Cocarnit^® (Lyophilisate) Instructions for Use

Marketing Authorization Holder

World Medicine İlaç San. ve Tic. A.Ş. (Turkey)

Manufactured By

Mefar İlaç Sanayii A.Ş. (Turkey)

Contact Information

World Medicine İlaç San. ve Tic. A.Ş. (Trokas Pharma LLC) (Turkey)

ATC Code

A11EX (B vitamins, in combination with other drugs)

Dosage Form

Cocarnit®

Lyophilisate for preparation of solution for intramuscular administration: fl. 187.125 mg 3 pcs. in set with solvent

Dosage Form, Packaging, and Composition

Lyophilisate for preparation of solution for intramuscular administration in the form of a pink lyophilized mass; reconstituted solution – clear, pink in color.

Excipients: glycine – 105.875 mg, methylparahydroxybenzoate – 0.6 mg, propylparahydroxybenzoate – 0.15 mg.

1 ampoule of solvent contains: active substance lidocaine hydrochloride – 10 mg;
excipient water for injections – up to 2 ml.

187.125 mg – dark glass vials with a volume of 4 ml, with a bromobutyl rubber stopper, crimped with a combined aluminum cap of the “flip off” type (3) in a set with solvent (amp. 2 ml 3 pcs.) – contour cell packaging (1) – cardboard packs.

Clinical-Pharmacological Group

A drug that improves the metabolism and regeneration of peripheral nervous system nerve fibers

Pharmacotherapeutic Group

Vitamins and metabolic agents

Pharmacological Action

The drug is a rationally selected complex of metabolic substances and vitamins.

Trifosadenine is an adenosine derivative, stimulates metabolic processes. It has a vasodilating effect, including on coronary and cerebral arteries. Improves metabolism and energy supply to tissues. It has hypotensive and antiarrhythmic effects. Under the influence of ATP, blood pressure decreases, smooth muscles relax, and nerve impulse conduction improves.

Cocarboxylase is a coenzyme formed in the body from externally supplied thiamine (vitamin B₁). It is part of the carboxylase enzyme that catalyzes the carboxylation and decarboxylation of α-keto acids. Indirectly promotes the synthesis of nucleic acids, proteins and lipids. Reduces the concentration of lactic and pyruvic acids in the body, promotes glucose absorption. Improves the trophism of nervous tissue.

Cyanocobalamin (vitamin B₁₂) is converted in the body into methylcobalamin and 5-deoxyadenosylcobalamin. Methylcobalamin is involved in the conversion of homocysteine to methionine and S-adenosylmethionine – key reactions in the metabolism of pyrimidine and purine bases (and consequently, DNA and RNA). In case of vitamin deficiency, it can be replaced by methyltetrahydrofolic acid in this reaction, which disrupts folate-dependent metabolic reactions.

5-deoxyadenosylcobalamin serves as a co-factor in the isomerization of L-methylmalonyl-CoA to succinyl-CoA – an important reaction in the metabolism of carbohydrates and lipids. Deficiency of vitamin B₁₂ leads to impaired proliferation of rapidly dividing cells of hematopoietic tissue and epithelium, as well as disruption of the formation of the myelin sheath of neurons.

Nicotinamide is one of the forms of vitamin PP, participates in redox processes in the cell, improves carbohydrate and nitrogen metabolism, and regulates tissue respiration.

Pharmacokinetics

Trifosadenine

After parenteral administration, it penetrates into the cells of organs, where it is broken down into adenosine and inorganic phosphate with the release of energy. Subsequently, the breakdown products are included in the resynthesis of ATP.

Cocarboxylase

Rapidly absorbed after intramuscular administration. Penetrates into most body tissues. Undergoes metabolic decomposition. Metabolites are excreted primarily by the kidneys.

Cyanocobalamin

In the blood, Cyanocobalamin binds to transcobalamins I and II, which transport it to the tissues. It is deposited mainly in the liver. Plasma protein binding is 0.9%. Rapidly and completely absorbed after intramuscular and subcutaneous administration. C_max after intramuscular administration is reached within 1 hour. It is excreted from the liver with bile into the intestine and reabsorbed into the blood. T_1/2 is 500 days. Excreted with normal renal function – 7-10% by the kidneys, about 50% through the intestines. With reduced renal function – 0-7% by the kidneys, 70-100% through the intestines. Penetrates the placental barrier, into breast milk.

Nicotinamide

Rapidly distributed to all tissues. Penetrates the placental barrier and into breast milk. Metabolized in the liver to form nicotinamide-N-methylnicotinamide. Excreted by the kidneys. T_1/2 from plasma is about 1.3 hours, steady-state V_d is about 60 L, total clearance is about 0.6 L/min.

Indications

• Symptomatic treatment of diabetic polyneuropathy.

ICD codes

Dosage Regimen

The drug is administered deep intramuscularly (into the gluteal muscle).

In cases of severe pain syndrome, it is advisable to start treatment with intramuscular administration of 2 ml (1 vial)/day until acute symptoms are relieved. Duration of use is 9 days.

After symptom improvement or in cases of moderately severe polyneuropathy symptoms, 2 ml (1 vial) is prescribed 2-3 times a week for 2-3 weeks. The recommended course of treatment is 3-9 injections depending on the severity of the disease.

The duration of treatment and the conduct of repeated courses is determined by the doctor depending on the nature and severity of the disease.

Data on the efficacy and safety of Cocarnit^® in children are lacking.

