How do you approach folate supplementation for methotrexate-related side effects?

All MTX users should be taking some form of folate supplement. Either daily folic acid or weekly folinic acid are used and generally are effective. Tracking the RBC MCV is one way to ensure that patients are receiving adequate folate supplementation.

The question has been raised whether folate supplementation can prevent MTX-related toxicities. A 2013 Cochrane review of six studies found that taking folic acid or folinic acid reduced the proportion of people on MTX who experienced GI-related issues (mostly GI upset, nausea) from 35% to 25%. The percentage of abnormal liver tests fell from 21% to 5%, and mouth sores were reduced from 22% to 16%.

Overall, fewer people discontinued methotrexate treatment if they used folic acid (10%) than if th...

We use folic acid at least 1 mg daily in all patients on methotrexate. Immunosuppressive effects of methotrexate for rheumatic disease treatment are dependent on the adenosine pathway. Inhibition of the folic acid pathway is important for the anti-cancer effects of methotrexate and is also responsible for many adverse effects of methotrexate. We recommend patients to take folic acid every day and not to skip it on the day of methotrexate (in rheumatology).

In patients who have folic acid-dependent adverse effects of methotrexate despite being on 1 mg daily dose of folic acid such as oral ulcers or macrocytic anemia, the dose of folic acid can be increased, and usually, 3 mg or 5 mg daily dose of folic acid dose prevents such adverse effects...

I use folic acid 1 mg PO daily. There have been suggestions that it may be best to skip the folic acid on the MTX day but the evidence is scarce. Some physicians use weekly dosages.