Trexall (Methotrexate) - Oral


Methotrexate can harm a developing fetus, potentially causing fetal death. Methotrexate should not be used during pregnancy for non-neoplastic diseases. For neoplastic diseases, advise people of reproductive potential to use effective contraception.

Methotrexate should also not be used in people with a history of severe hypersensitivity reactions to methotrexate, including anaphylaxis.

Serious adverse reactions, including death, have been reported with methotrexate. A healthcare provider should closely monitor for adverse reactions of the bone marrow, gastrointestinal tract, liver, lungs, skin, and kidneys.

What Is Trexall?

Trexall (methotrexate) is a pill taken by mouth and used to treat several different types of cancers and some autoimmune diseases.

Autoimmune diseases occur when the body’s immune system, meant to protect you from foreign bodies like viruses and bacteria, attacks your cells instead, causing conditions like rheumatoid arthritis (RA) and psoriasis.

Methotrexate is a dihydrofolate reductase inhibitor, which interferes with DNA processes and stops or slows cancer cell replication. It is not as well understood how methotrexate works for autoimmune diseases, but it seems to fight inflammation, which contributes to conditions like RA and psoriasis.

Methotrexate is only available by prescription, so you can’t purchase it over-the-counter (OTC). You’ll receive a prescription from your healthcare provider and the medication from your pharmacy.

Oral methotrexate is currently available under the brand names Trexall (in tablet form) and Xatmep (as a liquid). Methotrexate is also available as a subcutaneous injection. However, this article will focus on the oral forms of methotrexate.

Drug Facts

Generic Name: Methotrexate

Brand Name: Trexall, Xatmep

Drug Availability: Prescription

Therapeutic Classification: Dihydrofolate reductase inhibitor, DMARD (disease-modifying antirheumatic drug)

Available Generically: Yes

Controlled Substance: N/A

Administration Route: Oral

Active Ingredient: Methotrexate

Dosage Form: Tablet, solution

What Is Trexall Used For?

Trexall is used to treat a variety of conditions, including certain types of cancer and autoimmune diseases:

Methotrexate solution (Xatmep) is indicated to treat ALL and manage pJIA in people who did not respond well to other therapy.

Trexall (Methotrexate) Drug Information: A person stretches with bones and joints

Verywell / Dennis Madamba

How to Take Trexall

Always take your medication exactly as prescribed by your healthcare provider. Your dosage of methotrexate will depend on the condition being treated and treatment response.

Methotrexate Tablets

Take Trexall tablets on an empty stomach (an hour before food or two hours after food) because this improves how well your body absorbs it. However, if taking it on an empty stomach causes discomfort, take it with food. Do not take another dose if you vomit within a few hours of taking Trexall.

Trexall tablets must also be swallowed whole and not crushed, cut, or chewed.

Methotrexate Solution

Measure the dose of the solution using an accurate milliliter measuring device, not a household teaspoon. If you do not know what to use, ask your healthcare provider or pharmacist to recommend one.

If you are a female (sex assigned at birth) with any potential to get pregnant, it is crucial to use effective contraception while taking methotrexate and for six months after your last dose. This is equally important if you are male and sexually active with females who have any potential to get pregnant. Methotrexate is associated with multiple congenital disabilities (birth defects) when used during pregnancy.


Store Trexall at room temperature (between 68 F and 77 F) in its original container with the lid, out of reach of children and pets. Avoid storing your pill bottle in an area with a lot of heat and moisture, like the bathroom.

You can store the oral solution in the refrigerator (between 36 F and 46 F) or at room temperature. However, if stored at room temperature, discard the medication after 60 days.

If you’re traveling by plane, keep methotrexate in your carry-on luggage so that you aren’t separated from it if your checked baggage goes missing. If you’re traveling by car, take care not to leave your pill bottle in hot or cold temperatures for long periods, like overnight in the car.

Off-Label Uses

A healthcare provider may prescribe off-label treatments when the decision is supported by scientific evidence or expert clinical experience.

While Trexall is a newer brand name methotrexate product, the generic drug methotrexate has been around for quite some time. It was first approved in the 1950s.

Methotrexate may be used for medical conditions besides those listed above, such as:

Methotrexate can also be used to terminate an ectopic pregnancy, a dangerous condition that occurs when a fertilized egg implants outside of the uterus.