Adverse Reactions

The frequency of adverse reactions is given in accordance with the WHO classification: very common (more than 1/10); common (less than 1/10, but more than 1/100); uncommon (less than 1/100, but more than 1/1000); rare (less than 1/1000, but more than 1/10,000); very rare (less than 1/10,000), including isolated cases; frequency unknown.

Immune system disorders: rare – allergic reactions (skin rash, difficulty breathing, anaphylactic shock, angioedema).

Nervous system disorders: very rare – dizziness, headache, agitation, confusion.

Cardiac disorders: very rare – tachycardia; in isolated cases bradycardia, arrhythmia; frequency unknown – pain in the heart area, redness of the skin of the face and upper half of the body with a tingling and burning sensation, “hot flashes”.

Gastrointestinal disorders: very rare – vomiting, diarrhea.

Skin and subcutaneous tissue disorders: very rare – increased sweating, acne, itching, urticaria.

Musculoskeletal and connective tissue disorders: very rare – convulsions.

General disorders and administration site conditions: very rare – irritation, pain and burning at the injection site, weakness may occur.

If any of the indicated adverse reactions worsen or any other adverse reactions not listed in the instructions appear, the patient must inform the doctor.

In case of severe adverse reactions, the drug is discontinued.

Contraindications

• Hypersensitivity to any component of the drug or solvent;
• Cardiovascular diseases (acute heart failure, acute myocardial infarction, uncontrolled arterial hypertension, arterial hypotension, severe forms of bradyarrhythmia, II-III degree AV block, chronic heart failure (III-IV functional class according to NYHA), cardiogenic shock and other types of shock, QT prolongation syndrome, thromboembolism, hemorrhagic stroke);
• Inflammatory lung diseases, COPD, bronchial asthma;
• Pregnancy;
• Breastfeeding period;
• Age under 18 years;
• Hypercoagulation (including in acute thrombosis), erythremia, erythrocytosis;
• Gastric or duodenal ulcer in the acute phase;
• Gout;
• Hepatitis, liver cirrhosis.

Use with caution in angina pectoris.

Use in Pregnancy and Lactation

It is not recommended to use Cocarnit^® during pregnancy.

It is recommended to discontinue breastfeeding during treatment with the drug.

Use in Hepatic Impairment

Contraindicated in hepatitis, liver cirrhosis.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Special Precautions

If the symptoms of the disease worsen or there is no effect after 9 days, it is necessary to adjust the course of treatment.

When using Cocarnit^®, proper selection of the dose of the hypoglycemic drug and adequate control of the course of diabetes mellitus is necessary.

The color of the prepared solution should be pink. Do not use the drug if the color of the solution has changed.

The solution must be used immediately after preparation.

Use in pediatrics

Data on the efficacy and safety of Cocarnit^® in children are lacking.

Effect on ability to drive vehicles and machinery

If side effects from the central nervous system (dizziness, confusion) occur, it is recommended to refrain from driving vehicles and other mechanisms.

Overdose

The components of Cocarnit^® have a wide therapeutic range.

Symptoms

Trifosadenine. Exceeding the maximum daily dose (about 600 mg for an adult) can lead to the development of the following symptoms: dizziness, decreased blood pressure, short-term loss of consciousness, arrhythmia, II and III degree AV block, asystole, bronchospasm, ventricular disturbances, sinus bradycardia and tachycardia.

Cocarboxylase. The following symptoms have been reported after administration of a dose exceeding the recommended dose by more than 100 times: headache, muscle spasm, muscle weakness, paralysis, arrhythmia.

Cyanocobalamin. After parenteral administration in a high dose, eczematous skin disorders and a benign form of acne were observed. When used in high doses, hypercoagulation and purine metabolism disorders may develop.

Nicotinamide. When used in large doses, hyperpigmentation, jaundice, amblyopia, weakness, exacerbation of gastric and duodenal ulcers were observed. With long-term use, steatohepatosis developed, the concentration of uric acid in the blood increased, and glucose tolerance was impaired.

Treatment

Administration of the drug is immediately stopped, symptomatic therapy is prescribed, including desensitizing therapy.

Drug Interactions

In patients using hypoglycemic agents of the biguanide group (metformin), due to impaired absorption of cyanocobalamin from the gastrointestinal tract, a decrease in the concentration of cyanocobalamin in the blood may be observed. Drug interactions with other hypoglycemic agents have not been described.

Cyanocobalamin is incompatible with ascorbic acid, heavy metal salts, thiamine, thiamine bromide, pyridoxine, riboflavin, folic acid.

Cyanocobalamin should not be used simultaneously with drugs that increase blood clotting.

In addition, simultaneous use of cyanocobalamin with chloramphenicol should be avoided.

Aminoglycosides, salicylates, antiepileptic drugs, colchicine, and potassium preparations reduce the absorption of cyanocobalamin.

When drugs containing trifosadenine are used concomitantly with dipyridamole, the effect of dipyridamole is enhanced, in particular the vasodilating effect. Dipyridamole enhances the effect of trifosadenine.

Some antagonism is manifested when the drug is used concomitantly with purine derivatives (caffeine, theophylline).

Should not be administered simultaneously with cardiac glycosides in large doses, as the risk of adverse reactions from the cardiovascular system increases.

When used concomitantly with xantinol nicotinate, the effect of the drug is reduced.

Nicotinamide potentiates the effect of sedatives, tranquilizers, as well as antihypertensive agents.

Storage Conditions

The drug should be stored in a light-protected place, out of the reach of children, at a temperature from 15°C (59°F) to 25°C (77°F).

Shelf Life

The shelf life of the drug is 3 years, the solvent is 4 years. Do not use after the expiration date stated on the packaging.

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.