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Overview: Methotrexate is used to treat certain types of arthritis, cancer, and severe psoriasis. Common side effects include nausea or vomiting, upset stomach, and mouth sores. Serious side effects may include blood disorders, lung problems, or kidney or liver problems. Methotrexate comes in several forms, including tablets, liquid, and injections. Read and follow the instructions for the product you have, and make sure you understand how to prepare, use, and throw it away properly.

Uses

What is methotrexate used for?

Methotrexate is commonly used for the following conditions.

These uses may vary depending on the specific methotrexate product prescribed. 

Methotrexate may also be used for other conditions as determined by your health care provider.

How does methotrexate work (mechanism of action)?

Methotrexate works by blocking an enzyme that is important for cell growth. For treating cancer, methotrexate helps stop cancer cells from growing and spreading. For arthritis and psoriasis, methotrexate is thought to reduce inflammation by lowering the activity of the immune system. 

How is methotrexate supplied (dosage forms)?

Brands and other names

  • Jylamvo
  • Otrexup
  • Rasuvo
  • RediTrex
  • Rheumatrex
  • Trexall
  • Xatmep

Example dosage forms and strengths

  • 2 mg/mL, 2.5 mg/mL oral solution
  • 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg oral tablets
  • 7.5 mg/0.15 mL, 10 mg/0.2 mL, 12.5 mg/0.25 mL, 15 mg/0.3 mL, 17.5 mg/0.35 mL, 20 mg/0.4 mL, 22.5 mg/0.45 mL, 25 mg/0.5 mL, 30 mg/0.6 mL auto-injector
  • 10 mg/0.4 mL, 12.5 mg/0.4 mL, 15 mg/0.4 mL, 17.5 mg/0.4 mL, 20 mg/0.4 mL, 22.5 mg/0.4 mL, 25 mg/0.4 mL auto-injector

Methotrexate is also available in other injectable forms that are given by a health care provider.

How should I store methotrexate?

Many methotrexate products should only be stored at room temperature, between 68 F and 77 F (20 C and 25 C), and can be exposed to temperatures between 59 F and 86 F (15 C and 30 C) for shorter periods of time, such as when transporting them. Other methotrexate products may be stored in a refrigerator, between 36 F and 46 F (2 C and 8 C). Protect from light and do not freeze. Ask your pharmacist if you are unsure how to store your methotrexate product.

Side Effects

What are the most common side effects of methotrexate?

The most common side effects of methotrexate are listed below. These side effects may vary depending on the product you are using. Tell your health care provider if you have any of these side effects that bother you.

  • Mouth sores
  • Blood disorders (see below)
  • Nausea, vomiting, indigestion, diarrhea, or other stomach problems (see below)
  • Changes in liver function tests
  • General feeling of being unwell, tired, or not having your usual energy
  • Fever or chills
  • Infections (see below)
  • Rash or skin irritation
  • Headache
  • Hair loss
  • Dizziness

There may be other side effects of methotrexate that are not listed here. Contact your health care provider if you think you are having a side effect of a medicine. In the U.S., you can report side effects to the FDA at www.fda.gov/medwatch or by calling 800-FDA-1088 (800-332-1088). In Canada, you can report side effects to Health Canada at www.health.gc.ca/medeffect or by calling 866-234-2345.

What are the serious side effects of methotrexate?

While less common, the most serious side effects of methotrexate are described below, along with what to do if they happen.

Severe Allergic Reactions. Methotrexate may cause allergic reactions, which can be serious. Stop using methotrexate and get help right away if you have any of the following symptoms of a serious allergic reaction.

  • Breathing problems or wheezing
  • Racing heart
  • Fever or general ill feeling
  • Swollen lymph nodes
  • Swelling of the face, lips, mouth, tongue, or throat
  • Trouble swallowing or throat tightness
  • Itching or skin rash
  • Bumps on the skin called hives that can be red, pink, white, or brown, depending on your skin tone
  • Nausea or vomiting
  • Dizziness, feeling lightheaded, or fainting
  • Stomach cramps
  • Joint pain

Blood Disorders. Methotrexate may cause your bone marrow to not make enough cells. This can lead to low levels of important cells, such as red blood cells, white blood cells, platelets, and neutrophils. Bone marrow suppression can lead to infections or bleeding. This can be serious or even life-threatening. Keep all appointments to have your blood checked. Tell your health care provider right away if you have any of the following symptoms of bone marrow suppression.

  • Fever
  • Shortness of breath
  • Pale or yellowish skin
  • Easy bruising or bleeding
  • Frequent infections
  • Unusual weakness or tiredness
  • Dizziness, lightheadedness, or feeling like you are about to pass out
  • Headache
  • Fast or abnormal heartbeat

Infections. Methotrexate can increase your risk of infections, including serious ones. Call your health care provider right away if you have an infection or any of the following symptoms.

