Angiosil retard 35 mg n60 extended-release film-coated tablets
Latin name
Angiozil retard
Release form
Modified-release, film-coated tablets.
Package
60 pcs.
pharmachologic effect
Angiosil retard is a drug that improves the metabolism of the myocardium and neurosensory organs (inner ear, retina) under ischemic conditions. Has antianginal, antihypoxic effects. Angiosyl retard directly affects cardiomyocytes and neurons of the brain, optimizing their metabolism and function. The cytoprotective effect is due to an increase in energy potential, activation of oxidative decarboxylation and rationalization of oxygen consumption (increased aerobic glycolysis and blockade of fatty acid oxidation). Supports myocardial contractility, prevents a decrease in the intracellular content of ATP and phosphocreatinine.
Indications
— IHD: prevention of angina attacks (as part of complex therapy);
- chorioretinal vascular disorders;
- dizziness of vascular origin;
- cochleo-vestibular disorders of ischemic nature (tinnitus, hearing impairment).
Contraindications
- renal failure (KK - severe liver dysfunction;
- pregnancy;
- lactation period (breastfeeding);
- children and adolescents under 18 years of age (the effectiveness and safety of the drug have not been established);
- hypersensitivity to the components of the drug
special instructions
Angiosil retard is not intended for the relief of angina attacks. If an attack of angina develops, treatment should be adjusted. The use of Angiosil retard does not affect the ability to engage in potentially hazardous activities that require increased attention and high speed of psychomotor reactions.
Compound
1 tablet contains trimetazidine dihydrochloride 35 mg.
Directions for use and doses
Angiosil retard is prescribed 35 mg (1 tablet) 2 times a day. The tablets are taken orally during meals in the morning and evening. The duration of the course of therapy with Angiosil retard is determined individually.
Side effects
From the digestive system: rarely - gastralgia, nausea, vomiting.
Allergic reactions: skin itching.
Other: rarely - headache, feeling of palpitations.
Drug interactions
Interaction with other drugs has not been described.
Overdose
Currently, no cases of overdose of Angiosil retard have been reported.
Storage conditions
In a dry place, protected from light, at a temperature not exceeding + 25 ° C.
Best before date
2 years.
Conditions for dispensing from pharmacies
Dispensed with a doctor's prescription
Angiosil retard tablets 35 mg 60 pcs. in Novokuznetsk
Pharmacological action: Pharmacodynamics
Mechanism of action.
Trimetazidine prevents a decrease in intracellular ATP concentration by maintaining the energy metabolism of cells in a state of hypoxia. Thus, trimetazidine ensures the normal functioning of membrane ion channels, transmembrane transport of potassium and sodium ions and the preservation of cellular homeostasis.
Trimetazidine inhibits the oxidation of fatty acids due to selective inhibition of the enzyme 3-ketoacyl-CoA thiolase, a mitochondrial long-chain isoform of fatty acids, which leads to increased glucose oxidation and acceleration of glycolysis with glucose oxidation, which determines myocardial protection from ischemia. The switch of energy metabolism from fatty acid oxidation to glucose oxidation underlies the pharmacological properties of trimetazidine.
Pharmacodynamic properties.
Trimetazidine supports the energy metabolism of the heart and neurosensory tissues during ischemia; reduces the severity of intracellular acidosis and changes in transmembrane ion flow that occur during ischemia; reduces the level of migration and infiltration of polynuclear neutrophils in ischemic and reperfused heart tissues; reduces the size of myocardial damage; does not have a direct effect on hemodynamic parameters.
In patients with angina pectoris, trimetazidine increases coronary reserve, thereby slowing the onset of exercise-induced ischemia, starting from the 15th day of therapy; limits fluctuations in blood pressure caused by physical activity without significant changes in heart rate; significantly reduces the frequency of angina attacks and the need for short-acting nitroglycerin; improves contractile function of the left ventricle in patients with ischemic dysfunction.
The results of clinical studies have confirmed the effectiveness and safety of trimetazidine in patients with stable angina, both in monotherapy and as part of combination therapy when the effect of other antianginal drugs is insufficient.
In a study of 426 patients with stable angina, the addition of trimetazidine (60 mg/day) to metoprolol 100 mg/day (50 mg twice daily) for 12 weeks statistically significantly improved exercise test results and clinical symptoms compared with placebo. The total duration of the load tests was +20.1 s (p = 0.023), the total time to perform the load was +0.54 METs (p = 0.001), the time to the development of ST segment depression by 1 mm was +33.4 s (p = 0.003) , time to development of an angina attack +33.9 s (p <0.001), number of angina attacks per week -0.73 (p = 0.014) and consumption of short-acting nitrates per week -0.63 (p = 0.032) without hemodynamic changes .
