Short answer: It depends on why methotrexate is used. The Trexall label says to give folic or folinic acid with weekly methotrexate for rheumatoid arthritis, juvenile arthritis and psoriasis, to lower side effects. For cancer, it says folic acid may make methotrexate less effective and should be taken only if the provider says so. A Cochrane review found folate cut stomach side effects in rheumatoid arthritis without weakening the drug.
Methotrexate works by blocking dihydrofolate reductase, an enzyme the body needs to use folate (Trexall label, section 12.1). ODS calls it a folate antagonist. That is why folate can both soften its side effects and, at the cancer doses, blunt its effect.
| Use | What the label says about folic acid |
|---|---|
| Rheumatoid arthritis, juvenile arthritis, psoriasis | Give folic or folinic acid to reduce the risk of side effects; folate deficiency may increase them |
| Cancer (such as ALL, mycosis fungoides) | Products with folic acid may decrease effectiveness; take them only if the provider says to |
The patient Medication Guide puts it plainly for each group. For non-cancer uses, it says to take a folic or folinic acid supplement every day as instructed, "to help reduce the chance of developing certain side effects, such as mouth sores." For cancer, it says not to take folic or folinic acid unless the provider says to. ODS gives the same split and adds that people on methotrexate for cancer should check with their oncologist before taking folate supplements.
Multivitamins usually contain folic acid too, so this applies to them as well as to folic acid tablets.
A 2013 Cochrane review (Shea 2013) pooled six trials with 624 adults taking methotrexate (25 mg a week or less) for rheumatoid arthritis, with low-dose folic or folinic acid or placebo:
The review found no significant effect of folate on how well methotrexate treated the arthritis.
The Trexall label has a boxed warning that taking methotrexate tablets once daily by mistake, instead of once weekly, has caused deaths. The Medication Guide describes folic or folinic acid every day as instructed, while methotrexate for these uses is once a week. Two medicines on two rhythms is where reminders help: Dose Track can hold a weekly methotrexate reminder and a separate supplement schedule so the two do not get mixed up.
Read more on Dose Track: Dosing frequency abbreviations · Set up reminders in Dose Track · Boxed warning