A nurse is teaching a client who has a new prescription for methotrexate

Medically Reviewed by David Zelman, MD on September 29, 2020

Methotrexate is one of the most effective medications to treat rheumatoid arthritis (RA). It's the first drug most doctors prescribe after you’re diagnosed.

It will help ease symptoms like joint pain, fatigue, redness, and swelling. It may also help prevent damage to your organs and joints.

Methotrexate interrupts the process that causes RA inflammation, which damages your joints and organs over time.

Your doctor may call it a “DMARD,” which is a type of RA drug. (DMARD stands for disease-modifying antirheumatic drug).

You can take methotrexate in either pills or shots. There are prefilled methotrexate shots that are easy to take at home.

You will take 7.5 to 10 milligrams each week. Your doctor may raise that to 20-25 milligrams per week if needed.

The pills will come with directions about how many to take and when. If you’re not sure about those instructions, ask your doctor or a pharmacist.

Shots work better for some people, especially if you forget to take your pills on schedule or if the pills cause nausea. Methotrexate liquid comes in vials with a hypodermic needle or in prefilled pens with various doses.

You inject the drug under the skin on your stomach or thigh. Your doctor or nurse will show you how to do this at home. If you use a prefilled pen, you’ll stick the pen into your stomach or thigh and press on it to inject the drug. Try to give yourself your shot in a different spot each time. This will help you avoid skin reactions.

It can take 3 to 6 weeks to start to feel your methotrexate work. It takes even longer -- 12 weeks -- to get the full effects.

Your doctor will test your blood often to check on how well your treatment works and to make sure it’s safe for organs such as your liver.

Your doctor may prescribe methotrexate alone. Or you may also take other drugs like aspirin, nonsteroidal anti-inflammatory drugs, low-dose steroids, or other DMARDs.

You’ll probably take folic acid supplements along with methotrexate. This vitamin can help you lower your chance of certain side effects.

Talk to your doctor before you take any drug or supplement. Not all drugs mix well. Taking biologics is not recommended while taking methotrexate. 

You may notice these side effects while you take methotrexate:

Tell your doctor if you have them. They can adjust your dose so you feel better. Minor side effects should lessen over time.

This drug can harm your liver. You’ll visit the doctor regularly to check on how methotrexate affects your body. Your doctor might test your liver as often as once a month for the first 6 months you take the drug. After that, you may get a liver test every 3 months.

You’re more likely to get an infection while you take methotrexate. So take these steps to stay well:

  1. Try to avoid people with infections like colds or flu.
  2. Wash your hands regularly.
  3. Tell your doctor if you have fever, chills, or a cough.

Methotrexate can also:

  • Make lymphoma (cancer of the lymphatic system) more likely.
  • Make your skin more sensitive to the sun. Use sunscreen, wear protective clothing, and don’t use sunlamps or tanning beds.
  • Cause birth defects. If you or your partner could get pregnant, you should use birth control while on methotrexate. Men should continue to use protection for 3 months after the last dose. Women should stay on birth control for at least 1 menstrual cycle after the last dose and not breastfeed while taking methotrexate.
  • Cause lung problems, although this is rare. Tell your doctor if you cough frequently or have shortness of breath.

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Methotrexate is part of a class of drugs called immunosuppressants. It suppresses the body's immune response and reduces inflammation in your lungs. Because inflammation is the precursor to fibrosis (scarring), we hope methotrexate will prevent the formation of lung fibrosis and allow the inflamed lung to return to normal.

What special precautions should I follow?

Before taking methotrexate:

Tell your doctor and pharmacist if you are allergic to methotrexate, any other medications or any of the inactive ingredients in methotrexate tablets. Ask your pharmacist for a list of the inactive ingredients.

Tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements and herbal products you are taking or plan to take. Be sure to mention those listed in the important warning section of the medication insert, as well as any of the following:

  • Certain antibiotics such as chloramphenicol (Chloramycetin), penicillins, and tetracycyline (Bristacycline, Sumycin)
  • Folic acid
  • Rheumatoid arthritis medications
  • Phenytoin (Dilantin)
  • Probenecid (Benemid)
  • Sulfonamides such as co-trimoxazole (Bactrim, Septra), sulfadiazine, sulfamethizole (Urobiotic), and sulfisoxazole (Gantrisin)
  • Theopylline (Theochron, Theolair)

Your doctor may need to change the doses of your medication or monitor you more carefully for side effects.

Methotrexate may cause liver damage. Tell your doctor if you drink or have ever drunk large amounts of alcohol, or if you have or have ever had liver disease. Do not drink alcohol while you are taking methotrexate. Call your doctor immediately if you experience any of the following symptoms: nausea, extreme tiredness, lack of energy, loss of appetite, pain in the upper right part of the stomach, flu-like symptoms or yellowing of the skin or eyes.

Methotrexate may cause kidney damage. Be sure to drink plenty of fluids during your treatment with methotrexate, especially if you exercise or are physically active. Call your doctor if you think you might be dehydrated. You may become dehydrated if you sweat excessively or if you vomit, have diarrhea or have a fever.

Methotrexate may cause a decrease in the number of blood cells made by your bone marrow. Tell your doctor if you have, or have ever had, a low blood count (decrease in the number of blood cells in your body), anemia (red blood cells do not bring enough oxygen to all parts of the body), or any other problem with your blood cells.

Call your doctor immediately if you experience any of the following symptoms:

  • Confusion
  • Difficulty falling asleep or staying asleep
  • Dizziness
  • Excessive tiredness
  • Fast heartbeat
  • Pale skin
  • Shortness of breath
  • Sore throat, chills, fever or other signs of infection
  • Unusual bruising or bleeding
  • Weakness

Methotrexate may cause a severe rash that can be life-threatening. If you develop a rash, blisters or a fever, call your doctor immediately.

Methotrexate may cause damage to your intestines. Tell your doctor if you have or have ever had stomach ulcers or ulcerative colitis, a condition in which part or all of the lining of the intestine is swollen or worn away. If you develop sores in your mouth or diarrhea, stop taking methotrexate and call your doctor immediately.

Tell your doctor if you are breast-feeding. You should not breast-feed during your treatment with methotrexate.

Before having surgery, including dental surgery, tell the doctor or dentist that you are taking methotrexate.

Methotrexate may make your skin sensitive to real or artificial sunlight. Avoid unnecessary or prolonged exposure to sunlight and wear protective clothing, sunglasses and sunscreen. Do not use sunlamps during your treatment with methotrexate. If you have psoriasis, your sores may get worse if you expose them to sunlight while taking methotrexate.

What side effects can this medication cause?

Methotrexate may cause side effects. Tell your doctor if any of the following symptoms are severe or do not go away:

  • Acne
  • Changes in skin color
  • Hair loss
  • Headache
  • Irregular menstrual periods
  • Swollen, tender gums

Some side effects can be serious. If you experience any of the following symptoms or any symptoms listed in the important warning section of the medication insert, call your doctor immediately:

  • Blood in urine
  • Blurred vision
  • Chest pain
  • Difficulty moving one or both sides of the body
  • Difficulty speaking or slurred speech
  • Fainting
  • Pain or redness of one leg only
  • Seizures
  • Sudden loss of vision
  • Urgent or frequent need to urinate
  • Weakness or numbness of an arm or leg

Methotrexate may cause other side effects. Tell your doctor if you have any unusual problems while you are taking this medication.

What monitoring will I need?

Your doctor will order regular lab tests to check your response to methotrexate and monitor for toxicity. You will need to have your blood counts — white blood cells, red blood cells and platelets — and liver function checked regularly. Your doctor may order additional tests depending on the results.

For additional information on methotrexate, please visit MedlinePlus.gov.