Carnivit

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT KARNIVIT® (CARNIVIT)

Composition:

Active substance: levocarnitine;

1 ml of solution contains levocarnitine 200 mg;

Excipient: water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear, colorless or slightly yellowish liquid.

Pharmacotherapeutic group. Amino acids and their derivatives. ATC code A16AA01.

Pharmacological properties.

Pharmacodynamics.

Levocarnitine is a natural substance involved in energy metabolism as well as in ketone body metabolism. Only the L-isomer of carnitine is biologically active.

Carnivit® is necessary for the transport of long-chain fatty acids into mitochondria for their subsequent beta-oxidation and energy production. Fatty acids are used as an energy substrate by all tissues except the brain. In skeletal muscles and myocardium, fatty acids are the primary substrate for energy generation.

Levocarnitine plays an important role in cardiac metabolism, as fatty acid oxidation depends on the availability of sufficient amounts of this substance. Experimental studies have shown that under certain conditions such as stress, acute ischemia, myocarditis, a reduction in levocarnitine levels in myocardial tissue may occur. Numerous animal studies have confirmed the beneficial effects of levocarnitine in various induced cardiac disorders: acute and chronic ischemia, cardiac decompensation, heart failure due to myocarditis, drug-induced cardiotoxicity (taxanes, adriamycin, etc.).

By releasing coenzyme A from complex thioesters, levocarnitine also enhances carbohydrate oxidation in the Krebs tricarboxylic acid cycle, stimulates the activity of the key glycolysis enzyme pyruvate dehydrogenase, and in skeletal muscles, promotes the oxidation of branched-chain amino acids. Thus, levocarnitine directly or indirectly participates in most energy-producing processes, and its presence is essential for the oxidation of fatty acids, amino acids, carbohydrates, and ketone bodies.

In humans, physiological requirements for carnitine are met through dietary intake of carnitine-containing foods (primarily meat) and endogenous synthesis in the liver from trimethyllysine. The highest concentrations of levocarnitine are found in muscle tissue, myocardium, and liver.

Primary systemic carnitine deficiency is characterized by low levocarnitine concentrations in blood plasma, erythrocytes, and/or tissues. Secondary carnitine deficiency may result from congenital disorders of carnitine metabolism or iatrogenic interventions such as hemodialysis.

Pharmacokinetics.

Absorption

Levocarnitine is absorbed by the cells of the mucous membrane of the small intestine and enters the bloodstream relatively slowly; absorption is likely associated with an active trans-luminal mechanism. Absorption after oral administration is limited (< 10%) and variable.

Distribution

Absorbed levocarnitine is transported via blood to various organs; it is believed that erythrocyte transport systems are involved in this process.

Elimination

Levocarnitine is primarily excreted in urine. The rate of excretion is directly proportional to the concentration of carnitine in the blood.

Metabolism

Levocarnitine is practically not metabolized in the body.

Clinical characteristics.

Indications.

Primary and secondary carnitine deficiency in adults and children, including newborns and infants.

Secondary carnitine deficiency in patients undergoing hemodialysis.

Suspected secondary carnitine deficiency in patients undergoing hemodialysis in the following cases:

• severe persistent muscle cramps and/or hypotensive episodes during dialysis;
• energy deficiency leading to significant negative impact on quality of life;
• muscle weakness and/or myopathy;
• cardiomyopathy;
• anemia unresponsive to erythropoietin treatment or requiring high doses of erythropoietin;
• loss of muscle mass.

Contraindications.

Hypersensitivity to the components of the drug.

Interaction with other medicinal products and other forms of interaction.

Concomitant use of glucocorticoids leads to accumulation of levocarnitine in body tissues (except liver). Other anabolic agents enhance the effect of the drug.

In patients who received levocarnitine simultaneously with coumarin-derived anticoagulants (see section "Special instructions", "Adverse reactions"), very rare cases of increased international normalized ratio (INR) were observed. INR or another appropriate coagulation test should be performed weekly until values stabilize, and monthly thereafter in patients taking such anticoagulants together with levocarnitine.

Special precautions for use.

Levocarnitine improves glucose utilization; therefore, the use of Carnitiv® in patients with diabetes mellitus who are receiving antidiabetic medications may lead to hypoglycemia. In such cases, plasma glucose levels should be monitored regularly to allow timely adjustment of therapy.

Very rare cases of increased international normalized ratio (INR) have been observed in patients concurrently receiving levocarnitine and coumarin-derived anticoagulants (see sections "Interaction with other medicinal products and other forms of interaction" and "Undesirable effects").

