| Last Modified: January 14, 2012
Methotrexate competes with folic acid uptake in cells. This results in a folic acid deficiency in these cells and leads to cell death. By affecting the folic acid uptake, methotrexate also alters DNA replication and cell division. Cancer cells take up methotrexate faster than normal cells (because they are rapidly dividing and thus replicate their DNA more frequently) causing their cell death. Leucovorin is given starting 24 hours after methotrexate. Leucovorin is also known as folinic acid and is converted into a derivative of folic acid in the body. Therefore, Leucovorin is given in an attempt to prevent healthy cells from taking up too much methotrexate, but on the other hand, allowing time for the methotrexate to get into cancer cells to cause their death.
How to Take Methotrexate
Methotrexate is injected into a vein. In special situations, it may be injected into the spinal cord space (called intrathecal administration). It can also be given by mouth in the form of a tablet. The dosage is based on your body weight, medical condition and the regimen your physician is using. It can be given alone or with other drugs.
Possible Side Effects of Methotrexate
There are a number of things you can do to manage the side effects of Methotrexate. Talk to your doctor or nurse about these recommendations. They can help you decide what will work best for you. These are some of the most common side effects:
Low White Blood Cell Count (Leukopenia or Neutropenia)
White blood cells (WBC) are important for fighting infection. While receiving treatment, your WBC count can drop, putting you at a higher risk of getting an infection. You should let your doctor or nurse know right away if you have a fever (temperature greater than 100.4°), sore throat or cold, shortness of breath, cough, burning with urination, or a sore that doesn't heal.
Tips to preventing infection:
For more suggestions, read the Neutropenia Tip Sheet.
Low Red Blood Cell Count (Anemia)
Your red blood cells are responsible for carrying oxygen to the tissues in your body. When the red cell count is low, you may feel tired or weak. You should let your doctor or nurse know if you experience any shortness of breath, difficulty breathing or pain in your chest. If the count gets too low, you may receive a blood transfusion. Read the anemia tip sheet for more information.
Low Platelet Count (Thrombocytopenia)
Platelets help your blood clot, so when the count is low you are at a higher risk of bleeding. Let your doctor or nurse know if you have any excess bruising or bleeding, including nosebleeds, bleeding gums or blood in your urine or stool. If your platelet count becomes too low, you may receive a transfusion of platelets.
Read the thrombocytopenia tip sheet for more information.
Nausea and/or Vomiting
Take anti-nausea medications as prescribed. If you continue to have nausea or vomiting, notify your doctor or nurse so they can help you manage this side effect. In addition, dietary changes may help. Avoid things that may worsen the symptoms, such as heavy or greasy/fatty, spicy or acidic foods (lemons, tomatoes, oranges). Try antacids, (e.g. milk of magnesia, calcium tablets such as Tums), saltines, or ginger ale to lessen symptoms. Read the Nausea & Vomiting Tip Sheet for more suggestions.
Call your doctor or nurse if you are unable to keep fluids down for more than 12 hours or if you feel lightheaded or dizzy at any time.
Your oncology team can recommend medications to relieve diarrhea. Also, try eating low-fiber, bland foods, such as white rice and boiled or baked chicken. Avoid raw fruits, vegetables, whole grain breads, cereals and seeds. Soluble fiber is found in some foods that absorbs fluid and can help relieve diarrhea. Foods high in soluble fiber include: applesauce, bananas (ripe), canned fruit, orange and grapefruit sections, boiled potatoes, white rice and products made with white flour, oatmeal, cream of rice, cream of wheat, and farina. Drink 8-10 glasses on non-alcoholic, un-caffeinated fluid a day to prevent dehydration. Read Low Fiber Diet for Diarrhea for more tips.
Decrease in Appetite
Mouth Ulcers (Sores)
Certain cancer treatments can cause sores or soreness in your mouth and/or throat. Notify your doctor or nurse if your mouth, tongue, inside of your cheek or throat becomes white, ulcerated or painful. Performing regular mouth care can help prevent or manage mouth sores. If mouth sores become painful, your doctor or nurse can recommend a pain reliever.
Read the mouth ulcer tip sheet for more information.
Sexual and Reproductive Changes
This drug can affect your reproductive system, resulting in the menstrual cycle or sperm production becoming irregular or stopping permanently. Women may experience menopausal effects including hot flashes and vaginal dryness – read more about coping with vaginal dryness. In addition, the desire for sex may decrease during treatment.
Exposure of an unborn child to this medication could cause birth defects, so you should not become pregnant or father a child while on this medication. Effective birth control is necessary during treatment, even if your menstrual cycle stops or you believe your sperm is affected. You may want to consider sperm banking or egg harvesting if you may wish to have a child in the future. Discuss these options with your oncology team. See OncoLink's section on sexuality for helpful tips for dealing with these side effects.
Nail and Skin Changes
Your fingernails/toenails may become dark, brittle or fall off. You may notice dry skin or changes in the color or tone of your skin. Your skin will be more sensitive to the sun, which can result in severe sunburn or rash. Sun sensitivity can last even after chemotherapy is completed. Avoid the sun between 10-2pm, when it is strongest. Wear sunscreen (at least SPF 15) everyday; wear sunglasses and long sleeves/pants to protect your skin. Keep your fingernails and toenails clean and dry. You may use nail polish, but do not wear fake nails. Notify your doctor or nurse if any nails fall off. For more suggestions, read the Nail and Skin Care Tip Sheet.
Other Side Effects
Methotrexate can affect the kidney. Your oncology team will make sure you are well hydrated before the medication is given to prevent this from occurring.
Some less common side effects that have been reported include: liver changes, loss or thinning of scalp and body hair (alopecia) and eye irritation.
In rare cases, methotrexate can affect the nervous system or lungs. If you experience any dizziness, blurry vision, confusion, difficulty speaking, standing or walking, call your doctor right away. If you have any shortness of breath, cough or difficulty breathing, call your doctor right away.
Intrathecal (Spinal) Administration
When injected into the spinal cord space, methotrexate can cause headache, vomiting, fever or stiff neck. In rare cases, intrathecal administration can cause neurotoxicity, which presents with paralysis, speak difficulty, seizures or coma. This can occur up to several days after the treatment and resolves in a few days.
*If you have been prescribed leucovorin with this chemotherapy and are unable to take it, keep it down or miss a dose, call your healthcare team immediately.