Skip to Content

Methotrexate (Oral)

Generic Name: methotrexate (meth-oh-TREX-ate)

Oral route(Solution)

Severe Toxic Reactions, Including Embryo-Fetal ToxicityMethotrexate can cause severe or fatal toxicities. Monitor closely and modify dose or discontinue for the following toxicities: bone marrow suppression, infection, renal, gastrointestinal, hepatic, pulmonary, hypersensitivity and dermatologic.Methotrexate can cause embryo-fetal toxicity and fetal death. Use in polyarticular juvenile idiopathic arthritis is contraindicated in pregnancy. Consider the benefits and risks of methotrexate and risks to the fetus when prescribing methotrexate to a pregnant patient with a neoplastic disease. Advise patients to use effective contraception during and after treatment with methotrexate .

Oral route(Tablet)

Embryo-Fetal Toxicity Hypersensitivity Reactions, and Severe Adverse ReactionsMethotrexate tablets can cause embryo-fetal toxicity, including fetal death. For non-neoplastic diseases, Methotrexate tablets are contraindicated in pregnancy. For neoplastic diseases, advise patients of reproductive potential of the potential risk to a fetus and to use effective contraception.Methotrexate tablets are contraindicated in patients with a history of severe hypersensitivity reactions to methotrexate, including anaphylaxis.Serious adverse reactions, including death, have been reported with methotrexate. Closely monitor for adverse reactions of the bone marrow, gastrointestinal tract, liver, lungs, skin, and kidneys. Withhold or discontinue methotrexate tablets as appropriate .

Medically reviewed by Drugs.com. Last updated on Feb 24, 2021.

Commonly used brand name(s)

In the U.S.

  • Rheumatrex Dose Pack
  • Trexall
  • Xatmep

Available Dosage Forms:

  • Solution
  • Tablet

Therapeutic Class: Antineoplastic Agent

Pharmacologic Class: Antimetabolite

Uses for methotrexate

Methotrexate tablet is used alone or together with other medicines to treat several types of cancer, such as breast, head and neck, lung, blood (eg, acute lymphoblastic leukemia or ALL), bone, lymph node (eg, mycosis fungoides, relapsed or refractory non-Hodgkin lymphoma), or uterus cancer. It is also used to treat rheumatoid arthritis, severe psoriasis (a skin disease), and polyarticular juvenile idiopathic arthritis (pJIA).

Methotrexate oral solution is used to treat acute lymphoblastic leukemia (ALL) in children, and help manage polyarticular juvenile idiopathic arthritis (pJIA) in children who had other treatments that did not work well.

Methotrexate belongs to the group of medicines known as antineoplastics (cancer medicines). It blocks an enzyme that is needed by cells to live. This interferes with the growth of cancer cells, which are eventually destroyed by the body.

Methotrexate is available only with your doctor's prescription.

Before using methotrexate

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For methotrexate, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to methotrexate or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of methotrexate for the treatment of acute lymphoblastic leukemia and polyarticular juvenile idiopathic arthritis in children. However, safety and efficacy have not been established in children with other conditions.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of methotrexate in the elderly.

Breastfeeding

Studies in women breastfeeding have demonstrated harmful infant effects. An alternative to this medication should be prescribed or you should stop breastfeeding while using methotrexate.

Interactions with medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking methotrexate, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using methotrexate with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

  • Measles Virus Vaccine, Live
  • Mumps Virus Vaccine, Live
  • Rotavirus Vaccine, Live
  • Rubella Virus Vaccine, Live
  • Varicella Virus Vaccine, Live
  • Zoster Vaccine, Live

