Methotrexate Oral Formulation (Trexall®, Rheumatrex®, MTX)

Author: Christina Bach, MBE, LCSW, OSW-C
Last Reviewed: July 15, 2026

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Pronounce: meth-oh-TREK-sate

Classification: Antimetabolite

About Methotrexate Oral Formulation (Trexall®, Rheumatrex®, MTX)

Methotrexate affects the DNA in cancer cells. It stops cell growth and division, slowing or stopping cancer growth. Since cancer cells tend to divide faster than healthy cells, cancer cells are more sensitive to this damage. Methotrexate also lowers the levels of folic acid in cells, causing cell death. Cancer cells take up methotrexate faster than normal cells (because they are rapidly dividing and replicate their DNA more frequently), causing their cell death.

You may also receive a medication called leucovorin starting 24 hours after methotrexate. Leucovorin is also known as folinic acid. It is converted into a form of folic acid in your body. Leucovorin is given to try to prevent healthy cells from taking up too much methotrexate, while allowing time for the methotrexate to get into cancer cells to cause their death.

How to Take Oral Methotrexate

Methotrexate comes as a tablet you take by mouth. Your dose will depend on the disease being treated, as well as how your body responds to the medication. 

It is important to make sure you are taking the correct amount of medication every time. Before every dose, check that what you are taking matches what you have been prescribed.

The blood levels of this medication can be affected by certain foods and medications, so they should be avoided. These include: non-steroidal anti-inflammatory (NSAID) medications, including ibuprofen, tetracycline, penicillin, sulfamethoxazole/trimethoprim, some other oral antibiotics and folic acid. Be sure to tell your healthcare provider about all medications and supplements you take.

*If you have been prescribed leucovorin in combination with methotrexate and are unable to take it, keep it down, or if you miss a dose, call your provider right away.

You, or anyone you live with, should avoid having live or live-attenuated vaccines while receiving this medication. These include herpes zoster (Zostavax) for shingles prevention, oral polio, measles, nasal flu vaccine (FluMist®), rotavirus, and yellow fever vaccines.

Storage and Handling

Store your medication in the original container with the label. If you want to use a pillbox, talk to your pharmacist. Keep it in a dry place at room temperature unless your provider or pharmacist tells you otherwise. Keep containers out of reach of children and pets.

If a caregiver prepares your dose for you, they should consider wearing gloves or pour the pills directly from their container into the cap, a small cup, or directly into your hand. They should avoid touching the pills. They should always wash their hands before and after giving you the medication. Pregnant or nursing people should not prepare the dose for you. Ask your provider where to return any unused medication for disposal. Do not flush down the toilet or throw in the trash. 

Where Do I Get This Medication?

Some cancer medications are only available through specialty pharmacies. Your provider or pharmacist will start this process. Your insurance plan may also affect where you can get your medication. Call your prescription plan provider to find out which specialty pharmacies are in-network.

Insurance Information

This medication may be covered by your prescription plan. If you qualify, you may be able to get financial help through patient assistance programs (PAP). Co-pay cards may also be available to lower your out-of-pocket cost if you have commercial (not Medicare/Medicaid/Tricare) insurance. Your pharmacist, social worker, or navigator can help find resources for financial support.

Possible Side Effects

These are some of the most common or most serious side effects of this medication. Talk with your provider about the side effects you are having and how they can be managed.

Allergic Reactions

In some cases, patients can have an allergic reaction to this medication. Signs of a reaction can include: shortness of breath or difficulty breathing, chest pain, rash, flushing or itching, or a decrease in blood pressure. If you notice any changes in how you feel, let your provider know immediately. This medication can also severely affect your bone marrow, gastrointestinal (GI) tract, liver, lungs, skin, and kidneys. It is important to call your provider if you notice any new symptoms or side effects.

Nausea and/or Vomiting

Talk to your providers if you have nausea and/or vomiting. They can prescribe medications to help you. Making changes to your diet can also help. Avoid things that make your symptoms worse, like heavy or greasy/fatty foods and spicy or acidic foods, like tomatoes, lemons, and oranges. Try saltines or ginger ale to help your symptoms.  

Call your providers if you cannot keep fluids down for more than 12 hours or if you feel lightheaded or dizzy.

