Leufol 50 mg/ 5 ml Injection: Each 5 ml injection contains Calcium folinate 50 mg.
Leufol 100 mg/ 10 ml Injection: Each 10 ml injection contains Calcium folinate 100 mg.
Calcium folinate is a mixture of the diastereoisomers of the 5-formyl derivative of tetrahydrofolic acid (THF). The biologically active compound of the mixture is the (-)-L-isomer, known as Citrovorum factor or (-)-folinic acid. Administration of Calcium folinate can counteract the therapeutic and toxic effects of folic acid antagonists such as methotrexate, which act by inhibiting dihydrofolate reductase.
• To reduce toxicity and counteract the effects of impaired methotrexate elimination.
• To treat inadvertent overdosage of folic acid antagonists.
• After high-dose methotrexate therapy in osteosarcoma.
• To treat megaloblastic anemia due to folic acid deficiency.
• To treat megaloblastic anemia during pregnancy and infancy.
• For use in combination with 5-fluorouracil to prolong survival in the palliative treatment of advanced colorectal cancer.
DOSAGE AND ADMINISTRATION:
Advanced Colorectal Cancer
Either of the following regimens is recommended:
200 mg/m² administered by slow intravenous injection over at least 3 minutes, followed by 5-fluorouracil at 370 mg/m² by intravenous injection.
5-Fluorouracil and calcium folinate must be administered separately to prevent the formation of a precipitate.
Treatment is repeated daily for 5 days. This 5-day course may be repeated at 4-week (28-day) intervals for 2 courses, then at 4 to 5-week (28 to 35-day) intervals, provided the patient has fully recovered from the toxic effects of the previous treatment.
High-Dose Methotrexate Therapy
The recommendations for calcium folinate rescue are based on a methotrexate dose of 12 to 15 g/m², administered by IV infusion over 4 hours.
Calcium folinate rescue begins 24 hours after the start of the methotrexate infusion, at a dose of 15 mg (approximately 10 mg/m²) every 6 hours for 10 doses.
Calcium folinate administration, hydration, and urinary alkalization (to maintain pH ≥7.0) should continue until methotrexate levels drop below 5 × 10â»â¸ M (0.05 µM).
The calcium folinate dose should be adjusted or rescue extended based on the following guidelines:
Impaired Methotrexate Elimination or Inadvertent Overdosage
Calcium folinate 10 mg/m² should be administered IV/IM every 6 hours until serum methotrexate levels drop below 10â»â¸ M.
Serum creatinine and methotrexate levels should be measured every 24 hours.
If the 24-hour serum creatinine increases by 50% over baseline, or the 24-hour methotrexate level exceeds 5 × 10â»â¶ M, or the 48-hour level exceeds 9 × 10â»â· M, the calcium folinate dose should be increased to 100 mg/m² IV every 3 hours until methotrexate levels fall below 10â»â¸ M.Megaloblastic Anemia Due to Folic Acid Deficiency
Up to 1 mg daily.
METHOD OF ADMINISTRATION:
Calcium folinate is administered intravenously (IV) or intramuscularly (IM). Reconstitute with Bacteriostatic Water for Injection, USP (which contains benzyl alcohol) or with Sterile Water for Injection, USP.
Folic acid in large amounts may reduce the effectiveness of antiepileptic drugs, such as phenobarbital, phenytoin, and primidone.
Known hypersensitivity to calcium folinate or any of its excipients.
Pernicious anemia and other megaloblastic anemias caused by vitamin B12 deficiency.
Common:Nausea, vomiting, diarrhea, hand-foot syndrome.
Rare:Seizures, syncope.
Overdose:
Excessive calcium folinate may nullify the chemotherapeutic effects of folic acid antagonists.
USE IN PREGNANCY AND LACTATION:
Pregnancy: Category C: Use only if clearly needed.
Nursing Mothers:Not recommended.
PEDIATRIC AND GERIATRIC USE:
Pediatric Use:
High doses of folic acid may reduce the effectiveness of antiepileptic drugs (e.g., phenobarbital, phenytoin, primidone), leading to increased seizure frequency in susceptible children.
Geriatric Use:
Safe, but renal function should be monitored.
In the treatment of accidental overdosage of folic acid antagonists, intravenous calcium folinate should be administered as quickly as possible.
Calcium folinate must not be administered intrathecally, as it may be harmful or fatal.
Monitoring of serum methotrexate levels is essential to determine the optimal dose and duration of calcium folinate treatment.
When doses exceed 10 mg/m², calcium folinate for injection should be reconstituted with sterile water for injection, USP, and used immediately.
In very rare cases, severe skin reactions (sometimes fatal) have been reported in patients receiving calcium folinate alongside other medications with similar side effects.
No more than 160 mg/min of calcium folinate should be administered intravenously.
When used in palliative therapy for advanced colorectal cancer, 5-fluorouracil dosage must be reduced to prevent severe gastrointestinal toxicity.
Calcium folinate/5-fluorouracil therapy should be administered only by experienced oncologists.
Elderly and debilitated colorectal cancer patients are at higher risk of severe toxicity and require careful monitoring.
Store in a refrigerator at 2–8°C.
Protect from light.