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Calcium Folinate (Solution, Lyophilisate) Instructions for Use

ATC Code

V03AF03 (Calcium Folinate)

Active Substance

Folic acid (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Folic acid antagonists antidote

Pharmacotherapeutic Group

Other therapeutic agents; agents for reducing the toxicity of anticancer therapy

Pharmacological Action

B group vitamin (vitamin Bc, B9). In the body, Folic acid is reduced to tetrahydrofolic acid, which is a coenzyme involved in various metabolic processes.

It is necessary for the normal maturation of megaloblasts and the formation of normoblasts. It stimulates erythropoiesis, participates in the synthesis of amino acids (including methionine, serine), nucleic acids, purines and pyrimidines, and in the metabolism of choline and histidine.

During pregnancy, it protects the body from the effects of teratogenic factors. It promotes the normal maturation and functioning of the placenta.

Pharmacokinetics

After oral administration, it is well absorbed from the gastrointestinal tract. Binding to plasma proteins is high.

It is metabolized in the liver and tissues. It is excreted in bile and urine. It penetrates the blood-brain barrier, placenta, and is excreted in breast milk.

Indications

Macrocytic hyperchromic anemia caused by folic acid deficiency.

As part of combination therapy for the following diseases: anemia and leukopenia caused by drugs and ionizing radiation; sprue; chronic gastroenteritis; intestinal tuberculosis.

At the planning stage and during pregnancy to prevent the development of neural tube defects in the fetus in the presence of risk factors in the mother.

Treatment of megaloblastic anemia due to deficiency or increased utilization of folic acid (including during pregnancy, malabsorption syndrome).

ICD codes

ICD-10 code Indication
A18.3 Tuberculosis of intestines, peritoneum and mesenteric lymph nodes
D52 Folate deficiency anemia
D61.1 Drug-induced aplastic anemia
D63.8 Anemia in other chronic diseases classified elsewhere*
D64.8 Other specified anemias
K29 Gastritis and duodenitis
K52.9 Noninfective gastroenteritis and colitis, unspecified
K90.1 Tropical sprue
K90.9 Impaired intestinal absorption, unspecified
O25 Nutritional deficiencies in pregnancy
T66 Unspecified effects of radiation (radiation sickness)
ICD-11 code Indication
1B12.7 Tuberculosis of the digestive system
3A02.Z Folate deficiency anemia, unspecified
3A70.10 Drug-induced aplastic anemia
3A70.1Z Acquired aplastic anemias, unspecified
3A71.Z Anemia of chronic disease, unspecified
3A90 Anemia due to acute disease
3A9Y Other specified anemias or other diseases related to red blood cells
8E61.0 Radiation-induced brain injury
8E61.1 Radiation-induced spinal cord injury
DA42.Z Gastritis, unspecified
DA51.Z Duodenitis, unspecified
DA7Z Diseases of stomach or duodenum, unspecified
DA90.0 Syndromic diarrhea
DA96.01 Tropical sprue
DA96.0Z Intestinal malabsorption, unspecified
DE2Z Diseases of the digestive system, unspecified
JA64 Nutritional disorders during pregnancy
NF00 Exposure to radiation, not elsewhere classified

Dosage Regimen

The method of application and dosage regimen for a specific drug depend on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly adhere to the compliance of the dosage form of a specific drug with the indications for use and dosage regimen.

Lyophilisate

It is established individually, depending on the indications, clinical situation and the dosage form used.

Solution

The dosage regimen of calcium folinate after high-dose methotrexate IV infusions (12-15 g/m2 after 4 hours) is established individually, taking into account the state of renal excretory function, provided that plasma creatinine and methotrexate concentrations are systematically monitored (at least once a day).

With normal methotrexate elimination (plasma methotrexate level approximately 10 µM 24 hours after administration, 1 µM at 48 hours and less than 0.2 µM at 72 hours), Calcium folinate is used at a dose of 15 mg (approximately 10 mg/m2) orally, IV or IM every 6 hours for 60 hours (10 doses, starting 24 hours after the start of methotrexate administration).

