Methotrexate interactions

Food & lifestyle

• alcohol

  Moderate

  Synergy

  Coadministration of methotrexate with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Methotrexate, especially at higher dosages or during prolonged treatment, has been associated with severe hepatotoxicity including acute hepatitis, chronic fibrosis, cirrhosis, and fatal liver failure.

  What to do: The risk of hepatic injury should be considered when methotrexate is used with other potentially hepatotoxic agents (e.g., acetaminophen; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; kinase inhibitors; minocycline; nonsteroidal anti-inflammatory agents; nucleoside reverse transcriptase inhibitors; proteasome inhibitors; retinoids; sulfonamides; tamoxifen; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, niacin, and statins; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice). Baseline and periodic monitoring of hepatic function is recommended, while liver biopsy may be warranted during long-term use of methotrexate. Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, pale stools, and jaundice.

  3 sources

  1. "Product Information. Methotrexate (methotrexate)." Lederle Laboratories (2002):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. "Product Information. Methotrexate (methotrexate)." Hospira Inc (2023):

• coffee

  Moderate

  Antagonism

  Limited data suggest that consumption of greater than 180 mg/day of caffeine may interfere with the efficacy of methotrexate (MTX) in patients with rheumatoid arthritis. The exact mechanism of interaction is unknown but may be related to the antagonistic effect of caffeine on adenosine receptors, as anti-inflammatory properties of MTX is thought to result from the accumulation of adenosine.

  What to do: Until further information is available, the potential for interaction should be considered in patients who consume substantial amounts of caffeine and caffeine-containing foods and are prescribed methotrexate for rheumatoid arthritis. It may be appropriate to limit caffeine intake if an interaction is suspected in cases of treatment failure.

  1 source

  1. Nesher G, Mates M, Zevin S "Effect of caffeine consumption on efficacy of methotrexate in rheumatoid arthritis." Arthritis Rheum 48 (2003): 571-572

Conditions

Conditions in which Methotrexate needs care, as documented in this source.

• Bone Marrow Failure Disorders

  Major

  Methotrexate can induce myelosuppression causing leukopenia, thrombocytopenia, neutropenia, pancytopenia and anemia. Therapy with methotrexate is contraindicated as treatment of psoriasis in patients with bone marrow suppression or preexisting blood dyscrasias. Methotrexate should be discontinued immediately in patients with psoriasis or rheumatoid arthritis if there is a significant fall in blood cell counts. If need outweighs risk, therapy with methotrexate should be administered cautiously in patients with malignancy and hematopoietic impairment. Additionally, methotrexate should be used with extreme caution in patients with active infection, and it is usually contraindicated in patients with overt or laboratory evidence of immunodeficiency syndromes. Patients should be instructed to immediately report any signs or symptoms suggesting bone marrow suppression or infection such as fever, sore throat, or bleeding. Clinical monitoring of hematopoietic function is recommended.

  2 sources

  1. "Product Information. Rheumatrex (methotrexate)." Lederle Laboratories (2002):
  2. "Product Information. Methotrexate (methotrexate)." Lederle Laboratories

• Infections

  Major

  Because of their cytotoxic effects on rapidly proliferating tissues, antineoplastic agents frequently can, to varying extent, induce myelosuppression. The use of these drugs may be contraindicated in patients with known infectious diseases. All patients should be instructed to immediately report any signs or symptoms suggesting infection such as fever, sore throat, or local infection during antineoplastic therapy. Close clinical monitoring of hematopoietic function is recommended.

  39 sources

  1. Sanders C, Perez EA, Lawrence HJ "Opportunistic infections in patients with chronic lymphocytic leukemia following treatment with fludarabine." Am J Hematol 39 (1992): 314-5
  2. "Product Information. Methotrexate (methotrexate)." Lederle Laboratories (2002):
  3. "Product Information. Platinol (cisplatin)." Bristol-Myers Squibb (2001):
  4. "Product Information. Vepesid (etoposide)." Bristol-Myers Squibb (2001):
  5. "Product Information. Novantrone (mitoxantrone)." Immunex Corporation (2001):
  6. "Product Information. Mutamycin (mitomycin)." Bristol-Myers Squibb (2001):
  7. "Product Information. Ifex (ifosfamide)." Bristol-Myers Squibb (2001):
  8. "Product Information. Thiotepa (thiotepa)." Hikma USA (formerly West-Ward Pharmaceutical Corporation) (2001):

