Neoton (Powder) Instructions for Use

Marketing Authorization Holder

Alfasigma S.p.A. (Italy)

Contact Information

ALFASIGMA RUS LLC (Russia)

ATC Code

C01EB06 (Phosphocreatine)

Active Substance

Phosphocreatine (BP British Pharmacopoeia)

Dosage Form

Neoton

Powder for infusion solution preparation 1 g: vial 4 pcs.

Dosage Form, Packaging, and Composition

Powder for the preparation of solution for infusion white, crystalline.

1 g – vials (4) – carton packs.

Clinical-Pharmacological Group

Metabolic drug

Pharmacotherapeutic Group

Metabolic agent

Pharmacological Action

Phosphocreatine plays an important role in the energy mechanism of muscle contraction. It serves as an energy reserve in myocardial and skeletal muscle cells and is used for the resynthesis of ATP, the hydrolysis of which releases energy to power the actomyosin contraction process.

Insufficient energy supply to cardiomyocytes, associated with a slowdown in oxidative processes, is a key mechanism in the development and progression of myocardial damage. A deficiency of phosphocreatine leads to a decrease in myocardial contractile force and its ability for functional recovery. In myocardial damage, there is a close correlation between the amount of energy-rich phosphorylated compounds in the cells, cell viability, and their ability to restore contractile function. Preclinical and clinical studies have demonstrated the cardioprotective effect of phosphocreatine, which is manifested in a dose-dependent positive effect against toxic myocardial effects of isoprenaline, thyroxine, emetine, and p-nitrophenol; in a positive inotropic action during glucose, calcium ion deficiency, or potassium ion overdose; and in reducing the negative inotropic effect caused by anoxia.

Furthermore, the addition of phosphocreatine to cardioplegic solutions at a concentration of 10 mmol/l enhances the cardioprotective effect.

• The risk of myocardial ischemia during cardiopulmonary bypass surgery is reduced;
• The risk of reperfusion arrhythmia is reduced when infused prior to the development of experimental regional ischemia resulting from ligation of the anterior descending branch of the left coronary artery for 15 minutes;
• It reduces the degradation of ATP and phosphocreatine in myocardial cells, preserves the structure of mitochondria and sarcolemma, improves the process of functional myocardial recovery after cardiac arrest induced by high-dose potassium administration, and reduces the incidence of reperfusion arrhythmia.

Phosphocreatine exerts a cardioprotective effect in experimental myocardial infarction and arrhythmia induced by coronary artery occlusion: it preserves the cellular pool of adenine nucleotides by inhibiting the enzymes responsible for their catabolism, suppresses the degradation of phospholipids, possibly improves microcirculation in the ischemic zone, which is attributed to the suppression of ADP-mediated platelet aggregation, stabilizes hemodynamic parameters, prevents a sharp decrease in heart functional indicators, exerts an antiarrhythmic effect, reduces the frequency and duration of ventricular fibrillation, and limits the area of myocardial infarction.

Pharmacokinetics

Distribution

After a single intravenous infusion, the C_max of phosphocreatine in blood plasma is reached within 1-3 minutes. The greatest amount of phosphocreatine accumulates in skeletal muscles, myocardium, and the brain. Accumulation of phosphocreatine in liver and lung tissues is insignificant.

Elimination

The elimination of phosphocreatine is biphasic (rapid and slow phases), which is due to its accumulation in tissues followed by elimination from the body in the second phase. The T_1/2 in the rapid phase is 30-35 minutes; the T_1/2 in the slow phase is several hours. It is excreted by the kidneys.

Indications

As part of combination therapy

• Acute myocardial infarction;
• Chronic heart failure;
• Intraoperative myocardial ischemia;
• Intraoperative lower limb ischemia.

In sports medicine – for the prevention of acute and chronic physical overstrain syndrome and to improve the adaptation of athletes to extreme physical loads.