With delayed late methotrexate elimination (methotrexate level above 0.2 µM at 72 hours and above 0.05 µM at 96 hours after administration), Calcium folinate is continued to be administered at a dose of 15 mg orally, IV or IM every 6 hours until the plasma methotrexate level falls below 0.05 µM.

With delayed early elimination of methotrexate from the body (methotrexate level 50 µM and above at 24 hours, 5 µM and above at 48 hours, or an increase in plasma creatinine level by 100% or more within 24 hours after methotrexate administration), Calcium folinate is administered at a dose of 150 mg IV every 3 hours until the plasma methotrexate level falls below 1 µM, then at a dose of 15 mg IV every 3 hours until the plasma methotrexate level falls below 0.05 µM. Simultaneous hydration and administration of sodium bicarbonate (to prevent the development of renal failure) is mandatory.

In cases where severe toxic reactions are observed, treatment with calcium folinate should be continued additionally for another 24 hours (a total of 14 consecutive doses over 84 hours).

For megaloblastic anemia caused by folic acid deficiency, Calcium folinate is prescribed at a dose of up to 1 mg/day.

Adverse Reactions

From the digestive system rarely – anorexia, nausea, abdominal bloating, flatulence, bitter taste in the mouth.

From the immune system rarely – anaphylactic reactions (including shock).

Allergic reactions rarely – erythema, rash, itching, urticaria, shortness of breath.

Contraindications

Hypersensitivity to folic acid; long-term therapy of patients with untreated cobalamin deficiency (e.g., pernicious anemia, vitamin B12 deficiency, vegetarianism); malignant neoplasms; pregnant women without established folic acid deficiency and/or presence of risk factors for neural tube defects in the fetus; period of breastfeeding – depending on the dosage form; children and adolescents under 18 years of age.

Use in Pregnancy and Lactation

Contraindicated in pregnant women without established folic acid deficiency and/or presence of risk factors for neural tube defects in the fetus. It can be used during pregnancy if indicated in recommended doses.

It can be used during lactation (breastfeeding) strictly according to indications, in recommended doses and dosage forms. It is necessary to strictly follow the instructions in the folic acid drug leaflets regarding contraindications for use during breastfeeding for specific dosage forms of folic acid.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Special Precautions

In pernicious anemia, folic acid should be used only in combination with cyanocobalamin, since Folic acid, while stimulating hematopoiesis, does not prevent the development of neurological complications (including funicular myelosis).

Long-term use of folic acid (especially in high doses) is not recommended due to the risk of reducing the concentration of cyanocobalamin in the blood.

Drug Interactions

With simultaneous use with chloramphenicol, neomycin, polymyxins, tetracyclines, the absorption of folic acid is reduced.

With simultaneous use of analgesics (long-term therapy), anticonvulsants (including phenytoin, carbamazepine), estrogens, parenteral contraceptives, the need for folic acid increases.

With simultaneous use of folic acid, a decrease in plasma concentrations of phenobarbital, phenytoin, primidone is possible, and the risk of an epileptic seizure increases.

With simultaneous use of antacids (including calcium, aluminum and magnesium preparations), cholestyramine, sulfonamides (including sulfasalazine), the absorption of folic acid is reduced. Antacids should be used 2 hours after taking folic acid, cholestyramine – 4-6 hours before or 1 hour after taking folic acid.

With simultaneous use, methotrexate, pyrimethamine, triamterene, trimethoprim inhibit dihydrofolate reductase and reduce the effect of folic acid.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.

Medical Disclaimer

Brand (or Active Substance), Marketing Authorisation Holder, Dosage Form

Marketing Authorization Holder

Atoll LLC (Russia)

Manufactured By

Ozon Pharm, LLC (Russia)

Dosage Forms

Bottle Rx Icon Calcium Folinate Lyophilizate for the preparation of solution for intravenous and intramuscular injection 25 mg: fl. 15 ml 1 or 5 pcs.
Lyophilizate for the preparation of solution for intravenous and intramuscular injection 50 mg: fl. 15 ml 1 or 5 pcs.

Dosage Form, Packaging, and Composition

Lyophilizate for the preparation of solution for intravenous and intramuscular injection – lyophilized porous mass from light yellow to yellow in color with non-uniform coloration.