Diarrhea

Diarrhea is when you pass three or more stools in a day. Your providers can suggest medications to relieve diarrhea. Do not take any medications to manage your diarrhea without talking to your provider first, as your stool may need to be tested. To manage it, try eating foods that are low in fiber and bland, like white rice and boiled or baked chicken. Try not to eat raw fruits, vegetables, whole grain breads, cereals, and seeds. Soluble fiber is a type of fiber found in some foods that helps absorb (soak up) fluid. Foods high in soluble fiber are applesauce, bananas (ripe), canned fruit, oranges, boiled potatoes, white rice, foods made with white flour, oatmeal, cream of rice, cream of wheat, and farina. Stay hydrated by drinking 8 to 10 glasses of non-alcoholic, non-caffeinated fluid each day.

Low White Blood Cell Count (Leukopenia or Neutropenia)

White blood cells (WBC) help your body fight infection. While you are having treatment for cancer, your WBC count can drop, putting you at a higher risk of an infection. Tell your provider right away if you have a fever (temperature greater than 100.4°F or 38°C), sore throat or cold, shortness of breath, cough, burning with urination, or a sore that doesn't heal.

Tips for preventing infection:

  • Hand washing: both yours and your visitors is the best way to prevent the spread of infection.
  • Avoid large crowds and people who are sick (those who have a cold, fever, or cough, or live with someone with these symptoms).
  • When working outside, wear clothes that protect you, like long pants and gloves.
  • Do not handle pet waste.
  • Keep all cuts and scratches clean.
  • Shower or bathe daily. 
  • Brush your teeth at least twice a day.
  • Do not cut cuticles or ingrown nails. You may wear nail polish, but not fake nails.
  • Ask your providers before scheduling dental appointments or procedures.
  • Ask your providers before you or someone you live with has any vaccines

Low Red Blood Cell Count (Anemia)

Anemia is when your red blood cell count is lower than normal. Red blood cells carry oxygen to the tissues in your body. When your red cell count is low, you may feel tired or weak. Tell your providers if you have shortness of breath, trouble breathing, or pain in your chest. If your count gets too low, you may receive a blood transfusion.

Low Platelet Count (Thrombocytopenia)

Platelets are blood cells that help your blood clot. Thrombocytopenia is when your platelet count is lower than normal, and you are at a higher risk of bleeding. Tell your providers if you have any bruising or bleeding, including nose bleeds, bleeding gums, or blood in your urine or stool. If your count gets too low, you may receive platelets from a donor. 

  • Do not use a razor (an electric razor is fine).
  • Do not do activities that can cause injury or bleeding.
  • Talk to your provider before taking any non-steroidal, anti-inflammatory medications (NSAIDs) like Motrin/Advil (ibuprofen), Aleve (naproxen), Celebrex (celecoxib), and others. These can raise the risk of bleeding. 
  • Use a soft-bristle toothbrush to brush your teeth. Ask your provider about flossing or using toothpicks. 

Mouth Ulcers (Mucositis)

This medication can cause sores or soreness in your mouth and/or throat, called mucositis. Tell your providers if your mouth, tongue, inside of your cheek, or throat becomes white, has ulcers, or is painful. Medications can be used to manage pain. Regular mouth care can help prevent or manage mouth sores. Some things you can do are:

  • Brush with a soft-bristle toothbrush or cotton swab twice a day.
  • Avoid mouthwashes that contain alcohol. A baking soda and/or salt with warm water mouth rinse (2 level teaspoons of baking soda or 1 level teaspoon of salt in an eight-ounce glass of warm water) can be used a few times each day.
  • If your mouth gets dry, eat moist foods, drink plenty of fluids (6 to 8 glasses), and suck on sugarless hard candy.
  • Avoid smoking and chewing tobacco, and drinking alcoholic beverages and citrus juices.

Loss or Thinning of Scalp and Body Hair (Alopecia)

Alopecia is when your hair gets thin, brittle (breaks easily), or falls out. This may happen during the few weeks after treatment starts. Hair loss can be all of your body hair, including pubic, underarm, legs/arms, eyelashes, and nose hairs. You may want to use scarves, wigs, hats, and hairpieces. Your hair helps keep you warm in cold weather, and it can protect you from the sun, so it is important to wear a hat if you are in cold weather or in the sun. If you are going to be out in the sun, protect your scalp by using a sunscreen with SPF 30 or higher. Wash your scalp with a mild or baby shampoo. After you are done with treatment, hair often starts to grow back.

