Medical Information
United States

In order to provide you with relevant and meaningful content we need to know more about you.

Please choose the category that best describes you.

This content is intended for U.S. Healthcare Professionals. Would you like to proceed?

If you provide additional keywords, you may be able to browse through our database of Scientific Response Documents.

Our scientific content is evidence-based, scientifically balanced and non-promotional. It undergoes rigorous internal medical review and is updated regularly to reflect new information.

Methotrexate Vial Drug Interactions


7.1 Effects of Other Drugs on Methotrexate

Drugs that Increase Methotrexate Exposure

Coadministration of methotrexate with the following products may increase methotrexate plasma concentrations, which may increase the risk of methotrexate severe adverse reactions.

Increased organ specific adverse reactions may also occur when methotrexate is coadministered with hepatotoxic or nephrotoxic products. If coadministration cannot be avoided, monitor closely for methotrexate adverse reactions when coadministered with:

  • Penicillin or sulfonamide antibiotics
  • Highly protein-bound drugs (e.g., oral anticoagulants, phenytoin, salicylates, sulfonamides, sulfonylureas, and tetracyclines)
  • Proton pump inhibitors
  • Probenecid
  • Antifolate drugs (e.g., dapsone, pemetrexed, pyrimethamine and sulfonamides)
  • Aspirin and other nonsteroidal anti-inflammatory drugs
    Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of methotrexate (primarily at high dose) and nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Mercaptopurine
  • Hepatotoxic products
  • Weak acids (e.g., salicylates)
  • Nephrotoxic products

Nitrous Oxide

Coadministration of methotrexate with nitrous oxide anesthesia potentiates the effect of methotrexate on folate-dependent metabolic pathways, which may increase the risk of severe methotrexate adverse reactions. Avoid nitrous oxide anesthesia in patients receiving methotrexate. Consider alternative therapies in patients who have received prior nitrous oxide anesthesia.

Folic Acid

Coadministration of methotrexate with folic acid or its derivatives decreases the clinical effectiveness of methotrexate in patients with neoplastic diseases. Methotrexate competes with reduced folates for active transport across cell membranes. Instruct patients to take folic or folinic acid only as directed by their healthcare provider [see Warnings and Precautions (5.12)].

7.2 Effects of Methotrexate on Other Drugs


Coadministration of methotrexate with theophylline increases theophylline plasma concentrations which may increase the risk of theophylline adverse reactions. Monitor theophylline levels and adjust the theophylline dosage in accordance with approved product labeling.

Did you find an answer to your question? Yes No
Didn’t find what you were looking for? Contact us.
Report Adverse Event