Instructions for use Licartin-N solution for injection 400 mg/ml ampoule 5 ml No. 5

Composition

active substance: levocarnitine;

1 ml of solution contains 200 mg or 400 mg of levocarnitine;

other components: diluted hydrochloric acid, water for injections.

Medicinal form

Solution for injections.

The main physical and chemical properties: transparent from colorless to yellowish liquid.

Pharmacotherapeutic group

Amino acids and their derivatives. Levocarnitine.

ATX code A16A A01.

Pharmacological properties

Pharmacodynamics.

Carnitine is a natural component of cells in which it plays a fundamental role in the processes of energy synthesis and transportation. It is actually the only indispensable factor for the process of penetration of long-chain fatty acids into mitochondria and their participation in β-oxidation. In humans, physiological needs for carnitine are replenished due to the consumption of food products containing carnitine and through endogenous synthesis in the liver. Only the L-isomer of carnitine is biologically active. Levocarnitine plays an important role in lipid metabolism, as well as in the metabolism of ketone bodies. Levocarnitine is necessary for the transport of long-chain fatty acids into mitochondria for further beta-oxidation. Releasing coenzyme A from complex thioesters, levocarnitine enhances the oxidation of carbohydrates in the Krebs cycle of tricarboxylic acids and stimulates the activity of the key enzyme of glycolysis - pyruvate dehydrogenase, and in skeletal muscles - the oxidation of branched chain amino acids. Thus, levocarnitine directly or indirectly participates in most energy processes, its presence is mandatory for the oxidation of fatty acids, amino acids, glucose, and ketone bodies.

Pharmacokinetics.

Absorbed levocarnitine is transported to different organs and systems through the blood. The presence of membrane-bound proteins in some tissues of the body, including red blood cells that bind carnitine, suggests that for its active assimilation in some tissues there are blood transport systems and the necessary cell systems.

The concentration of levocarnitine in blood serum and tissues depends on the activity of metabolic processes, the rate of biosynthesis of levocarnitine, the characteristics of nutrition, the transfer of levocarnitine to tissues and tissues, the rate of its metabolism and excretion. All these factors can affect the concentration of carnitine in tissues.

Suction

Levocarnitine is absorbed by the cells of the mucous membrane of the small intestine and enters the bloodstream relatively slowly; probably, the absorption is connected with an active transluminal mechanism. Absorption after ingestion is limited (< 10%) and variable.

Distribution

Absorbed levocarnitine is transported to different organs through the blood; they believe that the transport system of erythrocytes is involved in this process.

Conclusion

Levocarnitine is mainly excreted in the 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.

Indications

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

Secondary carnitine deficiency in patients undergoing hemodialysis.

Suspicion of secondary carnitine deficiency in patients undergoing hemodialysis in the following cases:

• strong and persistent muscle spasms and/or hypotensive episodes during dialysis;
• energy deficit, which significantly worsens the quality of life;
• muscle weakness and/or myopathy;
• cardiopathy;
• anemia caused by uremia, unresponsive to treatment with erythropoietin or requiring high doses of erythropoietin;
• loss of muscle mass.

Contraindications

Hypersensitivity to the active substance and/or other components of the medicinal product.

Interaction with other medicinal products and other types of interaction

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

In some cases, when taking levocarnitine with coumarin anticoagulants, an increase in the international normalized ratio (INR) is possible, so their simultaneous use requires caution. MEC or other coagulation tests should be checked weekly until they stabilize, and monthly thereafter in patients taking such anticoagulants together with levocarnitine.

Features of application

The safety and efficacy of oral levocarnitine in patients with renal failure have not been studied. Long-term oral administration of high doses of levocarnitine to patients with severe renal failure or end-stage renal failure undergoing hemodialysis may lead to the accumulation of potentially toxic metabolites in the blood, trimethylamine (TMA) and trimethylamine-M-oxide (TMAO), since they are excreted by the kidneys. This phenomenon is not observed after administration of levocarnitine.

In very rare cases, an increase in the international normalized ratio (INR) has been reported with the simultaneous use of levocarnitine with coumarin drugs (see the sections "Interaction with other medicinal products and other types of interactions" and "Side effects").

Seizures have been reported in patients with a history of seizure activity, but it is unclear whether levocarnitine increases the incidence and/or severity of seizures. In the event that levocarnitine is the suspected cause of the trial, the advisability of stopping treatment should be considered.

High doses and long-term use of levocarnitine can cause diarrhea.

Use during pregnancy or breastfeeding

Pregnancy

at the highest studied dose of 600 mg/kg of body weight in rabbits, a statistically insignificant increase in the frequency of post-implantation fetal death in the early stages of pregnancy was noted. The significance of these results for humans is unknown. There is no experience of using levocarnitine in pregnant women with primary systemic carnitine deficiency.

Taking into account the serious consequences of carnitine deficiency for a pregnant woman, the risk of interruption of drug treatment for the mother is considered greater than the theoretical risk for the fetus in case of continued treatment.