In a study of 223 patients with stable angina, the addition of trimetazidine 35 mg twice daily to atenolol 50 mg once daily for 8 weeks, 12 hours after dosing, increased the time to ischemic heart disease. ST segment depression by 1 mm (+34.4 s, p = 0.03) during stress tests in a subgroup of patients (N = 173) compared with the placebo group. Similar results were also obtained for the time of development of angina attacks (p = 0.049). There were no significant differences between groups for other secondary endpoints (total exercise test duration, total exercise time, and clinical endpoints).
In a study of 1962 patients with stable angina, trimetazidine at two doses (70 and 140 mg/day) was added to atenolol 50 mg/day versus placebo. In the general population, including both asymptomatic and symptomatic patients with angina, trimetazidine did not demonstrate benefit on ergometric (total duration of exercise tests, time to onset of ischemic ST-segment depression of 1 mm, and time to onset of angina) and clinical endpoints. However, in a post hoc analysis in a subgroup of patients with symptomatic angina (N=1574), trimetazidine (140 mg) significantly improved total exercise test time (+23.8 s versus +13.1 s for placebo; p=0.001) and time to development of an angina attack (+46.3 s compared with +32.5 s for placebo; p=0.005).
Pharmacokinetics
Absorption
Extended release.
After oral administration, trimetazidine has a linear pharmacokinetic profile and reaches Cmax in plasma approximately 14 hours after administration. In the intervals between doses (i.e. within 24 hours), the concentration of trimetazidine in the blood plasma for 15 hours after administration remains at a level of at least 75% of Cmax. An equilibrium state is achieved after taking the 3rd dose (after 3 days). Food intake does not affect the bioavailability of trimetazidine.
Modified release
. After oral administration, trimetazidine is rapidly absorbed, Tmax in blood plasma is approximately 5 hours.
Over 24 hours, the concentration of trimetazidine in the blood plasma remains at a level exceeding 75% of the concentration determined after 11 hours. The equilibrium state is reached after 60 hours. Food intake does not affect the bioavailability of trimetazidine.
Distribution.
Vd is 4.8 l/kg, which indicates good distribution of trimetazidine in tissues (the degree of binding to plasma proteins is quite low, about 16%
in vitro
).
Excretion.
Trimetazidine is excreted mainly by the kidneys, mainly unchanged. T1/2 in young healthy volunteers is about 7 hours, in patients over 65 years old - about 12 hours.
Renal clearance of trimetazidine directly correlates with creatinine clearance; hepatic clearance decreases with patient age.
Special patient groups
Patients over 75 years of age.
Patients over 75 years of age may experience increased exposure to trimetazidine due to age-related decline in renal function. A special study was conducted in a population of patients over 75 years of age while taking trimetazidine at a dose of 35 mg 2 times a day. An analysis performed by a kinetic population method showed an average twofold increase in plasma trimetazidine exposure in patients with severe renal impairment (Cl creatinine <30 ml/min) compared with patients with Cl creatinine >60 ml/min.
No differences were found regarding the safety of trimetazidine in patients over 75 years of age compared to the general population.
Kidney failure.
Trimetazidine exposure was increased on average by 2.4 times in patients with moderate renal failure (Cl creatinine 30–60 ml/min) and on average 4 times in patients with severe renal failure (Cl creatinine <30 ml/min). min) compared to healthy volunteers with normal kidney function.
No differences were found regarding the safety of trimetazidine in this patient population compared with the general population.
Children and teenagers.
The pharmacokinetics of trimetazidine in children and adolescents under 18 years of age have not been studied.
Angiosil retard tablets 35 mg 60 pcs. in Gatchina
Pharmacological action: Pharmacodynamics
Mechanism of action.
Trimetazidine prevents a decrease in intracellular ATP concentration by maintaining the energy metabolism of cells in a state of hypoxia. Thus, trimetazidine ensures the normal functioning of membrane ion channels, transmembrane transport of potassium and sodium ions and the preservation of cellular homeostasis.
Trimetazidine inhibits the oxidation of fatty acids due to selective inhibition of the enzyme 3-ketoacyl-CoA thiolase, a mitochondrial long-chain isoform of fatty acids, which leads to increased glucose oxidation and acceleration of glycolysis with glucose oxidation, which determines myocardial protection from ischemia. The switch of energy metabolism from fatty acid oxidation to glucose oxidation underlies the pharmacological properties of trimetazidine.
Pharmacodynamic properties.
Trimetazidine supports the energy metabolism of the heart and neurosensory tissues during ischemia; reduces the severity of intracellular acidosis and changes in transmembrane ion flow that occur during ischemia; reduces the level of migration and infiltration of polynuclear neutrophils in ischemic and reperfused heart tissues; reduces the size of myocardial damage; does not have a direct effect on hemodynamic parameters.
