Is Folate (Folic Acid / L-Methylfolate) Safe with Methotrexate?
Free · No account · based on published sources including NIH ODS, FDA drug labels, and peer-reviewed literature
Do not take folate supplements during methotrexate treatment for ectopic pregnancy or gestational trophoblastic disease. Folate supplementation should be withheld until treatment is confirmed complete by your provider.
Why this interaction occurs
Methotrexate works as a folate antagonist by inhibiting dihydrofolate reductase. Supplemental folate directly competes with this mechanism and can reduce methotrexate's therapeutic efficacy. This interaction is critical when methotrexate is used to treat ectopic pregnancies — a common scenario in fertility patients.
Evidence
Evidence level: strong.
Reported safety data
The FDA’s adverse event reporting system (FAERS) has received 499,559 reports mentioning Methotrexate. This reflects reported cases involving the medication in general — not confirmed causation, and not specific to the Methotrexate + supplement combination on this page.
FAERS reports are voluntary and cannot prove that a drug caused an event. Do not use report counts to assess the safety of this specific drug-supplement pair.
Frequently asked questions
Related interactions
All Folate (Folic Acid / L-Methylfolate) interactions → · All Methotrexate interactions →
Already checked this one — check your whole list
Educational only — not medical advice.
Always confirm with your doctor or pharmacist.