Methotrexate Drug Interactions

Methotrexate belongs to a group of drugs known as disease-modifying anti-rheumatic drugs, or DMARDs for short. They are typically used to treat rheumatoid arthritis and related diseases. Although methotrexate is a very useful drug that is capable of treating several conditions, it can have adverse effects when taken in combination with other medications. These effects range from moderate to severe and may manifest themselves differently in different patients.

Drugs Reducing Methotrexate Effectiveness

Certain types of medication may reduce the effectiveness of methotrexate when used in conjunction with it. For example, folic acid is typically prescribed with methotrexate in order to reduce the potential side effects of the latter, but certain research findings suggest folic acid may also reduce the effectiveness of the drug. There are some reports of methotrexate being less effective in treating psoriasis when taken with a daily dose of 5mg of folic acid. However, patients taking both methotrexate and folic acid should not stop taking folic acid before consulting with their healthcare provider.

Significant Methotrexate Drug Interactions

Administering high dosages of methotrexate therapy concomitantly with certain groups of drugs may elevate and prolong serum methotrexate levels, in some cases leading to deaths from severe hematologic and gastrointestinal toxicity. Such methotrexate drug interactions may occur with some NSAIDs, including ibuprofen, celebrex, diclofenac, etodolac, indomethacin, naproxen, meloxicam and piroxicam, and penicillin antibiotics like amoxicillin, ampicillin, dicloxacillin and penicillin.

Whilst methotrexate may be used together with NSAIDs or penicillins, patients should be closely monitored.

Other Drugs That Can Potentially Interact With Methotrexate

Methotrexate is a hepatotoxic agent, meaning it can be injurious to the liver. When methotrexate is administered concomitantly with other hepatotoxic agents such as azathioprine, retinoids or sulfasalazine, there is the potential for increased hepatotoxicity. In other words, such a combination of drugs may cause liver conditions like toxic hepatitis.  Other groups of drugs that may affect methotrexate include, but are not limited to:

• The antiepileptic drugs phenobarbital and carbamazepine
• Oral diabetes medications including acetohexamide, chlorpropamide, glipizide, glimepiride, metformin and tolbutamide
• Medicines that decrease stomach acid including esomeprazole (nexium), lansoprazole (prevacid), omeprazole (prilosec) and pantoprazole (protonix)
• Salicylates including aspirin, Disalcid, Doan's Pills, Dolobid, Salflex and Tricosal

Methotrexate Interactions with Food and Drink

This drug may also interact with caffeine and alcohol, which are both fellow potential hepatotoxins.

Limited data suggests that consuming more than 180mg of caffeine a day may interfere with the efficacy of methotrexate in patients being treated for rheumatoid arthritis. It should be remembered that not only do tea, coffee and other drinks contain caffeine, but also certain foods such as chocolate. Consuming any amount of alcohol whilst on methotrexate is not recommended. Herbal and nutritional supplements including black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice are also to be avoided.

This is by no means a comprehensive list of methotrexate drug interactions. Patients should always consult their doctor on potential interactions with their current medications before starting methotrexate.  The patient’s current prescription medicines should be taken into account along with over-the-counter medications, vitamins and nutritional and herbal supplements.