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  • Writer's pictureIndira, Rheumatoid Strong

Methotrexate in RA - Is it a safe drug?

Methotrexate is commonly prescribed for the treatment of rheumatoid arthritis (RA). This medication is a disease-modifying antirheumatic drug (DMARD). DMARDs are used to slow the progression of RA by regulating the immune system to reduce inflammation and autoimmune attacks on the joints. These medications constitute an important part of managing your RA and keeping it under control. The American College of Rheumatology recommends methotrexate as the first-line treatment for RA. Sold as a generic in the US, methotrexate is often prescribed along with other oral DMARD medications or with biologicals.


Is Methotrexate a chemotherapy drug?


Methotrexate is a chemotherapy drug and has been used in the treatment of many different types of cancers. However, it has also been used as an immunosuppresant in autoimmune disease like RA, lupus, psoriasis etc. Different mechanisms of action has been noted for methotrexate when used in cancer and in autoimmune disease. In cancer, methotrexate acts as an antifolate antimetabolite. In autoimmune disease it leads to immunosuppression by repression of T-cell activation and down-regulation of B-cells.


Methotrexate pill bottle

How is Methotrexate to be taken?


The doses used in RA (and other autoimmune diseases) are much lower than those used for chemotherapy. In RA, It is mostly given orally as tablets. However the injectable form is also available for those who cannot tolerate the oral form.


Methotrexate is usually prescribed to be taken once per week on the same day.

Food does not significantly affect the absorption of methotrexate for RA, however it is better to take it with food as it can be irritating to the stomach lining.


Another important thing to remember is to take folic acid 1 g daily (except on the day you take methotrexate). Taking folic acid daily can help to reduce side effects of methotrexate.


What are the side effects of Methotrexate?

Following are some of the most common side effects that patients can experience while taking methotrexate for RA.

  • Stomach pain, diarrhea, nausea, or vomiting; the injectable form can help combat this problem.

  • Oral problems such as bleeding gums or sores in the mouth or lips

  • Itchy or discolored skin or pinpoint red spots

  • “Methotrexate fog,” such as headaches, fatigue, and feeling unwell

  • Hair loss


Supplementing with folate or folic acid can help reduce most of the above mentioned side effects. Also eating a healthy nutrient dense diet like the AIP diet (rich in leafy green vegetables, organ meat etc )can help considerably to reduce the side-effects of methotrexate.


What are some other side effects that can be caused by methotrexate?

It is also important to be aware that methotrexate can cause serious side effects too in some cases. These include liver damage, lung disease and severe infections. So it is very important to do regular blood work to monitor for any issues. Your rheumatologist will order blood work to be done on a regular basis and you should make every effort to comply with those.


Methotrexate is teratogenic meaning it can harm fetal cells. Hence methotrexate is contraindicated in pregnancy. Your doctor will advise you to take double precautions if you are of a childbearing age woman. In males, a recent study has shown that paternal methotrexate use does not lead to congenital abnormalities in children. It can however reduce fertility and chances of conception in males.


Methotrexate can have an impact on female hormones. A recent study has shown that methotrexate may lead to early menopause. Some women may experience increased severity of menopausal symptoms like night sweats and hot flashes while on methotrexate.


Some people can experience photosensitivity (sensitivity to sunlight) while using methotrexate.


Some useful strategies while on Methotrexate

Following tips will help you to minimize the adverse effects of methotrexate while maximizing its benefits for RA.

  • Take Folic Acid

Doctors usually prescribe folic acid to people who are taking methotrexate for RA to reduce common side effects of the drug. These include nausea, vomiting, and mouth sores. Folic acid can also help lower the risk of developing liver problems while taking methotrexate. Usually, folic acid is prescribed once daily for people taking methotrexate. It is important to take folic acid exactly as prescribed by your doctor.

  • Avoid Pregnancy and Use Contraception

Your doctor may recommend that you avoid pregnancy and use contraception if you’re taking methotrexate. Taking the drug can result in severe birth defects, both for women and men. Effective contraception methods could include abstinence, oral contraceptives, IUDs, or condoms plus spermicidal foam.

  • Follow a nutrient dense diet like AIP

The autoimmune protocol or the AIP diet is a nutrient dense diet where you eat a lot of vegetables and avoid processed foods. You also initially avoid some inflammatory foods that are otherwise healthy. My cookbook, AIP Indian Fusion is a great cookbook with AIP recipes that are delicious and full of Indian flavors.

  • Supplement with herbals and nutrients or HRT to help increase estrogen levels

Consult with a nutritional therapist or a naturopathic doctor who can guide you regarding herbal and nutritional supplements that can help increase estrogen levels and help you overcome perimenopause/menopausal symptoms. If supplements do not help, you can work with an experienced functional medicine doctor to start Hormonal Replacement therapy where you can take bioidentical hormones (estradiol patch and micronized progesterone) to help you overcome your severe menopausal symptoms.

  • Limit Sun Exposure if your are sensitive

Avoiding or limiting sun exposure may be important for some people taking methotrexate as it can cause sun sensitivity in some folks. Precautions such as limiting sun exposure, wearing clothing that covers more skin, and using sunscreen are recommended.

  • Abstain From Alcohol

Because methotrexate can damage the liver, it is recommended to avoid alcohol while on methotrexate. This is because alcohol also causes liver damage and in the presence of methotrexate the damage can be greater.


In conclusion, Methotrexate can be an extremely useful medication to suppress your RA symptoms either alone or in combination with other DMARDs as long as you take some precautions.

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