Cernevit (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Baxter, S.A. (Belgium)

Manufactured By

Pierre Fabre Medicament Production (France)

Primary Packaging

Pierre Fabre Medicament Production (France)

Packaging and Quality Control Release

BAXTER, S.A. (Belgium)

Contact Information

BAXTER (USA)

ATC Code

B05XC (Vitamins)

Dosage Form

Cernevit

Lyophilizate for solution for intravenous administration: vial 0.747 g 10 pcs.

Dosage Form, Packaging, and Composition

Lyophilisate for preparation of solution for intravenous administration in the form of a loose yellow-orange solid mass, odorless.

Excipients: glycine – 250 mg, glycocholic acid – 140 mg, soybean phosphatides (soybean lecithin) – 112.5 mg, sodium hydroxide – to pH 5.9, hydrochloric acid – to pH 5.9.

747 mg – dark glass vials (10) – plastic contour trays (1) – cardboard boxes.

Clinical-Pharmacological Group

Vitamins for addition to parenteral nutrition solutions

Pharmacotherapeutic Group

Multivitamin agent

Pharmacological Action

Cernevit is a balanced mixture of water-soluble and fat-soluble vitamins. It provides a complete supply of vitamins to the body during parenteral nutrition.

The pharmacodynamic properties are determined by the properties of the vitamins included in the preparation.

Vitamin A is involved in cell growth and differentiation processes, as well as in the physiological mechanisms of vision.

Vitamin D₃ regulates the processes of calcium and phosphorus metabolism in bones and kidneys.

Vitamin E is an antioxidant, prevents the formation of toxic oxidation products, and protects cellular components.

Vitamin B₁ (thiamine) interacts with ATP to form a coenzyme involved in carbohydrate metabolism.

Vitamin B₂ (riboflavin) acts as a coenzyme and participates in cellular energy metabolism, tissue respiration, and macronutrient metabolism.

Vitamin B₃ (PP) as a component of NAD and NADP coenzymes participates in redox processes necessary for macronutrient metabolism and tissue respiration.

Vitamin B₅ (pantothenic acid) is a precursor of coenzyme A, associated with the oxidative metabolism of carbohydrates, gluconeogenesis, and the synthesis of fatty acids, sterols, steroid hormones, and porphyrins.

Vitamin B₆ (pyridoxine) acts as a coenzyme and participates in the metabolism of proteins, carbohydrates, and fats.

Vitamin B₁₂(Cyanocobalamin) is of exogenous origin, necessary for the synthesis of nucleoproteins and myelin, cell reproduction, normal growth, and maintenance of normal erythropoiesis.

Vitamin C (Ascorbic acid) is an antioxidant, necessary for the formation and maintenance of intercellular substance and collagen, biosynthesis of catecholamine, synthesis of carnitine and steroids, and metabolism of folic acid and tyrosine.

Folic acid is of exogenous origin, necessary for the synthesis of nucleoproteins and maintenance of normal erythropoiesis.

Biotin is associated with at least four enzymes and participates in energy metabolism (including gluconeogenesis).

Pharmacokinetics

In patients receiving Cernevit, plasma concentrations of vitamins A, D, and E are restored and maintained at normal levels throughout the period of long-term parenteral nutrition.

The pharmacokinetic properties are determined by the properties of the vitamins included in the preparation.

• Vitamin A – normal serum level 80-300 IU/ml, protein-bound, excreted mainly by the kidneys and with bile;
• Vitamin D – activated in the liver and kidneys by hydroxylation, protein-bound, excreted mainly by the kidneys and with bile;
• Vitamin E – enters the blood with lipoproteins, converted to lactone in the liver, excreted predominantly by the kidneys;
• Vitamin B₁ (thiamine) – 90% concentrated in erythrocytes, in plasma predominantly bound to albumin, excreted mainly by the kidneys;
• Vitamin B₂ (riboflavin) – in plasma bound to proteins, plasma vitamin levels can vary greatly, excreted predominantly by the kidneys in unbound form or as metabolites;
• Vitamin B₃ (PP) – in plasma exists in the form of acid and amide, excreted by the kidneys in unbound form or as metabolites;
• Vitamin B₅ (pantothenic acid) – exists in unbound form or in the form of vitamin A in plasma and erythrocytes, excreted by the kidneys;
• Vitamin B₆ (pyridoxine) – metabolized in the liver and excreted by the kidneys;
• Vitamin B₁₂ (Cyanocobalamin) – normal serum level 200-900 pg/ml, protein-bound, accumulates in the liver, detected in milk, 50-90% excreted by the kidneys;
• Vitamin C (Ascorbic acid) – at normal concentrations (8-14 mg/l) completely reabsorbed in the kidneys, excess excreted by the kidneys;
• Folic acid – normal plasma concentrations 0.005-0.015 mcg/ml, distributed to all tissues, metabolized and accumulated in the liver, at high levels maximum renal reabsorption prevails, excreted by the kidneys;
• Biotin – in plasma exists in free form or protein-bound form, excreted by the kidneys predominantly unchanged.

