Lovorin

Lovorin

calcium folinate

Manufacturer:

UNILAB, Inc

Distributor:

UNILAB, Inc
Full Prescribing Info
Contents
Calcium folinate.
Indications/Uses
In combination with fluorouracil (5-FU) for the treatment of advanced colorectal cancer.
To diminish the toxicity of methotrexate after high-dose methotrexate therapy in the management of several cancer types.
To diminish the toxicity and counteract the effects of overdosage of folic acid antagonists (methotrexate, trimetrexate, pyrimethamine, and trimethoprim).
For the treatment of megaloblastic anemias due to folate deficiency (e.g., in sprue and other nutritional deficiencies); and megaloblastic anemias of pregnancy and infancy (see Contraindications)
Dosage/Direction for Use
Folinic acid should be given by IM or IV injection and must NOT be administered intrathecally.
Folinic acid should be administered parenterally rather than orally in patients with gastrointestinal (GI) toxicity, nausea, or vomiting and when individual doses greater than 25 mg are to be administered. When folinic acid is administered by IV infusion, the infusion should be given over several minutes and the infusion rate should not exceed 16 mL (160 mg of folinic acid) per minute because of the calcium concentration of the solution.
In Combination with 5-FU for the Treatment of Advanced Colorectal Cancer: Different regimens and dosages are used, without any dosage having been proven to be the optimal one. The following regimens have been used in adults and elderly in the treatment of advanced or metastatic colorectal cancer: Bimonthly regimen: Folinic acid 200 mg/m2 by IV infusion over two hours, followed by IV bolus 5-FU 400 mg/m2 and 22-hour infusion of 5-FU 600 mg/m2 for two consecutive days, every two weeks on days 1 and 2.
Weekly regimen: Folinic acid 20 mg/m2 IV bolus injection or 200 to 500 mg/m2 as IV infusion over two hours plus IV bolus injection of 5-FU 500 mg/m2 in the middle or at the end of the folinic acid infusion.
Monthly regimen: Folinic acid 20 mg/m2 IV bolus injection or 200 to 500 mg/m2 as IV infusion over two hours immediately followed by IV bolus injection of 5-FU 425 or 370 mg/m2 during five consecutive days.
Modification of 5-FU dosage and the treatment-free interval should be determined by toxicity and/or tolerance to the previous course. Dosage of 5-FU in subsequent doses should be adjusted based on the tolerance of the patient; the dose of folinic acid is generally not adjusted according to toxicity (see 5-FU product information).
Use After Chemotherapy with Methotrexate: As part of high dose methotrexate regimen in cancer chemotherapy, start folinic acid rescue therapy within 24 hours of methotrexate administration. Folinic acid rescue is necessary when methotrexate is given at doses exceeding 500 mg/m2 and should be considered with methotrexate doses of 100 to 500 mg/m2. The use of high-dose methotrexate and folinic acid rescue therapy in treating certain types of cancer is an evolving science and the optimum dosage schedule has not been established.
A typical folinic acid rescue dosage schedule: 10 mg/m2 administered parenterally followed by 10 mg/m2 orally (if there is adequate GI function) every six hours until serum methotrexate concentration has declined to <10-8 M. Serum creatinine and methotrexate levels should be determined at 24 hour intervals. If at 24 hours after methotrexate administration the patient's serum creatinine has increased to 50% or more above the serum creatinine prior to methotrexate or the serum methotrexate concentration is >5 x 10-6 M, or if at 48 hours after methotrexate administration the serum methotrexate concentration is <9 x 10-7 M, increase folinic acid dosage immediately to 100 mg/m2 every three hours until the serum methotrexate concentration is less than 10-8 M.
To Diminish the Toxicity and Counteract the Effects of Overdosage of Folic Acid Antagonists: Administer IV or IM folinic acid in amounts equal to the suspected dose of the folic acid antagonist given, as soon as the overdosage is detected and preferably within the first hour. The treatment may be ineffective if a period of more than four hours intervenes.
Antidote to Methotrexate Toxicity: Generally, folinic acid can be administered six to 24 hours after methotrexate infusion without affecting the activity of the antineoplastic drug. When large doses or overdoses of methotrexate are given, administer folinic acid by IV infusion in doses up to 75 mg within 12 hours, followed by 12 mg IM every six hours for four doses. When average methotrexate doses appear to have an adverse effect, 6 to 12 mg of folinic acid may be given IM every six hours for four doses. Prompt administration of folinic acid is essential.
Antidote to Trimetrexate Toxicity: The usual folinic acid dose for the prevention of potentially serious and life-threatening toxicities in immunocompromised patients receiving trimetrexate is 20 mg/m2 every six hours (total daily dose of 80 mg/m2). Folinic acid should be given daily during trimetrexate treatment either orally or IV (over five to 10 minutes) and should be continued for at least 72 hours after the last trimetrexate dose. The recommended course of trimetrexate therapy is 21 days and that of folinic acid is 24 days.
Dosage of trimetrexate and folinic acid should be adjusted according to the hematologic response of the patient. For overdosage with trimetrexate (possibly occurring with doses above 90 mg/m2 without concomitant folinic acid administration), Folinic acid is given at 40 mg/m2 IV every six hours for three days (see specific product information for trimetrexate dosage adjustments).
Antidote to Pyrimethamine Toxicity: The dosage of folinic acid necessary to prevent hematologic toxicity associated with pyrimethamine varies depending on the dosage of the folic acid antagonist and the clinical status of the patient. The usual dosage is 3 to 9 mg per day IM for three days or until platelet and leukocyte counts have reached safe levels. Folinic acid does not impair the effectiveness of pyrimethamine.