How Long Does Trexall Take to Work?

If you’re taking Trexall for an autoimmune disease (like rheumatoid arthritis), expect to see symptom improvement within about 12 to 16 weeks after starting treatment. Talk to your healthcare provider if you don’t notice any improvement after several months.

What Are the Side Effects of Trexall?

This is not a complete list of side effects and others may occur. A healthcare provider can advise you on side effects. If you experience other effects, contact your pharmacist or a healthcare provider. You may report side effects to the Food and Drug Administration (FDA) at or 1-800-FDA-1088.

Common Side Effects

Common side effects that you may experience while taking Trexall include:

Severe Side Effects

Potentially severe side effects of Trexall may include:

  • Serious infections: You may be at a higher risk of developing infections since methotrexate suppresses the immune system. These may be bacterial or fungal infections or viruses. Trexall can increase the risk of reactivating hepatitis B or tuberculosis if you have previously had either of these infections.
  • Secondary cancers: The risk of new skin cancer is increased in people with psoriasis taking Trexall. Certain new blood cancers may also happen during treatment with Trexall.
  • Tumor lysis syndrome: This occurs when cancer cells are quickly destroyed. It can cause kidney failure, abnormal heart rhythm, or seizures. Your healthcare provider may need to monitor your blood if you are taking Trexall to treat cancer.
  • Leukopenia, or low white blood cell count
  • Myelosuppression, which makes the bone marrow less able to produce all other types of blood cells (red blood cells, white blood cells, and platelets)

Call your healthcare provider immediately if you experience any potentially serious side effects. Call 911 if your symptoms feel life-threatening or if you think you’re having a medical emergency.

Report Side Effects

Trexall may cause other side effects. Call your healthcare provider if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your healthcare provider may send a report to the FDA's MedWatch Adverse Event Reporting Program or by phone (800-332-1088).

Dosage: How Much Trexall Should I Take?

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The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For oral dosage form (tablets):
    • For acute lymphoblastic leukemia (ALL):
      • Adults and children—Dose is based on body size and must be determined by your doctor. At first, 20 milligrams (mg) per meter squared (m(2)) of body size once a week. Your doctor may adjust your dose as needed and tolerated.
    • For mycosis fungoides:
      • Adults—
        • Used alone: 25 to 75 milligrams (mg) once a week.
        • Used with other medicines: Dose is based on body size and must be determined by your doctor. The dose is usually 10 mg per meter squared (m(2)) of body size 2 times a week.
      • Children—Use and dose must be determined by your doctor.
    • For non-Hodgkin lymphoma:
      • Adults—2.5 milligrams (mg) 2 to 4 times a week. Your doctor may adjust your dose as needed and tolerated. However, the dose is usually not more than 10 mg per week.
      • Children—Use and dose must be determined by your doctor.
    • For polyarticular juvenile arthritis (pJIA):
      • Children—Dose is based on body size and must be determined by your doctor. At first, 10 milligrams (mg) per meter squared (m2) once a week. Your doctor may adjust your dose as needed and tolerated.
    • For psoriasis:
      • Adults—At first, 10 to 25 milligrams (mg) once a week. Your doctor may adjust your dose as needed and tolerated. However, the dose is usually not more than 30 mg per week.
      • Children—Use and dose must be determined by your doctor.
    • For rheumatoid arthritis:
      • Adults—At first, 7.5 milligrams (mg) once a week Your doctor may adjust your dose as needed and tolerated.
      • Children—Use and dose must be determined by your doctor.
  • For oral dosage form (solution):
    • For acute lymphoblastic leukemia (ALL):
      • Children—Dose is based on body size and must be determined by your doctor. At first, 20 milligrams (mg) per meter squared (m(2)) of body size once a week. Your doctor may adjust your dose as needed.
    • For polyarticular juvenile idiopathic arthritis (pJIA):
      • Children—Dose is based on body size and must be determined by your doctor. At first, 10 milligrams (mg) per meter squared (m(2)) of body size once per week. Your doctor may adjust your dose as needed.


In pregnancy:

Trexall should never be used in pregnant people who are taking it for anything besides cancer treatment. If you have cancer and become pregnant, talk to your healthcare provider about the risk of taking methotrexate to the fetus.