In patients with angina pectoris, trimetazidine increases coronary reserve, thereby slowing the onset of exercise-induced ischemia, starting from the 15th day of therapy; limits fluctuations in blood pressure caused by physical activity without significant changes in heart rate; significantly reduces the frequency of angina attacks and the need for short-acting nitroglycerin; improves contractile function of the left ventricle in patients with ischemic dysfunction.
The results of clinical studies have confirmed the effectiveness and safety of trimetazidine in patients with stable angina, both in monotherapy and as part of combination therapy when the effect of other antianginal drugs is insufficient.
In a study of 426 patients with stable angina, the addition of trimetazidine (60 mg/day) to metoprolol 100 mg/day (50 mg twice daily) for 12 weeks statistically significantly improved exercise test results and clinical symptoms compared with placebo. The total duration of the load tests was +20.1 s (p = 0.023), the total time to perform the load was +0.54 METs (p = 0.001), the time to the development of ST segment depression by 1 mm was +33.4 s (p = 0.003) , time to development of an angina attack +33.9 s (p <0.001), number of angina attacks per week -0.73 (p = 0.014) and consumption of short-acting nitrates per week -0.63 (p = 0.032) without hemodynamic changes .
In a study of 223 patients with stable angina, the addition of trimetazidine 35 mg twice daily to atenolol 50 mg once daily for 8 weeks, 12 hours after dosing, increased the time to ischemic heart disease. ST segment depression by 1 mm (+34.4 s, p = 0.03) during stress tests in a subgroup of patients (N = 173) compared with the placebo group. Similar results were also obtained for the time of development of angina attacks (p = 0.049). There were no significant differences between groups for other secondary endpoints (total exercise test duration, total exercise time, and clinical endpoints).
In a study of 1962 patients with stable angina, trimetazidine at two doses (70 and 140 mg/day) was added to atenolol 50 mg/day versus placebo. In the general population, including both asymptomatic and symptomatic patients with angina, trimetazidine did not demonstrate benefit on ergometric (total duration of exercise tests, time to onset of ischemic ST-segment depression of 1 mm, and time to onset of angina) and clinical endpoints. However, in a post hoc analysis in a subgroup of patients with symptomatic angina (N=1574), trimetazidine (140 mg) significantly improved total exercise test time (+23.8 s versus +13.1 s for placebo; p=0.001) and time to development of an angina attack (+46.3 s compared with +32.5 s for placebo; p=0.005).
Pharmacokinetics
Absorption
Extended release.
After oral administration, trimetazidine has a linear pharmacokinetic profile and reaches Cmax in plasma approximately 14 hours after administration. In the intervals between doses (i.e. within 24 hours), the concentration of trimetazidine in the blood plasma for 15 hours after administration remains at a level of at least 75% of Cmax. An equilibrium state is achieved after taking the 3rd dose (after 3 days). Food intake does not affect the bioavailability of trimetazidine.
Modified release
. After oral administration, trimetazidine is rapidly absorbed, Tmax in blood plasma is approximately 5 hours.
Over 24 hours, the concentration of trimetazidine in the blood plasma remains at a level exceeding 75% of the concentration determined after 11 hours. The equilibrium state is reached after 60 hours. Food intake does not affect the bioavailability of trimetazidine.
Distribution.
Vd is 4.8 l/kg, which indicates good distribution of trimetazidine in tissues (the degree of binding to plasma proteins is quite low, about 16%
in vitro
).
Excretion.
Trimetazidine is excreted mainly by the kidneys, mainly unchanged. T1/2 in young healthy volunteers is about 7 hours, in patients over 65 years old - about 12 hours.
Renal clearance of trimetazidine directly correlates with creatinine clearance; hepatic clearance decreases with patient age.
Special patient groups
Patients over 75 years of age.
Patients over 75 years of age may experience increased exposure to trimetazidine due to age-related decline in renal function. A special study was conducted in a population of patients over 75 years of age while taking trimetazidine at a dose of 35 mg 2 times a day. An analysis performed by a kinetic population method showed an average twofold increase in plasma trimetazidine exposure in patients with severe renal impairment (Cl creatinine <30 ml/min) compared with patients with Cl creatinine >60 ml/min.
No differences were found regarding the safety of trimetazidine in patients over 75 years of age compared to the general population.
Kidney failure.
Trimetazidine exposure was increased on average by 2.4 times in patients with moderate renal failure (Cl creatinine 30–60 ml/min) and on average 4 times in patients with severe renal failure (Cl creatinine <30 ml/min). min) compared to healthy volunteers with normal kidney function.
No differences were found regarding the safety of trimetazidine in this patient population compared with the general population.
Children and teenagers.
The pharmacokinetics of trimetazidine in children and adolescents under 18 years of age have not been studied.