Breastfeeding period

Levocarnitine is a common component of human milk. The use of levocarnitine supplements in nursing mothers has not been studied. During breastfeeding, the drug should be used only if the expected benefit for the mother exceeds the potential risk for the child caused by excessive exposure to carnitine.

Fertility

Clinical studies have not revealed a negative effect on fertility.

The ability to influence the speed of reaction when driving a motor vehicle or other mechanisms

Unknown.

Method of application and dosage

The drug is administered slowly intravenously for 2–3 minutes.

Adults, children, babies and newborns

During therapy, it is advisable to control the level of carnitine and acylcarnitine both in plasma and in urine.

Use in congenital metabolic disorders

The required dose depends on the specifics of the congenital metabolic disorder and the severity of the disease.

In case of acute decompensation, the recommended dose may be up to 100 mg/kg/day in 3–4 administrations. If necessary, higher doses can be used, although side reactions, in particular diarrhea, may increase.

Secondary carnitine deficiency in patients undergoing hemodialysis

Before starting therapy with Lykartin-H, it is necessary to monitor the level of carnitine in the blood plasma.

Secondary carnitine deficiency is diagnosed when the ratio of acylcarnitine to free carnitine in blood plasma is greater than 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 bolus at the end of each dialysis session (allowing 3 sessions per week). The general reaction should be determined by monitoring the levels of acylcarnitine and free carnitine in blood plasma and assessing the patient's condition. Normalization of the carnitine content in muscle tissue and cardiomyocytes occurs 3 months after the normal concentration of carnitine in blood plasma is reached. If the administration of carnitine is stopped, its level will necessarily begin to decrease again. The need for a repeated saturating course of treatment is determined by quantitative determination of carnitine in blood plasma at regular intervals and by monitoring the patient's condition.

Hemodialysis is supportive therapy

After a saturating course of administration of levocarnitine, use a maintenance dose of 1 g of the drug per day orally. On the day of dialysis, the drug should be administered orally in a dose of 1 g immediately after the end of the next session.

Elderly patients

There is no need to change the dosage for such patients. In clinical studies, the safety profile in young patients and elderly patients was similar.

Children

The medicinal product can be used in pediatric practice, including h. for newborns and infants.

Overdose

There have been no reports of levocarnitine toxicity in overdose. To treat an overdose, supportive therapy should be carried out. Large doses of the drug can cause diarrhea. Levocarnitine is easily removed from blood plasma by dialysis. Treatment: take measures to remove the drug from the digestive tract when taken orally, conduct symptomatic and supportive therapy.

No cases of life-threatening overdose have been reported.

Side effects

The frequency of adverse reactions is classified as follows: very often (≥ 1/10), often (≥ 1/100, < 1/10), rarely (≥ 1/1000, < 1/100), rarely (≥ 1/10000, < 1/1000), very rarely (< 1/10000), frequency unknown (cannot be estimated based on available data).

From the side of the nervous system: infrequently - headache.

On the part of blood vessels: rarely — arterial hypotension, arterial hypertension.

From the gastrointestinal tract: often nausea, vomiting, diarrhea, abdominal pain.

From the side of the skin and subcutaneous tissue: rarely - a specific body odor, the frequency is unknown - itching, rash.

On the part of the skeletal-muscular system and connective tissue: rarely — muscle spasms; frequency is unknown - muscle tension.

General disorders and disorders at the injection site: rarely — abnormal sensations, pyrexia.

Research: infrequently - blood pressure increase; very rarely - an increase in the Ministry of Emergency Situations 2.

1 Cases of convulsions have been reported in patients with or without convulsive activity receiving levocarnitine orally or intravenously (see section "Particulars of use").

2 In very rare cases, an increase in the international normalized ratio (INR) has been reported with the simultaneous use of levocarnitine with coumarin drugs (see the sections "Interaction with other medicinal products and other types of interactions" and "Peculiarities of application").

3 High doses and long-term intake of levocarnitine can cause diarrhea. Dose reduction often reduces or eliminates gastrointestinal symptoms. When taking oral levocarnitine for a long time, it is necessary to control the specific odor of the body (decrease the dose weakens or eliminates the odor caused by the drug). It is necessary to carefully monitor the tolerability of the drug during the first week of administration and after increasing the dose.

Reports of suspected adverse reactions

Notification of adverse reactions after registration of the medicinal product is important. This allows monitoring the benefit/risk ratio when using this medicine. Medical and pharmaceutical workers, as well as patients or their legal representatives, should be notified of all cases of suspected adverse reactions and ineffectiveness of the medicinal product through the Automated Pharmacovigilance Information System at https://aisf.dec.gov.ua.

Expiration date

2 years.

Storage conditions

Store in the original packaging at a temperature not higher than 25 °C. Store in a place inaccessible to children.

Packaging

5 ml in an ampoule. 5 ampoules in a pack.

Leave category

According to the recipe.

Manufacturer

LLC "PHARMASEL".

The location of the manufacturer and its address of the place of implementation of the activity.

Ukraine, 07408, Kiev region, Brovarskoy district, village Kvytnevoe, st. Proreznaya, 3.