+ -Text Size

Methotrexate

(meth-oh-TREKS-ate)

Trade/other name(s): Folex, Mexate, MTX, Methotrex (formerly Amethopterin)

Why would this drug be used?

Methotrexate is used to treat choriocarcinoma, leukemia in the spinal fluid, osteosarcoma, breast cancer, lung cancer, non-Hodgkin lymphoma, and head and neck cancers. It is also used to treat other cancers and non-cancerous conditions.

How does this drug work?

Methotrexate is part of a general group of chemotherapy drugs known as anti-metabolites. It prevents cells from using folate to make DNA and RNA. Because cancer cells need these substances to make new cells, methotrexate helps to stop the growth of cancer cells.

Before taking this medicine

Tell your doctor…

  • If you are allergic to anything, including medicines, dyes, additives, or foods.
  • If you have any medical conditions such as kidney disease, liver disease (including hepatitis), heart disease, congestive heart failure, diabetes, gout, infections, or if you have had kidney stones. These conditions may require that your medicine dose, regimen, or timing be changed.
  • If you have stomach ulcers or ulcerative colitis. Methotrexate may worsen these problems.
  • If you are pregnant, trying to get pregnant, or if there is any chance of pregnancy. It is not known if this drug might cause problems if either the male or female is taking it at the time of conception or during pregnancy. Check with your doctor about what kinds of birth control can be used with this medicine.
  • If you are breast-feeding. The drug passes into breast milk and may harm the baby.
  • If you think you might want to have children in the future. This drug may cause sterility. Talk with your doctor about the possible risk associated with this drug and the options that may preserve your ability to have children.
  • If you have ever been treated for cancer with radiation or chemotherapy. Some of these treatments may affect your response to this medicine.
  • If you drink heavily, or if you have abused alcohol in the past. This can increase your chances of liver damage with methotrexate.
  • About any other prescription or over-the-counter medicines you are taking, including vitamins and herbs. In fact, keeping a written list of each of these medicines (including the doses of each and when you take them) with you in case of emergency may help prevent complications if you get sick.

Interactions with other drugs

Medicines such as aspirin and other non-steroid medicines for pain, fever, or inflammation, like ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn), fenoprofen, diclofenac, fenaprofen, indomethacin, suprofen, tolmetin, meclofenamate, and others can cause methotrexate to stay in your system longer. This can seriously worsen its side effects. Check with your doctor, nurse, or pharmacist to find out if any of the medicines you are taking are NSAIDs. Most of these medicines must be stopped a few days before you get methotrexate, and cannot be resumed until the third day after the dose is given.

Any drugs or supplements that interfere with blood clotting can raise the risk of bleeding during treatment with methotrexate. These include:

  • Vitamin E
  • Non-steroid anti-inflammatory drugs (see examples above)
  • Warfarin (Coumadin)
  • Ticlopidine (Ticlid)
  • Clopidogrel (Plavix)

Note that many cold, flu, fever, and headache remedies contain aspirin or ibuprofen. Ask your pharmacist if you aren't sure what's in the medicines you take.

Penicillins, probenicid, phenylbutazone, and the anti-seizure drug phenytoin can also worsen methotrexate's side effects.

Proton pump inhibitors (PPIs), such as omeprazole, esomeprazole, and pantoprazole, that are used to reduce stomach acid can worsen the bad effects of methotrexate.

People taking certain drugs along with methotrexate may have a higher risk of liver damage:

  • Sulfasalazine (Azulfidine)
  • Azathioprine (Azasan or Imuran)
  • Retinoids such as isotretinoin (Accutane), acitretin (Soriatane), bexarotene (Targretin) etretinate (Tegison), tretinoin (Vesanoid), and others

Trimethoprim-sulfa (Bactrim, Septra) and other sulfa drugs may worsen methotrexate's effects on blood counts.

Vitamins that contain folic acid may interfere with methotrexate.

Certain antibiotics such as tetracycline or chloramphenicol may block methotrexate from being absorbed when methotrexate is taken in pill form.

Theophylline levels may be increased by methotrexate, which can worsen the side effects of theophylline.

Check with your doctor, nurse, or pharmacist about other medicines, vitamins, herbs, and supplements that may cause problems with this medicine.

Interactions with foods

No serious interactions with food are known at this time. Check with your doctor, nurse, or pharmacist about whether foods may be a problem.

Tell all the doctors, dentists, nurses, and pharmacists you visit that you are taking this drug.

How is this drug taken or given?

Methotrexate is given in different ways: as a pill by mouth (usually as a single dose at bedtime), as an injection in a vein for up to 20 minutes, or as an injection into a muscle. This drug is also sometimes injected directly into the spinal cord in order to kill cells there. The pills may cause stomach upset; if you have problems, take an antacid or anti-nausea pill 1 hour before taking the methotrexate.

If you're receiving medium or high doses of methotrexate, you will be given leucovorin calcium 24 hours later, then every 6 hours for up to 8 doses to "rescue" normal cells. Your dose based on several factors: your size, the type of cancer being treated, and how well your kidneys are working. It is very important to take this medicine on time and exactly as prescribed.

Your doctor or nurse will tell you if you need to drink extra fluids and take bicarbonate pills to reduce your risk of kidney damage.

If you are taking methotrexate pills, take them exactly as directed by your doctor. If you have any questions or do not understand the instructions, talk to your doctor or nurse. Store the medicine in a tightly closed container away from heat and moisture and out of the reach of children and pets.

