Folicinat (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Pharmasintez, JSC (Russia)

ATC Code

V03AF03 (Calcium folinate)

Active Substance

Calcium folinate (Rec.INN registered by WHO)

Dosage Forms

	Folicinat	Lyophilisate for preparation of solution for intravenous and intramuscular administration 10 mg: vial 1, 5 or 10 pcs.
		Lyophilisate for preparation of solution for intravenous and intramuscular administration 30 mg: vial 1, 5 or 10 pcs.
		Lyophilisate for preparation of solution for intravenous and intramuscular administration 50 mg: vial 1, 5 or 10 pcs.
		Lyophilisate for preparation of solution for intravenous and intramuscular administration 25 mg: vial 1, 5 or 10 pcs.

Dosage Form, Packaging, and Composition

Lyophilisate for preparation of solution for intravenous and intramuscular administration in the form of a porous mass from white with a yellowish tint to yellow of non-uniform color; solvent is a colorless liquid.

Excipients: methylparahydroxybenzoate, propylparahydroxybenzoate.

10 mg – vial (1) – cardboard packs with insert.
10 mg – vial (5) – cardboard packs with insert.
10 mg – vial (10) – cardboard packs with insert.
10 mg – vial (1) – cardboard packs with insert in a set with solvent.
10 mg – vial (5) – cardboard packs with insert in a set with solvent.
10 mg – vial (10) – cardboard packs with insert in a set with solvent.

Lyophilisate for preparation of solution for intravenous and intramuscular administration in the form of a porous mass from white with a yellowish tint to yellow of non-uniform color; solvent is a colorless liquid.

Excipients: methylparahydroxybenzoate, propylparahydroxybenzoate.

30 mg – vial (1) – cardboard packs with insert.
30 mg – vial (5) – cardboard packs with insert.
30 mg – vial (10) – cardboard packs with insert.
30 mg – vial (1) – cardboard packs with insert in a set with solvent.
30 mg – vial (5) – cardboard packs with insert in a set with solvent.
30 mg – vial (10) – cardboard packs with insert in a set with solvent.

Lyophilisate for preparation of solution for intravenous and intramuscular administration in the form of a porous mass from white with a yellowish tint to yellow of non-uniform color; solvent is a colorless liquid.

Excipients: methylparahydroxybenzoate, propylparahydroxybenzoate.

50 mg – vial (1) – cardboard packs with insert.
50 mg – vial (5) – cardboard packs with insert.
50 mg – vial (10) – cardboard packs with insert.
50 mg – vial (1) – cardboard packs with insert in a set with solvent.
50 mg – vial (5) – cardboard packs with insert in a set with solvent.
50 mg – vial (10) – cardboard packs with insert in a set with solvent.

Lyophilisate for preparation of solution for intravenous and intramuscular administration in the form of a porous mass from white with a yellowish tint to yellow of non-uniform color; solvent is a colorless liquid.

Excipients: methylparahydroxybenzoate, propylparahydroxybenzoate.

25 mg – vial (1) – cardboard packs with insert.
25 mg – vial (5) – cardboard packs with insert.
25 mg – vial (10) – cardboard packs with insert.
25 mg – vial (1) – cardboard packs with insert in a set with solvent.
25 mg – vial (5) – cardboard packs with insert in a set with solvent.
25 mg – vial (10) – cardboard packs with insert in a set with solvent.

Clinical-Pharmacological Group

Folic acid antagonists antidote

Pharmacotherapeutic Group

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

Pharmacological Action

It is an antidote to folic acid antagonists (folinic acid is an active derivative of folic acid).

It reduces the therapeutic and toxic effects of folic acid antagonists (for example, methotrexate), promotes the restoration of nucleic acid biosynthesis and replenishes folic acid deficiency in the body.

Pharmacokinetics

It penetrates the blood-brain barrier.

It accumulates in the liver.

It is metabolized in the liver and in the intestinal mucosa with the formation of an active metabolite; the degree and rate of metabolism are higher when taken orally than with parenteral administration.

The average T_1/2 is 6 hours.

It is excreted mainly by the kidneys.

Indications

Prevention and treatment of toxic effects of methotrexate, overdose of folic acid antagonists.

Treatment of megaloblastic anemia caused by folic acid deficiency.

Palliative therapy for cancer of the colon and rectum (in combination with fluorouracil).

ICD codes

Dosage Regimen

The dosage regimen of calcium folinate after high-dose methotrexate intravenous 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, intravenously or intramuscularly 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, intravenously or intramuscularly 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 intravenously every 3 hours until the plasma methotrexate level falls below 1 µM, then at a dose of 15 mg intravenously 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, calcium folinate treatment 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 when taken orally – nausea, vomiting (in this case, parenteral use is indicated).

Allergic reactions urticaria, anaphylactic shock.

Contraindications

Megaloblastic anemia caused by vitamin B₁₂ deficiency, hypersensitivity to calcium folinate.

Use in Pregnancy and Lactation

If it is necessary to use calcium folinate during pregnancy, the intended benefit of therapy for the mother and the potential risk to the fetus should be carefully assessed.

If it is necessary to use during lactation, breastfeeding should be discontinued.

Use in Renal Impairment

Calcium folinate should be used with caution in renal impairment. Renal function and urine pH should be monitored before and during therapy.

Pediatric Use

When used in children, it should be borne in mind that Calcium folinate may increase the frequency of seizures in predisposed patients, due to a decrease in the effectiveness of anticonvulsant drugs.

Special Precautions

During methotrexate treatment, in cases where clinical signs of toxicity or any abnormalities in laboratory parameters are noted, the possibility of an increase in plasma methotrexate concentration due to interaction with other drugs that impair methotrexate excretion or displace it from plasma albumin binding should be excluded.

Calcium folinate should be used with caution in acidic urine reaction, ascites, dehydration, exudative pleurisy, and renal impairment.

It should be taken into account that with nausea and vomiting, the absorption of calcium folinate may be impaired (parenteral administration is preferable).

Renal function and urine pH should be monitored before and during therapy.

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

When used in children, it should be borne in mind that Calcium folinate may increase the frequency of seizures in predisposed patients, due to a decrease in the effectiveness of anticonvulsant drugs.

Drug Interactions

Calcium folinate reduces the therapeutic and toxic effects of folic acid antagonists.

When used in high doses, Calcium folinate reduces the anticonvulsant effect of phenobarbital, phenytoin, primidone and increases the frequency of seizures in predisposed patients.

Calcium folinate enhances the antitumor and toxic effect of fluorouracil, especially on the gastrointestinal tract.

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.