What are the uses of Leukovorin (folinic acid)?

Uses of Leukovorin (Folinic Acid)

Leukovorin is primarily used to diminish the toxicity and counteract the effects of impaired methotrexate elimination and inadvertent overdosages of folic acid antagonists. 1

Primary Clinical Applications

1. Rescue Therapy After High-Dose Methotrexate

• Used to prevent life-threatening toxicity from high-dose methotrexate (HDMTX) therapy
• Dosing is based on methotrexate levels measured at 24,48, and 72 hours after infusion 2
• Typically started 24 hours after beginning HDMTX infusion
• For HDMTX toxicity, aggressive rescue with leucovorin 100 mg/m² may be required 2
• In cases of significantly delayed methotrexate elimination, leucovorin rescue should continue until methotrexate levels are <0.05 μmol/L 2

2. Component of Chemotherapy Regimens for Colorectal Cancer

• Used in combination with 5-fluorouracil (5-FU) in various regimens:
  • Roswell-Park regimen: Leucovorin 500 mg/m² IV over 2 hours, days 1,8,15,22,29, and 36 3
  • Simplified biweekly infusional 5-FU/leucovorin (sLV5FU2): Leucovorin 400 mg/m² IV over 2 hours on day 1 3
  • Weekly regimen: Leucovorin 20 mg/m² IV over 2 hours 3

3. Treatment of Low-Dose Methotrexate Toxicity

• Used for severe toxicity with low-dose methotrexate (≤50 mg/week)
• Dosing ranges from 15 to 25 mg IV every 6 hours 4
• No significant difference in survival or hematological recovery between 15 mg and 25 mg doses 4

Mechanism of Action

Leukovorin works by:

• Providing reduced folate that bypasses the enzymatic block caused by methotrexate 5
• Competing with methotrexate at the dihydrofolate reductase level 5
• After oral administration, almost all leukovorin is converted to 5-methyltetrahydrofolic acid, which is the active rescue form 6

Administration Routes

• Oral administration:

  • Peak serum folate levels occur approximately 3 hours after oral administration 6
  • Almost all folate appears in serum as 5-methyltetrahydrofolic acid 6
  • Can be used for rescue protocols in certain situations 6

• Parenteral administration:

  • Faster onset with peak levels at approximately 30 minutes 6
  • About one-third of folate appears as folinic acid and the remainder as 5-methyltetrahydrofolic acid 6
  • Preferred for urgent rescue situations 2

Formulations

• Available as the calcium salt in tablet form (5 mg or 25 mg) 1
• Available as l-folinic acid (the biologically active form) or as d,l-folinic acid (racemic mixture) 7
• The l-form is twice as potent as the racemic mixture, so dosing should be adjusted accordingly (6 mg/m² of l-form equals 12 mg/m² of d,l-form) 7

Important Clinical Considerations

• Leucovorin does not prevent or reverse CNS toxicity of methotrexate
• Acidic beverages should be avoided during treatment as they may interfere with elimination 2
• Concurrent medications that increase methotrexate toxicity (NSAIDs, sulfonamides, trimethoprim) should be avoided 2
• For patients with MTHFR deficiency, higher doses of folic acid supplementation may be required 2

Leukovorin remains a critical component in oncology practice, both as a rescue agent and as part of established chemotherapy protocols for colorectal cancer.