Using methotrexate with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Aceclofenac
  • Acemetacin
  • Acetazolamide
  • Adenovirus Vaccine
  • Amoxicillin
  • Amtolmetin Guacil
  • Asparaginase
  • Aspirin
  • Bacillus of Calmette and Guerin Vaccine, Live
  • Beet Root
  • Bentiromide
  • Bromfenac
  • Bufexamac
  • Capecitabine
  • Capmatinib
  • Celecoxib
  • Chloral Hydrate
  • Cholera Vaccine, Live
  • Choline Salicylate
  • Clonixin
  • Dantrolene
  • Darolutamide
  • Dengue Tetravalent Vaccine, Live
  • Dexibuprofen
  • Dexketoprofen
  • Dexlansoprazole
  • Diclofenac
  • Dicloxacillin
  • Diflunisal
  • Dipyrone
  • Doxifluridine
  • Doxycycline
  • Droxicam
  • Esomeprazole
  • Etodolac
  • Etofenamate
  • Felbinac
  • Fenbufen
  • Fenoprofen
  • Fepradinol
  • Feprazone
  • Floctafenine
  • Floxacillin
  • Flufenamic Acid
  • Fluorouracil
  • Flurbiprofen
  • Foscarnet
  • Fosphenytoin
  • Hydrochlorothiazide
  • Ibuprofen
  • Ibuprofen Lysine
  • Indomethacin
  • Influenza Virus Vaccine, Live
  • Ketoprofen
  • Ketorolac
  • Lasmiditan
  • Leflunomide
  • Levetiracetam
  • Lornoxicam
  • Loxoprofen
  • Lumiracoxib
  • Meclofenamate
  • Mefenamic Acid
  • Meloxicam
  • Mezlocillin
  • Morniflumate
  • Nabumetone
  • Naproxen
  • Nepafenac
  • Niflumic Acid
  • Nimesulide
  • Nimesulide Beta Cyclodextrin
  • Nitrous Oxide
  • Omeprazole
  • Oxaprozin
  • Oxyphenbutazone
  • Pantoprazole
  • Parecoxib
  • Penicillin G
  • Penicillin V
  • Pexidartinib
  • Phenylbutazone
  • Phenytoin
  • Piketoprofen
  • Piperacillin
  • Piroxicam
  • Pirprofen
  • Poliovirus Vaccine, Live
  • Pristinamycin
  • Probenecid
  • Proglumetacin
  • Proguanil
  • Propionic Acid
  • Propyphenazone
  • Proquazone
  • Pyrimethamine
  • Rabeprazole
  • Salicylic Acid
  • Salsalate
  • Sapropterin
  • Silver Sulfadiazine
  • Simeprevir
  • Smallpox Vaccine
  • Sodium Salicylate
  • Sulfacetamide
  • Sulfacytine
  • Sulfadiazine
  • Sulfamethizole
  • Sulfamethoxazole
  • Sulfapyridine
  • Sulfisoxazole
  • Sulindac
  • Tamoxifen
  • Tegafur
  • Tenoxicam
  • Teriflunomide
  • Tiaprofenic Acid
  • Ticarcillin
  • Tolfenamic Acid
  • Tolmetin
  • Tolvaptan
  • Triamterene
  • Trimethoprim
  • Typhoid Vaccine
  • Valdecoxib
  • Warfarin
  • Yellow Fever Vaccine
  • Zonisamide

Using methotrexate with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Amiodarone
  • Cyclosporine
  • Eltrombopag
  • Etoricoxib
  • Mercaptopurine
  • Procarbazine
  • Rofecoxib
  • Theophylline

Interactions with food/tobacco/alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using methotrexate with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use methotrexate, or give you special instructions about the use of food, alcohol, or tobacco.

  • Cola

Other medical problems

The presence of other medical problems may affect the use of methotrexate. Make sure you tell your doctor if you have any other medical problems, especially:

  • Alcohol abuse, or history of or
  • Anemia or
  • Leukopenia (low white blood cells) or
  • Liver disease, severe or
  • Thrombocytopenia (low platelet blood level) or
  • Weak immune system—Methotrexate tablets should not be used in patients with these conditions.
  • Ascites (extra fluid in the stomach area) or
  • Kidney disease or
  • Pleural effusion (extra fluid in the lung)—Use with caution. The effects may be increased because of slower removal of the medicine from the body.
  • Diabetes or
  • Obesity or
  • Stomach or bowel problem (eg, peptic ulcers, ulcerative colitis)—Use with caution. May cause side effects to become worse.
  • Infection (eg, bacteria, fungus, virus)—Use with caution. May decrease your ability to fight an infection.