Precautions

Do not drink alcohol while drinking methotrexate, to reduce the risk of serious liver damage. Be sure your doctor knows about all the medicines, vitamins, herbs, and supplements that you are taking before you start methotrexate (see "Interactions with other drugs", above.)

This drug can cause the rapid killing of tumor cells, which in some cases has led to serious kidney damage within the first 24 hours of treatment (a condition known as tumor lysis syndrome). This is more likely if you have a very large number of cancer cells in the body. If your doctor feels you might be at risk, he or she will give you medicines and/or fluids to help prevent this.

Your doctor will likely test your blood throughout your treatment, looking for possible effects of the drug on blood counts (described below) or on the liver or kidneys. Based on the test results, you may be given medicines to help treat any effects. Your doctor may also need to reduce or delay your next dose of this drug, or even stop it altogether. Keep all your appointments for lab tests and doctor visits.

This drug can lower your white blood cell count, especially in the weeks after the drug is given. A low white blood cell count increases your chance of getting an infection. Be sure to let your doctor or nurse know right away if you have any signs of infection, such as fever (100.5° or higher), chills, pain when passing urine, a new cough, or bringing up sputum.

This drug may lower your platelet count in the weeks after it is given, which can increase your risk of bleeding. Speak with your doctor before taking any drugs or supplements that might affect your body's ability to stop bleeding, such as aspirin or aspirin-containing medicines, warfarin (Coumadin), or vitamin E. Tell your doctor right away if you have unusual bruising, or bleeding such as nosebleeds, bleeding gums when you brush your teeth, or black, tarry stools.

This drug may lower your red blood cell count. If this occurs, it is usually a few weeks after starting treatment. A low red blood cell count (known as anemia) can cause shortness of breath, or make you to feel weak or tired all the time. Your doctor may give you medicines to help prevent or treat this condition, or you may need to get blood transfusions.

Do not get any immunizations (vaccines), either during or after treatment with this drug, without your doctor's OK. Methotrexate may affect your immune system. This could make vaccinations ineffective, or could even lead to serious infections if you get a live virus vaccine during or soon after treatment. Try to avoid contact with people who have recently received a live virus vaccine, such as the oral polio vaccine or smallpox vaccine. Check with your doctor about this.

If you are taking high-dose methotrexate, you will get fluids with a substance called sodium bicarbonate to flush the medicine through your kidneys. This is given through your vein. After the treatment, drink extra liquids and take the bicarbonate tablets as directed by your nurse or doctor to help protect your kidneys.

While you're taking this drug, you will likely be very sensitive to sunlight or bright ultraviolet light and can get severely burned. When possible, avoid being outdoors between the hours of 10 and 4. Wear sunglasses, hat, and protective clothes when outside, even on hazy days. Always apply sunscreen half an hour before going out in the sun, and follow the instructions for repeat applications. Avoid tanning beds.

Methotrexate can also cause radiation recall. When a person receives this drug, the skin or tissue damage from prior radiation therapy can become red and appear damaged again. Tell your doctor or nurse if your skin gets red in areas where radiation was given.

Let your doctor know right away if you have cough, shortness of breath, fever, vomiting, diarrhea, stomach pain, mouth sores, or if you suspect that you are getting dehydrated.

While taking this medicine, and for a few days afterward, there is a slight chance of a serious skin reaction. Symptoms often start as a skin rash with redness or blistering in the mouth, nose, or eyes, along with fever and body aches. If this happens, stop the drug and get help right away.

Methotrexate works to treat many cancers, and is given at low, medium, and high doses. At medium and high doses, severe side effects are prevented by giving it with leucovorin. Leucovorin MUST be taken exactly as directed. Leucovorin is also given when methotrexate is injected into the spinal canal to kill cancer cells in the spinal fluid.

Avoid pregnancy during and for at least a few months after treatment, since exposure to the drug can harm the fetus. Talk with your doctor about this.

Possible side effects

You will probably not have most of the following side effects, but if you have any talk to your doctor or nurse. They can help you understand the side effects and cope with them.

Common

  • Nausea (high dose)
  • Vomiting (high dose)
  • Sores in mouth or on lips*
  • Diarrhea
  • Increased risk of sunburn*
  • Skin changes in areas previously treated with radiation*
  • Loss of appetite

Less common

  • Low white blood cell count with increased risk of infection*
  • Low platelet count with increased risk of bleeding*
  • Kidney damage
  • Chills and fever

Rare

  • Nausea (low and medium dose)
  • Vomiting (low and medium dose)*
  • Liver damage that can cause poor appetite, weakness, yellow skin and eyes (usually only with prolonged use)
  • Lung collapse (high dose)
  • Inflammation or scarring of the lung with cough and shortness of breath*
  • Hair loss or thinning, which can include face and body hair
  • Rash, itching
  • Severe skin reaction that can blister and become burn-like*
  • Dizziness
  • Blurred vision
  • Stroke-like symptoms such as seizures, paralysis, confusion, or coma (more risk with high doses)
  • Death from infection, lung damage, skin reactions, holes in the intestines, and other causes

*See "Precautions" section for more detailed information.

There are some other side effects not listed above that can also occur in some patients. Tell your doctor or nurse if you develop these or any other problems.

FDA approval

Yes – first approved before 1984 (FDA cannot verify dates of drugs approved before 1984.)

Disclaimer: This information does not cover all possible uses, actions, precautions, side effects, or interactions. It is not intended as medical advice, and should not be relied upon as a substitute for talking with your doctor, who is familiar with your medical needs.

Last Medical Review: 12/29/2011
Last Revised: 12/29/2011