Exposure to methotrexate during the first trimester of pregnancy is linked to an increased risk of spontaneous abortions, plus birth defects like skull anomalies, facial dysmorphism, central nervous system and limb abnormalities, and sometimes cardiac anomalies and intellectual impairment.

Adverse outcomes associated with exposure during the second and third trimesters of pregnancy include restricted growth and functional abnormalities.

In breastfeeding:

Avoid breastfeeding during treatment with methotrexate and for a week after your final dose. It is unknown exactly how much of the drug gets into breast milk and how it may affect an infant.

In children:

Methotrexate is only approved for use in children when treating ALL and pJIA. However, it is sometimes used off-label for other conditions, like Crohn's disease.

In kidney impairment:

Make sure to let your healthcare provider know if you have kidney disease. This may cause methotrexate to stay in your system longer, so your dose may need to be adjusted, especially if your creatinine clearance is less than 90 milliliters per minute.

Missed Dose

You may take Trexall just once a week or several times a week. This will affect what you should do if you miss a dose. Ask your healthcare provider what you should do if you miss a dose.

Overdose: What Happens If I Take Too Much Trexall?

Methotrexate overdose is also referred to as methotrexate toxicity. It can occur if there is too much Trexall in the body. Signs of early toxicity include:

  • Stomach problems like nausea, vomiting, or diarrhea
  • Mouth sores
  • Muscle pain
  • Headache
  • Dizziness

More serious cases of overdose can cause lung damage, liver damage, and nerve cell damage. Symptoms of lung damage may include a persistent dry cough and trouble breathing. Nerve cell damage may cause confusion, weakness, and seizures.

Several drugs exist to prevent or treat toxicity. Khapzory (leucovorin) is sometimes taken along with methotrexate to minimize side effects. Voraxaze (glucarpidase) is an antidote for methotrexate toxicity.

Contact your healthcare provider immediately or go to the nearest emergency department if you have signs of toxicity or overdose.

What Happens If I Overdose on Trexall?

If you think you or someone else may have overdosed on Trexall, call a healthcare provider or the Poison Control Center (800-222-1222).

If someone collapses or isn't breathing after taking Trexall, call 911 immediately.


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It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly and to check for unwanted effects. Blood and urine tests may be needed to check for unwanted effects.

Using this medicine while you are pregnant can harm your unborn baby. The medicine may also cause birth defects if it is used by the father when his sexual partner becomes pregnant. If you are a woman who can bear children, your doctor may give you a pregnancy test before you start using this medicine to make sure you are not pregnant. Female patients should use an effective form of birth control during treatment and for at least 3 months after the last dose. Male patients who have female partners should use an effective form of birth control during treatment and for at least 3 months after the last dose. Tell your doctor right away if pregnancy occurs while you are using this medicine.

This medicine may cause serious allergic reactions, including anaphylaxis, which may be life-threatening and require immediate medical attention. Check with your doctor right away if you have a rash, itching, dizziness, fainting, fast heartbeat, trouble breathing or swallowing, or chest tightness while you are using this medicine.

Talk with your doctor before using this medicine if you plan to have children. Some men and women who use this medicine have become infertile (unable to have children).

Limit alcohol use with this medicine. Alcohol may increase the risk for liver problems.

Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, vomiting, or yellow eyes or skin. These could be symptoms of a serious liver problem.

Methotrexate can lower the number of white blood cells in your blood, which increases the chance of getting an infection. It can also lower the number of platelets, which are necessary for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding:

  • If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.
  • Check with your doctor immediately if you notice any unusual bleeding or bruising, black, tarry stools, blood in the urine or stools, or pinpoint red spots on your skin.
  • Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.
  • Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.
  • Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail cutters.
  • Avoid contact sports or other situations where bruising or injury could occur.

This medicine may cause stomach and bowel problems. Check with your doctor right away if you have stomach pain, black, tarry stools, constipation, diarrhea, loss of appetite, nausea, pain in the back of the throat or chest when swallowing, or vomiting blood or material that looks like coffee grounds.

Check with your doctor right away if you have cough, fever, or trouble breathing. These could be symptoms of a serious lung or breathing problems (eg, acute or chronic interstitial pneumonitis).

