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Folinic acid (Leucovorin) 💊
📘 About
- Always check the BNF for latest prescribing advice.
- Folinic acid (leucovorin calcium) is the reduced, active form of folic acid (vitamin B9).
- It is used as an antidote to methotrexate (MTX) toxicity and to reduce adverse effects of MTX therapy in cancer and autoimmune disease.
- Unlike folic acid, it does not require activation by dihydrofolate reductase, meaning it can bypass the blockade caused by MTX.
⚙️ Mode of Action
- MTX inhibits dihydrofolate reductase → blocks conversion of folic acid to tetrahydrofolate → impaired DNA synthesis.
- Folinic acid “rescues” normal cells by replenishing tetrahydrofolate pools and allowing DNA and RNA synthesis to continue.
- This “leucovorin rescue” is the rationale for using folinic acid alongside or after high-dose MTX.
📋 Indications & Example Doses
- Prevention of MTX side effects (e.g., in rheumatoid arthritis): Folic or folinic acid reduces GI upset, oral ulcers, cytopenias. Commonly folic acid 5–10 mg once weekly, but folinic acid can be used in intolerance.
- High-dose MTX therapy (oncology): Folinic acid 5 mg every 6 hours for 24 hours, started 12–24 hours after MTX infusion. Then continued PO, IM, IV or IV infusion according to local protocol. Dose is adjusted depending on plasma MTX levels.
- Suspected MTX overdosage: Initial folinic acid dose equal to or greater than the MTX dose, given at a maximum IV rate of 160 mg/min. Continue with frequent dosing until plasma MTX level is safe. Always consult poisons information services and local oncology protocols.
🔄 Interactions
- See BNF for complete list.
- May reduce efficacy of antifolate chemotherapy (e.g., trimetrexate, pyrimethamine).
⚠️ Cautions
- Use under specialist supervision in oncology/poisoning contexts.
- Do not use simultaneously with intrathecal MTX (risk of enhanced CNS toxicity).
🚫 Contraindications
- See BNF – none absolute, but inappropriate use can reduce MTX anticancer activity.
💥 Side Effects
- Generally well tolerated.
- Occasional: Fever, agitation, insomnia.
- Rare: Allergic reactions (rash, urticaria, anaphylaxis).
📖 References
- BNF – Folinic Acid
- Rang & Dale’s Pharmacology – Antimetabolites & Rescue Therapy.
📝 Revisions
- September 2025 – Expanded clinical context, added rescue therapy details and toxicity considerations.
| The content on this website is provided for educational and informational purposes only to support exam preparation (e.g., MLA, MRCP, USMLE) and learning. This is NOT medical advice, diagnosis, treatment, or professional guidance. It does not replace consultation with a qualified healthcare professional, official guidelines (e.g., NICE, GMC, BNF), or supervised clinical practice. Always verify information with current, authoritative sources. Makindo and its contributors accept no liability for any reliance on this content, including errors, omissions, or any resulting harm, loss, or consequences. By using this site, you agree to these terms. |
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