Leucovorin-Teva solution 10mg/ml 5ml vials, 1pc

Composition

>1 ml contains: active ingredients: calcium folinate pentahydrate – 12.71 mg, which corresponds to the content of calcium folinate 10.8 mg, in terms of folinic acid 10 mg, Excipients: sodium chloride, sodium hydroxide 1% or hydrochloric acid 1 M, water d / I.

Pharmacological action

Pharmaco-therapeutic group: Vitamin-reduced toxicity of cytostatic therapy

Pharmacological action

Calcium folinate is a reduced form of folic acid and is used as an antidote to drugs that act as folic acid antagonists.

Folic acid antagonists, such as methotrexate, inhibit dihydrofolate reductase and thus prevent the formation of tetrahydrofolate from folic acid, which is a cofactor for the transfer of single-carbon residues in the biosynthesis of nucleic acids. As a result, nucleic acid synthesis and cell division are blocked. Calcium folinate, unlike folic acid, does not require reduction by dihydrofolate reductase for conversion to tetrahydrofolate, which allows its use to restore the disturbed process of DNA, RNA and protein biosynthesis. The protective effect of calcium folinate is manifested only in relation to healthy cells. Due to these properties, calcium folinate prevents the toxic effect of methotrexate on bone marrow and gastrointestinal cells, but does not significantly affect the already developed nephrotoxic effect of methotrexate.

The drug helps to fill the deficiency of folic acid in the body.

Calcium folinate may also enhance the antitumor effect of fluorouracil. When these two drugs interact, a stable complex of components is formed containing thymidylate synthetase, which inhibits and suppresses DNA synthesis.

The onset of action of the drug with intravenous use – in 10-20 minutes, with intravenous use-in less than 5 minutes. The duration of action is about 3-6 hours, regardless of the method of use.

Pharmacokinetics

of_cmax of reduced folate in blood serum with intramuscular use is achieved on average in 40 minutes, with intravenous use – in 10 minutes and with oral use in 1 h 40 minutes. Penetrates the blood-brain barrier in moderate amounts; accumulates to a greater extent in the liver. It is mainly metabolized in the liver and intestinal mucosa to the active metabolite 5-methyltetrahydrofolate. The half-life is 6.2 hours, regardless of the method of use.

80-90% is excreted by the kidneys,5-8% by the intestines.

Indications

• toxicity of folic acid antagonists (methotrexate, trimethoprim, and pyrimethamine);
• prevention of the toxic effects of methotrexate used at high doses;
• colorectal cancer (combination therapy with fluorouracil);
• megaloblastic anemia caused by folic acid deficiency (including on the background of the syndrome of malabsorption, malnutrition, pregnancy, sprue, in early childhood for congenital insufficiency of dihydrofolate reductase).

Contraindications

• hypersensitivity to calcium folinate or any other component that is part of the drug;
• megaloblastic anemia due to a deficiency of cyanocobalamin (vitamin_B12);
• pregnancy and lactation.

With caution:  for alcoholism, epilepsy, chronic renal failure (CRF), children under 2 years of age (safety and efficacy have not been established).

Side effects

The following adverse events reported with Leucovorin-Teva are distributed according to the frequency of occurrence in accordance with the following gradation: very common (≥1/10), common (≥1/100 to <1/10), infrequent (≥1/1000 to <1/100), rare (≥1/10000 to <1/1000), extremely rare (

From the immune system:  very rarely – allergic reactions: skin rash, urticaria, pruritus, anaphylactic shock.

Nervous system disorders:  rarely – insomnia, agitation, depression, agitation, increased frequency of epileptic seizures.

From the digestive system:  rarely-dyspeptic phenomena (when using high doses of calcium folinate).

Other services:  infrequently-fever.

Interaction

of Calcium folinate with simultaneous use reduces the effectiveness of folic acid antagonists.

Reduces the anticonvulsant activity of phenobarbital, phenytoin and primidone. Its use can lead to an increase in both the therapeutic and toxic effects of fluorouracil, and therefore, when used together, the dose of fluorouracil should be reduced.

How to take, course of use and dosage

The solution is administered intravenously or intravenously.

When choosing the dosage and mode of use of the drug in each individual case, you should refer to the special literature.

Usually when the drug is prescribed in combination with high doses of methotrexate (12-15 mg / m2) use begins 24 hours after the end of treatment with methotrexate at a dose of 10 mg / m2 every 6 hours for 72 hours or until the concentration of methotrexate in blood plasma is less than 5 x 10-8 M.

In patients with an acidic urine reaction, exudative effusions, impaired renal function, or intestinal obstruction, a higher dose of calcium folinate and/or a longer duration of treatment may be required, since the elimination of methotrexate in this group of patients may be delayed. The use of Leucovorin-Teva in these cases is recommended to be based on the mandatory determination of the concentration of methotrexate in blood plasma.

To prevent the development of CRF, hydration is performed (3 liters/day) and sodium bicarbonate is administered to maintain the pH of urine at a level of 7 or higher.

In case of accidental overdose of methotrexate, Leucovorin-Teva is administered at a dose equal to or exceeding the dose of methotrexate administered no later than 1 hour after the injection of methotrexate, then the drug is administered every 3 hours at 10 mg/m2 until the signs of toxicity disappear.

When combined with fluorouracil, Leucovorin-Teva is administered:

• at a dose of 200 mg / m2 IV slowly (at least 3 minutes) or iv drip followed by iv use of fluorouracil at a dose of 370 mg / m2 or
• at a dose of 20 mg/m2 IV followed by iv use of fluorouracil at a dose of 425 mg/m2.

Drugs are administered daily for 5 days with an interval of 4-5 weeks for repeated courses.

In the treatment of megaloblastic anemia caused by folic acid deficiency, Leucovorin-Teva is prescribed 1 mg/day iv or iv.

Preparation of the drug for injection

The Leucovorin-Teva preparation is diluted in Ringer’s solution; Ringer’s solution with lactate; 10% dextrose solution in water; 5% dextrose solution in water; 0.9% sodium chloride solution to a concentration from 0.06 mg / ml to 1 mg / ml. The resulting solution remains stable for 24 hours. Do not use the solution remaining after the injection.

Overdose

of Calcium folinate is slightly toxic. Even with high doses, there are no signs of overdose.

Special instructions

The use of calcium folinate in pernicious and other megaloblastic anemia caused by cyanocobalamin (vitamin_B12) deficiency can lead to hematological remission with simultaneous progression of neurological disorders.

It may increase the frequency of epileptic seizures in children predisposed to them due to a decrease in the effect of antiepileptic drugs-derivatives of hydantoin and primidone (hexamidine).

Calcium folinate is used with caution in cases of acidic urine reaction, ascites, dehydration, exudative pleurisy, and impaired renal function.

Before and during therapy, kidney function and urine pH should be monitored.

In case of accidental overdose of methotrexate, calcium folinate should be started as soon as possible.

Storage conditions

List B.

The drug should be stored at a temperature of 2 to 8°C, in a place protected from light.

Keep out of reach of children.

Shelf

life is 2 years.

Do not use after the expiration date indicated on the package.

Active ingredient

Calcium Folinate

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection and infusion