What You Should Know Before Taking Methotrexate (Rheumatrex)

Usage, Side Effects, Dosage, Contraindications, and Safety

Methotrexate belongs to the class of drugs known as antineoplastics. Antineoplastics impede the body’s natural chemical processes, such as DNA production and cell division. They are helpful in cancer treatments because they will prevent cancer cells from thriving. Methotrexate may also be given to treat ankylosing spondylitis, rheumatoid arthritis, psoriasis, and Crohn’s disease.

doctor talks to a patient about a medication
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How Methotrexate Is Taken

Methotrexate should be taken exactly as prescribed by the doctor. A physical will tailor the dosage to the needs of each individual patient. Methotrexate may be given as a tablet, infusion or injection. If it is taken once a week, it's best to take it on the same day every week.

How It's Prescribed

Because methotrexate blocks cell metabolism, it is prescribed for conditions where abnormal cell growth is a problem, such as psoriasis or cancer. Methotrexate has also been found useful for treating some cases of Crohn’s disease and rheumatoid arthritis. Methotrexate has also been used to induce miscarriage in ectopic pregnancies.


Tell your doctor if you have ever had any of the following conditions:

  • Currently pregnant
  • Kidney disease
  • Liver disease or cirrhosis
  • Lung disease or fibrosis
  • Neurologic disease
  • Recurrent infections

Potential Side Effects

Bothersome side effects of methotrexate include headache, drowsiness, itching, skin rash, dizziness, and hair loss. Serious side effects include toxicity of the liver, bone marrow or, rarely, lungs.

Potential Food Interactions

Alcoholic beverages should not be consumed while taking methotrexate, as it could cause damage to the liver, leading to cirrhosis.

Medication Interactions

People taking methotrexate should avoid vaccinations with a live virus. Methotrexate causes the body’s immune system to be suppressed, so the live virus vaccine may actually cause illness instead of an immune response.

The FDA recommends caution in taking methotrexate along with a proton pump inhibitor (PPI), which are drugs that help reduce the amount of acid in the stomach. Some common PPIs include Prilosec (omeprazole), Nexium (esomeprazole), and Protonix (pantoprazole). The concern is largely indicated in those who are taking higher doses of methotrexate.

The problem is that PPIs may increase serum levels (the amount found in the blood) of methotrexate. High serum levels could mean that there is a toxic amount of methotrexate building up in the body. The full effects of this interaction are still being studied, but the FDA has released a warning about taking methotrexate along with a PPI. 

Methotrexate may interact with the following medications:

  • Arthritis drugs (ibuprofen, Advil, Motrin, Naprosyn, Voltaren, Lodine)
  • Aspirin or other salicylates
  • Azathioprine (Imuran)
  • Bismuth subsalicylate (Pepto Bismol)
  • Carbenicillin (Geocillin)
  • Cholestyramine (Questran)
  • Blood thinners (Coumadin)
  • Cyclosporine (Sandimmune, Neoral)
  • Digoxin (Lanoxin)
  • Etretinate (Tegison)
  • Phenytoin (Dilantin)
  • Probenecid
  • Proton pump inhibitors (PPIs)
  • Sulfa drugs (Bactrim)
  • Thiazide diuretics (Dyazide, hydrochlorothiazide)

Safety During Pregnancy

The FDA has classified methotrexate as a type X drug. This means that studies in animals or pregnant women have demonstrated positive evidence of fetal abnormalities. Methotrexate should not be used during pregnancy as it can cause a miscarriage or birth defects in an embryo.

Men should discontinue methotrexate for at least 3 months before conception. Women should discontinue methotrexate for one full ovulation cycle before conception. Methotrexate does pass into breast milk and could affect a nursing infant. The FDA recommends that methotrexate not be used in women of childbearing age unless "there is clear medical evidence that the benefits can be expected to outweigh the considered risks."

Long-Term Safety

Methotrexate may take several weeks to be effective in treating Crohn’s disease. It should only be taken for a long period of time (months or years) under the close supervision of a physician.

Other side effects not listed above may also occur in some patients. If you notice any other effects, check with your doctor. This information is meant only as a guideline. Always consult a physician or pharmacist for complete information about prescription medications.

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  1. Chan ES, Cronstein BN. Methotrexate--how does it really work?. Nat Rev Rheumatol. 2010;6(3):175-8. doi:10.1038/nrrheum.2010.5

  2. Wang W, Zhou H, Liu L. Side effects of methotrexate therapy for rheumatoid arthritis: A systematic review. Eur J Med Chem. 2018;158:502-516. doi:10.1016/j.ejmech.2018.09.027

  3. Hall JJ, Bolina M, Chatterley T, Jamali F. Interaction Between Low-Dose Methotrexate and Nonsteroidal Anti-inflammatory Drugs, Penicillins, and Proton Pump Inhibitors. Ann Pharmacother. 2017;51(2):163-178. doi:10.1177/1060028016672035

  4. Dawson AL, Riehle-colarusso T, Reefhuis J, Arena JF. Maternal exposure to methotrexate and birth defects: a population-based study. Am J Med Genet A. 2014;164A(9):2212-6. doi:10.1002/ajmg.a.36625

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