Methotrexate (low strength injection, oral)/Select Salicylates 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:

Serious. These medicines may interact and cause very harmful effects. Contact your healthcare professional (e.g. doctor or pharmacist) for more information.

How the interaction occurs:

When these two medicines are taken together, your body may not process methotrexate properly.

What might happen:

Your blood levels of methotrexate may increase and cause toxic effects such as fever, chills, mouth sores, unusual bruising or bleeding, or black stools. 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.

View Reference
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  • 2.Baker H. Intermittent high dose oral methotrexate therapy in psoriasis. Br J Dermatol 1970 Jan;82(1):65-9.
  • 3.Mandel MA. The synergistic effect of salicylates on methotrexate toxicity. Plast Reconstr Surg 1976 Jun;57(6):733-7.
  • 4.Taylor JR, Halprin KM. Effect of sodium salicylate and indomethacin on methotrexate-serum albumin binding. Arch Dermatol 1977 May;113(5):588-91.
  • 5.Tracy TS, Krohn K, Jones DR, Bradley JD, Hall SD, Brater DC. The effects of a salicylate, ibuprofen, and naproxen on the disposition of methotrexate in patients with rheumatoid arthritis. Eur J Clin Pharmacol 1992;42(2):121-5.
  • 6.Harrison PV. Methotrexate-induced epidermal necrosis. Br J Dermatol 1987 Jun;116(6):867-9.
  • 7.Fries JF, Singh G, Lenert L, Furst DE. Aspirin, hydroxychloroquine, and hepatic enzyme abnormalities with methotrexate in rheumatoid arthritis. Arthritis Rheum 1990 Nov;33(11):1611-9.
  • 8.Furst DE, Herman RA, Koehnke R, Ericksen N, Hash L, Riggs CE, Porras A, Veng-Pedersen P. Effect of aspirin and sulindac on methotrexate clearance. J Pharm Sci 1990 Sep;79(9):782-6.
  • 9.Stewart CF, Fleming RA, Germain BF, Seleznick MJ, Evans WE. Aspirin alters methotrexate disposition in rheumatoid arthritis patients. Arthritis Rheum 1991 Dec;34(12):1514-20.
  • 10.Seideman P, Muller-Suur R. Renal effects of aspirin and low dose methotrexate in rheumatoid arthritis. Ann Rheum Dis 1993 Aug;52(8):613-5.
  • 11.Kremer JM, Hamilton RA. The effects of nonsteroidal antiinflammatory drugs on methotrexate (MTX) pharmacokinetics: impairment of renal clearance of MTX at weekly maintenance doses but not at 7.
  • 12 mg. J Rheumatol 1995 Nov;22(11):2072-7.
  • 13.Rheumatrex (methotrexate, oral) US prescribing information. Dava Pharmaceuticals, Inc. February, 2013.
  • 14.Methotrexate sodium Inj. US prescribing information. Hospira Worldwide, Inc. March, 2018.
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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.