Methotrexate (Generic Name)

Other Names: Amethopterin, Mexate®, Folex®

About This Drug

Methotrexate is a drug used to treat cancer. This drug is given in the vein (IV), by mouth (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. This may raise your risk of infection, make you tired and weak (fatigue), and raise your risk of bleeding.
  • Soreness of the mouth and throat. You may have red areas, white patches, or sores that hurt.
  • Nausea and throwing up (vomiting). These symptoms may happen within a few hours after your treatment and may last up to 24 hours. Medicines are available to stop or lessen these side effects.
  • Loose bowel movements (diarrhea) that may last for a few days
  • Rash
  • This drug may affect how your kidneys work. Your kidney function will be checked as needed. 

Possible Side Effects (Less Common)

  • Changes in your liver function. Your doctor will check your liver function as needed.
  • Sensitivity to light (photosensitivity). You may become more sensitive to the light from the sun, sun lamps, and tanning beds. Your eyes may water more, mostly in bright light.
  • Hair loss. You may notice hair getting thin. Some patients lose their hair. Your hair often grows back when treatment is done.
  • Blurred or double vision
  • Feeling dizzy
  • Trouble breathing because of fluid build-up in your lungs
  • Cough
  • Seizure. Common symptoms of a seizure can include confusion, blacking out, passing out, loss of hearing or vision, blurred vision, unusual smells or tastes (such as burning rubber), trouble talking, tremors or shaking in parts or all of the body, repeated body movements, tense muscles that do not relax, and loss of control of urine and bowels. There are other less common symptoms of seizures. If you or your family member suspects you are having a seizure, call 911 right away.
  • Muscle twitching
  • Effects on the bladder. This drug may cause irritation and bleeding in the bladder. You may have blood in your urine. To help stop this, you will get extra fluids to help you pass more urine. You may also get a drug called mesna, which helps to decrease irritation and bleeding. You may also get a medicine to help you pass more urine. You may have a catheter (tube) placed in your bladder so that your bladder will be washed with this drug.
  • Joint pain or stiffness
  • Changes in your central nervous system can happen. The central nervous system is made up of your brain and spinal cord. You could feel extreme tiredness, agitation, confusion, hallucinations (see or hear things that are not there), trouble understanding or speaking, loss of control of your bowels or bladder, eyesight changes, numbness or lack of strength to your arms, legs, face, or body, and coma. If you start to have any of these symptoms call your doctor right away.

Treating Side Effects

  • Drink 6-8 cups of fluids each day unless your doctor has told you to limit your fluid intake due to some other health problem. A cup is 8 ounces of fluid. If you throw up or have loose bowel movements you should drink more fluids so that you do not become dehydrated (lack water in the body due to losing too much fluid).
  • Mouth care is very important. Your mouth care should consist of routine, 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 ½ teaspoon of baking soda in 8 ounces of water. This should be done at least after each meal and at bedtime.
  • If you have mouth sores, avoid mouthwash that has alcohol. Also avoid alcohol and smoking because they can bother your mouth and throat.
  • Ask your doctor or nurse about medicine that is available to help stop or lessen the loose bowel movements.
  • Talk with your nurse about getting 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 getting chemotherapy can learn about wigs, turbans and scarves as well as makeup techniques and skin and nail care.
  • If you get a rash do not put anything on it unless your doctor or nurse says you may. Keep the area around the rash clean and dry. Ask your doctor for medicine if your rash bothers you.
  • Wear dark sunglasses and use sunscreen with SPF 30 or higher when you are outdoors even for a short time. 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.
  • If you are dizzy, get up slowly after sitting or lying.

Food and Drug Interactions

  • Folic acid supplements may interfere with how methotrexate works. Avoid use of folic acid supplements while taking this drug.
  • This drug may also interact with other medicines. Tell your doctor and pharmacist about all the medicines and dietary supplements (vitamins, minerals, herbs and others) that you are taking at this time. The safety and use of dietary supplements and alternative diets are often not known. Using these might 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 help.

Important Information

  • Do not handle methotrexate if you are pregnant or intend to become pregnant.
  • Store methotrexate at room temperature, in the original prescription bottle, and away from heat and direct light. Avoid freezing Methotrexate Injection.
  • Do not store methotrexate in the bathroom, near the kitchen sink, or in other damp places. Heat or moisture may cause the medicine to break down.
  • Do not drink alcohol while taking this drug.
  • Missed dose: If you missed a scheduled dose, call your doctor right away for further instruction.
  • If you are getting very high dose therapy or getting 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. Please talk to your doctor about these side effects.

When to Call the Doctor

Call your doctor or nurse right away if you have any of these symptoms:

  • Fever of 100.5 F (38 C) or higher
  • Chills
  • Seizures
  • Easy bleeding or bruising
  • Dizziness when changing positions (from lying to sitting, or sitting to standing)
  • Coughing or trouble catching your breath
  • Loose bowel movements (diarrhea) 5 times in one day or diarrhea with weakness or lightheadedness
  • Nausea that stops you from eating or drinking
  • Throwing up (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

Sexual Problems and Reproduction Concerns

  • Pregnancy warning: This drug may cause very harmful effects on an unborn child. Methotrexate should never be used by women who are pregnant or who could become pregnant while taking the drug. Even 1 dose taken by a pregnant woman can cause these very harmful effects. Your healthcare team will talk to you and give you written information about this risk.
  • Breast feeding warning: Women should not breast feed during treatment because this drug could enter the breast milk and badly harm a breast feeding baby.
  • Sexual problems and reproduction concerns may happen. In both men and women, this drug may affect your ability to have children. This cannot be determined before your treatment. Talk with your doctor or nurse if you plan to have children.  Ask for information on sperm or egg banking.

Revised November 2014

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