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Why should I take folic acid with methotrexate?

Medically reviewed by Leigh Ann Anderson, PharmD. Last updated on April 1, 2023.

Official answer


You should take folic acid with methotrexate to help prevent a folate deficiency. Taking methotrexate can lower folate levels in your body and cause symptoms like extreme tiredness, mouth sores, confusion, pale color and weakness.

Folate occurs naturally as a B-9 vitamin and is an essential nutrient your body needs for cell metabolism and growth. You need folate to help with skin, hair and nail growth. Folic acid is a man-made form of this B vitamin available as an oral supplement. in a pill. Your doctor may prescribe folic acid to be taken with your methotrexate.

Folate is essential to good health so folic acid is also added to foods such as breakfast cereals, bread products, pasta and rice. Folate can be found in many non-fortified natural food sources like asparagus, beans or peas, oranges or spinach. Fortified foods have help to prevent folate deficiencies in many countries.

Methotrexate is a medicine that is commonly prescribed for people with rheumatoid arthritis, cancer or psoriasis.

What are the symptoms of folate deficiency?

Common symptoms of folate deficiency can include:

  • tiredness or fatigue, lack of energy
  • muscle weakness
  • headache
  • dizziness
  • shortness of breath
  • low blood cell counts
  • neurological (nervous system) problems, like the feeling of pins and needles, tingling, or burning in your hands, arms or legs
  • mental health problems such as depression, confusion, memory problems, and difficulty with judgement and understanding
  • upset stomach (nausea, vomiting) or stomach pain
  • diarrhea
  • weight loss

What is methotrexate?

Methotrexate is a medicine used to treat a variety of conditions such as some types of cancer, rheumatoid arthritis, severe psoriasis, or polyarticular juvenile idiopathic arthritis (pJIA). It is in a group of medicines known as antimetabolites.

  • Methotrexate can be used to treat leukemia (cancer that begins in the white blood cells) and certain types of cancer of the breast, head and neck, lung, or uterus. Methotrexate treats cancer by slowing the growth of cancer cells.
  • When used to treat rheumatoid arthritis, it is called a disease modifying antirheumatic drug (DMARD). Methotrexate treats rheumatoid arthritis by slowing down the activity of the immune system that can lead to inflammation and pain.

Methotrexate works by blocking an enzyme known as dihydrofolic acid reductase that is needed by cells for growth. Methotrexate interferes with DNA synthesis, repair, and cellular replication.

How does methotrexate come?

Methotrexate is available as an oral tablet, oral solution, and as an injection. You may only need to take it once per week, so be sure to follow your doctor's dosing instructions exactly. It comes as a generic option, in brand names and as a prescription or over-the-counter (OTC) product.

Medical uses vary by the brand names of methotrexate, which include:

Women should not take methotrexate if they are pregnant or breastfeeding. Both women and men should stop taking methotrexate one to three months prior to attempting to conceive a child. Do not stop treatment without talking to your doctor first.

To learn more about methotrexate warnings and side effects, review this drug information.

This is not all the information you need to know about methotrexate or folic acid for safe and effective use and does not take the place of talking to your doctor about your treatment. Review the full methotrexate and folic acid information, and discuss this information and any questions you have with your doctor or other health care provider.


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