1 fl.
Folic acid 25 mg
   (in terms of calcium folinate hydrate) 27.95 mg

Excipients : methylparahydroxybenzoate – 0.5 mg.

25 mg – 15 ml vials (1) (with solvent: sodium chloride solution 0.9% (ampoules) 2 ml – 1 pc.) – contour cell packaging – cardboard packs.
25 mg – 15 ml vials (5) (with solvent: sodium chloride solution 0.9% (ampoules) 2 ml – 5 pcs.) – contour cell packaging – cardboard packs.

Lyophilizate for the preparation of solution for intravenous and intramuscular injection – lyophilized porous mass from light yellow to yellow in color with non-uniform coloration.

1 fl.
Folic acid 50 mg
   (in terms of calcium folinate hydrate) 55.9 mg

Excipients : methylparahydroxybenzoate – 0.5 mg.

50 mg – 15 ml vials (1) (with solvent: sodium chloride solution 0.9% (ampoules) 2 ml – 1 pc. – contour cell packaging – cardboard packs.
50 mg – 15 ml vials (5) (with solvent: sodium chloride solution 0.9% (ampoules) 2 ml – 5 pcs. – contour cell packaging – cardboard packs.

Marketing Authorization Holder

Novosibkhimpharm, JSC (Russia)

Dosage Form

Bottle Rx Icon Calcium folinate Solution for intravenous and intramuscular administration 10 mg/ml

Dosage Form, Packaging, and Composition

Solution for intravenous and intramuscular administration

1 ml
Calcium folinate 10 mg

10 ml – ampoules (10 pcs.) – cardboard boxes – By prescription
10 ml – ampoules (10 pcs.) – cardboard packs – By prescription
10 ml – ampoules (3 pcs.) – cardboard packs – By prescription
10 ml – ampoules (5 pcs.) – cardboard packs – By prescription
10 ml – ampoules (6 pcs.) – cardboard packs – By prescription
5 ml – ampoules (10 pcs.) – cardboard boxes – By prescription
5 ml – ampoules (10 pcs.) – cardboard packs – By prescription
5 ml – ampoules (3 pcs.) – cardboard packs – By prescription
5 ml – ampoules (5 pcs.) – cardboard packs – By prescription
5 ml – ampoules (6 pcs.) – cardboard packs – By prescription

Marketing Authorization Holder

Pharmpotrebsoyuz, LLC (Russia)

Manufactured By

Bryntsalov-A, JSC (Russia)

Dosage Forms

Bottle Rx Icon Calcium folinate Solution for intravenous and intramuscular administration 5 mg/ml
Solution for intravenous and intramuscular administration 10 mg/ml

Dosage Form, Packaging, and Composition

Solution for intravenous and intramuscular administration

1 ml
Calcium folinate 5 mg

10 ml – vials – cardboard packs – By prescription
10 ml – vials (10 pcs.) – cardboard packs – By prescription
10 ml – vials (5 pcs.) – cardboard packs – By prescription
10 ml – vials (50 pcs.) – cardboard boxes – for hospitals
3 ml – vials – cardboard packs – By prescription
3 ml – vials (10 pcs.) – cardboard packs – By prescription
3 ml – vials (5 pcs.) – cardboard packs – By prescription
3 ml – vials (50 pcs.) – cardboard boxes – for hospitals
5 ml – vials – cardboard packs – By prescription
5 ml – vials (10 pcs.) – cardboard packs – By prescription
5 ml – vials (5 pcs.) – cardboard packs – By prescription
5 ml – vials (50 pcs.) – cardboard boxes – for hospitals

Solution for intravenous and intramuscular administration

1 ml
Calcium folinate 10 mg

10 ml – vials – cardboard packs – By prescription
10 ml – vials (10 pcs.) – cardboard packs – By prescription
10 ml – vials (5 pcs.) – cardboard packs – By prescription
10 ml – vials (50 pcs.) – cardboard boxes – for hospitals
3 ml – vials – cardboard packs – By prescription
3 ml – vials (10 pcs.) – cardboard packs – By prescription
3 ml – vials (5 pcs.) – cardboard packs – By prescription
3 ml – vials (50 pcs.) – cardboard boxes – for hospitals
5 ml – vials – cardboard packs – By prescription
5 ml – vials (10 pcs.) – cardboard packs – By prescription
5 ml – vials (5 pcs.) – cardboard packs – By prescription
5 ml – vials (50 pcs.) – cardboard boxes – for hospitals

