Methotrexate (Generic Name)

Other Names: Amethopterin, Mexate®, Folex®

About This Drug

Methotrexate is a drug used to treat cancer. This drug is given intravenously (IV), orally, or by injection into the fluid that surrounds the brain and spinal cord (intrathecally).

Possible Side Effects (More Common)

  • Bone marrow depression. This is a decrease in the number of white blood cells, red blood cells, and platelets. Bone marrow depression usually occurs four to 10 days after the drug is given and may increase your risk of infection, fatigue, and bleeding.
  • Soreness of the mouth and throat. You may have red areas, white patches, or sores that are painful.
  • Nausea and vomiting. These symptoms may occur within four to 12 hours after the drug is given and may last up to 24 hours.
  • Diarrhea that may last several days
  • Itchy rash. A rash (like a sunburn) may develop one to five days after you receive methotrexate.
  • This drug may affect how your kidneys work. Your kidney function will be checked as needed.  Electrolyte changes.  Your blood will be checked for electrolyte changes as needed.

Possible Side Effects (Less Common)

  • Changes in liver function may occur with long-term use. Your liver function will be checked as needed.
  • Sensitivity to light (photosensitivity). Photosensitivity means that you may become more sensitive to the effects of the sun, sun lamps, and tanning beds. Your eyes may water more, especially in bright light.
  • Hair loss. Most patients experience some scalp hair loss. You may notice thinning several days after receiving this drug. Usually hair loss is temporary; your hair should grow back when drug treatment is completed.
  • Blurred or double vision
  • Dizziness
  • Difficulty breathing
  • Cough
  • Seizure
  • Muscle twitching
  • Painful, frequent, or difficulty urinating
  • Joint pain or stiffness
  • Changes in mental state

Sexual Problems and Reproductive Concerns

  • In men and women both, this drug may temporarily or permanently affect your ability to have children. This cannot be determined before your therapy. In men, this drug may interfere with your ability to make sperm, but it should not change your ability to have sexual relations. In women, menstrual bleeding may become irregular or stop while you are receiving this drug. Do not assume that you cannot become pregnant if you do not have a menstrual period. Women may experience signs of menopause like vaginal dryness or itching.
    • Pregnancy warning: This drug is known to have harmful effects on the unborn child, so effective methods of birth control should be used during your cancer treatment. Women must have a negative pregnancy test before beginning this medication because of the risk of harm to the unborn child.
    • Speak with your doctor or nurse if you plan to have children.  Ask for information on sperm or egg banking
    • Genetic counseling is available to you to discuss the effects of this drug therapy on future pregnancies. In addition, a genetic counselor can review the potential risks of problems in the fetus due to this medication if an exposure during pregnancy has occurred. 
    • Breast feeding warning Women are advised not to breast feed during treatment because this drug could enter the breast milk and seriously harm a breast feeding infant.
    • Vaginal lubricants can be used to lessen vaginal dryness, itching, and pain during sexual relations.

Treating Side Effects

  • Drink 6-8 cups of fluids every day unless your doctor has told you to restrict your fluid intake due to another medical condition. A cup is 8 ounces of fluid. If you vomit or have diarrhea, you should drink more fluids so that you do not become dehydrated.
  • Mouth care is very important. Your mouth care should consist of regular, gentle cleaning of your teeth or dentures and rinsing your mouth with a mixture of 1/2 teaspoon of salt in 8 ounces of water or 1/2 teaspoon of sodium bicarbonate (baking soda) in 8 ounces of water. This should be done at least after every meal and at bedtime.
  • If you have mouth sores, avoid mouthwash that contains alcohol. Avoid alcohol and smoking because they can irritate your mouth and throat.
  • Speak with your nurse about obtaining a wig before you lose your hair.  Also, call the American Cancer Society at 800-ACS-2345 to find out information about the “Look Good...Feel Better” program close to where you live. It is a free program where women undergoing chemotherapy learn about wigs, turbans and scarves as well as makeup techniques and skin and nail care.
  • Ask your doctor or nurse about medication that is available to help prevent or lessen nausea, vomiting, diarrhea, sore mouth and throat, and rash.
  • Do not put anything on a rash unless your doctor or nurse says you may. Keep the skin around the rash clean and dry.
  • Cover up when you are out in the sun. Wear wide-brimmed hats, long-sleeved shirts, and pants. Keep your neck, chest, and back covered.
  • Use sunscreen with SPF 30 or higher when you are outdoors even for a short time.
  • Avoid sunlamps, tanning booths, and tanning beds.

Food and Drug Interactions

Folic acid supplements may interfere with how Methotrexate works. Methotrexate may interact with other medication. Tell your doctor and pharmacist about all the medication and dietary supplements (vitamins, minerals, herbs and others) that you are currently taking. The safety and effectiveness of dietary supplements and alternative diets are often unknown. Using these might unexpectedly affect your cancer or interfere with your treatment. Until more is known, you should not use dietary supplements or alternative diets without your cancer doctor's advice.

Other Instructions

  • The oral form of medication should be stored at room temperature in its prescription bottle protected from light.
  • If you are receiving very high dose therapy or receiving this drug by injection into the fluid that surrounds the brain and spinal cord (intrathecal) your side effects might be different than those listed above. If you are receiving the high dose therapy or intrathecal injection please discuss your possible side effects with your doctor.

When to Call the Doctor

Call your doctor or nurse immediately if you have any of the following symptoms:

  • Fever of 100.5 F (38 C) or higher
  • Chills
  • Unusual bleeding or bruising
  • Dizziness when changing positions (from lying to sitting, or sitting to standing)
  • Coughing or difficulty catching your breath
  • Diarrhea of five stools a day or diarrhea with weakness or lightheadedness
  • Uncontrolled nausea that prevents you from eating or drinking
  • Vomiting more than twice in one day
  • Yellowing of skin or eyes
  • Pain in the right side of the abdomen
  • Puffiness of the ankles or hands
  • Blurred or double vision


Revised January 2012


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