Emerg Med 1999 Jul;34(1):98-100 -- Pediatric case of accidental oral overdose of methotrexate. -- Gibbon BN, Manthey DE.

Omeprazole may delay methotrexate elimination; therefore, when prescribing methotrexate, an alternative to omeprazole should be considered.
- Ann Pharmacother 2000 Sep;34(9):1024-7 -- Potential interaction between methotrexate and omeprazole. -- Beorlegui B, Aldaz A, Ortega A, Aquerreta I, Sierrasesumega L, Giraldez J.

Methotrexate, a drug commonly used at low doses for the treatment of psoriasis, rheumatoid arthritis and certain liver disorders, limits the availability of methyl groups derived from one-carbon metabolism by inhibiting competitively a key enzyme in the intracellular folate metabolism.
- Eur J Clin Nutr 2000 Mar;54 Suppl 1:S69-74 -- Drugs-nutrient interactions: a potential problem during adolescence. -- Alonso-Aperte E, Varela-Moreiras G.

Among the potential safety issues are interaction between folic acid and zinc, interaction between folic acid and drugs (phenytoin, methotrexate etc.).
- Schweiz Rundsch Med Prax 2002 Jan 9;91(1-2):7-16 -- Safety aspects of folic acid for the general population -- Eichholzer M, Luthy J, Moser U, Stahelin HB, Gutzwiller F.

last update: November 2008

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