CARTAN

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT KARTAN (CARTAN)

Composition:

Active substance: levocarnitine;

1 ml of solution contains 100 mg of levocarnitine;

Excipients: sorbitol solution 70%, methylparaben (E 218), sodium saccharin, sodium citrate, orange flavor, hydrochloric acid, water for injections.

Pharmaceutical form. Oral solution.

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

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

Pharmacological Properties

Pharmacodynamics. Levocarnitine is present as a natural component in tissues of animals, microorganisms, and plants. In humans, physiological requirements for carnitine are met through the consumption of food containing carnitine (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 the metabolism of ketone bodies. Levocarnitine is necessary for the transport of long-chain fatty acids into mitochondria for subsequent beta-oxidation. By releasing coenzyme A from complex thioethers, 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, carnitine 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 an important role in cardiac metabolism, since 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, etc., a decrease 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.).

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 the blood to various organs; it is believed that the erythrocyte transport system is involved in this process.

Elimination

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

Metabolism

Levocarnitine is practically not metabolized in the body.

Clinical characteristics.

Indications.

Treatment of primary and secondary carnitine deficiency.

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 deficit leading to a 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 active substance and other components of the medicinal product.

Interaction with other medicinal products and other types of interactions.

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

If any other medicinal products are used concomitantly with the medicinal product Cartan, this must be reported to the physician.

Interactions between levocarnitine and coumarin agents cannot be excluded. In very rare cases, an increased international normalized ratio (INR) has been reported with concomitant use of levocarnitine and coumarin agents (see sections "Special precautions for use", "Adverse reactions"). When these agents are used concomitantly, INR should be monitored or other coagulation tests performed weekly until stabilized, and monthly thereafter (see section "Special precautions for use").

Concomitant use of levocarnitine with agents that induce hypocarnitinemia by enhancing renal excretion of carnitine (e.g., valproic acid, pivonil-containing prodrugs, cephalosporins, cisplatin, carboplatin, ifosfamide) may reduce its levels.

Special precautions for use

Levocarnitine improves glucose utilization; therefore, administration of Cartan to diabetic patients receiving antidiabetic therapy may lead to hypoglycemia. In such cases, plasma glucose levels should be monitored regularly to allow timely adjustment of therapy.

Long-term oral administration of high doses of levocarnitine is not recommended in patients with severe renal impairment or end-stage renal disease (chronic kidney disease), as it may lead to accumulation in blood of potentially toxic metabolites—trimethylamine (TMA) and trimethylamine-N-oxide (TMAO)—due to insufficient renal excretion. This accumulation results in increased TMA levels in urine.

Prolonged use without potassium supplementation may cause hypoglycemia; therefore, electrolyte balance should be monitored during treatment with the drug.

The recommended doses of the medicinal product should not be exceeded. If adverse effects occur, the drug should be discontinued.

If a patient has known intolerance to certain sugars, medical advice should be sought before taking this medicinal product, as it contains sorbitol solution, sodium saccharin, and sodium citrate.

Methylparaben (E 218) may cause hypersensitivity reactions, including delayed-type reactions, and in rare cases, bronchospasm.

This medicinal product contains sodium compounds in the form of sodium saccharin and sodium citrate.

Caution is advised in patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding

No teratogenic effects were observed during studies of the drug. When the highest tested dose of 600 mg/kg body weight was administered to animals, a statistically non-significant increase in the frequency of post-implantation fetal loss in early pregnancy was observed. The relevance of these findings to humans is unknown.

Considering the serious consequences of carnitine deficiency in pregnant women, the risk of discontinuing Cartan therapy 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.

Ability to affect reaction speed when driving or operating machinery

Unknown.

Administration and Dosage.

The dosage and duration of treatment are determined individually by a physician, depending on age, body weight, and the nosological form of the disease. Take orally, 30 minutes before meals. Use the provided dosing syringe or measuring cup for accurate dosing. It is recommended to dilute the medication in a glass of water before administration. During therapy, monitoring of free carnitine and acyl-carnitine levels in blood plasma and urine is advisable.

Primary and secondary carnitine deficiency.

The required dosage depends on the specific congenital metabolic disorder and the severity of the condition. Generally, the recommended oral dose ranges from 100 to 200 mg/kg/day, divided into 2–4 doses. In less severe cases, a lower dose (50–100 mg/kg/day) may be sufficient. If clinical and biochemical parameters do not improve, the dose may be increased temporarily. In acute metabolic decompensation, higher doses (up to 400 mg/kg/day) or intravenous administration of levocarnitine at a daily dose of 100 mg/kg may be required.

Secondary carnitine deficiency in patients undergoing hemodialysis.

If significant clinical improvement is achieved after the initial course of intravenous administration, maintenance therapy can be continued orally at a dose of 1 g per day. On dialysis days, the oral dose should be taken after the dialysis procedure.

Children.

The medicinal product can be administered to children from the first day of life, including premature infants.
In children, treatment is initiated at a dose of 50 mg/kg/day. The usual doses for children range from 50–100 mg/kg/day (see table).

The maximum daily dose for children is 3 g (30 ml).

It is recommended to dissolve the medication in a glass of water before administration.

Overdose.

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

Treatment: gastric lavage, symptomatic and supportive therapy. There have been no reports of life-threatening overdose cases.

Adverse reactions.

Various mild gastrointestinal disturbances have been observed during long-term oral administration of levocarnitine, including transient nausea and vomiting, abdominal pain, and diarrhea. Reducing the dose often diminishes or eliminates gastrointestinal symptoms. Careful monitoring of tolerability is necessary during the first week of treatment and after any dose increase.

Reporting of adverse reactions following drug registration is of great importance. It enables continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua

Shelf life. 4 years.

Storage conditions. Store in the original packaging in a place protected from light and inaccessible to children, at a temperature not exceeding 25 °C.

Packaging. 10 ml in an ampoule. 10 ampoules per cardboard box.

Availability. Over-the-counter (without prescription).

Manufacturer. DEMO SA Pharmaceutical Industry / DEMO SA Pharmaceutical Industry.

Manufacturer's address and location of operations.

21st km National Road Athens – Lamia, Krioneri Attiki, 145 68, Greece / 21st km National Road Athens - Lamia, Krioneri Attikі, 14568, Greece