Methotrexate; Pralatrexate/NSAIDs 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 or pralatrexate properly.

What might happen:

Your blood levels of methotrexate or pralatrexate may increase and cause easy bruising or bleeding, persistent sore throat or fever, or fatigue. These effects are more likely if you are taking a high dose of methotrexate, such as those used in the treatment of cancer or psoriasis.

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
  • 1.Methotrexate sodium Inj. US prescribing information. Hospira Worldwide, Inc. March, 2018.
  • 2.Folotyn (pralatrexate) US prescribing information. Allos Therapeutics, Inc. May, 2016.
  • 3.Thyss A, Milano G, Kubar J, Namer M, Schneider M. Clinical and pharmacokinetic evidence of a life-threatening interaction between methotrexate and ketoprofen. Lancet 1986 Feb 1;1(8475):256-8.
  • 4.Tracy TS, Worster T, Bradley JD, Greene PK, Brater DC. Methotrexate disposition following concomitant administration of ketoprofen, piroxicam and flurbiprofen in patients with rheumatoid arthritis. Br J Clin Pharmacol 1994 May;37(5):453-6.
  • 5.Combe B, Edno L, Lafforgue P, Bologna C, Bernard JC, Acquaviva P, Sany J, Bressolle F. Total and free methotrexate pharmacokinetics, with and without piroxicam, in rheumatoid arthritis patients. Br J Rheumatol 1995 May;34(5):421-8.
  • 6.Skeith KJ, Russell AS, Jamali F, Coates J, Friedman H. Lack of significant interaction between low dose methotrexate and ibuprofen or flurbiprofen in patients with arthritis. J Rheumatol 1990 Aug;17(8):1008-10.
  • 7.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.
  • 8.Wallace CA, Smith AL, Sherry DD. Pilot investigation of naproxen/methotrexate interaction in patients with juvenile rheumatoid arthritis. J Rheumatol 1993 Oct;20(10):1764-8.
  • 9.Stewart CF, Fleming RA, Arkin CR, Evans WE. Coadministration of naproxen and low-dose methotrexate in patients with rheumatoid arthritis. Clin Pharmacol Ther 1990 Apr;47(4):540-6.
  • 10.Anaya JM, Fabre D, Bressolle F, Bologna C, Alric R, Cocciglio M, Dropsy R, Sany J. Effect of etodolac on methotrexate pharmacokinetics in patients with rheumatoid arthritis. J Rheumatol 1994 Feb;21(2):203-8.
  • 11.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.
  • 12.Dupuis LL, Koren G, Shore A, Silverman ED, Laxer RM. Methotrexate-nonsteroidal antiinflammatory drug interaction in children with arthritis. J Rheumatol 1990 Nov;17(11):1469-73.
  • 13.Adams JD, Hunter GA. Drug interaction in psoriasis. Australas J Dermatol 1976 Aug;17(2):39-40.
  • 14.Maiche AG. Acute renal failure due to concomitant action of methotrexate and indomethacin. Lancet 1986 Jun 14;1(8494):1390.
  • 15.Frenia ML, Long KS. Methotrexate and nonsteroidal antiinflammatory drug interactions. Ann Pharmacother 1992 Feb;26(2):234-7.
  • 16.Singh RR, Malaviya AN, Pandey JN, Guleria JS. Fatal interaction between methotrexate and naproxen. Lancet 1986 Jun 14;1(8494):1390.
  • 17.Ng HW, Macfarlane AW, Graham RM, Verbov JL. Near fatal drug interactions with methotrexate given for psoriasis. Br Med J (Clin Res Ed) 1987 Sep 26;295(6601):752-3.
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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.