Calcium folinate, also known as leucovorin calcium, is a chemically reduced derivative of folic acid. It is commonly used in oncology and as an antidote in specific conditions related to folate metabolism. Produced by Fresenius Kabi, a global leader in injectable medications, this formulation ensures high quality and efficacy. 

Indications:

Rescue Therapy in Methotrexate Overdose:

• Calcium folinate is used to prevent or treat toxic effects caused by high doses of methotrexate (a chemotherapeutic agent).
• This therapy is known as leucovorin rescue.

Combination Therapy in Cancer:

• It enhances the efficacy of 5-fluorouracil (5-FU) in the treatment of colorectal cancer and other solid tumors.

Folate Deficiency Treatment:

• Used in the treatment of megaloblastic anemia caused by folate deficiency.

Antidote for Folate Antagonists:

• Serves as an antidote for toxicity caused by folate antagonists such as trimethoprim and pyrimethamine.

Mechanism of Action:

• Calcium folinate bypasses the dihydrofolate reductase enzyme, entering the folate cycle directly as tetrahydrofolate.
• It provides an active form of folate required for:
  • DNA synthesis and repair.
  • Stabilization of the thymidylate synthase-5-FU complex, enhancing the cytotoxicity of 5-fluorouracil.

Dosage and Administration:

Rescue Therapy for Methotrexate Overdose:

• Dosage: Varies based on methotrexate levels and the timing of administration. Typically starts at 15 mg/m² every 6 hours.
• Administer until serum methotrexate levels are reduced to safe levels (< 0.05 µM).

Combination with 5-Fluorouracil:

• Dosage: 200-400 mg/m² of calcium folinate as an IV injection over 2 hours, followed by 5-FU administration.
• Repeated as part of chemotherapy cycles.

Folate Deficiency or Anemia:

• Dosage: 1-5 mg daily, depending on the severity of deficiency.

Antidote for Folate Antagonists:

• Dosage: 10-20 mg per day until symptoms improve.

Route of Administration:

• Can be administered as an intravenous (IV) infusion, intramuscular (IM) injection, or oral tablet, depending on the indication.

Side Effects:

Common Side Effects:

• Nausea
• Vomiting
• Fatigue
• Diarrhea

Serious Side Effects:

• Hypersensitivity reactions (rash, itching, or anaphylaxis)
• Seizures in patients with pre-existing epilepsy
• Gastrointestinal disturbances, especially in combination with 5-FU.

Precautions:

In Combination with 5-FU:

• Calcium folinate enhances 5-FU's effects, potentially leading to increased gastrointestinal and hematologic toxicity. Close monitoring is required.

Renal Impairment:

• In patients with compromised renal function, calcium folinate clearance may be reduced, requiring dose adjustments.

Folate Supplementation:

• Calcium folinate should not be used as a substitute for folic acid in patients with nutritional folate deficiency.

Pregnancy and Lactation:

• Should be used during pregnancy only if clearly needed. Discuss with a healthcare provider before use in breastfeeding mothers.

Drug Interactions:

Methotrexate:

• Used as a rescue agent to mitigate methotrexate's toxic effects.

5-Fluorouracil (5-FU):

• Enhances the cytotoxic effects of 5-FU, increasing its therapeutic efficacy and associated side effects.

Anticonvulsants:

• May reduce the efficacy of phenobarbital, phenytoin, and primidone, potentially leading to an increased risk of seizures.

Sulfonamides and Pyrimethamine:

• Can interfere with the action of folate antagonists, potentially reducing their effectiveness.

Contraindications:

• Known hypersensitivity to calcium folinate or any of its components.
• Pernicious anemia or other vitamin B12 deficiency-related anemias. Calcium folinate does not correct neurological damage associated with B12 deficiency.

Monitoring:

Methotrexate Rescue:

• Monitor serum methotrexate levels, renal function, and hematologic parameters.

In Combination with 5-FU:

• Frequent monitoring of complete blood counts (CBC) and gastrointestinal symptoms.

General Use:

• Periodic monitoring of serum folate levels in patients with folate deficiency.

Storage:

• Store below 25°C (77°F), protected from light.
• Reconstituted solutions should be used immediately or stored per manufacturer instructions, typically not exceeding 24 hours at controlled room temperature.