Why Can't I Take Folic Acid the Same Day As Methotrexate?

Ask your doctor if it’s OK to take methotrexate and folic acid on the same day, because there's no one-size-fits-all guideline.
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When you take methotrexate to treat cancer, rheumatoid arthritis or psoriasis, this may lead to a folic acid deficiency. In order to correct this, your doctor may suggest you take supplemental folic acid, also called folate.



Ask your doctor if it’s OK to take methotrexate and folic acid on the same day, because there's no one-size-fits-all guideline. Always make sure you take methotrexate exactly as prescribed, and watch out for side effects.

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Some people can take methotrexate and folic acid on the same day, while others may be advised not to. It depends on your methotrexate dosage, schedule, other medications and any other health considerations. Check with your doctor before taking any supplements while on methotrexate.

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Read more: How to Determine if a Vitamin or Supplement Is Actually Right for You

What Is Methotrexate?

The Mayo Clinic says that methotrexate, which is sold under the brand names Rheumatrex and Trexall, is an antineoplastic medication used to treat cancer. It can also be used to treat symptoms of severe psoriasis and severe rheumatoid arthritis.

Methotrexate is a prescription medication available as a tablet or an oral solution. The dosage of methotrexate and how often you take the medication will vary depending on what you're taking it for, your body size and your doctor's prescribed treatment schedule.


Some people taking methotrexate for psoriasis or rheumatoid arthritis may take the medicine only once a week. If you're taking methotrexate for cancer, your doctor may recommend periods during which you take the medication every day, interspersed with rest periods.

It's important to take methotrexate exactly as prescribed by your physician. If you're confused about how often to take the medication or have questions about any other medications or supplements interfering with methotrexate, ask your doctor right away. If you miss a dose, don't try to double up or remedy the situation yourself — call your doctor and ask for further instructions.


Methotrexate Side Effects

According to MedlinePlus, methotrexate side effects can be extremely serious — and in some cases life-threatening. The site stresses that you should speak with your doctor about any other health conditions you have or medications that you take and that you should take methotrexate only as prescribed.

If you experience debilitating side effects or side effects that last for a long time, be sure to speak with your physician about it. More common methotrexate side effects include:



  • Black, tarry-looking stools
  • Blood in the urine
  • Blood in the stools
  • Bloody vomit
  • Diarrhea
  • Joint pain
  • Skin reddening
  • Sores in your mouth or on your lips
  • Stomach pain
  • Swollen feet
  • Swollen lower legs

Less common side effects include:

  • Back pain
  • Coughing or hoarseness
  • Dizziness
  • Drowsiness
  • Fever
  • Chills
  • Headaches
  • Shortness of breath


MedlinePlus says to immediately contact a doctor if you experience any of the following methotrexate side effects, which are considered severe:

  • Sudden vision loss
  • Blurred vision
  • Confusion
  • Seizures
  • Weakness
  • Trouble moving one or both sides of your body
  • Loss of consciousness

Methotrexate and Folic Acid

Methotrexate is a folate antagonist, meaning it affects the levels of folic acid in the body. That means that people who take methotrexate may also need to take folic acid supplements to correct a folate deficiency. Supplemental folic acid may help prevent some methotrexate side effects, according to a May 2013 review of literature published in the Cochrane Database of Systematic Reviews.


Researchers reviewed six trials with 624 patients and found that patients who took supplemental folic acid alongside methotrexate were 26 percent less likely to experience gastrointestinal side effects like nausea, abdominal pain and vomiting.

Read more: The Benefits of Taking Folic Acid in Nonpregnant Women

Some sources say it's fine to take methotrexate and folic acid on the same day. For example, Johns Hopkins Arthritis Center recommends that patients taking methotrexate once a week to treat rheumatoid arthritis should also take 1 milligram of folic acid each day.



However, you should check with your prescribing physician before you take folic acid supplements with methotrexate. A doctor can recommend the appropriate dosage and let you know when it's safe to take the supplements.

Methotrexate and Antibiotics

Another potential interaction to look out for is methotrexate and antibiotics. The Cleveland Clinic says that methotrexate interacts with penicillins, tetracycline and chloramphenicol. Interactions can cause side effects or make medications less effective.

To avoid interactions, the clinic recommends you keep a list of everything you take — including medications, dietary supplements and nonprescription drugs — to share with any physician who might prescribe you a new medication.

As well as methotrexate and antibiotics, other potential interactions include retinoids like isotretinoin and tretinoin, steroid medicines including prednisone or cortisone, nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen or aspirin and certain vaccines.

Folic Acid Deficiency

Folic acid is found in food and available in a synthetic form from supplements. The Linus Pauling Institute at Oregon State University explains that a deficiency in folate or vitamin B12 can contribute to a type of vitamin deficiency anemia called megaloblastic anemia.

Megaloblastic anemia is a blood disorder where the body creates large, odd-shaped red blood cells. This interferes with the body's ability to transport oxygen from the lungs to your organs and tissues.

Symptoms of a vitamin deficiency anemia range from mild to severe. Common symptoms include extreme fatigue, feeling dizzy, shortness of breath, an irregular heartbeat, pale skin and feeling cold in the hands and feet.

Read more: Side Effects of Folic Acid Tablets

Folate deficiency in pregnant people is also linked to congenital anomalies like neural tube defects. As such, people trying to conceive are often advised to take folic acid supplements and load up on folate-rich foods.

The American Pregnancy Association recommends that women of childbearing age consume 400 to 800 micrograms of folate each day, noting that neural tube defects typically develop within the first 28 days of pregnancy — a time at which many people may not even know that they're pregnant.

Fruits and vegetables containing folate include avocado, asparagus, dark leafy greens, broccoli, citrus fruits and cantaloupe. Some breads and cereals are fortified to contain folic acid, and beans are another rich source of folic acid.




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