Calcium Folinate [Folinic Acid]

Available brands

Indications

Calcium Folinate is indicated in:

To diminish the toxicity and counteract the effect of impaired Methotrexate elimination.
To treat the Megaloblastic anemia due to folate deficiency, as in sprue, nutritional deficiency.
To treat the Megaloblastic anemia of pregnancy and infancy.

Description

Folinic Acid is the formyl 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 defference in membrane transport mechanism. This principle is applied in high dose methotrexate therapy with Folinic Acid rescue.

Pharmacology

Folinic acid is a 5-formyl derivative of tetrahydrofolic acid. It is readily converted to other reduced folic acid derivatives (e.g., tetrahydrofolate), and thus has vitamin activity equivalent to that of folic acid. Since it does not require the action of dihydrofolate reductase for its conversion, its function as a vitamin is unaffected by the inhibition of this enzyme by drugs such as methotrexate. This is the classical view of folinic acid rescue therapy. In the 1980s, however, folinic acid was found to reactivate the dihydrofolate reductase itself even when methotrexate exists. Although the mechanism is not very clear, the polyglutamylation of methotrexate and dihydrofolate in malignant cells is considered to play an important role in the selective reactivation of dihydrofolate reductase by folinic acid in normal cells. Folinic acid, therefore, allows for some purine/pyrimidine synthesis to occur in the presence of dihydrofolate reductase inhibition, so some normal DNA replication processes can proceed.

Dosage & Administration

Oral-

Reduction of harmful effects of folic acid antagonists such as Methotrexate, Trimethoprim etc: The dose is usually one 5-15mg tablet every 6 hours for 2 to 3 days.
Megaloblastic anemia: In the treatment of Megaloblastic anemia, the dose is one 5-15 mg tablet daily. Or, as directed by the registered physician.

Intravenous-

Advanced Colorectal Cancer: Leucovorin is administered at 200 mg/m² by slow intravenous injection followed by 5-fluorouracil at 370 mg/m² by intravenous injection. Or 20 mg/m 2 by slow intravenous injection followed by 5-fluorouracil at 425 mg/m² by intravenous injection. Treatment is repeated daily for 5 days. This 5 day treatment course may be repeated at 4 weeks interval, for 2 courses and then may repeated at 4-5 weekly intervals if the patient has recovered completely from the toxic effects of the prior treatment course.
Folinic acid rescue after high dose Methotrexate Therapy: Leucovorin starts 24 hours after the beginning of the methotrexate infusion at dose of 15mg (10 mg/m² ) every 6 hours for 10 doses.

Intramuscular-

Folate deficient megaloboastic anaemia: Up to 1 mg/day. Or, as directed by the registered physician.

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Contraindications

Calcium Folinate therapy is contraindicated for the following:

Known hypersensitivity to Calcium Folinate, or to any components of the product formulation.
Pernicious anemia or other Megaloblastic anemia where Vitamin B₁₂ is deficient.

Side Effects

Allergic reaction: one may experience a sudden itchy rash (hives), swelling of the hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty in swallowing or breathing).
Fits and fainting.

Pregnancy & Lactation

There are no adequate and well-controlled clinical studies conducted in pregnant or breastfeeding women. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Calcium Folinate is administered to a nursing mother.

Precautions & Warnings

Calcium Folinate treatment may mask pernicious anemia and other Megaloblastic anemia resulting from Vitamin B12 deficiency.

Calcium Folinate should only be used with 5-fluorouracil or Methotrexate under the direct supervision of a clinician experienced in the use of cancer chemotherapeutic agents.

Many cytotoxic medicinal products- direct or indirect DNA synthesis inhibitors- lead to macrocytosis (hydroxycarbamide, cytarabine, mercaptopurine, thioguanine). Such macrocytosis should not be treated with Folinic acid.

In epileptic patients treated with Phenobarbital, Phenytoin, Primidone, and Succinimides, there is a risk to increase the frequency of seizures due to a decrease of plasma concentrations of anti-epileptic drug.

Overdose Effects

There have been no reported sequelae in patients who have received significantly more Calcium Folinate than the recommended dosage. However, excessive amounts of Calcium Folinate may nullify the chemotherapeutic effect of folic acid antagonists.