Actifol is indicated in: Neutralising the immediate toxic effects of folic acid antagonists, e.g. methotrexate. Calcium folinate rescue- a treatment technique using calcium folinate in conjunction with folic acid antagonists, e.g. methotrexate, to minimise systemic toxicity. The treatment of megaloblastic anaemias due to sprue, nutritional deficiency, pregnancy, infancy, liver disease and malabsorption syndrome.
This is the preparation of Calcium Folinate Hydrate which is calcium salt of folinic acid (5-formyl derivative of tetrahydrofolic acid). It is a metabolite and active form of folic acid that is involved as a cofactor for 1-carbon transfer reactions in the biosynthesis of purine and pyrimidines of nucleic acids. Impairment of thymidylate synthesis in patients with folic acid deficiency is thought to account for the defective DNA synthesis that leads to megaloblast formation and megaloblastic and macrocytic anemias. Because of its ready conversion to other tetrahydrofolic acid derivatives, Folinate is a potent antidote for both hematopoietic and reticuloendothelia toxic effects of folic acid antagonists, (e.g. methotrexate, pyrimethamine, trimethoprim). It is postulated that in some cancers, folinate enters and "rescues" normal cells from the toxic effects of folic acid antagonists, in preference to tumour cells, because of a difference in membrane transport mechanisms; this principle is the basis of high-dose methotrexate therapy with "Folinate rescue".
Folinic Acid rescue : Folinic Acid rescue should begin as soon as possible after an inadvertent overdosage and within 24 hours of methotrexate administration when there is delayed excretion. There are no fixed guidelines regarding the dose of methotrexate that triggers an automatic subsequent Folinic Acid administration, since tolerance to this folate antagonist depends on various factors. The dose of methotrexate varies, nevertheless folinate rescue is necessary when methotrexate is given at doses exceeding 500 mg/m2 and has to be considered with doses of 100 mg-500 mg/m2. Folinic Acid rescue treatment should commence approximately 24 hours after the beginning of methotrexate infusion. Dosage regimens vary depending upon the dose of methotrexate administered. In general, Folinic Acid should be administered at a dose of 15 mg (approximately 10 mg/m2) every 6 hours for 10 doses. The recommended dose of Folinic Acid to counteract hematologic toxicity from folic acid antagonists with less affinity for mammalian dihydrofolate reductase than methotrexate (i.e., trimethoprim, pyrimethamine) is substantially less and 5 mg to 15 mg of Folinic Acid per day has been recommended. Neutralising the immediate toxic effects of folic acid antagonists : If overdosage of methotrexate is suspected, the dose of Folinic Acid should be equal to or greater than the dose of methotrexate and should be administered within one hour of the methotrexate administration. Megaloblastic anaemia (folate deficiency) : 5 mg to 15 mg of Folinic Acid per day. Use in children and adolescents : The safety and efficacy of folinic acid in children and adolescents have not been established.
Always consult a registered doctor before taking any medicine. This information is for general knowledge only.
The most common side effects of Actifol are mucositis, stomatitis, leukopenia and/or diarrhea, which may be dose-limiting.
Folinic Acid is contraindicated to patients with known hypersensitivity to calcium folinate or any other components of this product. It is also contraindicated in pernicious anemia or other megaloblastic anemia where vitamin B12 is deficient. Patients with rare hereditary problems of galactose intolerance, the lapp lactase deficiency or glucose-galactose malabsorption should not take calcium folinate tablets.
Folinates given in large amounts may counteract the antiepileptic effect of phenobarbitone, phenytoin and primidone and increase the frequency of seizures in susceptible patients. Caution is required during concurrent administration of calcium folinate with fluoropyrimidine as this has been associated with seizures and syncope.
Actifol should only be used with methotrexate or 5-FU under the direct supervision of a clinician experienced in the use of cancer chemotherapeutic agents. In the treatment of inadvertent overdosage of a folic acid antagonist, folinate should be administered as soon as possible; if a period exceeding 4 hours intervenes, the treatment may not be effective. In general, Actifol should not be given simultaneously with folic acid antagonists, e.g. methotrexate, to abort clinical toxicity as the therapeutic effect of the antagonist may be nullified. Flowever, Actifol given concurrently with folate antagonists, such as pyrimethamine and trimethoprim does not inhibit their antibacterial activity. Measures to ensure the prompt excretion of methotrexate are important as part of Actifol Rescue Therapy. These measures include: Alkalinisation of urine so that the urinary pH is greater than 7.0 before methotrexate infusion (to increase solubility of methotrexate and its metabolites). Maintenance of urine output of 1800-2000 cc/m 2 /24 hour by increased oral or intravenous fluids on days 2, 3 and 4 following methotrexate therapy. Plasma methotrexate concentration, BUN and creatinine should be measured on days 2, 3 and 4. These measures must be continued until the plasma methotrexate level is less than 10 -7 molar.