Leucovorin Injection Administration
Leucovorin injection should be administered intravenously at a rate not exceeding 160 mg per minute (16 mL of 10 mg/mL solution or 8 mL of 20 mg/mL solution per minute), and must NEVER be given intrathecally as this can be fatal. 1
Route and Rate of Administration
- Intravenous (IV) administration only for injection formulations
- Maximum infusion rate: 160 mg/minute due to calcium content of the solution 1
- Intramuscular (IM) administration is acceptable for certain indications (e.g., methotrexate rescue) 1
- CRITICAL WARNING: Do not administer leucovorin intrathecally—this may be harmful or fatal 1
Reconstitution Guidelines
The reconstitution method depends on the dose being administered:
- For doses ≤10 mg/m²: Reconstitute with Bacteriostatic Water for Injection, USP (benzyl alcohol preserved); use within 7 days 1
- For doses >10 mg/m²: Reconstitute with Sterile Water for Injection, USP and use immediately due to benzyl alcohol toxicity concerns 1
Reconstitution Concentrations
- 200 mg vial + 20 mL diluent = 10 mg/mL concentration
- 500 mg vial + 50 mL diluent = 10 mg/mL concentration 1
Context-Specific Administration
For Methotrexate Rescue
- Timing is critical: Begin as soon as possible after methotrexate overdose, ideally within 24 hours 1
- Standard rescue dose: 15 mg (approximately 10 mg/m²) IV, IM, or PO every 6 hours for 10 doses, starting 24 hours after methotrexate infusion begins 1
- Route selection: Use parenteral (IV or IM) administration if gastrointestinal toxicity, nausea, or vomiting is present 1
- Effectiveness decreases with time: Leucovorin's ability to counteract methotrexate toxicity diminishes as the interval between methotrexate administration and leucovorin rescue increases 1
For Colorectal Cancer (with 5-Fluorouracil)
Two FDA-approved regimens exist:
- High-dose regimen: 200 mg/m² by slow IV injection over minimum 3 minutes, followed by 5-FU 1
- Low-dose regimen: 20 mg/m² by IV injection, followed by 5-FU 1
Important: Administer 5-FU and leucovorin separately to avoid precipitate formation 1
Critical Safety Considerations
- Never mix leucovorin with 5-fluorouracil in the same infusion—this leads to precipitate formation 1
- Inspect solution visually for particulate matter and discoloration before administration 1
- The calcium content necessitates the rate limitation to prevent adverse cardiovascular effects 1
Pharmacokinetic Considerations
While oral administration is possible for certain indications (particularly as adjunct therapy with methotrexate for psoriasis 2), parenteral administration achieves more predictable plasma concentrations. Research shows that after oral administration, nearly all folate converts to 5-methyltetrahydrofolic acid, whereas parenteral administration maintains approximately one-third as folinic acid 3. For rescue situations requiring immediate and reliable drug levels, the parenteral route is mandatory.
Common Pitfalls to Avoid
- Do not confuse dosing schedules: Leucovorin for methotrexate rescue requires every-6-hour dosing, not daily dosing
- Do not delay administration: In overdose situations, every hour counts—effectiveness drops significantly after 24 hours 1
- Do not use benzyl alcohol-preserved diluent for high doses: This can cause toxicity, particularly in neonates and with doses >10 mg/m² 1
- Do not assume oral bioavailability is equivalent: Parenteral administration is required when rapid, predictable drug levels are needed