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

Femi Aremu, PharmD, is a professional pharmacist with experience in clinical and community pharmacy. He currently practices in Chicago, Illinois.

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.

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.

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

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.

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.

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.

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.

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.

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.

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 fda.gov/medwatch or 1-800-FDA-1088.

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

Potentially severe side effects of Trexall may include:

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.

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).

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.

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.

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.

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.

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.

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.

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:

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.

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.

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:

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.

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

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.

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

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

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.

Trexall is approved for use along with other chemotherapy drugs to treat several blood cancers including acute lymphoblastic leukemia (ALL) and Non-Hodgkin lymphoma. It is also used for rheumatoid arthritis and severe psoriasis, plus polyarticular juvenile idiopathic arthritis (pJIA) in children.

Common side effects when taking Trexall include mouth sores (also called stomatitis), nausea and upset stomach, and thrombocytopenia (a low platelet count). More severe side effects include infections, which are possible because methotrexate suppresses your immune system, plus blood issues such as leukopenia and myelosuppression.

Some medicines may cause too much Trexall to accumulate in your system, increasing the risk of side effects. These medicines include proton pump inhibitors like Protonix (pantoprazole), antibiotics like Bactrim and doxycycline, NSAID drugs like Advil (ibuprofen), and salicylates like aspirin.

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.

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.

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