While you are being treated with methotrexate, and after you stop treatment with it, do not have any immunizations (vaccines) without your doctor's approval. Methotrexate may lower your body's resistance and the vaccine may not work as well or you might get the infection the vaccine is meant to prevent. In addition, you should not be around other persons living in your household who receive live virus vaccines because there is a chance they could pass the virus on to you. Some examples of live vaccines include measles, mumps, influenza (nasal flu vaccine), poliovirus (oral form), rotavirus, and rubella. Do not get close to them and do not stay in the same room with them for very long. If you have questions about this, talk to your doctor.

Serious skin reactions (eg, toxic epidermal necrolysis, Stevens-Johnson syndrome, exfoliative dermatitis, skin necrosis, or erythema multiforme) can occur with this medicine. Check with your doctor right away if you have blistering, peeling, or loosening of the skin, blue-green to black skin discoloration, cough, cracks in the skin, diarrhea, itching, joint or muscle pain, loss of heat from the body, red irritated eyes, red skin lesions, often with a purple center, sore throat, sores, ulcers, or white spots in the mouth or on the lips, fever or chills, or unusual tiredness or weakness while you are using this medicine.

This medicine may make your skin more sensitive to sunlight. Wear sunscreen, eye protection, and a hat. Do not use sunlamps or tanning beds.

Tell your doctor right away if you have a change in how much or how often you urinate, rapid weight gain, swelling in the legs, ankles, or feet, or trouble breathing. These could be symptoms of a serious kidney problem.

This medicine may cause serious nerve problems. Check with your doctor right away if you have seizures, confusion, tingling or numbness in your hands, feet, or lips, trouble seeing, or headache.

This medicine may increase your risk for other cancers, including blood or skin cancer. The risk for skin cancer may be increased if you take cyclosporine after receiving treatment with methotrexate for psoriasis.

This medicine may cause a serious reaction called tumor lysis syndrome. Your doctor may give you a medicine to help prevent this. Tell your doctor right away if you have a change in urine amount, joint pain, stiffness, or swelling, lower back, side, or stomach pain, rapid weight gain, swelling of the feet or lower legs, or unusual tiredness or weakness.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

What Are Reasons I Shouldn't Take Trexall?

Trexall is not or may not be the best choice for you if:

  • You’re pregnant: If you’re taking Trexall for anything besides cancer, you shouldn’t take it while pregnant. However, if you are taking it for cancer, you and your healthcare provider should discuss the risks to the fetus, including the possibility of multiple birth defects and spontaneous abortion.
  • You have an allergy to Trexall: If you have experienced any hypersensitivity reactions after taking Trexall, including anaphylaxis, do not take it again.
  • You consume alcohol heavily: The risk of liver damage is increased in people who drink a heavy amount of alcohol. This risk seems to be enhanced with a higher methotrexate dose. In people with psoriasis, liver damage may occur without symptoms or abnormal liver tests.
  • Kidney disease: Make sure to let your healthcare provider know if you have kidney disease. This may cause methotrexate to stay in your system longer. Your dose may need to be adjusted if your creatinine clearance is less than 90 milliliters per minute. You may not be able to take Trexall if your kidney function is very low.

What Other Medications Interact With Trexall?

Tell your healthcare provider about all prescription and over-the-counter (OTC) medications, vitamins, and herbal supplements you take. The combined use of some drugs with Trexall may require monitoring by a healthcare provider.

When taken with methotrexate, certain drugs may increase the amount of methotrexate in your system. This may lead to an increased risk of side effects:

If taking these drugs while on methotrexate is unavoidable, be extra vigilant for side effects and let your healthcare provider know immediately if any occur.

What Medications Are Similar to Trexall?

Methotrexate is available generically in several formulations under different brand names:

  • Methotrexate: Available generically as 2.5-milligram (mg) tablets and 25 milligrams per milliliter (mL) vials for injection
  • Reditrex: Brand name injectable methotrexate that comes in prefilled syringes at 25 milligrams per milliliter concentration
  • Rasuvo and Otrexup: Both are brand names for injectable methotrexate that come in auto-injectors with a variety of doses available
  • Xatmep: Brand name 2.5 milligrams per milliliter methotrexate liquid taken by mouth

Methotrexate is sometimes called a DMARD, which stands for disease-modifying antirheumatic drug. Other DMARDs used to treat autoimmune diseases like RA include:

  • Arava (leflunomide) has similar side effects to methotrexate and is sometimes used in combination with it. It can also treat psoriasis and psoriatic arthritis.
  • Plaquenil (hydroxychloroquine) is an antimalarial drug that somewhat tempers the immune system to fight RA.
  • Azulfidine (sulfasalazine) is commonly used for juvenile RA and sometimes for Crohn’s disease and psoriasis.

