Methotrexate/Nitrous Oxide Interactions

This information is generalized and not intended as specific medical advice. Consult your healthcare professional before taking or discontinuing any drug or commencing any course of treatment.

Medical warning:

Very Serious. These medicines may interact and cause very harmful effects and are usually not taken together. Contact your healthcare professional (e.g. doctor or pharmacist) for more information.

How the interaction occurs:

When these two medicines are taken together, you are at greater risk of experiencing potentially serious side effects.

What might happen:

Your blood levels of methotrexate may increase and cause toxic effects such as fever, chills, mouth sores, unusual bruising or bleeding, black stools or loss of muscle control. These effects are more likely if you are taking a higher dose of methotrexate, such as doses used in the treatment of cancer or severe psoriasis, or if you are regularly taking higher doses of aspirin, e.g. more than 4 adult-strength aspirin tablets per day.

What you should do about this interaction:

Contact your healthcare professionals (e.g. doctor or pharmacist) as soon as possible about taking these two medicines together. They may already be aware of this drug interaction and may be monitoring you for it. Do not start, stop, or change the dosage of any medicine before checking with them first.

  • 1.Methotrexate sodium Inj. US prescribing information. Hospira Worldwide, Inc. March, 2018.
  • 2.Methotrexate (tablets, injection) Canada prescribing information. Pfizer Canada Inc. July 8, 2019.
  • 3.Forster VJ, McDonnell A, Theobald R, McKay JA. Effect of methotrexate/vitamin B12 on DNA methylation as a potential factor in leukemia treatment-related neurotoxicity. Epigenomics 2017 Sep; 9(9):1205-1218.
  • 4.Lobel U, Trah J, Escherich G. Severe neurotoxicity following intrathecal methotrexate with nitrous oxide sedation in a child with acute lymphoblastic leukemia. Pediatr Blood Cancer 2015 Mar;62(3):539-41.
  • 5.Forster VJ, van Delft FW, Baird SF, Mair S, Skinner R, Halsey C. Drug interactions may be important risk factors for methotrexate neurotoxicity, particularly in pediatric leukemia patients. Cancer Chemother Pharmacol 2016 Nov;78(5):1093-1096.

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CONDITIONS OF USE: The information in this database is intended to supplement, not substitute for, the expertise and judgment of healthcare professionals. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for you or anyone else. A healthcare professional should be consulted before taking any drug, changing any diet or commencing or discontinuing any course of treatment.