What is Leucovorin

Leucovorin is a racemic mixture of the diastereoisomers of the 5-formyl derivative of tetrahydrofolic acid ((d,l)-5-formyltetrahydrofolate), a reduced form of folic acid.

The isomers have different pharmacokinetics and activity. The biologically active component is the l-isomer, and is also known as citrovorum factor or folinic acid.

Citrovorum factor is the natural product, which on a molar basis is about twice as active as synthetic leucovorin. The d-isomer is considered biologically inactive.

Leucovorin is commonly used to rescue cells exposed to folate antagonists (i.e., methotrexate, pyrimethamine, or trimethoprim) and to treat folate-deficient megaloblastic anemias associated with pregnancy, sprue, anemias of infancy, and nutritional deficiencies.

In order to avoid medication errors, leucovorin should not be referred to as citrovorum factor or folinic acid.

The term ‘folinic acid’ could be confused with folic acid and result in serious systemic antifolate toxicity should the wrong rescue treatment be prescribed.

Leucovorin is also administered in combination with fluorouracil (5-FU) to potentiate the efficacy of 5-FU in the treatment of colon cancer.

The FDA originally approved leucovorin in 1952.


  1. colorectal cancer
  2. fluorouracil therapy
  3. folate deficiency megaloblastic anemia
  4. methotrexate toxicity prophylaxis
  5. pancreatic cancer
  6. pyrimethamine toxicity
  7. pyrimethamine toxicity prophylaxis
  8. trimethoprim toxicity
  9. trimetrexate toxicity
  10. trimetrexate toxicity prophylaxis

For methotrexate toxicity prophylaxis

NOTE: Leucovorin has been designated an orphan drug by the FDA for this indication.

Monitoring Parameters

  • CBC with differential


  • benzyl alcohol hypersensitivity
  • breast-feeding
  • folic acid hypersensitivity
  • geriatric
  • intrathecal administration
  • neonates
  • pernicious anemia
  • pregnancy
  • seizure disorder
  • stomatitis
  • vitamin B12 deficiency megaloblastic anemia
  • vomiting

Leucovorin is contraindicated in patients with a history of folic acid hypersensitivity or folinic acid hypersensitivity.


  • Acetaminophen; Butalbital
  • Acetaminophen; Butalbital; Caffeine
  • Acetaminophen; Butalbital; Caffeine; Codeine
  • Amobarbital
  • Aspirin, ASA; Butalbital; Caffeine
  • Aspirin, ASA; Butalbital; Caffeine; Codeine
  • Atropine; Hyoscyamine; Phenobarbital; Scopolamine
  • Barbiturates
  • Belladonna Alkaloids; Ergotamine; Phenobarbital
  • Butabarbital
  • Capecitabine
  • Floxuridine
  • Fluorouracil, 5-FU
  • Fosphenytoin
  • Glucarpidase
  • Mephobarbital
  • Methohexital
  • Pentobarbital
  • Phenobarbital
  • Phenytoin
  • Primidone
  • Secobarbital
  • Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole
  • Thiopental
  • Trimethoprim
  • Trimetrexate

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