ICD codes

Dosage Regimen

For intravenous use only (drip or as a rapid infusion).

Acute myocardial infarction

Day 1: 2-4 g of the drug, diluted in 50 ml of water for injections, as a rapid intravenous infusion followed by an intravenous infusion of 8-16 g in 200 ml of a 5% dextrose (glucose) solution over 2 hours.

Day 2: 2-4 g in 50 ml of water for injections intravenously by drip (infusion duration not less than 30 minutes) 2 times/day.

Day 3: 2 g in 50 ml of water for injections intravenously by drip (infusion duration not less than 30 minutes) 2 times/day. If necessary, a course of infusions of 2 g of the drug 2 times/day can be carried out for up to 6 days.

Chronic heart failure

Depending on the patient’s condition, treatment can be started with loading doses of 5-10 g of the drug in 200 ml of a 5% dextrose (glucose) solution intravenously by drip at a rate of 4-5 g/hour for 3-5 days, and then switch to intravenous drip administration (infusion duration not less than 30 minutes) of 1-2 g of the drug, diluted in 50 ml of water for injections, 2 times/day, for 2-6 weeks, or start immediately with intravenous drip administration of Neoton in maintenance doses (1-2 g in 50 ml of water for injections 2 times/day for 2-6 weeks).

Intraoperative myocardial ischemia

A course of intravenous drip infusions lasting not less than 30 minutes of 2 g of the drug in 50 ml of water for injections 2 times/day for 3-5 days preceding the surgical intervention and for 1-2 days after it is recommended. During the surgical intervention, Neoton is added to the standard cardioplegic solution at a concentration of 10 mmol/l or 2.5 g/l immediately before administration.

Intraoperative lower limb ischemia

2-4 g of Neoton in 50 ml of water for injections as a rapid intravenous infusion before the surgical intervention, followed by intravenous drip administration of 8-10 g of the drug in 200 ml of a 5% dextrose (glucose) solution at a rate of 4-5 g/hour during the surgical intervention and during the reperfusion period.

In sports medicine for the prevention of acute and chronic physical overstrain syndrome and to improve the adaptation of athletes to extreme physical loads, Neoton should be used at a dose of 1 g/day in 50 ml of water for injections intravenously by drip (infusion duration not less than 30 minutes) for 3-4 weeks.

Adverse Reactions

Allergic reactions: manifestations of hypersensitivity to the drug.

Cardiovascular system: decrease in blood pressure (with rapid intravenous administration).

Contraindications

• Hypersensitivity to the components of the drug;
• Chronic renal failure (for use in doses of 5-10 g/day);
• Age under 18 years (efficacy and safety have not been established).

Use in Pregnancy and Lactation

There are no clinical data on the use of Neoton during pregnancy. However, animal studies have not shown a toxic effect of the drug on rat fertility and embryofetal development in rabbits. Neoton can be used during pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus.

If it is necessary to use the drug during lactation, breastfeeding should be discontinued.

Use in Renal Impairment

Contraindicated in chronic renal failure (for use in doses of 5-10 g/day).

Pediatric Use

Contraindicated for use under 18 years of age.

Special Precautions

The drug should be administered as soon as possible after the onset of signs of ischemia, which ensures a more favorable disease prognosis.

The use of Neoton in high doses (5-10 g/day) is accompanied by increased phosphate uptake in the kidneys, which affects calcium metabolism, the secretion of hormones regulating homeostasis, kidney function, and purine metabolism; therefore, long-term use of Neoton in high doses is not recommended.

Overdose

There have been no reports of Neoton overdose to date.

Drug Interactions

When used as part of combination therapy, Neoton helps to increase the effectiveness of antiarrhythmic, antianginal drugs and drugs with positive inotropic action.

Neoton remains stable in water for injections, 5% dextrose (glucose) solution, and in cardioplegic solutions.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 30°C (86°F).

Shelf Life

Shelf life – 3 years. Do not use after the expiration date printed 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.