[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Chemotherapy supportive agents](https://durgical.com/en/pharmacology/classes/chemotherapy-supportive-agents/) › Calcium folinate [Pharmacology](https://durgical.com/en/pharmacology/) · [Chemotherapy supportive agents](https://durgical.com/en/pharmacology/classes/chemotherapy-supportive-agents/) # Calcium folinate An already-reduced folate (leucovorin) that rescues normal cells from methotrexate and strengthens fluorouracil. Never given intrathecally. Updated 2026-11-01 - Class: [Chemotherapy supportive agents](https://durgical.com/en/pharmacology/classes/chemotherapy-supportive-agents/) - Target: Reduced-folate pool (bypasses dihydrofolate reductase) - ATC code: V03AF03 - WHO Model List of Essential Medicines Also called: leucovorin, folinic acid, 5-formyltetrahydrofolate ## Mechanism of action Calcium folinate is 5-formyl-tetrahydrofolate, a folate that is already reduced. It does not need dihydrofolate reductase, so it refills the one-carbon folate pool even while methotrexate blocks that enzyme, rescuing normal cells. With fluorouracil it acts the other way: it is converted to 5,10-methylene-tetrahydrofolate, which locks fluorouracil's active metabolite (FdUMP) onto thymidylate synthase and makes the block stronger. - Folinate is a reduced folate: no DHFR needed - It refills the folate pool despite methotrexate - With fluorouracil, it locks FdUMP onto thymidylate synthase ## Pharmacokinetics **Absorption** Intravenous, intramuscular or oral; oral absorption is saturable, so larger doses are given intravenously. **Metabolism** Rapidly converted to 5-methyl-tetrahydrofolate (after oral use, mainly in the intestinal mucosa). **Half-life** Total reduced folates: about 6 hours. ## Indications - Rescue after high-dose methotrexate (for example in osteosarcoma), impaired methotrexate elimination or overdose of folate antagonists. - Megaloblastic anaemia due to folate deficiency when oral therapy is not feasible. [Megaloblastic anaemia (B12 or folate deficiency) →](https://durgical.com/en/conditions/megaloblastic-anaemia/) - Advanced colorectal cancer, combined with fluorouracil. [Colorectal cancer →](https://durgical.com/en/conditions/colorectal-cancer/) ## Adverse effects ### Common - Allergic sensitisation (hives, anaphylactoid reactions), uncommon - With fluorouracil: more diarrhoea, mouth sores and low blood counts ### Serious (rare, important) - Harmful or fatal if given intrathecally - Severe or fatal gastrointestinal toxicity with fluorouracil, especially in elderly or debilitated patients - Seizures or fainting, rarely, mostly with fluoropyrimidines ## Contraindications - Pernicious anaemia and other megaloblastic anaemias from vitamin B12 deficiency (the blood improves while nerve damage progresses) ## Key interactions **Methotrexate** Counteracts its effects (the purpose of rescue); high doses may reduce the effect of intrathecal methotrexate. **Fluorouracil** Enhances both its antitumour effect and its toxicity. **Trimethoprim–sulfamethoxazole for Pneumocystis pneumonia in HIV** The combination was linked to more treatment failure and morbidity. **Phenobarbital, phenytoin, primidone** Large amounts of folate may reduce their antiseizure effect in susceptible children. ## What is monitored - Serum methotrexate levels and creatinine during rescue (they decide the dose and how long it continues) - Blood count, electrolytes and liver tests when combined with fluorouracil ## Administration and safety - Never given intrathecally. - Rescue doses are given on time: the longer the delay after methotrexate, the less it protects. - Not mixed in the same infusion as fluorouracil (a precipitate may form). - Injected slowly because of its calcium content; for larger doses it is reconstituted with sterile water rather than diluents containing benzyl alcohol. ## Nursing care - Check that calcium folinate (leucovorin) is not confused with folic acid: they are different drugs. - Keep the rescue schedule exactly and check each methotrexate level result. - If the patient vomits, an oral dose may not be absorbed: report it so the route can be changed. - Encourage fluids and check urine output during methotrexate rescue. ## Pregnancy and breastfeeding Effects in pregnancy are not known; it is used only if clearly needed. ## Memory aid Folinate «rescues» from methotrexate but «recruits» for fluorouracil. Folinic is not folic, and it never goes into the spine. ## Test yourself Think of the answer, then tap the question to see it. ## Why can calcium folinate rescue normal cells from methotrexate? It is already reduced, so it bypasses the dihydrofolate reductase that methotrexate blocks. ## Why is calcium folinate given with fluorouracil? It forms 5,10-methylene-tetrahydrofolate, which stabilises FdUMP binding to thymidylate synthase and enhances inhibition. ## Why is calcium folinate improper therapy for pernicious anaemia? It can correct the blood picture while the neurological damage of vitamin B12 deficiency continues. ## What happens to the protective effect when methotrexate rescue is delayed? It decreases: the longer the interval, the less folinate counteracts toxicity. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/calcium-folinate/) ## Related drugs - [Oxaliplatin](https://durgical.com/en/pharmacology/oxaliplatin/) - [Irinotecan](https://durgical.com/en/pharmacology/irinotecan/) - [Mesna](https://durgical.com/en/pharmacology/mesna/) ## Related conditions - [Megaloblastic anaemia (B12 or folate deficiency)](https://durgical.com/en/conditions/megaloblastic-anaemia/) - [Colorectal cancer](https://durgical.com/en/conditions/colorectal-cancer/) [← Back to the class: Chemotherapy supportive agents](https://durgical.com/en/pharmacology/classes/chemotherapy-supportive-agents/) Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given. Sources: [DailyMed - LEUCOVORIN CALCIUM injection, powder, lyophilized, for solution](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=82c445f5-4cb7-4457-af19-3b5b8a121b4f) (DailyMed (U.S. National Library of Medicine), 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 70 (McGraw Hill, 2023); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=V03AF03) (WHO Collaborating Centre for Drug Statistics Methodology, 2026); [eEML - Electronic Essential Medicines List](https://list.essentialmeds.org/) (World Health Organization, 2025). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/pharmacology/calcium-folinate/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/calcium-folinate/