This is NOT a list of drugs recommended to take with Trexall, though some may be used in combination. Discuss any questions or concerns with your pharmacist or a healthcare provider.

Frequently Asked Questions

How Can I Stay Healthy While Taking Trexall?

Trexall, or methotrexate, is an effective drug used for various medical conditions, including autoimmune diseases like rheumatoid arthritis and psoriasis. It can also work alongside other chemotherapy drugs for cancer treatment.

You may have heard about methotrexate's negative side effects. However, it is generally safe to take. Correct dosing, close monitoring, and taking it exactly as prescribed can help reduce the risk of unwanted side effects. Make sure to ask your healthcare provider or pharmacist if you’re unsure of how to take Trexall.

Methotrexate can lower the amounts of folic acid in the body, which may worsen side effects. Ask your healthcare provider about taking a folic acid supplement. However, in cases of cancer, adding folic acid may decrease the effectiveness of methotrexate. Therefore, talking to your healthcare provider before adding any new supplements to your regimen is very important.

You may also want to ask your healthcare provider about leucovorin, commonly referred to as a rescue drug for methotrexate. This is because leucovorin is used as an antidote for adverse side effects due to high methotrexate doses. In addition, it is beneficial in lessening side effects related to blood count and the stomach.

Medical Disclaimer

Verywell Health's drug information is meant for educational purposes only and is not intended to replace medical advice, diagnosis, or treatment from a healthcare provider. Consult your healthcare provider before taking any new medication(s). IBM Watson Micromedex provides some of the drug content, as indicated on the page.

11 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Food and Drug Administration. Trexall (methotrexate tablet) prescribing information.

  2. Cronstein BN, Aune TM. Methotrexate and its mechanisms of action in inflammatory arthritis. Nat Rev Rheumatol.  2020;16(3):145-154. doi:10.1038/s41584-020-0373-9

  3. Food and Drug Administration. Xatmep label.

  4. Dawson AL, Riehle-Colarusso T, Reefhuis J, Arena JF; National Birth Defects Prevention Study. Maternal exposure to methotrexate and birth defects: a population-based study. Am J Med Genet A. 2014;164A(9):2212-2216. doi:10.1002/ajmg.a.36625

  5. van Huizen AM, Vermeulen FM, Bik CMJM, et al. On which evidence can we rely when prescribing off-label methotrexate in dermatological practice? - a systematic review with GRADE approach. J Dermatolog Treat. 2022;33(4):1947-1966. doi:10.1080/09546634.2021.1961999

  6. Elmamoun M, Chandran V. Role of methotrexate in the management of psoriatic arthritis. Drugs. 2018;78(6):611-619. doi:10.1007/s40265-018-0898-2

  7. Sakthiswary R, Suresh E. Methotrexate in systemic lupus erythematosus: a systematic review of its efficacy. Lupus. 2014;23(3):225-235. doi:10.1177/0961203313519159

  8. Djurić Z, Šaranac L, Budić I, Pavlović V, Djordjević J. Therapeutic role of methotrexate in pediatric Crohn's disease. Bosn J Basic Med Sci. 2018;18(3):211-216. doi:10.17305/bjbms.2018.2792

  9. Lipscomb GH, Meyer NL, Flynn DE, Peterson M, Ling FW. Oral methotrexate for treatment of ectopic pregnancy. Am J Obstet Gynecol. 2002;186(6):1192-1195. doi:10.1067/mob.2002.123825

  10. West J, Ogston S, Foerster J. Safety and efficacy of methotrexate in psoriasis: a meta-analysis of published trials. PLoS One. 2016;11(5):e0153740. doi:10.1371/journal.pone.0153740

  11. Howard SC, McCormick J, Pui CH, Buddington RK, Harvey RD. Preventing and managing toxicities of high-dose methotrexate. Oncologist. 2016;21(12):1471-1482. doi:10.1634/theoncologist.2015-0164

By Sara Hoffman, PharmD
Sara is a clinical pharmacist that believes everyone should understand their medications, and aims to achieve this through her writing.