Folinic acid

Leucovorin

Mechanism :

Leucovorin is a mixture of the diastereoisomers of the 5¬formyl derivative of tetrahydrofolic acid. The biologically active component of the mixture is the L isomer, known as Citrovorum factor, or folinic acid. Leucovorin does not require reduction by the enzyme dihydrofolate reductase in order to participate in reactions utilizing folates as a source of one carbon moieties.

Indication :

• Dihydrobiopterin reductase (DHPR) deficiency
• Uridine monophosphate synthase (UMPS) deficiency
• Methylene synthase deficiency
• Hereditary folate malabsorption
• Methylene tetrahydrofolate reductase deficiency
• Cobalamin metabolism
• Folate rescue after methotrexate therapy

Contraindications :

Contraindicated in pernicious anemia and other megaloblastic anemias secondary to the lack of vitamin B12.

Dosing :

Usual Pediatric Dose for Methotrexate Rescue:

10 mg/m² PO/IM/IV every 6 hours x 10 doses. If the serum methotrexate levels are >50 or 5 micromolar at 24 and 48 hours, or if there is a 50% or more increase in serum creatinine within the first 24 hours after the beginning of the methotrexate infusion, the dosage of leucovorin should be increased 20-fold (twice the dose and frequency) to 100 mg/m² IV every 3 hours until the MTX level is <0.05 micromolar.

Usual Pediatric Dose for Megaloblastic Anemia:

1 mg IV or IM once a day. Vitamin B12 should be replenished prior to or during folate replacement lest neurologic symptoms persist or worsen during hematologic remission.

Usual Pediatric Dose for Folic Acid Antagonist (TMP-SMX) Overdose:

2 to 15 mg/day orally for 3 days or until blood counts are normal or 5 mg orally every 3 days. 6 mg/day orally is recommended for use in patients with platelet counts <100,000/mm³.

Adverse Effect :

Allergic sensitization (anaphylactoid reactions, urticaria), pyrexia

Interaction :

Phenobarbital, Phenytoin and Primidone: In large amounts may counteract the antiepileptic effect of phenobarbital, phenytoin and primidone, and increase the frequency of seizures in susceptible children.

Leucovorin: May enhance the toxicity of fluorouracil.

Renal Dose :

Hepatic Dose :