What is the recommended dose and duration for folinic acid (leucovorin) intravenous (IV) drip?

Folinic Acid IV Drip Protocols

For methotrexate overdose or high-dose methotrexate rescue, administer folinic acid (leucovorin) at an initial dose of up to 100 mg/m² IV, followed by doses every 6 hours until methotrexate levels fall below 0.05 µmol/L. 1

Methotrexate Overdose/Rescue Protocol

Initial Management:

• Begin folinic acid IV infusion as soon as possible after methotrexate exposure—efficacy is highest within the first few hours and becomes doubtful after 24 hours 1
• Use an initial dose of up to 100 mg/m² IV when methotrexate level is unknown 1
• Administer subsequent doses (oral or IV) every 6 hours, with specific dosing adjusted based on measured methotrexate levels (consult Toxbase for level-specific dosing) 1

Duration and Monitoring:

• Continue folinic acid until methotrexate levels drop below 0.05 µmol/L OR until hematological abnormalities normalize and mucosal ulceration heals 1
• Measure serum methotrexate levels at least 4 hours after ingestion 1
• Maintain aggressive hydration to enhance renal elimination of methotrexate 1
• Consider urine alkalinization with sodium bicarbonate to prevent methotrexate precipitation in renal tubules 1

Chemotherapy Protocols (Colorectal Cancer)

Standard FOLFOX/FOLFIRI Regimens:

• The National Comprehensive Cancer Network recommends leucovorin 400 mg/m² IV infused over 2 hours on day 1, repeated every 2 weeks 2, 3, 4
• This dose applies whether leucovorin is used alone or combined with bevacizumab, cetuximab, or panitumumab 3

Critical Dosing Distinction:

• Levoleucovorin (the pure L-isomer) requires only 200 mg/m² because it contains only the active stereoisomer, which is equivalent to 400 mg/m² of standard racemic leucovorin 3, 4
• Never confuse leucovorin with levoleucovorin—using the wrong dose could result in either underdosing (if levoleucovorin dose is used for standard leucovorin) or overdosing (if standard leucovorin dose is used for levoleucovorin) 3, 4

Alternative Regimens:

• Roswell-Park regimen: leucovorin 500 mg/m² IV over 2 hours on days 1,8,15,22,29, and 36, repeated every 8 weeks 4
• Simplified biweekly regimen (sLV5FU2): uses the same 400 mg/m² dose as FOLFOX/FOLFIRI 4

Chronic Methotrexate Supplementation

Low-Dose Prophylaxis:

• For prevention of methotrexate toxicity in patients on chronic low-dose methotrexate therapy, the American Academy of Pediatrics recommends folinic acid 10-20 mg orally three times weekly 2, 3
• This dose is appropriate regardless of patient weight 2

Special Populations

Pediatric Toxoplasmosis:

• For children with congenital toxoplasmosis receiving pyrimethamine, administer leucovorin 10 mg orally three times weekly to prevent hematologic toxicity 2, 4

Trimetrexate Rescue:

• When trimetrexate glucuronate is used for Pneumocystis pneumonia, leucovorin 20 mg/m² every 6 hours for 24 days is required per CDC recommendations 4

Safety Considerations

Medication Error Prevention:

• Limit chemotherapy orders to 24-hour units to minimize medication errors 3, 4
• The National Comprehensive Cancer Network emphasizes the critical importance of distinguishing between leucovorin and levoleucovorin formulations 3, 4

Route of Administration:

• IV administration is preferred for chemotherapy protocols and acute rescue situations 2, 3
• Oral administration is acceptable for long-term supplementation with chronic methotrexate therapy 2

Monitoring Requirements:

• Monitor complete blood count, liver function, and renal function regularly during therapy 2
• For methotrexate overdose, continue monitoring until hematological parameters normalize 1