Can You Take Methotrexate & Folic Acid Together?

In our latest question and answer, our pharmacist discusses whether or not methotrexate can be taken with folic acid.

Nov 28, 2017

BYear2017 asked

I currently take methotrexate tablets one day a week for psoriasis. I take them on Mondays (today) but I mistakenly took a folic acid tablet instead. Is it okay to go ahead and take my methotrexate dose tonight or should I wait until tomorrow? Is there any effect to take them together?


In most cases, it is OK to take methotrexate and folic acid together. In fact, many doctors prescribe folic acid 1 mg daily to those who are taking methotrexate to lessen the potential side effects.

Methotrexate commonly causes folate deficiency which may then lead to mouth sores, nausea, vomiting, and gastrointestinal problems. Supplementing with folic acid often helps to alleviate these problems. The general recommendation is to supplement with folic acid at a dose of 5 to 7 mg/week.

Don't be too concerned with online searches or references that state there is a drug interaction between methotrexate and folic acid as this answer is out of the context and more on the theoretical side. An interaction is listed between the two due to the mechanism of action of methotrexate. 

Methotrexate works by inhibiting an enzyme known as dihydrofolate reductase. This enzyme coverts folic acid to tetrahydrofolate. Tetrahydrofolate is an important component to many biological reactions, many of which contribute to certain diseases such as rheumatoid arthritis and different types of cancers. Inhibiting dihydrofolate reductase can aid in the treatment of these diseases.

As mentioned, due to how methotrexate works, a folate deficiency can develop, bringing a slew of adverse reactions. While it may seem counter-intuitive to supplement with folic acid while taking methotrexate (given how methotrexate works), there doesn't appear to be any evidence that methotrexate loses effectiveness with supplementation, even when they are taken on the same day. Numerous studies and anecdotal evidence show that supplementation with folic acid lessens methotrexate associated side effects. 

Having said that, some practitioners recommend that folic acid be given at least 24 hours apart from methotrexate (if methotrexate is given as a weekly dose) so we recommend speaking with you doctor regarding their recommendation.

In regard to your missed dose of methotrexate, take as soon as you remember without concern to the folic acid tablet that you took. There should be no problems and you want to try and keep a consistent schedule in regard to methotrexate administration. 

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