  • Burning or stinging when you pee
  • Cough or coughing up blood
  • Fever, sweats, chills, or muscle aches
  • Shortness of breath
  • Diarrhea or stomach pain
  • Weight loss

Kidney Damage. Kidney damage can happen when using methotrexate. Call your health care provider right away if you have any of the following symptoms of kidney damage.

  • Reduced need to pee
  • Making more or less pee than usual
  • Swelling in your feet, ankles, or legs
  • Weakness or unusual tiredness
  • Difficulty catching your breath or chest pain/pressure
  • Confusion
  • Nausea
  • Seizures

Stomach Problems. Methotrexate can increase your risk of stomach problems, including diarrhea, vomiting, inflammation of your mouth (stomatitis), inflammation and bleeding of your stomach, and tears (perforation). Call your health care provider right away if you have these symptoms or if you have any of the following.

  • Vomiting blood
  • Black or tarry poop
  • Stomach pain that does not go away or is severe
  • Severe constipation
  • Feeling faint
  • Fever and chills

Liver Damage. Liver damage, also called hepatotoxicity, can happen when using methotrexate. Call your health care provider right away if you have any of the following symptoms of liver damage.

  • Nausea or vomiting
  • Stomach or belly pain
  • Fever
  • Weakness or unusual tiredness
  • Easy bruising or bleeding
  • Itching
  • Loss of appetite or weight loss
  • Light-colored poop
  • Dark-colored urine (pee)
  • Your skin or the whites of your eyes turning yellowish in color (also called jaundice)

Lung Inflammation. Methotrexate can cause inflammation in your lungs, also called interstitial lung disease or pneumonitis. This can be serious or even life-threatening. Get emergency help if you have trouble breathing. You may also have a cough, fever, or chest pain. 

Severe Skin Reactions. Methotrexate can cause severe skin reactions, such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). These can lead to death if not treated. If you get a rash, stop methotrexate and call your health care provider right away. Get emergency help if you have any of the following symptoms of SJS or TEN.

  • Painful red or purple skin that looks burned and peels off
  • Flat red rash or blisters on your skin, mouth, nose, and genitals
  • Red, painful, watery eyes
  • Flu-like symptoms, including fever, chills, and muscle aches

Cancer. Methotrexate can cause a new cancer to develop or cause a previously treated cancer to recur. Tell your health care provider about any new symptoms that you may get. 

Brain and Nervous System Effects. Methotrexate can affect your brain or central nervous system (CNS). These effects can be serious. Get emergency help if you have any of the following symptoms.

  • Confusion
  • Seizures
  • Balance problems or weakness
  • Trouble talking or moving
  • Vision changes
  • Stiff neck

Tumor Lysis Syndrome. Methotrexate can cause a fast breakdown of cancer cells. This can lead to a condition called tumor lysis syndrome, which can be serious. It is important to drink plenty of water while using methotrexate and to keep all appointments for blood tests so your health care provider can see how your body is responding to methotrexate. Tell your health care provider right away if you have any of the following signs of tumor lysis syndrome while using methotrexate. 

  • Nausea and vomiting
  • Weakness
  • Swelling or fluid retention
  • Shortness of breath
  • Muscle cramps
  • Seizures

Warnings & Precautions

Who should not use methotrexate?

Allergies to Ingredients. People who are allergic to any of the following should not use methotrexate.

  • Jylamvo
  • Methotrexate
  • Otrexup
  • Rasuvo
  • RediTrex
  • Rheumatrex
  • Xatmep
  • Trexall
  • Any of the ingredients in the specific product dispensed

Your pharmacist can tell you all of the ingredients in the specific methotrexate products they stock.

Pregnancy. Methotrexate should not be used to treat certain conditions if you are pregnant. If you become pregnant, contact your health care provider right away. See the Pregnancy section for more details.

Certain Health Conditions. Some methotrexate products should not be used if you have the following conditions. 

What should I know about methotrexate before using it?

Do not use methotrexate unless it has been prescribed to you by a health care provider. 

Use methotrexate exactly as prescribed. How often you should use methotrexate (such as weekly or daily) depends on the condition being treated. Using methotrexate incorrectly can lead to serious side effects or death.

Do not share methotrexate with other people, even if they have the same condition as you. It may harm them.

Keep methotrexate out of the reach of children. If your methotrexate product is kept in a refrigerator, take special precautions to make sure children can’t access it.

Methotrexate can affect your coordination and may cause dizziness or tiredness. Do not drive or do other activities that require alertness or coordination until you know how methotrexate affects you.

Methotrexate can make your skin more sensitive to light from the sun, sunlamps, and tanning beds. This is called photosensitivity. Exposure to this light can cause severe sunburns, blisters, and swelling. If you need to be in sunlight, wear sunscreen, a hat, and clothing that covers your skin.

Keep all appointments with your health care provider, including for blood tests and other tests, before you start and while you are using methotrexate. This helps your health care provider make sure it is safe for you to use methotrexate.

There are multiple forms of methotrexate available. Read and follow the instructions for the product you have, and make sure you understand how to prepare, use, and throw it away properly. If you have any questions, talk to your health care provider.

