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Methotrexate for Rheumatoid Arthritis

Methotrexate for Rheumatoid Arthritis Patients – all your questions answered

Methotrexate is a common medication used for patients with rheumatoid arthritis. This medication can be used alone or in combination with other medications. When I start my patients on this therapy here are the most common questions that I clarify for patients.

  • What is Methotrexate?
  • What is the effect of Methotrexate in Rheumatoid Arthritis Patients?
  • Is Methotrexate a pill or an injectable medication?
  • Is Methotrexate a “chemo” drug?
  • Can Methotrexate be combined with other medications such as biologics?
  • What are the most common side effects?
  • How to monitor if methotrexate is safe for my body?
  • Can methotrexate affect my organs?
  • Why do I need to take folic acid with methotrexate?
  • Can I drink while taking methotrexate?
  • Can I get more infections while on methotrexate?
  • Can I get vaccinated while taking methotrexate?
  • Is Methotrexate safe for pregnancy?

What is Methotrexate?

Methotrexate is a common medication used in patients with rheumatoid arthritis for many decades (since 1951). However, many rheumatologists started to use this drug routinely in the 1980’s. In Rheumatoid arthritis patients, methotrexate is used for modulation of the immune system and decreasing inflammation.

Rheumatoid Arthritis treatment

What is the effect of Methotrexate in Rheumatoid Arthritis Patients?

Patients with rheumatoid arthritis have high levels of inflammation. Inflammation may be present systemic (affecting many organs) and, or in the joints. Methotrexate has anti-inflammatory and immuno-modulatory effects. Methotrexate decreases the activation of certain immune system cells (T and B cells) and the production of certain pro-inflammatory cytokines (interleukin-1 and Interleukin-6), while increasing the production of anti-inflammatory cytokines (interleukin-10).

Is Methotrexate a pill or an injectable medication?

Methotrexate can be a pill or an injection that can be given subcutaneously or intramuscular. As a pill, you can take methotrexate with or without food. The absorption of oral methotrexate can vary and sometimes, your doctor will decide to change the oral methotrexate to an injectable form for a better absorption. Some patients do not tolerate oral methotrexate due to nausea or other gastrointestinal effects. 

In that case, your doctor will decide to change to the injectable form of methotrexate.

Is Methotrexate a “chemo” drug?

Although methotrexate is commonly used in patients with cancers, in rheumatology we use methotrexate for the anti-inflammatory effect of the medication. The doses that we use are considered relatively low compared to those used in cancer patients.

Methotrexate will inhibit the folic acid metabolism by competing for the enzyme that binds the folic acid.

Can Methotrexate be combined with other medications such as biologics?

Methotrexate can be combined with other medications such as NSAIDs, Hydroxychloroquine, Sulfasalazine and biologics. At times, only under close monitoring, methotrexate can be combined with leflunomide. Be careful when combining methotrexate with other medications such as bactrim (trimethoprim-sulfamethoxazole) or probenecid. Discuss with your rheumatologist when you have to take additional medications in combination with methotrexate.

What are the most common side effects?

Here are listed the most common side effects reported by patients on low-dose methotrexate:

  • Gastrointestinal problems, such as nausea, stomach upset, and loose stools
  • Stomatitis or soreness of the mouth
  • Mild elevation of liver enzymes
  • Rash (often, small pinpointed) often affecting the elbows and knees, but sparing the trunk
  • Central nervous system symptoms, including headache, fatigue, malaise, or impaired ability to concentrate
  • Alopecia
  • Fever, which is drug-related, although fever can also occur due to infection
  • Hematologic abnormalities (elevated red blood cell size/ MCV), decreased leukocytes
  • Nodulosis -increased nodules on the hands due to methotrexate use.

How to monitor if methotrexate is safe for my body?

Laboratory blood work should be done for all patients prior to starting methotrexate, then monitoring monthly labs for the first three months, followed by every two months and, if laboratory results are normal, continue with laboratory tests every 3 months.

Methotrexate Safety For Rheumatoid Arthritis

Can methotrexate affect my organs?

LIVER -methotrexate can cause mild elevation of the liver enzymes. Severe liver damage is uncommon, but that is why it is important to follow up with your rheumatologist and have regular blood work done. Your doctor will screen you before treatment for hepatitis B and C. If you suffer from hepatitis C, it is important to have this infection cleared before starting methotrexate. Using daily folic acid will decrease the risk of liver toxicity.

LUNG – lung toxicity can be seen in patients taking methotrexate and is more common in the first year of treatment. Your doctor will obtain a chest Xray before the beginning of the treatment.

BONE MARROW– bone marrow suppression is rare in patients receiving low doses of methotrexate and is more common in patients receiving high doses for cancers.

KIDNEY – rarely kidney function may be affected. Since methotrexate is cleared by kidneys, then monitoring and dose adjustments will be needed, if you suffer from kidney impairment.

Why do I need to take folic acid with methotrexate?

Methotrexate impairs the folic acid metabolism and impairs purine and pyrimidine biosynthesis. Taking daily supplementation of folic acid (1mg and up to 5mg) or leucovorin will decrease the chance to develop side effects. Folic acid can be taken daily, including the day on which Methotrexate is administered, as there is no evidence that taking both in the same day will affect the efficacy of methotrexate. Folic acid is passively taken up by the cell and does not compete with Methotrexate.

Can I drink while taking methotrexate?

It is recommended that you avoid drinking alcohol while taking methotrexate. If you have intermittent alcohol intake, that may be tolerated, but it is recommended to disclose this to your rheumatologist to have frequent laboratory monitoring.

Can I get more infections while on methotrexate?

The doses used for methotrexate in patients for rheumatoid arthritis are more likely to modulate the immune system, rather than suppress the immune system. It is rare for methotrexate to cause opportunistic infections like tuberculosis or pneumocystis. If you develop a severe infection, like pneumonia, the therapy with methotrexate should be stopped until the infection is cleared. At all times, remain in contact with the rheumatologist.

Can I get vaccinated while taking methotrexate?

Yes you may be vaccinated while taking methotrexate. However it may be best to withhold therapy with methotrexate for two weeks after the vaccines are given to make sure you get a proper vaccine response. For patients receiving COVID-19 vaccine, it is recommended to hold for one or two weeks after vaccine is given.

Vaccines for Rheumatoid Arthritis

Is Methotrexate safe for pregnancy?

NO, the use of methotrexate should be avoided in women who are considering becoming pregnant due to severe effects on the embryonic and fetal organs. If you are a female during childbearing age, you should use TWO methods of contraception. If you are on therapy with methotrexate, then you should discontinue the therapy at least 3 months before considering conceiving.

DISCLAIMER

This medication information is limited. Patients should use it as a tool to better understand the medication role in the disease treatment. It is not supposed to be comprehensive and does NOT include all information about a diagnosis, treatment, medication, side effects, or risks that may apply to a specific patient. It is not intended to be medical advice or a substitute for the medical advice, diagnosis, or treatment of a physician. Patients must speak with their physician for complete information about their health, medical questions, and treatment options, including any risks or benefits regarding use of medications. This information does not endorse any treatments or medications as safe, effective, or approved for treating a specific patient. 

Author:

Diana M. Girnita is a rheumatologist and founder and CEO, Rheumatologist OnCall. She can also be reached on FacebookInstagram, and YouTube.

 

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