What is the Dose of Folic Acid to use with Methotrexate therapy for Rheumatoid Arthritis?

· London and South East Regional Medicines Information Service

There is no definitive answer regarding the optimal dose of folic acid for patients with rheumatoid arthritis who are being treated with methotrexate. It is generally agreed that folic acid supplementation reduces the toxicity of methotrexate without significantly affecting efficacy; although there seems to be a consensus of opinion that folic acid supplementation should be avoided on the day of methotrexate in case it adversely affects absorption. Folic acid supplementation should be continued for the duration of methotrexate therapy because adverse effects can occur at any time.

There have not been any dose determining trials but regimens used in some of the studies include:

¥ 5mg folic acid taken the day after the methotrexate dose ¥ 1mg folic acid daily except on the day of methotrexate ¥ 5mg folic acid daily except on the day of methotrexate

It is considered that the folic acid dose should be high enough to prevent folate deficiency. Many reviewers have extrapolated the data from the studies and recommend using 5mg folic acid weekly. Some administer this dose the day after the methotrexate dose and others suggest that a dose taken 48 hours prior to the methotrexate dose may give added protection against the gastrointestinal adverse effects. The dose can be increased to 10mg if the patient experiences any adverse effects to the methotrexate.

The British Society for Rheumatology guidelines for disease modifying anti-rheumatic drug therapy recommends a typical folic acid dose of 5mg once weekly, preferably the day after the methotrexate. They state that folic acid can be given any day as long as it is not on the same day as methotrexate. Folic acid reduces toxic effects and improves continuation of therapy and compliance.

Acute CareMethotrexateMusculo-skeletal disordersPrimary CareQ&A