Indications

• Addition to parenteral nutrition for the prevention of hypo- and avitaminosis for adults and children over 11 years of age.

ICD codes

Dosage Regimen

The drug is intended for intravenous administration only.

The recommended dose is 5 ml (1 vial)/day.

Cernevit can be used throughout the entire period of parenteral nutrition. The duration of use is in accordance with the doctor’s prescription.

Rules for preparation and administration of the solution

Using a syringe, inject 5 ml of water for injections or 5% dextrose (glucose) solution, or 0.9% sodium chloride solution into the vial. Gently mix until the lyophilisate is completely dissolved. The resulting solution has a yellow-orange color.

The resulting solution is slowly administered intravenously by bolus (for at least 10 minutes).

The drug solution can be added to two-component (glucose solution with electrolytes and amino acids) or three-component (glucose solution with electrolytes, amino acids, fat emulsion) parenteral nutrition solutions, provided compatibility is ensured.

Before use, check the integrity of the packaging.

Aseptic conditions must be observed.

Do not store the vial with unused drug residues or with a drug whose color after dissolution does not match the description.

Adverse Reactions

Allergic reactions: since the drug contains vitamin B₁, anaphylactic reactions rarely (> 1/10,000 – < 1/1000) develop in patients with delayed-type allergy.

The patient should inform the doctor about any occurring side effects.

Contraindications

• Children under 11 years of age;
• Hypersensitivity to the components of the drug, especially to vitamin B₁.

Relative contraindication simultaneous use of levodopa preparations.

Use in Pregnancy and Lactation

Since there are no clinical data on the use of Cernevit in pregnant women, the drug should not be prescribed during pregnancy.

The use of the drug during lactation is not recommended, as vitamins are excreted in breast milk.

Use in Hepatic Impairment

Due to the presence of glycocholic acid as an excipient, with repeated and prolonged administration of the drug in patients with jaundice or severe cholestasis (changes in laboratory liver function test indicators), liver function should be carefully monitored.

Pediatric Use

Contraindication: children under 11 years of age.

Special Precautions

Due to the presence of glycocholic acid as an excipient, with repeated and prolonged administration of the drug in patients with jaundice or severe cholestasis (changes in laboratory liver function test indicators), liver function should be carefully monitored.

The deficiency of one or more vitamins should be corrected by administering the missing vitamin preparation.

Cernevit does not contain vitamin K, which can be administered separately if necessary.

After dilution, the drug is stable at a temperature not exceeding 25°C (77°F) for 24 hours, but the drug is recommended to be used immediately after dilution or stored for no more than 24 hours at a temperature from 2°C (35.6°F) to 8°C (46.4°F).

Effect on ability to drive vehicles and machinery

Since Cernevit is intended for patients receiving parenteral nutrition and in severe and moderate condition, the ability to drive a car and work with machinery has not been assessed.

Overdose

Overdose is mainly caused by excessive doses of vitamin A.

Symptoms of acute vitamin A overdose (doses exceeding 150,000 IU) – gastrointestinal disorders, headache, increased intracranial pressure, optic disc edema, mental disorders, excitability, sometimes convulsions, delayed generalized epithelial desquamation; with chronic vitamin A overdose – increased intracranial pressure, cortical hyperostosis and premature closure of the epiphyseal plate, which is usually expressed by the occurrence of sensitive or painful subcutaneous edema on the fingers of the upper and lower extremities. On radiographic examination, diaphyseal periosteal thickenings are noticeable on the ulnar, fibular, clavicular, and costal bones.

Treatment: discontinue the drug, reduce calcium intake, increase diuresis and perform adequate body rehydration.

Drug Interactions

Due to the presence of pyridoxine (vitamin B₆) in the drug, concomitant use with levodopa preparations is contraindicated due to the acceleration of levodopa metabolism with the participation of a pyridoxine-dependent enzyme. To prevent this interaction, a dopa decarboxylase inhibitor, carbidopa, can be used.

Due to the presence of folic acid in the drug, caution should be exercised when used concomitantly with antiepileptic drugs containing phenobarbital, phenytoin, or primidone. Clinical monitoring and, if possible, monitoring of the plasma concentration of antiepileptic drugs is necessary, with adjustment of the antiepileptic drug dosage regimen during and after discontinuation of folic acid use.

Compatibility should be checked during preparation with other infusion solutions, especially if Cernevit is added to binary parenteral mixtures containing glucose, electrolytes and amino acid solutions or to mixtures containing glucose, electrolytes, amino acid solutions and lipids.

The patient should inform the doctor about any medications that were used previously.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 2 years.

Dispensing Status

The drug is dispensed by prescription.

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.