Marketing Authorization Holder

Elzapharm, LLC (Russia)

Manufactured By

Velpharm, LLC (Russia)

Dosage Forms

Bottle Rx Icon Calcium folinate Solution for intravenous and intramuscular administration 5 mg/1 ml: amp. 2 ml, 5 ml, or 10 ml 3, 5, 6, or 10 pcs.
Solution for intravenous and intramuscular administration 10 mg/1 ml: amp. 3 ml, 5 ml, 10 ml, or 20 ml 3, 5, 6, or 10 pcs.

Dosage Form, Packaging, and Composition

Solution for intravenous and intramuscular administration from colorless to yellow, transparent.

1 ml
Calcium folinate hydrate (leucovorin calcium) 5.4 mg,
   In terms of folinic acid 5 mg

Excipients : sodium chloride, sodium hydroxide solution 1M or hydrochloric acid solution 1M – to pH 6.5-8.5, water for injections.

2 ml – glass ampoules (3) – contour cell packaging (1) – cardboard packs.
2 ml – glass ampoules (3) – contour cell packaging (2) – cardboard packs.
2 ml – glass ampoules (5) – contour cell packaging (1) – cardboard packs.
2 ml – glass ampoules (5) – contour cell packaging (2) – cardboard packs.
5 ml – glass ampoules (3) – contour cell packaging (1) – cardboard packs.
5 ml – glass ampoules (3) – contour cell packaging (2) – cardboard packs.
5 ml – glass ampoules (5) – contour cell packaging (1) – cardboard packs.
5 ml – glass ampoules (5) – contour cell packaging (2) – cardboard packs.
10 ml – glass ampoules (3) – contour cell packaging (1) – cardboard packs.
10 ml – glass ampoules (3) – contour cell packaging (2) – cardboard packs.
10 ml – glass ampoules (5) – contour cell packaging (1) – cardboard packs.
10 ml – glass ampoules (5) – contour cell packaging (2) – cardboard packs.

Solution for IV and IM administration from colorless to yellow, transparent.

1 ml
Calcium folinate hydrate (calcium leucovorin) 10.8 mg,
   In terms of folinic acid 10 mg

Excipients : sodium chloride, 1M sodium hydroxide solution or 1M hydrochloric acid solution – to pH 6.5-8.5, water for injections.

3 ml – glass ampoules (3) – contour cell packs (1) – cardboard boxes.
3 ml – glass ampoules (3) – contour cell packs (2) – cardboard boxes.
3 ml – glass ampoules (5) – contour cell packs (1) – cardboard boxes.
3 ml – glass ampoules (5) – contour cell packs (2) – cardboard boxes.
5 ml – glass ampoules (3) – contour cell packs (1) – cardboard boxes.
5 ml – glass ampoules (3) – contour cell packs (2) – cardboard boxes.
5 ml – glass ampoules (5) – contour cell packs (1) – cardboard boxes.
5 ml – glass ampoules (5) – contour cell packs (2) – cardboard boxes.
10 ml – glass ampoules (3) – contour cell packs (1) – cardboard boxes.
10 ml – glass ampoules (3) – contour cell packs (2) – cardboard boxes.
10 ml – glass ampoules (5) – contour cell packs (1) – cardboard boxes.
10 ml – glass ampoules (5) – contour cell packs (2) – cardboard boxes.
20 ml – glass ampoules (3) – contour cell packs (1) – cardboard boxes.
20 ml – glass ampoules (3) – contour cell packs (2) – cardboard boxes.
20 ml – glass ampoules (5) – contour cell packs (1) – cardboard boxes.
20 ml – glass ampoules (5) – contour cell packs (2) – cardboard boxes.

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