STEATEL

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT STEATEL (STEATEL)

Composition:

Active substance: levocarnitine;

1 ml of solution contains 200 mg of levocarnitine;

Excipients: diluted hydrochloric acid, water for injections.

Pharmaceutical form. Injection solution.

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

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

Pharmacological Properties

Pharmacodynamics

Levocarnitine is present as a natural component in animal tissues, microorganisms, and plants. In humans, physiological requirements for carnitine are met through dietary intake of carnitine-containing foods (primarily meat products) and by endogenous synthesis in the liver from trimethyllysine. Only the L-isomer is biologically active. Levocarnitine plays an important role in lipid metabolism as well as in ketone body metabolism. Levocarnitine is essential for the transport of long-chain fatty acids into mitochondria for subsequent beta-oxidation. By releasing coenzyme A from complex thioesters, levocarnitine also enhances carbohydrate oxidation in the Krebs cycle, stimulates the activity of the key glycolytic enzyme pyruvate dehydrogenase, and in skeletal muscles, promotes oxidation of branched-chain amino acids. Thus, levocarnitine directly or indirectly participates in most energy-producing processes; its presence is essential for the oxidation of fatty acids, amino acids, carbohydrates, and ketone bodies.

The highest concentrations of levocarnitine are found in muscle tissue, myocardium, and liver. Levocarnitine plays a crucial 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, and myocarditis, myocardial tissue levels of levocarnitine may decrease. 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, and drug-induced cardiotoxicity (taxanes, adriamycin, etc.).

Pharmacokinetics

Absorption

Levocarnitine is absorbed by the epithelial cells of the small intestine mucosa 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.

Excretion

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

Metabolism

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

Contraindications.

Hypersensitivity to the components of the drug.

Special safety precautions.

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

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 drug's effect.

Special precautions for use.

Use during pregnancy or breastfeeding.

Teratogenic effects of the drug have not been observed in preclinical studies.

Considering the serious consequences of carnitine deficiency for a pregnant woman, the risk of discontinuing treatment with the drug for the mother is considered to be greater than the theoretical risk to the fetus (if treatment continues).

Levocarnitine is a normal component of breast milk.

Ability to influence reaction rate when driving or operating machinery.

Unknown.

Administration and Dosage

The drug is 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 given in 3–4 doses. Higher doses may be used if necessary, although this may increase the risk of adverse effects, particularly diarrhea.

Secondary carnitine deficiency in patients undergoing hemodialysis

Prior to initiating therapy, monitoring plasma carnitine levels is recommended.

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

A dose of 2 g should be administered intravenously as a 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 concentrations. If carnitine administration is discontinued, its levels will inevitably begin to decrease again. The need for repeated loading courses of treatment is determined by periodic quantitative assessment of plasma carnitine levels and monitoring of the patient's condition.

Hemodialysis – maintenance therapy

After completion of the intravenous levocarnitine loading course, maintenance therapy consists of 1 g of the drug per day administered orally. On dialysis days, the drug is 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 premature infants.

Overdose

There have been no reports of levocarnitine toxicity in cases of 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 in case of oral ingestion; administer symptomatic and supportive therapy. No life-threatening cases of overdose have been reported.

Side effects.

Various mild gastrointestinal disturbances have been observed during prolonged oral administration of levocarnitine, including nausea and vomiting, which quickly resolve, abdominal pain, and diarrhea. Reducing the dose often diminishes or eliminates gastrointestinal symptoms. Careful monitoring of drug tolerance is necessary during the first week of treatment and after any dose increase. Intravenous administration of the drug is generally well tolerated.

Shelf life. 3 years.

Storage conditions.

Store at a temperature not exceeding 25 °C, in a light-protected place. Keep out of reach of children.

Incompatibility.

Do not mix with other medicinal products.

Packaging.

5 ml in a vial, 5 vials in a cardboard pack.

Prescription status.

Prescription only.

Manufacturer.

HELP S.A.

HELP S.A.

Manufacturer's address and location of business activity.

Pedini Ioanninon, Ioannina, 45500, Greece.