Use during pregnancy or breastfeeding.

Teratogenic effects were not observed in preclinical studies of the drug. In animal studies using the highest investigated dose of 600 mg/kg body weight, a statistically non-significant increase in the frequency of post-implantation fetal loss during early pregnancy was noted. The relevance of these findings to humans is unknown. Data on the use of levocarnitine injection solution in pregnant women and during breastfeeding are lacking.

Considering the serious consequences of carnitine deficiency in pregnant women, the risk of discontinuing Carnitiv® treatment for the mother is considered greater than the theoretical risk to the fetus if treatment is continued.

Levocarnitine is a normal component of human breast milk. However, the use of levocarnitine in breastfeeding mothers has not been studied.

Ability to influence reaction rate when driving or operating machinery.

Unknown.

Administration and Dosage

The drug should be administered intravenously slowly over 2–3 minutes.

Use in congenital metabolic disorders

During therapy, it is advisable to monitor levels of carnitine and acyl-carnitine both in blood plasma and urine.

The required dose depends on the specific type of congenital metabolic disorder and the severity of disease manifestations.

In cases of acute decompensation, the recommended dose may be up to 100 mg/kg per day administered in 3–4 doses. Higher doses may be used if necessary, although this may intensify adverse effects, particularly diarrhea.

Secondary carnitine deficiency in patients undergoing hemodialysis

Prior to initiating therapy with Carnitivit®, it is advisable to measure plasma carnitine levels.

Secondary carnitine deficiency is diagnosed when the ratio of acyl-carnitine to free carnitine in plasma exceeds 0.4 and/or when the concentration of free carnitine is less than 20 µmol/L.

A dose of 20 mg/kg should be administered intravenously as a slow bolus at the end of each dialysis session. The overall response should be assessed by monitoring plasma levels of acyl-carnitine and free carnitine, as well as by evaluating the patient's clinical condition. Normalization of carnitine content in muscle tissue and cardiomyocytes occurs approximately 3 months after achieving normal plasma carnitine concentration. If carnitine administration is discontinued, its levels will inevitably begin to decrease again. The need for repeated repletion therapy should be determined by periodic quantitative assessment of plasma carnitine levels and monitoring of the patient's clinical status.

Hemodialysis – maintenance therapy

After completing the initial intravenous loading phase, maintenance therapy should be administered orally at a dose of 1 g of levocarnitine per day. On dialysis days, Carnitivit® should be administered intravenously at a dose of 1 g immediately after completion of the dialysis session.

Children

The drug can be administered to children from the first day of life, including preterm infants.

Overdose

There have been no reports of toxicity associated with levocarnitine overdose. High doses of the drug may cause diarrhea. Levocarnitine is readily removed from plasma by dialysis.

Treatment: take measures to remove the drug from the gastrointestinal tract if administered orally. Provide symptomatic and supportive therapy. There have been no reports of life-threatening overdose cases.

Side effects.

The adverse reactions listed below are classified by organ systems and frequency of occurrence. By frequency of occurrence, they are divided into the following categories: very common (≥ 1/10), common (≥ 1/100 and < 1/10), uncommon (≥ 1/1,000 and < 1/100), rare (≥ 1/10,000 and < 1/1,000), very rare (< 1/10,000).

All adverse reactions listed below occurred very rarely.

Gastrointestinal disorders

Various mild gastrointestinal disturbances have been observed during prolonged oral administration of levocarnitine, including transient nausea and vomiting, abdominal pain, and diarrhea. A characteristic body odor has also been reported in patients. Reducing the dose often reduces or eliminates gastrointestinal symptoms and the characteristic body odor.

Blood and lymphatic system disorders

In very rare cases, an increased international normalized ratio (INR) has been observed in patients (see section "Dosage and administration", "Interaction with other medicinal products and other forms of interaction").

Tolerance should be carefully monitored during the first week of treatment and after any dose increase. Intravenous administration of Carnivit® is generally well tolerated.

Shelf life. 2 years.

Storage conditions.

Store at a temperature not exceeding 30 °C in the original packaging.

Keep out of reach of children.

Packaging.

5 ml in a vial; 5 vials in a blister pack; 1 blister pack in a carton.

Prescription category. Prescription only.

Manufacturer. LLC "Yuria-Pharm".

Manufacturer's address and location of business activity.

108, Kozbirska Street, Cherkasy, Cherkasy region, 18030, Ukraine. Tel. (044) 281-01-01.