Nail and Skin Changes

It is important to keep your fingernails and toenails clean and dry. Your fingernails/toenails may become dark, brittle, or fall off. If any nails fall off, clean the nail bed well with soap and water and cover it with a band-aid. Nail polish is safe to use, but do not wear fake nails (gels, acrylics, overlay).

You may notice dry skin or changes in the color or tone of your skin. This medication can make your skin more sensitive to the sun, which can result in a severe sunburn or rash. Sun sensitivity can last even after you are done with chemotherapy. Avoid the sun between 10 am and 4 pm, when it is strongest. Wear sunscreen every day and reapply when you are in the sun. The best sunscreen is SPF 30 or higher and protects against both types of sunlight, UVA and UVB. Wear sunglasses, a hat, and long sleeves/pants to protect your skin, a lip balm with SPF of at least 30, and stay in the shade whenever possible.

Tell your providers if you develop red, painful, or itchy skin, sunburn, skin irritation, bumps, or thick, dry skin.

Secondary Cancers

A secondary cancer happens as a result of cancer treatment for another cancer. This is rare, but you should know your risk. Secondary cancers can be related to chemotherapy and other anti-cancer medications. Often, a secondary cancer is a blood cancer. This can happen years after treatment and is often related to repeated treatments or high doses. Your provider will watch your labs closely. They may suggest you have a blood test called a complete blood count with differential. This is often done each year if you had high risk therapies.

Kidney Problems

This medication can cause kidney problems, like an increased creatinine level. Your provider may monitor for kidney problems with blood tests. Symptoms may be:

  • Less urine output than normal.
  • Blood in the urine.
  • Swelling in the ankles.
  • Loss of appetite.

Tell your provider if you have any of these symptoms.

Tumor Lysis Syndrome

Tumor Lysis Syndrome (TLS) is a side effect that happens when tumor cells die too quickly, and their waste overwhelms the body. You may be given a medication (allopurinol) and IV fluids to help prevent this. TLS can affect your kidney function. Your provider will monitor your kidney function with blood work. Symptoms may be:

  • Nausea.
  • Vomiting.
  • Diarrhea.
  • Lethargy (feeling tired, drowsy, sluggish).
  • Little or no urine output.

Tell your provider right away if you have any of these symptoms.

Radiation Recall

Radiation recall is when a medication causes a rash that looks like sunburn in an area where you had radiation treatment.

  • Redness.
  • Swelling.
  • Soreness.
  • Peeling skin.

You may be told to put a topical steroid cream on your skin, or you may need to wait to have your next scheduled dose of chemotherapy. Tell your provider if you notice any of these symptoms.

Reproductive Concerns

There is a higher risk of health problems for your baby if you are pregnant, become pregnant, or get someone pregnant while on this medication. To lower the risk of birth defects, you should use birth control (contraception) to avoid pregnancy.

Talk with your provider about what kind of birth control is safest for you and your partner.

If you can become pregnant, you will need to use effective birth control during treatment and for 6 months after the last dose of this medication, even if your menstrual cycle has stopped or changed.

If you can get someone pregnant, you will need to use effective birth control during treatment and for 3 months after the last dose of this medication, even if you believe you are not producing sperm.

You should not breastfeed during treatment and for 1 week after the last dose of this medication.

Important but Less Common Side Effects

Lung Changes

This medication can cause an opportunistic infection called pneumocystis pneumonia. This medication can also cause interstitial pneumonitis, especially when high doses have been received. Interstitial pneumonitis can develop months to years after treatment is done and may be more common in people with pre-exirting lung conditions. Call your provider right away if you have shortness of breath, a new or worsening cough, wheezing, or difficulty breathing.

Liver Toxicity

This medication can cause liver toxicity, or liver problems, which your provider may monitor for with blood tests called liver function tests. Symptoms may be:

  • Yellowing of your skin or eyes.
  • Dark or brown urine.
  • Pain in your abdomen (belly).

Tell your provider if you have any of these symptoms.

Eye Problems

This medication can cause your eyes to become irritated or watery and you may be more sensitive to light. Notify your provider if you develop any eye changes.