If you are taking methotrexate liquid, use an accurate measuring device to measure your dose. A household spoon is not an accurate measuring device and may cause you to take the wrong dose. Ask your pharmacist what measuring device to use.

Methotrexate may make it hard for you to get pregnant or get your partner pregnant. If you have concerns, talk to your health care provider.

What should I tell my health care provider before using methotrexate?

Tell your health care provider about all of your health conditions and any prescription or over-the-counter (OTC) medicines, vitamins/minerals, herbal products, and other supplements you are using. This will help them determine if methotrexate is right for you.

In particular, make sure that you discuss any of the following.

Current and Past Health Conditions. Tell your health care provider if you have any of the following.

Alcohol Use. Tell your health care provider if you drink alcohol or if there are any changes in the amount of alcohol you drink.

Upcoming Surgeries. Tell your health care provider if you plan to have any surgeries (including dental surgeries) where you will be put to sleep with anesthesia.

Radiation. Tell your health care provider if you are planning to have any radiation therapy or have had it in the past.

Vaccines. Talk with your health care provider about any vaccines that you may need. You should not receive certain vaccines right before or while using methotrexate. Tell your health care provider about any vaccines you have recently received or have scheduled.

Pregnancy. Methotrexate can cause harm to a fetus. Tell your health care provider if you are pregnant or plan to become pregnant. Your health care provider may do a pregnancy test to make sure you are not pregnant before starting methotrexate. If you become pregnant or think you might be pregnant, stop using methotrexate right away and contact your health care provider. If you can get pregnant, use effective birth control while using methotrexate and for at least six months after your last dose. If you can get your partner pregnant, use effective birth control while using methotrexate and for at least three months after your last dose. 

Breastfeeding. Do not breastfeed while you are using methotrexate and for at least one week after your last dose. Methotrexate can pass into breast milk. Tell your health care provider if you are breastfeeding or plan to breastfeed.

Other Medicines and Supplements. Methotrexate may interact with other medicines and supplements. Before using methotrexate, tell your health care provider about any prescription or over-the-counter (OTC) medicines, vitamins/minerals, herbal products, and other supplements you are using. See the Interactions section for more details.

Interactions

Does methotrexate interact with foods or drinks?

There are no known interactions between methotrexate and foods or nonalcoholic drinks.

It is not recommended to drink alcohol while using methotrexate. Both methotrexate and alcohol can increase your risk of side effects, such as bleeding and dizziness. 

Does methotrexate interact with other medicines (drug interactions)?

Always tell your health care provider about any prescription or over-the-counter (OTC) medicines, vitamins/minerals, herbal products, and other supplements you are using.

In particular, make sure that you discuss if you are using any of the following before using methotrexate.

  • An antibiotic, such as doxycycline, minocycline, neomycin, penicillin, or sulfamethoxazole/trimethoprim, which is used to treat certain bacterial infections
  • A medicine that can affect your liver, such as azathioprine (Azasan), a retinoid (such as acitretin), or sulfasalazine (Azulfidine)
  • A medicine that can affect your kidneys, such as cisplatin
  • Probenecid, which is a medicine commonly used for gout
  • A nonsteroidal anti-inflammatory drug (NSAID), such as ibuprofen, naproxen, and others, which is in many prescription and OTC products for pain, swelling, and fever
  • Aspirin, which is in many prescription and OTC products, including those for pain, swelling, and fever
  • A salicylate, such as diflunisal or salsalate, which is a medicine used for arthritis
  • A corticosteroid, such as dexamethasone, methylprednisolone, or prednisone, which is a medicine for certain inflammatory conditions
  • Theophylline (Theo-24, Elixophyllin), which is a medicine for asthma or certain other breathing problems
  • Folic acid or folate supplements (also known as vitamin B9), or medicines that affect folate levels in your body, such as dapsone (Aczone), pemetrexed (Alimta, Pemfexy), or pyrimethamine (Daraprim)
  • A blood thinner, which is a medicine used to treat or prevent blood clots
  • A sulfonylurea, such as glimepiride, glipizide, or glyburide, which is a medicine used to treat type 2 diabetes
  • Phenytoin (Dilantin, Phenytek, and others), which is a medicine used to control seizures
  • A proton pump inhibitor (PPI), such as esomeprazole (Nexium), lansoprazole (Prevacid), omeprazole (Prilosec), pantoprazole (Protonix), or rabeprazole (Aciphex)
  • Mercaptopurine (Purixan), which is a medicine used to treat a type of blood cancer

This may not be a complete list of medicines that can interact with methotrexate. Always check with your health care provider.

Does interact with other drugs you are taking?

Enter your medication into the WebMD interaction checker

Overdose/Missed Dose

What should I do if I accidentally use too much methotrexate?

If you or someone else has used too much methotrexate, get medical help right away, call 911, or contact a Poison Control center at 800-222-1222.

What should I do if I miss a dose of methotrexate?

If you miss a dose of methotrexate, call your health care provider right away for instructions on when you should use or receive your next dose.

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