Antidote to Trimethoprim Toxicity: After stopping trimethoprim, 3 to 10 mg/day folinic acid until recovery of blood cell counts.
For the Treatment of Megaloblastic Anemias Due to Folate Deficiency: Folinic acid IM, up to 1 mg folinic acid daily; larger doses do not increase the effect. The duration of therapy depends on the hematologic response to folinic acid. Oral folinic acid is preferred to parenteral therapy, except where cases of severe vomiting impair drug absorption when administered orally.
Contraindications
Hypersensitivity to folinic acid or any ingredients in the product.
Undiagnosed anemia, pernicious anemia, vitamin B12 deficiency or other megaloblastic anemia secondary to vitamin B12 deficiency.
Special Precautions
General: Consider the possibility of allergic reactions to folinic acid as these have been reported following parenteral folic acid administration.
There is potential danger in administering folinic acid to patients with undiagnosed anemia. Folinic acid may obscure the diagnosis of pernicious anemia by alleviating hematologic manifestations of the disease while allowing neurologic complications to progress. This may result in severe nervous system damage before the correct diagnosis is made. Adequate doses of vitamin B12 may prevent, halt or improve neurologic changes caused by pernicious anemia.
Folinic Acid/Methotrexate: Folinic Acid should be used with caution when used after methotrexate in the following conditions: Aciduria (urine pH less than 7).
Ascites.
Dehydration.
Gastrointestinal obstruction.
Pleural or peritoneal effusions.
Renal function impairment.
When Folinic Acid rescue is used in conjunction with high-dose methotrexate therapy, it is highly recommended that the drugs be administered only by physicians experienced in cancer chemotherapy and in centers where facilities for measuring blood methotrexate concentrations are available. Folinic Acid is usually effective in counteracting severe methotrexate toxicity in these regimens, but toxic reactions to methotrexate may occur despite Folinic Acid therapy, especially when methotrexate's half-life is increased. Therefore, it is extremely important that Folinic Acid be administered until methotrexate's blood concentration declines to nontoxic concentrations.
Folinic Acid/5-FU: Since Folinic Acid enhances 5-FU's toxicity, it is recommended that adjunctive therapy with Folinic Acid and 5-FU be given only by, or under the supervision of, physicians experienced in cancer chemotherapy and in the use of metabolites.
There is some evidence suggesting that risk of 5-FU-induced GI toxicity may be increased in patients receiving Folinic Acid concomitantly with the drug. Death secondary to severe enterocolitis, diarrhea and dehydration has occurred in geriatric patients receiving the drugs concomitantly. Concomitant granulocytopenia and fever were present but not all cases. Exercise extreme caution in geriatric or debilitated patients administered with combined Folinic Acid and 5-FU therapy since these patients are most likely to develop serious 5-FU toxicity.
Folinic Acid should not be mixed with 5-FU in the same IV injection or infusion.
Effects on Ability to Drive or Use Machines: There is no evidence that Folinic Acid has an effect on the ability to drive or use machines.
Use in Children: Folinic Acid may increase the frequency of seizures in susceptible children.
Use in Elderly: Elderly patients are at a greater risk of developing severe toxicity when treated with the combination of Folinic Acid plus 5-FU for advanced colorectal cancer (see Precautions).
Use In Pregnancy & Lactation
Use in Pregnancy: Pregnancy Category A: Animal reproduction studies have not been performed with leucovorin. It is also not known whether Folinic Acid can cause fetal harm when administered to pregnant women. Folinic Acid should be used in pregnancy only when clearly needed.
Use in Lactation: It is not known if Folinic Acid is distributed into milk; use with caution in breastfeeding women.
Adverse Reactions
Folinic Acid appears to be nontoxic in therapeutic doses; however, thrombocytosis has been reported in patients receiving Folinic Acid during intra-arterial infusion of methotrexate.
Hypersensitivity reactions, including anaphylactoid reactions and urticaria, have been reported with both oral and parenteral leucovorin. While Folinic Acid can potentiate the toxic effects of 5-FU, potentially resulting in increased severity and frequency of certain effects, the observed toxicity is generally associated with 5-FU.
Pyrexia has occurred rarely after injections. Gastrointestinal disturbances, insomnia, agitation, and depression have been reported rarely, after high doses.
Drug Interactions
Folic acid antagonists (e.g., methotrexate, trimetrexate, pyrimethamine, trimethoprim): Folinic Acid may reduce or nullify the effect of these antagonists.
5-FU: Concurrent use of Folinic Acid may increase therapeutic and toxic effects (especially on the GI tract) of 5-FU; however, these medications may be used together for therapeutic advantage.
Anticonvulsants: In epileptic patients treated with phenobarbital, phenytoin, primidone, and succinimides, Folinic Acid may increase the frequency of seizures due to a decrease of plasma concentrations of the anticonvulsants.
Direct or indirect DNA synthesis inhibitors: These cytotoxic medications (e.g., hydroxycarbamine, cytarabine, mercaptopurine, thioguanine) may lead to macrocytosis, which should not be treated with folinic acid.
ATC Classification
V03AF03 - calcium folinate ; Belongs to the class of detoxifying agents used in antineoplastic treatment.
Presentation/Packing
Soln for inj (vial) 50 mg/5 mL x 1's.
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