Proper use of methotrexate

Take methotrexate only as directed by your doctor. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered.

Measure the oral liquid medicine with a marked measuring spoon, oral syringe, or medicine cup.

Swallow the tablet whole. Do not crush, break, or chew it. Do not take the tablet if you cannot swallow it.

For patients with rheumatoid arthritis, psoriasis, or polyarticular juvenile idiopathic arthritis: Your doctor may give you folic acid or folinic acid supplement to help reduce the unwanted effects of methotrexate.

For patients with cancer: Do not take folic acid or folinic acid supplement unless directed by your doctor.

Dosing

The dose of methotrexate 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 methotrexate. 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.

Missed dose

Methotrexate needs to be given on a fixed schedule. If you miss a dose or forget to use your medicine, call your doctor or pharmacist for instructions.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions while using methotrexate

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

Using methotrexate 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 methotrexate to make sure you are not pregnant. Female patients should use an effective form of birth control during treatment and for at least 6 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 methotrexate.

Methotrexate 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 methotrexate.

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

Limit alcohol use with methotrexate. 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.

Methotrexate 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 methotrexate. Check with your doctor right away if you have blistering, peeling, or loosening of the skin, red skin lesions, severe acne or a skin rash, sores or ulcers on the skin, or fever or chills while you are using methotrexate.

Methotrexate may make your skin more sensitive to sunlight. Wear sunscreen. 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.

Methotrexate 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.

Methotrexate 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.

Methotrexate 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.

Methotrexate side effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

  • Black, tarry stools
  • bleeding gums
  • blood in the urine or stools
  • bloody vomit
  • diarrhea
  • increased heartbeat
  • itching, rash, reddening of the skin
  • joint pain
  • nausea
  • pinpoint red spots on the skin
  • sores in the mouth or lips
  • stomach pain
  • swelling of the eyelids, face, lips, hands, feet, or lower legs
  • swelling or inflammation of the mouth
  • trouble breathing
  • unusual bleeding or bruising
  • vomiting
  • yellow eyes or skin

Less common

  • Back pain
  • bloody nose
  • blurred vision
  • body and muscle pain
  • burning while urinating
  • confusion
  • continuing ringing, buzzing, or other unexplained noise in the ears
  • cough or hoarseness
  • cracked, dry, scaly skin
  • dark urine
  • dizziness
  • drowsiness
  • ear congestion
  • fever or chills
  • headache
  • loss of appetite
  • loss of hearing
  • loss of voice
  • lower back or side pain
  • painful or difficult urination
  • pale skin
  • runny nose
  • seizures
  • sneezing
  • sore throat
  • stuffy or runny nose
  • unusual tiredness or weakness
  • weight loss
  • white or brownish vaginal discharge

Incidence not known

  • Anxiety
  • blistering, peeling, or loosening of the skin
  • bloating
  • blurred or change in vision
  • changes in skin color
  • confusion
  • constipation
  • decreased interest in sexual intercourse
  • difficulty in moving
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • dry mouth
  • dryness or soreness of throat
  • eye pain
  • fruit-like breath odor
  • heartburn
  • inability to have or keep an erection
  • increased hunger or thirst
  • indigestion
  • irritation in the mouth
  • large, flat, blue, or purplish patches in the skin
  • loss in sexual ability, desire, drive, or performance
  • loss of consciousness
  • menstrual problem
  • night blindness
  • pain in the chest or groin
  • pain, redness, swelling, or tenderness in the arm or leg
  • red skin lesions, often with a purple center
  • red, wart-like spots on the skin
  • sudden loss of coordination
  • sudden onset of slurred speech
  • swelling or soreness of the breasts
  • swollen, painful, or tender lymph glands in the neck or armpit
  • tingling or numbness in the hands, feet, or lips

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

  • Hair loss or thinning

Less common

  • Blemishes on the skin
  • hard, red, swollen skin irritation
  • pimples

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Frequently asked questions

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.