Leucovorin (Folinic Acid)

Table of contents

  • Brand Names
  • Drug Combinations
  • Chemistry
  • Pharmacologic Category
  • Mechanism of Action
  • Therapeutic Use
  • Unlabeled Use
  • Pregnancy and Lactation Implications
  • Contraindications
  • Warnings and Precautions
  • Adverse Reactions
  • Caution and personalized dose adjustment in patients with the following genotypes
  • Other genes that may be involved
  • Drug Interactions
  • Dosage
  • Pharmacokinetics and Pharmacodynamics
  • Special Considerations

Brand Names

Europe

Austria: Calciumfolinat, Sodiofolin; Belgium: Folinate EG, Leucovorin, Rescuvolin, Vorina; Bulgaria: Calcium Folinate, Calciumfolinat; Cyprus: Calciumfolinat, Calciumfolinate; Czech Republic: Calcium Folinate, Calciumfolinat, Leucovorin; Denmark: Calciumfolinat; Estonia: Calciumfolinat; Finland: Antrex, Calciumfolinat, Kalciumfolinat; France: Elvorine, Folinate De Calcium, Folinoral, Lederfoline, Osfolate; Germany: Axifolin, Bendafolin, Ca-Folinat, Calciumfolinat, Degalin, Ebefolinat, Eurofolic, Foli-Cell, Folinsäure, Folisachs, Haemato-folin, Lafolin, Lederfolat, Leucovorin, Medicofolin, Neofolin, O.R.C.A. Folin, Oncofolin, Rescuvolin, Ribofolin, Vorina, Zyofolin, Zytofolin; Greece: Leucovorin, Rescuvolin; Hungary: Calciumfolinat, Leucovorin; Ireland: Folicid, Folinic Acid (as Calcium Folinate), Leucovorin; Italy: Calcio Folinato, Calcifolin, Calfolex, Calinat, Citofolin, Divifolin, Ecofol, Eparmefolin, Folaren, Folidar, Sanifolin, Sulton, Tonofolin; Latvia: Leucovorin; Lithuania: Calciumfolinat, Leucovorin; Luxembourg: Ledervorin Calcium, Refolinon, Rescuvolin; Malta: Calcium Folinate; Netherlands: Calciumfolinaat; Poland: Antrex, Calciumfolinat, Leucovorin, Rescuvolin, Vorina; Portugal: Dodepar, Foli-Cell, Folinato de Calcio, Folinovo, Lederfoline, Medifolin; Romania: Calcium Folinat, Calciumfolinat, Folcasin, Folinat de Calciu; Slovakia: Calciumfolinat, Leucovorin; Slovenia: Calciumfolinat; Spain: Folidan, Folinato Calcico, Hepa-Factor, Lederfolin, Sodiofolin; Sweden: Calciumfolinat, Kalciumfolinat; UK: Calcium Folinate, Refolinon.

North America

Canada: Leucovorin; USA: Leucovorin.

Latin America

Argentina: Estroquin, Folinfabra, Leucocalcin, Leucovorina, Novizet; Brazil: Folicorin, Legifol CS, Levorin-Leucovorina Cálcica, Prevax, Tecnovorin; Mexico: Dalisol, Medsavorina.

Asia

Japan: Leucovorin, Uzel.

Drug combinations

Leucovorin and Fluorouracil

Leucovorin, Bevacizumab, and Fluorouracil

Leucovorin, Fluorouracil, and Irinotecan

Leucovorin, Bevacizumab, Fluorouracil, and Irinotecan

Leucovorin, Bevacizumab, Fluorouracil, and Oxaliplatin

Chemistry

Leucovorin Calcium: C~20~H~21~CaN~7~O~7~. Mw: 511.50. (1) L-Glutamic acid, N-[4-[[(2-amino-5-formyl-1,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-, calcium salt (1:1); (2) Calcium N-[p-[[[(6RS)-2-amino-5-formyl-5,6,7,8-tetrahydro-4-hydroxy-6-pteridinyl]methyl]amino]benzoyl]-L-glutamate (1:1). CAS-1492-18-8; CAS-6035-45-6 (pentahydrate); CAS-58-05-9 (leucovorin).

Pharmacologic Category

Antidotes. Chemotherapy Modulating Agent. Rescue Agent (Chemotherapy). Water Soluble Vitamin. (ATC-Code: V03AF03).

Mechanism of action

Counteracts therapeutic and toxic effects (e.g. hematologic toxicity) of folic acid antagonists (e.g. methotrexate). Enhances therapeutic and toxic effects of fluoropyrimidines (e.g. fluorouracil) by stabilizing binding of fluorouracil metabolite (fluorodeoxyridylic acid) to thymidylate synthase (enzyme responsible for DNA repair and replication), thus enhancing inhibition of this enzyme.

Therapeutic use

Antidote for folic acid antagonists (methotrexate, trimethoprim, pyrimethamine) and rescue therapy following high-dose methotrexate. Treatment of colon cancer (in combination with fluorouracil). Treatment of megaloblastic anemias when folate is deficient.

Pregnancy and lactiation implications

Leucovorin is a biologically active form of folic acid. Adequate amounts of folic acid recommended during pregnancy and in breast-feeding women.

Unlabeled use

I.T. administration following I.T. methotrexate overdose. Adjunctive cofactor therapy in methanol toxicity.

Contraindications

Pernicious anemia or vitamin B~12~-deficient megaloblastic anemias.

Warnings and precautions

Leucovorin may increase toxicity of 5-fluorouracil. Possible potentiation of fluorouracil toxicity when used concomitantly with other chemotherapeutic agents. Seizures and/or syncope reported rarely in cancer patients with CNS metastases or other predisposing factors. Anaphylactoid reactions and urticaria reported. Possible decreased anticonvulsant effect in pediatric patients receiving anticonvulsant therapy concomitantly with large amounts of folic acid. Possible increased frequency of seizures in susceptible patients. Use with extreme caution in the elderly.

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