Rheumatoid arthritis (RA) is a chronic condition that occurs when the immune system attacks healthy joints. Doctors may treat the resulting inflammation and pain with methotrexate, a drug that suppresses the immune system.

Since the 1940s, doctors have used methotrexate as a treatment for cancer. In the 1980s, scientists discovered that it could also help ease the pain and swelling of RA, as well as other symptoms of the condition. Three years later, the Food and Drug Administration approved the drug for this purpose, and it is now a first-line treatment for RA.

Methotrexate is a disease-modifying antirheumatic drug (DMARD). This means that it is one of a group of drugs that changes the course of RA and can slow its effect on the joints.

In this article, we explore methotrexate for RA, including the average dosages and safety considerations.

Senior black man sits on an examination table taking medication  Methotrexate for Rheumatoid ArthritisShare on Pinterest
Senior black man sits on an examination table taking medication Methotrexate for Rheumatoid Arthritis

The average dosage of oral methotrexate for RA starts at 7.5–10 milligrams (mg) weekly. This is equivalent to 3 or 4 pills taken once a week.

If necessary, a doctor can raise the dosage to 25 mg per week or more, depending on what a person can tolerate. A 2017 review notes that methotrexate alone can significantly reduce the progression of RA at dosages of 7.5–25 mg per week.

A person’s RA may respond better to a combination of methotrexate and another DMARD. Researchers have yet to determine conclusively whether a single-drug or a combined approach is more effective.

It is important to note that taking methotrexate by mouth involves taking weekly — not daily — doses. This can cause confusion. In some cases, people assume that this instruction is a mistake and take their weekly doses every day. This is dangerous and can cause an overdose.

Always follow the instructions from a pharmacist or doctor carefully when taking methotrexate. Anyone who is unsure about the right dosage should check with a medical professional.

The average dosage for injectable methotrexate is the same as for oral methotrexate. The dosage is always weekly.

If a person does not respond well to oral methotrexate, they may respond better to the injectable form of the drug. This is because administering the drug under the skin allows it to bypass the digestive system. This helps methotrexate act more efficiently without increasing the risk of side effects.

A doctor may recommend a weekly starting dosage of 7.5 mg for methotrexate. A dosage lower than this may not be as effective, but anyone who is interested in a lower dosage should speak with their doctor.

Many studies report that the upper dosage of methotrexate is 25–30 mg. However, some people who experience no side effects may benefit from higher dosages.

Doctors start people on low dosages of methotrexate to allow them to monitor for adverse effects. It may take 3–6 weeks before the drug starts improving RA symptoms, so it may not be immediately effective.

According to the Arthritis Foundation, medical professionals regard methotrexate as one of the safest arthritis drugs. However, some people may experience side effects, such as:

Many of methotrexate’s side effects happen because of the drug’s effects on folate levels in the body. People may be able to alleviate the side effects by taking a daily folate or folic acid supplement. A doctor can provide instructions about the best dosage to try.

A healthcare professional may also recommend other measures to reduce side effects, such as splitting the dose, switching from oral methotrexate to injections, taking antinausea medication, and using a pain-relieving rinse for mouth sores.

A high or long-term dosage of methotrexate can be dangerous. In some cases, it can cause serious adverse reactions. For example, taking methotrexate for a long period can increase the risk of liver damage, particularly for those who:

  • drink large amounts of alcohol
  • have preexisting liver disease
  • are older adults
  • have diabetes
  • have obesity

People with a high risk of liver damage may not be able to take this drug.

Other potential risks of methotrexate treatment include:

  • severe infections, due to suppression of the immune system
  • lung damage
  • damage to the lining of the digestive tract
  • severe skin reactions

Methotrexate is also not safe for people who are pregnant or could be pregnant, or people who breastfeed.

It is also important to know that methotrexate interacts with some common medications. Only take this drug as prescribed, and let the doctor or a pharmacist know before taking any other medications or supplements.

It is important to store and use methotrexate safely.


A person should store methotrexate tablets at room temperature, away from excess heat and moisture. Store injectable vials of the drug at temperatures of 68–77°F (20–25°C) and away from light.


To use methotrexate, follow the instructions on the medication carefully, unless a doctor or pharmacist has a different recommendation.

For injections, manufacturers typically supply methotrexate in prefilled syringes. To use one:

  1. Prepare the equipment: Gather the supplies, including an alcohol swab, a cotton ball, the methotrexate syringe, and a puncture-resistant container for disposing of the needle afterward.
  2. Check the medication: Check the date to ensure that it has not expired. The liquid should be yellow and contain no lumps or particles. But air bubbles are normal.
  3. Wash the hands: Use soap and warm water and wash thoroughly.
  4. Choose an injection site: This should be the stomach or thigh. Do not inject methotrexate into the arms or within 2 inches of the belly button. Also, avoid any tender, bruised, or scarred areas.
  5. Clean the injection site: Use the alcohol swab and allow the skin to dry. Do not touch the area before administering the injection, and do not fan or blow on the skin to dry it faster.
  6. Prepare the syringe and needle: Hold the body of the syringe and remove the needle cover. Do not touch the needle or allow it to touch anything else. To inject, squeeze the area of cleaned skin and, using a swift motion, insert the needle into the skin at a 45-degree angle. Slowly push the plunger down until the syringe is empty.
  7. After the injection: Gently remove the needle and cover the site with a cotton ball for 10 seconds. Dispose of the syringe needle and cap in the puncture-resistant container. Record the date and site of the injection.

Remember to dispose of used syringes in an sharps container that the FDA has approved.

Learn more about disposing of needles and syringes safely.

If a person forgets to take their dose of methotrexate, they should take it as soon as they remember. However, if the dose is more than 2 days late, contact the doctor for advice.

Do not take two doses together to compensate for a missed dose.

Ask a doctor or pharmacist any questions about using methotrexate for RA.

It is important to understand:

  • whether it is safe to take
  • the right dosage
  • when to take it
  • how to manage any side effects
  • what medications to avoid during the treatment

Anyone who does not notice an improvement in their RA symptoms should let their doctor know. The doctor might increase the dosage or combine methotrexate with another medication for better overall effects.

Anyone who develops any of these symptoms after taking methotrexate needs medical attention right away:

  • signs of an infection, such as a fever, chills, or a sore throat
  • unusual bruising or bleeding
  • pale skin
  • severe tiredness
  • shortness of breath
  • a severe rash or blistering of the skin
  • confusion or seizures

Call 911 or the local emergency number if a person has taken too much methotrexate — possibly because they took two doses close together — or if they have taken another medication that may cause an interaction.

Describe what the person has taken, and how much, to the emergency services responder.

Methotrexate is an immunosuppressant drug that doctors often use to treat the pain and inflammation of RA. It is a DMARD that can slow RA’s damage to the joints.

Unlike many medications, methotrexate has a weekly, not a daily, dosing schedule. This true whether a person takes methotrexate tablets or injects the medication.

Regardless of the form of the drug, the starting dosage is 7.5 mg weekly, which doctors can increase gradually to 25–30 mg per week.

Methotrexate is generally safe with proper use, but like all drugs, it can cause side effects. It is important to be aware of these and other associated risks, such as drug interactions and overdose.

If a person has any questions or concerns about taking methotrexate for RA, they should contact a pharmacist, doctor, or another healthcare professional.