Calcium folinate is a white or light yellow, amorphous or crystalline powder, sparingly soluble in water and practically insoluble in acetone and ethanol. Calcium folinate potency is usually expressed in terms of equivalent units of folinic acid. It’s molecular waight is 511.5 and the chemical structure of calcium folinate is shown below,
Each vial contains Folinic Acid (as Calcium Folinate) BP 100 mg.
Each vial contains Folinic Acid (as Calcium Folinate) BP 50 mg.
Mechanism of action
Folinic Acid is the formal derivative of tetrahydrofolic acid which is a metabolite and active form of folic acid. It is effective in the treatment of megaloblastic anemia caused by folic acid deficiency and is a potent antidote for both the haematompoietic and reticuloendothelial toxic effects of folic acid antagonist, e.g. methotrexate, pyrimethamine,
trimethoprim. In some cancers, Folinic Acid enters and ‘rescues’ normal cells, from the toxic effect of folic acid antagonists, due to a difference in membrane transport mechanism. This principle is applied in high dose methotrexate therapy with Folinic Acid rescue.
Bioavailability Dose dependent
Protein binding ~15%
Half –life 6.2 hours
Folinic Acid has shown good results in the treatment of certain megaloblastic anemias resulting from folic acid deficiency. This mainly occurs in infants, during pregnancy, in malabsorption syndromes, liver disease, sprue and malnutrition. It is not more effective than folic acid for these conditions. Folinic Acid has also shown good results in reducing the toxicity and circumventing the effect of folic acid
Folicid®Inj. Folinic Acid (as Calcium Folinate) BP 50 mg & 100 mg
Folic acid Derivative antagonists, if therapeutically desired. Combination use with 5-Fluorouracil for advanced colorectal carcinoma.
Dosage and administration
Calcium folinate should not be mixed in the same infusion as fluorouracil as a precipitate may form. Calcium folinate may be administered by intravenous infusion or by intramuscular injection. Calcium folinate should not be administered intrathecally.
As an antidote following methotrexate therapy: The recommendations for Calcium folinate rescue are based on a methotrexate dose of 12-15 grams/m² administered by intravenous
infusion over 4 hours. Calcium folinate rescue starts 24 hours after the beginning of the methotrexate infusion at a dose of 15 mg (approximately 10 mg/m²) every 6 hours for 10 doses. In the presence of gastrointestinal toxicity, nausea or vomiting, Calcium folinate should be administered parenterally. Most investigators have successfully used doses of 6-25 mg per dose, repeated at 6 hourly intervals for up to 6-12 doses. Goldie and
Price have applied up to a total of 2 grams Calcium folinate in 6, fractions, which is the maximum dose recommended. To avoid discomfort to patients from multiple injections, Calcium folinate oral tablets may be given for 24 hours after the initial Calcium folinate -Rescue parenteral injection. A complete oral Calcium folinate -Rescue is also possible and has been used by somem authors. Patients with malabsorption syndromes or other gastrointestinalm disturbances such as vomiting and diarrhoea should not be
treated orally. Serum creatinine and methotrexate levels should be determined at
least once daily. Calcium folinate administration, hydration (3 L/day) and urinary alkalinisation (with bicarbonate and/or acetazolamide to pH of 7.0 or greater) should be continued until the methotrexate level is below 5 x 10-8 M (0.05 micromolar). The Calcium folinate dose should be adjusted or Calcium folinate rescue extended based
on the following guidelines:
GUIDELINES FOR CALCIUM LEUCOVORIN DOSAGE AND ADMINISTRATION
Patients who experience delayed methotrexate elimination are likely to develop reversible renal failure. These patients require continuing hydration, urinary alkalinisation and close monitoring of fluid and electrolyte status, until the serum methotrexate level has fallen to below 0.05 micromolar and the renal failure has resolved. Clinical Situation Laboratory Findings Calcium Leucovorin Dosage and Duration Normal
Methotrexate Elimination Serum methotrexate level approximately 10 micromolar at 24 hours after administration, 1 micromolar at 48 hours, and less than 0.2 micromolar at 72 hours.
15 mg PO, IM or IV q6 hours for 60 hours (10 doses starting at 24 hours
after start of methotrexate infusion). Delayed Methotrexate Elimination
Serum methotrexate level remaining above 0.2 micromolar at 72 hours, and more than 0.05 micromolar at 96 hours after administration. Continue 15 mg PO, IM or IV q6
hours, until methotrexate level is less than 0.05 micromolar.
Possible side effects
Allergic sensitisation, including anaphylactoid reactions and urticaria, has been reported following both oral and parenteral administration of folic acid. Nausea and vomiting with very high doses of Calcium folinate have been reported. Seizures and/or syncope have been reported rarely in cancer patients receiving Calcium folinate, usually in association with fluoropyrimidine administration.
Calcium folinate is improper therapy for pernicious anaemia and other megaloblastic anaemias secondary to the lack of Vitamin B12. When treating these conditions with Calcium folinate, haematological remission may occur, but neurological manifestations are likely to progress.
Folic acid in large amounts may counteract the antiepileptic effect of phenobarbital, phenytoin and primidone, and increase the frequency of seizures in susceptible children.
High oral, intravenous or intramuscular doses of Calcium folinate may reduce the efficacy of intrathecally administered methotrexate. Calcium folinate may enhance the toxicity of fluorouracil. Calcium folinate has been reported to be incompatible with droperidol and phosphonosuslphate.
In the treatment of accidental overdose of folic acid antagonists e.g methotrexate, Calcium folinate should be given as soon as possible. As the time interval between antifolate administration and Calcium folinate rescue increases, it’s effectiveness in counteracting toxicity diminishes. Monitoring of serum methotrexate concentration is essential in
determining the optimal dose and duration of treatment with Calcium folinate. Delayed methotrexate excretion may be caused by a third space fluid accumulation (i.e. ascites, pleural effusion), renal insufficiency or inadequate hydration. Under such circumstances, higher doses of Calcium folinate or prolonged administration may be indicated. Calcium folinate is not suitable for the treatment of pernicious anaemias and other anaemias resulting from lack of Vitamin B12. Haematological remissions may occur, while the neurological manifestations remain progressive. Simultaneous therapy with a folic acid antagonist and Calcium folinate is not recommended because the effect of the folic acid
antagonist is either reduced or completely inhibited. Seizures and/or syncope have been reported rarely in cancer patients receiving Calcium folinate, usually in association with fluoropyrimidine administration, and most commonly in those with CNS metastases. Since patients had recurrent neurological symptoms on rechallenge with Calcium folinate, further treatment with Calcium folinate is not recommended in these circumstances.
How to use
Calcium folinate injection contains no antimicrobial agent. This product is for single use in one patient only. When required for intravenous infusion Calcium folinate injection may be diluted in 1 litre of 5% w/v glucose in water for injection or normal saline. Such solutions are stable for 24 hours when stored between 2°C to 8°C. However, to avoid microbial contamination hazards, infusion should be commenced as soon as practicable after preparation of the solution. Infusion should be completed within 24 hours and any residue discarded.
Store at 2oC to 8oC. Do not freeze. Protect from light and keep out of the reach of the children.
Folicid® 50 mg Inj.: Each vial contains Folinic Acid (as Calcium Folinate) BP 50 mg.