Folinic acid
Synonym :
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.
Partial seizure:
3-12 years:
Start with 10-15 mg/kg/day orally in three divided doses initially; adjust in approximately 3 days to effective maintenance dose.
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 :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Dose as in normal renal function |
| 10-20 | Dose as in normal renal function |
| <10 | Dose as in normal renal function |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Some removal likely. Dose as in normal renal function |
| HD | Some removal likely. Dose as in normal renal function |
| HDF/High flux | Dialysed. Dose as in normal renal function |
| CAV/VVHD | Some removal likely. Dose as in normal renal function |
Hepatic Dose :
No dosage adjustments are recommended.