  Show all 39 sourcesShow fewer sources

  9. Girmenia C, Mauro FR, Rahimi S "Late listeriosis after fludarabine plus prednisone treatment." Br J Haematol 87 (1994): 407-8
  10. Schilling PJ, Vadhan-Raj S "Concurrent cytomegalovirus and pneumocystis pneumonia after fludarabine therapy for chronic lymphocytic leukemia." N Engl J Med 323 (1990): 833-4
  11. Frame JN, Dahut WL, Crowley S "Fludarabine and acute tumor lysis in chronic lymphocytic leukemia." N Engl J Med 327 (1992): 1396-7
  12. Bastion Y, Coiffier B, Tigaud JD, Espinouse D, Bryon PA "Pneumocystis pneumonia in a patient treated with fludarabine for chronic lymphocytic leukemia." Eur J Cancer 27 (1991): 671
  13. "Product Information. Fludara (fludarabine)." Berlex Laboratories (2001):
  14. "Product Information. Idamycin (idarubicin)." Pharmacia and Upjohn (2001):
  15. "Product Information. Matulane (procarbazine)." Roche Laboratories (2001):
  16. "Product Information. DTIC-Dome (dacarbazine)." Bayer (2001):
  17. "Product Information. Adriamycin PFS (doxorubicin)." Pharmacia and Upjohn (2001):
  18. "Product Information. Leustatin (cladribine)." Ortho Biotech Inc (2001):
  19. "Product Information. Gemzar (gemcitabine)." Lilly, Eli and Company (2001):
  20. "Product Information. Hycamtin (topotecan)." SmithKline Beecham (2001):
  21. "Product Information. Taxotere (docetaxel)." Rhone Poulenc Rorer (2001):
  22. "Product Information. Taxol (paclitaxel)." Bristol-Myers Squibb (2001):
  23. "Product Information. Nipent (pentostatin)." Hospira Inc (2001):
  24. "Product Information. Tabloid (thioguanine)." Prasco Laboratories (2001):
  25. "Product Information. Xeloda (capecitabine)." Roche Laboratories (2001):
  26. "Product Information. Alkeran (melphalan)." Glaxo Wellcome (2022):
  27. "Product Information. Purinethol (mercaptopurine)." Glaxo Wellcome (2001):
  28. "Product Information. Leukeran Tablets (chlorambucil)." Glaxo Welcome, Research Triangle Pk, NC.
  29. "Product Information. Doxil (doxorubicin liposomal)." Sequus Pharmaceuticals Inc (2001):
  30. "Product Information. Cytosar-U (cytarabine)." Pharmacia and Upjohn (2001):
  31. "Product Information. Uracil Mustard (uracil mustard)." Roberts Pharmaceutical Corporation (2001):
  32. "Product Information. Jevtana (cabazitaxel)." sanofi-aventis (2010):
  33. "Product Information. Halaven (eribulin)." Eisai Inc (2010):
  34. "Product Information. Keytruda (pembrolizumab)." Merck & Co., Inc (2014):
  35. "Product Information. Blincyto (blinatumomab)." Amgen USA (2014):
  36. "Product Information. Opdivo (nivolumab)." Bristol-Myers Squibb (2014):
  37. "Product Information. Unituxin (dinutuximab)." United Therapeutics Corporation (2015):
  38. "Product Information. Empliciti (elotuzumab)." Bristol-Myers Squibb (2015):
  39. "Product Information. Pepaxto (melphalan flufenamide)." Oncopeptides Inc. (2021):

• Kidney Diseases

  Major

  Methotrexate is primarily eliminated by the kidney via glomerular filtration and active secretion. Clearance rates for methotrexate vary and at higher doses are generally decreased due to saturation of renal tubular reabsorption. Renal impairment or third space effusion (ascites, pleural effusions), decrease elimination and increase methotrexate serum concentrations. Therapy with methotrexate should be administered cautiously and at reduced dosages in patients with compromised renal function. Administration of leucovorin reduces toxicity from high dose methotrexate regimens or delayed elimination. Clinical monitoring of renal function is recommended.

  2 sources

  1. "Product Information. Rheumatrex (methotrexate)." Lederle Laboratories (2002):
  2. "Product Information. Methotrexate (methotrexate)." Lederle Laboratories

• Liver Diseases

  Major

  The use of methotrexate is contraindicated as treatment for psoriasis or rheumatoid arthritis in patients with alcoholism, alcoholic liver disease or other chronic liver diseases. Methotrexate causes hepatotoxicity, fibrosis and cirrhosis, usually after long-term therapy. Fibrosis and cirrhosis may not be preceded by symptoms or abnormal liver function tests. If methotrexate is used, patients should be instructed to immediately report any signs or symptoms suggestive of hepatic dysfunction such as jaundice, dark urine, right upper quadrant pain, or anorexia. Persistent liver function test abnormalities and/or depression of serum albumin may require evaluation, including a liver biopsy.

  2 sources

  1. "Product Information. Rheumatrex (methotrexate)." Lederle Laboratories (2002):
  2. "Product Information. Methotrexate (methotrexate)." Lederle Laboratories

• Stomatitis

  Major

  Methotrexate induces stomatitis within the oral mucosa and gastrointestinal tract. Therapy with methotrexate should be administered with extreme caution in patients with peptic ulcer disease or ulcerative colitis. If vomiting, diarrhea or ulcerative stomatitis occur, treatment should be discontinued until recovery to avoid the risk of hemorraghic enteritis or intestinal perforation which could be fatal.

  2 sources

  1. "Product Information. Rheumatrex (methotrexate)." Lederle Laboratories (2002):
  2. "Product Information. Methotrexate (methotrexate)." Lederle Laboratories