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Methotrexate; Pralatrexate/Sulfonamides; Trimethoprim

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) about taking these two medicines together. They may already be aware of this interaction and may be monitoring you for it. If you experience swelling or soreness of the mouth or tongue, easy bruising or bleeding, persistent sore mouth or fever, or unusual fatigue, contact your doctor. Do not start, stop, or change the dosage of any medicine before checking with them first.


1.Kobrinsky NL, Ramsay NK. Acute megaloblastic anemia induced by high-dose trimethoprim- sulfamethoxazole. Ann Intern Med 1981 Jun;94(6):780-1.

2.Dan M, Shapira I. Possible role of methotrexate in trimethoprim-sulfamethoxazole-induced acute megaloblastic anemia. Isr J Med Sci 1984 Mar;20(3):262-3.

3.Thomas MH, Gutterman LA. Methotrexate toxicity in a patient receiving trimethoprim- sulfamethoxazole. J Rheumatol 1986 Apr;13(2):440-1.

4.Maricic M, Davis M, Gall EP. Megaloblastic pancytopenia in a patient receiving concurrent methotrexate and trimethoprim-sulfamethoxazole treatment. Arthritis Rheum 1986 Jan;29(1):133-5.

5.Frain JB. Methotrexate toxicity in a patient receiving trimethoprim- sulfamethoxazole. J Rheumatol 1987 Feb;14(1):176-7.

6.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.

7.Groenendal H, Rampen FH. Methotrexate and trimethoprim-sulphamethoxazole--a potentially hazardous combination. Clin Exp Dermatol 1990 Sep;15(5):358-60.

8.Govert JA, Patton S, Fine RL. Pancytopenia from using trimethoprim and methotrexate. Ann Intern Med 1992 Nov 15;117(10):877-8.

9.Beach BJ, Woods WG, Howell SB. Influence of co-trimoxazole on methotrexate pharmacokinetics in children with acute lymphoblastic leukemia. Am J Pediatr Hematol Oncol 1981 Summer;3(2):115-9.

10.Liegler DG, Henderson ES, Hahn MA, Oliverio VT. The effect of organic acids on renal clearance of methotrexate in man. Clin Pharmacol Ther 1969 Nov-Dec;10(6):849-57.

11.el-Tamtamy S. Letter: Co-trimoxazole and the blood. Lancet 1974 May 11; 1(7863):929-30.

12.Bernstein LS. Adverse reactions to trimethoprim-sulfamethoxazole, with particular reference to long-term therapy. Can Med Assoc J 1975 Jun 14; 112(13 Spec No):96-8.

13.Haagsma CJ, van Riel PL, de Rooij DJ, Vree TB, Russel FJ, van't Hof MA, van de Putte LB. Combination of methotrexate and sulphasalazine vs methotrexate alone: a randomized open clinical trial in rheumatoid arthritis patients resistant to sulphasalazine therapy. Br J Rheumatol 1994 Nov;33(11):1049-55.

14.Ferrazzini G, Klein J, Sulh H, Chung D, Griesbrecht E, Koren G. Interaction between trimethoprim-sulfamethoxazole and methotrexate in children with leukemia. J Pediatr 1990 Nov;117(5):823-6.

15.Steuer A, Gumpel JM. Methotrexate and trimethoprim: a fatal interaction. Br J Rheumatol 1998 Jan;37(1):105-6.

16.Folotyn (pralatrexate) US prescribing information. Allos Therapeutics, Inc. May, 2012.

Selected from data included with permission and copyrighted by First Databank, Inc. This copyrighted material has been downloaded from a licensed data provider and is not for distribution, expect as may be authorized by the applicable terms of use.

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.

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