by Tracey Kellett, with contributions by Dr Andrew Harrison

Methotrexate and folic acid are often talked about together because folic acid is prescribed as a supplement to combat the side effects caused by methotrexate interfering with how our body absorbs, or metabolises, folic acid.

Folic acid is the supplemental form of the essential nutrient, folate, also known as vitamin B9. Folate is famous for being a pregnancy supplement as it reduces the risk of neural tube defects at birth. However, it’s essential for all stages of life throughout the body in its functional form in a process called methylation. Methylation is important for heart and brain health, getting rid of heavy metals in the body, energy, immunity, and moods. In most cases, people can get enough folate through their diet from foods such as dark green vegetables, brussel sprouts, asparagus, whole grains, legumes, fruit, peanuts, sunflower seeds, liver, and kaimoana and there’s no need to take a supplement. For some people with arthritis, folic acid is prescribed as a supplement alongside methotrexate.

Methotrexate is a non-biologic disease-modifying antirheumatic drug (DMARD) often prescribed for treating inflammatory arthritis, particularly psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis. Methotrexate and folic acid are usually prescribed together.

We asked rheumatologist Dr Andrew Harrison some of your frequently asked questions about methotrexate and folic acid that pop up in our online support groups.

Why am I prescribed folic acid with methotrexate?

Methotrexate (MTX) interferes with folic acid metabolism, which can lead to side effects including nausea, vomiting, mouth sores, and hair loss, so those who have been prescribed MTX will be prescribed a folic acid supplement at the same time to override this interference.

What is the optimal interval between methotrexate and folic acid doses?

Rheumatologist Andrew Harrison says there are no studies that determine the optimal interval between folic acid and MTX. Some of the early studies gave it two days before MTX, and that is how he regularly prescribes.

I’ve heard I should take methotrexate on Monday and folic acid on Friday. Is this true?

This regimen is simply an alliteration technique to help patients remember to take their medication. The general consensus among rheumatologists is that it can be taken any day of the week except the day MTX is taken, and even that is not based on good evidence.

Is there any harm in accidentally taking folic acid and methotrexate on the same day?

While there is no harm in doing this, rheumatologists usually advise taking folic acid and MTX on different days due to an (unlikely) possibility that taking them together might diminish the effectiveness of MTX.

What should I do if I forget to take my folic acid?

Missing 1 or 2 doses probably will not matter. But if you keep forgetting to take your folic acid or do not want to take it, speak to your doctor.

If you forget to take folic acid, what to do depends on how often you take it:

Once a day – take your missed dose as soon as you remember unless it’s nearly time for your next dose. In this case, skip the missed dose and take your next dose at the usual time. Don’t double up. If you remember, on the day you take your methotrexate, skip that dose and continue your normal routine the following day.

Once a week – take your missed dose as soon as you remember unless you take methotrexate that day. If you remember, on the day you take your methotrexate, wait a day and take your missed dose the following day. After this, go back to taking your weekly dose on your normal day.

If you have trouble remembering to take your medication, you could set an alarm to help you remember. Alternatively, speak to your pharmacist; they may be able to help you.

Should I avoid folate-containing food if I am taking a folic acid supplement?

No. Folate-containing foods have many benefits, including reducing inflammation. If you take a multivitamin containing folic acid, let your prescriber know how much you are already taking.

This article was medically reviewed by rheumatologist Dr Andrew Harrison. 2023.

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