IndicationsCalcium Folinate is indicated in:To diminish the toxicity and counteract the effect of impaired Methotrexate eliminationTo treat the Megaloblastic anemia due to folate deficiency, as in sprue, nutritional deficiencyTo treat the Megaloblastic anemia of pregnancy and infancyTherapeutic ClassSupportive Care TherapyDescri... Read more →
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
Supportive Care Therapy
Calcium Folinate is a Calcium salt of Folinic acid (citrovorum factor), is a mixture of the diastereoisomers of the 5-formyl derivative of Tetrahydrofolic acid. It is a metabolite of Folic acid and an essential coenzyme for nucleic acid synthesis used in cytotoxic therapy.
Folinic acid is a 5-formyl derivative of tetrahydrofolic acid. It is readily converted to other reduced folic acid derivatives (e.g., tetrahydrofolate), 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 inhibition of this enzyme by drugs such as methotrexate. This is the classical view of folinic acid rescue therapy.
In 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
Reduction of harmful effects of folic acid antagonists such as. Methotrexate, Trimethoprime etc.: The dose is usually one 15 mg tablet every 6 hours for 2 to 3 days.
Megaloblastic anemia: In the treatment of Megaloblastic anemia, the dose is one 15 mg tablet daily.
Adjunct to fluorouracil in colorectal cancer: 200 mg/m2 BSA by slow IV inj over at least 3 min followed by 370 mg/m2 fluorouracil by IV inj. Treatment is given for 5 consecutive days and repeated at intervals of 28 days for 2 courses. Subsequently, may repeat at 4-5 wkly intervals if the patient has recovered completely from the toxic effects of the prior treatment course.
Folate-deficient megaloblastic anaemia: Up to 1 mg/day.
Calcium Folinate therapy is contraindicated in known hypersensitivity to Calcium Folinate, or to any components of the product formulation. Pernicious anemia or other Megaloblastic anemia where Vitamin B12 is deficient
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)
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.
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.