Folita

It rescue is indicated after high dose methotrexate therapy in osteosarcoma. It is also indicated to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages of folic acid antagonists. It is indicated in the treatment of megaloblastic anemias due to folic acid defi ciency when oral therapy is not feasible. It is also indicated for use in combination with 5-fl uorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer. It should not be mixed in the same infusion as 5-fl uorouracil because a precipitate may form.

Anticancer

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".

Advanced Colorectal Cancer: Either of the following two regimens is recommended: 1. It is administered at 200 mg/m2 by slow intravenous injection over a minimum of 3 minutes,followed by 5-fl uorouracil at 370 mg/m2 by intravenous injection. 2. It is administered at 20 mg/m2 by intravenous injection followed by 5-fl uorouracil at 425 mg/m2 by intravenous injection. 5-Fluorouracil and leucovorin should be administered separately to avoid the formation of a precipitate. Treatment is repeated daily for fi ve days. This fi ve-day treatment course may be repeated at 4 week (28-day) intervals,for 2 courses and then repeated at 4 to 5 week (28 to 35 day) intervals provided that the patient has completely recovered from the toxic effects of the prior treatment course. In subsequent treatment course,the dosage of 5-fl uorouracil should be adjusted based on patient tolerance of the prior treatment course. The daily dosage of 5-fl uorouracil should be reduced by 20% for patients who experienced moderate hematologic or gastrointestinal toxicity in the prior treatment course,and by 30% for patients who experienced severe toxicity (see PRECAUTIONS: Laboratory Tests). For patients who experienced no toxicity in the prior treatment course,5-fl uorouracil dosages may be increased by 10%. Leucovorin dosages are not adjusted for toxicity. Leucovorin Rescue After High-Dose Methotrexate Therapy: The recommendations for leucovorin rescue are based on a methotrexate dose of 12 to 15 grams/m2 administered by intravenous infusion over 4 hours (see methotrexate package insert for full prescribing information). Leucovorin rescue at a dose of 15 mg (approximately 10 mg/m2) every 6 hours for 10 doses starts 24 hours after the beginning of the methotrexate infusion. In the presence of gastrointestinal toxicity,nausea or vomiting,leucovorin should be administered parenterally. Do not administer leucovorin intrathecally. Serum creatinine and methotrexate levels should be determined at least once daily. Leucovorin administration,hydration,and urinary alkalization (pH of 7.0 or greater) should be continued until the methotrexate level is below 5 x 10-8 M (0.05 micromolar). The leucovorin dose should be adjusted or leucovorin rescue extended based on the following guidelines: GUIDELINES FOR LEUCOVORIN DOSAGE AND ADMINISTRATION DO NOT ADMINISTER LEUCOVORIN INTRATHECALLY Clinical Situation Laboratory Findings Leucovorin Dosage and Duration Normal Serum methotrexate level approximately 10 micromolar at 15 mg PO,IM,or IV q 6 hours for Methotrexate 24 hours after administration,1 micromolar at 48 hours, 60 hours (10 doses starting at 24 hours Elimination and less than 0.2 micromolar at 72 hours. after start of methotrexate infusion). Delayed Late Serum methotrexate level remaining above 0.2 micromolar Continue 15 mg PO,IM,or IV q Methotrexate at 72 hours,and more than 0.05 micromolar at 96 hours 6 hours,until methotrexate Elimination after administration. level is less than 0.05 micromolar. Delayed Early Serum methotrexate level of 50 micromolar or more at 24 150 mg IV q 3 hours,until Methotrexate hours,or 5 micromolar or more at 48 hours after adminismethotrexate level is less than Elimination and/or tration,OR; a 100% or greater increase in serum creatinine 1 micromolar; then 15 mg IV q Evidence of Acute level at 24 hours after methotrexate administration (e.g.,an 3 hours until methotrexate level Renal Injury increase from 0.5 mg/dL to a level of 1 mg/dL or more). is less than 0.05 micromolar. Patients who experience delayed early methotrexate elimination are likely to develop reversible renal failure. In addition to appropriate leucovorin therapy,these patients require continuing hydration and urinary alkalization,and close monitoring of fl uid and electrolyte status,until the serum methotrexate level has fallen to below 0.05 micromolar and the renal failure has resolved. Some patients will have abnormalities in methotrexate elimination or renal function following methotrexate administration,which are signifi cant but less severe than abnormalities described in the table above. These abnormalities may or may not be associated with signifi cant clinical toxicity. If signifi cant clinical toxicity is observed,leucovorin rescue should be extended for an additional 24 hours (total of 14 doses over 84 hours) in subsequent courses of therapy. The possibility that the patient is taking other medications which interact with methotrexate (e.g.,medications which may interfere with methotrexate elimination or binding to serum albumin) should always be reconsidered when laboratory abnormalities or clinical toxicities are observed. Impaired Methotrexate Elimination or Inadvertent Overdosage: Leucovorin rescue should begin as soon as possible after an inadvertent overdosage and within 24 hours of methotrexate administration when there is delayed excretion (see WARNINGS). Leucovorin 10 mg/m2 should be administered IV,IM,or PO every 6 hours until the serum methotrexate level is less than 10-8 M. In the presence of gastrointestinal toxicity,nausea,or vomiting,leucovorin should be administered parenterally. Do not administer leucovorin intrathecally.

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.

It is improper therapy for pernicious anemia and other megaloblastic anemias secondary to the lack of vitamin B12. A hematologic remission may occur while neurologic manifestations continue to progress.In the treatment of accidental overdosages of folic acid antagonists,intravenous should be administered as promptly as possible. As the time interval between antifolate administration (e.g.,methotrexate) and leucovorin rescue increases,its’s effectiveness in counteracting toxicity decreases. In the treatment of accidental overdosages of intrathecally adminstered folic acid antagonists,do not adminster it intrathecally. It MAY BE HARMFUL OR FATAL IF GIVEN INTRATHECALLY.

The most common side effects of Folinic Acid are mucositis, stomatitis, leukopenia and/or diarrhea, which may be dose-limiting.

There are no adequate and well-controlled clinical studies conducted in pregnant women. Folinic Acid should only be used in pregnant women if the potential benefit justifies the potential risk to the fetus. 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.

There have been no reported sequelae in patients who have received significantly more calcium folinate than the recommended dosage. Flowever, excessive amounts of calcium folinate may nullity the chemotherapeutic effect of folic acid antagonists. There is no specific antidote to calcium folinate overdose. In cases of overdosage patients should be given appropriate supportive care.

Do not store above 30°C. Keep away from light and out of the reach of children.

Each tablet contains- Calcium Folinate Hydrate BP 6.249 mg equivalent to Folinic Acid 5 mg. Calcium Folinate Hydrate BP 18.746 mg equivalent to Folinic Acid 15 mg.