What to Know About Methotrexate for Rheumatoid Arthritis

Methotrexate is a disease-modifying anti-rheumatic drug (DMARD) used to treat rheumatoid arthritis (RA) and other rheumatic illnesses such as lupus and psoriatic arthritis. Sold under the brand names Rheumatrex, Trexall, Otrexup, and Rasuvo, methotrexate is the recommended top-line treatment for people with RA. 

A slow-acting medication, methotrexate is taken once a week as either a pill or injection to relieve RA pain and inflammation. Originally developed as a leukemia drug in the 1940s, it was approved for use in arthritis in 1988. More than 30 years worth of research shows it is effective in relieving symptoms and improving the disease course in people with RA.

Uses

Methotrexate is used to reduce joint pain and swelling associated with rheumatoid arthritis, prevent joint damage, and lower the risk of disability by slowing disease progression.

In addition to RA, methotrexate may be prescribed for:

• Psoriatic arthritis
• Lupus
• Ankylosing spondylitis
• Vasculitis
• Juvenile arthritis
• Certain cancers including breast cancer, lung cancer, some cancers of the head and neck, gestational trophoblastic disease, certain types of lymphoma, and leukemia

Methotrexate is in a class of medicines known as antimetabolites and interferes with enzymes that impact immune system function. One enzyme, dihydrofolate reductase, is used in the production of a form of folic acid required for actively growing cells.

In cancer treatment, methotrexate inhibits the growth of cancer cells. In psoriasis, it slows the growth of skin cells, preventing psoriatic scales from forming. Methotrexate is theorized to treat rheumatoid arthritis by decreasing the activity of the immune system in a similar way.

Before Taking

Methotrexate is the first-line treatment for RA. If your healthcare provider suspects you have RA due to painful, swollen joints, positive rheumatoid factor blood work, or other indications of the disease, methotrexate is typically the first medication tried.

Your practitioner will order lab tests before prescribing methotrexate to ensure it is safe for you. Methotrexate is often prescribed alongside short-acting medicines including corticosteroids like prednisone and non-steroidal anti-inflammatories (NSAIDs) to provide relief of symptoms before methotrexate takes effect.

Talk to your healthcare provider about all medications, supplements, and vitamins that you currently take. Your practitioner and pharmacist will be aware of unsafe drug interactions.

Precautions and Contraindications

Methotrexate is not without risks and it may not be right for everyone.

People with the following conditions should take methotrexate with caution:

• Known chronic liver or kidney disease
• Severe anemia, low white blood cell counts, or low platelet counts
• Compromised immunity
• A history of excess fluid in the chest or abdomen

Your healthcare provider will go over the potential benefits and risks for your individual situation to determine if methotrexate is right for you.

Methotrexate is a folate antagonist and may lead to a deficiency in the B vitamin. A folic acid supplement is typically taken along with Methotrexate to prevent a folate deficiency and to reduce the risk of methotrexate side effects, such as nausea and vomiting.

Couples of childbearing age are advised to use contraception while either partner is taking methotrexate and for three months after stopping the drug. Methotrexate may interfere with DNA integrity in sperm. Methotrexate does not appear to affect future fertility.

Your healthcare provider will order regular lab work during your treatment to check your body's response to methotrexate and to treat side effects before they become severe.

Dosage

Methotrexate is taken one day a week for rheumatoid arthritis. The oral dose is available in 2.5 milligrams (mg) tablets and the typical starting dose for adults is 7.5 mg to 10 mg. If needed, the total dose may be increased to 20 mg or 25 mg once a week.

Rheumatrex comes in blister cards containing the exact number of pills to take each week. Trexall is available in 5 mg, 7.5 mg, 10 mg, and 15 mg tablets.

Methotrexate is also available in an injectable form under the brand names Otrexup, Rasuvo, or Reditrex. The medicine is given as a shot under your skin, usually on the stomach or thigh. Most patients are able to self-inject their weekly dose. Follow the instructions on the patient information handout from the pharmacist. 

All listed dosages are according to the drug manufacturer and may vary from patient to patient. Check your prescription and talk to your healthcare provider if you have any questions about the appropriate dose for you.

How to Take and Store

Methotrexate is taken once a week on the same day each week. If you miss a dose or forget to take your medicine, call your healthcare provider or pharmacist for guidance. Do not take two doses at once.

The drug can be taken with or without food, but it should not be taken with caffeine, such as coffee, tea, cola, or medications like Excedrin. The American College of Rheumatology warns that consuming caffeine near the time you plan to take methotrexate may affect the absorption of the drug.

Side Effects

Many people experience no significant side effects while taking methotrexate, but if you do, adjusting the dose (as instructed by your healthcare provider) may eliminate the problem.

Common

Common side effects of methotrexate include:

• Nausea
• Vomiting
• Diarrhea
• Hair loss (gradual)
• Sun sensitivity
• Fatigue

Supplementing with folic acid alongside methotrexate has been shown to reduce side effects for some people.

Less Common

Less common side effects of methotrexate include:

• Acne
• Boils on skin
• Pale skin
• Skin rash or itching

Serious 

Methotrexate can lead to serious adverse events, including organ and bone marrow damage, birth defects, serious skin reactions, and even death.

If you experience the following symptoms, call your healthcare provider immediately:

• Black, tarry, or bloody stools
• Blisters or peeling skin
• Diarrhea lasting more than 24 hours
• Dry cough
• Extreme tiredness or lack of energy
• Fever
• Flu-like symptoms
• Mouth sores
• Loss of appetite
• Pain in the upper right part of the stomach
• Severe nausea
• Severe skin rash
• Shortness of breath
• Unusual bruising or bleeding
• Vomit that is bloody or looks like coffee grounds
• Yellowing of the skin or eyes

Warnings and Interactions

Methotrexate may cause very serious, life-threatening complications including:

• Abnormal blood counts due to decreased blood cell production
• Breathing problems due to lung damage
• Decreased kidney function
• Gastrointestinal disorders
• Life-threatening skin reactions
• Liver damage
• Opportunistic infections due to decreased immune system response

Methotrexate may also increase the risk of certain cancers. The elevated risk of lymphoma in particular may be corrected when the drug is stopped.

It's important to be aware that the risk of certain adverse effects is greater in certain individuals. You should take care to ensure that all avoidable risk factors are eliminated if you are taking methotrexate and that your healthcare provider is aware of all of those that you cannot modify.

Liver Function

The risk of abnormal liver function/liver damage increases significantly for people who drink alcohol, are elderly or obese, or have diabetes.

Taking certain medications alongside methotrexate may also increase the risk of liver damage. These include:

• Soriatane (acitretin)
• Imuran (azathioprine)
• Accutane (isotretinoin)
• Azulfidine (sulfasalazine)
• Vesanoid (tretinoin)

If you drink alcohol, be honest with your healthcare provider prior to taking methotrexate. It is important to routinely have your liver function monitored with blood work so your practitioner can monitor you for adverse effects.

A Word From Verywell

Methotrexate is among the most commonly prescribed drugs used to treat rheumatoid arthritis. In some cases, it is taken alone. In other cases, methotrexate is prescribed as part of combination therapy, where it is taken along with another DMARD or biologic drug.

It is imperative that you take methotrexate exactly as directed. It is also essential that you be aware of potential side effects and report anything unusual to your healthcare provider immediately. Methotrexate can be a safe and effective medication when used properly.