What is the dose of folinic acid (leucovorin) for children?

Folinic Acid Dosing for Children

For children receiving methotrexate therapy, give folinic acid (leucovorin) 1 mg daily (or 6 days per week, sparing the methotrexate administration day), as this dosing regimen decreases gastrointestinal intolerance and hepatic adverse effects better than once-weekly dosing. 1

Dosing by Clinical Indication

Methotrexate Supplementation (Most Common Pediatric Use)

• Standard dose: 1 mg daily is recommended during methotrexate treatment for inflammatory skin diseases including psoriasis, atopic dermatitis, and other dermatologic conditions 1
• Daily dosing (or 6 days per week) is superior to once-weekly dosing for reducing methotrexate-related adverse effects including gastrointestinal symptoms, oral mucositis, fatigue, and headache 1
• Continue throughout the entire duration of methotrexate therapy 1

Congenital Toxoplasmosis Treatment

Neonates and infants (first year of life):

• 10 mg orally three times weekly throughout the 12-month treatment course 1, 2
• This dose prevents hematologic toxicity from pyrimethamine while the infant receives daily pyrimethamine/sulfadiazine 1

Older children (diagnosed beyond neonatal period) with active chorioretinitis:

• 10-20 mg orally three times weekly during the 4-6 week treatment course 1, 2
• Continue for at least 1-2 weeks after resolution of all signs and symptoms 1

Critical monitoring requirement: Weekly complete blood counts are mandatory during pyrimethamine therapy to detect bone marrow suppression despite leucovorin supplementation 2, 3

Cerebral Folate Deficiency (FOLR-1 Mutations)

Initial oral therapy:

• Start at 0.5-1 mg/kg/day orally 2
• May escalate to 2-3 mg/kg/day based on CSF 5-methyltetrahydrofolate monitoring 2

High-dose intravenous therapy (for inadequate oral response):

• 6 mg/kg/day IV for 24 hours, then 12 mg/kg/day IV for 48 hours as initial loading 4
• Maintenance: 20-25 mg/kg IV monthly has shown sustained clinical improvement 4
• This aggressive approach is warranted when oral therapy fails to control refractory epilepsy or neurological regression 4

Methotrexate Rescue (Severe Pneumocystis Pneumonia)

• 20 mg/m² IV every 6 hours for 24 days when used with trimetrexate glucuronate 2
• Do not discontinue prematurely—leucovorin must extend beyond the antifolate therapy 2

Nutritional Folate Deficiency

• 1-5 mg orally daily for dietary deficiency or chronic hemodialysis 1
• Continue for 4 months or until the underlying cause is corrected 1, 3
• After normalization, transition to maintenance dosing 1

Critical Safety Considerations

Vitamin B12 Deficiency Must Be Excluded First

• Always evaluate for concomitant vitamin B12 deficiency before treating with folinic acid, as treating folate deficiency alone can worsen neurological manifestations of B12 deficiency 1, 3
• Both vitamins cause megaloblastic anemia, making clinical differentiation impossible without laboratory testing 1

Monitoring Requirements

• Measure folate status at first assessment in patients with macrocytic anemia or malnutrition risk 1
• Repeat folate levels within 3 months after supplementation to verify normalization 1, 3
• Target serum folate ≥10 nmol/L and red blood cell folate ≥340 nmol/L 1

Drug-Specific Precautions

With pyrimethamine (toxoplasmosis):

• Continue leucovorin for 1 week after pyrimethamine discontinuation due to pyrimethamine's long half-life 3, 5
• Weekly CBC monitoring is non-negotiable 2, 3

With methotrexate:

• Perform laboratory monitoring at least 4-6 days after methotrexate dosing to avoid detecting transient transaminase elevations 1
• Patients with renal insufficiency require dose adjustments of both methotrexate and leucovorin 3

Common Pitfalls to Avoid

• Do not use once-weekly folinic acid dosing with methotrexate—daily dosing provides superior adverse effect mitigation 1
• Do not stop leucovorin prematurely in rescue protocols—it must extend beyond antifolate therapy 2
• Do not assume oral therapy is adequate for cerebral folate deficiency if neurological symptoms persist—consider high-dose IV therapy 4
• Do not use folinic acid in hematopoietic stem cell transplantation at doses >185 mg/m² before day +21, as this increases graft rejection risk, particularly with reduced-intensity conditioning 6