Folic Acid Supplementation with Methotrexate Therapy

Introduction to Folic Acid Dosing

• The American College of Rheumatology recommends prescribing at least 5 mg of folic acid per week for any patient starting methotrexate 12.5 mg weekly, with Grade A evidence supporting its use to reduce methotrexate toxicity without compromising efficacy 1

Recommended Dosing Regimens

• The British Association of Dermatologists supports multiple acceptable approaches, all providing at least 5 mg weekly, including 5 mg once weekly, taken the day after methotrexate administration to avoid competitive cellular uptake 2
• The American Academy of Dermatology recommends 1 mg daily, taken every day except the day methotrexate is administered, as an alternative dosing regimen 3

Protective Effects of Folic Acid

• Folic acid supplementation has a protective effect against hepatotoxicity and mucosal side effects, according to the British Association of Dermatologists 2

Timing and Administration

• The British Association of Dermatologists advises against administering folic acid on the same day as methotrexate, as it may theoretically compete with methotrexate for cellular uptake when given simultaneously, potentially reducing efficacy 2

Choice of Folic Acid vs. Folinic Acid

• The British Association of Dermatologists recommends using folic acid rather than folinic acid (leucovorin) for routine supplementation, as meta-analysis shows folinic acid offers no advantages over folic acid and is significantly more expensive 2

Dose Adjustment Considerations

• In cases of intolerable side effects despite standard folic acid supplementation, the British Association of Dermatologists suggests increasing folic acid to 5 mg daily (except methotrexate day) as a first step 2