Preduktal OD sustained release capsules 80mg, 60pcs

Composition

1 capsule of

trimetazidine dihydrochloride (in granules) 80 mg

.1 solid capsule with prolonged release contains:

film-coated trimetazidine dihydrochloride granules: 144.85 mg.

Auxiliary substances:

sugar spheres* * (710-850 microns) – 36.68 mg,

hypromellose-6.4 mg.

The composition of the film shell of granules:

ethylcellulose-8 mg,

tributylacetyl citrate-1.2 mg,

talc-12 mg.

The composition of the mixture for powdering pellets:

talc-0.43 mg,

magnesium stearate-0.14 mg.

Solid gelatin capsule No. 2 with a white body and an orange-red lid, the company logo and the inscription “80” are printed on the lid in white*: 61.000 mg.

Capsule body composition:

titanium dioxide (E 171) – 0.732 mg,

gelatin*** – 35.868 mg.

Capsule cap composition:

titanium dioxide (E 171) – 0.122 mg,

iron oxide red (E 172) – 0.366 mg,

gelatin*** – 23.912 mg.

* Printing of the logo and inscription on the capsule is applied in white ink, which includes shellac, titanium dioxide, simethicone, propylene glycol, ammonium hydroxide. The total amount of ink per capsule is approximately 0.15 mg

. * * Composition of sugar spheres: sucrose-no more than 92% (in terms of dry matter), corn starch. It may also contain starch hydrolysis products and colorants.

*** Contains an average of 14.5% water (weight loss during drying).

Pharmacological action

Trimetazidine prevents a decrease in the intracellular concentration of adenosine triphosphate (ATP) by maintaining the energy metabolism of cells in a state of hypoxia. Thus, the drug 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 by selectively inhibiting the enzyme 3-ketoacyl-CoA-thiolase (3-CAT) of the mitochondrial long-chain isoform of fatty acids, which leads to increased glucose oxidation and accelerated glycolysis with glucose oxidation, which determines the protection of the myocardium from ischemia.

Switching energy metabolism from fatty acid oxidation to glucose oxidation underlies the pharmacological properties of trimetazidine.

Pharmacodynamic properties

-supports the energy metabolism of the heart and sensorineural tissues during ischemia;

– reduces the severity of intracellular acidosis and changes in the transmembrane ion flux 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 directly affect hemodynamic parameters.

In patients with angina, trimetazidine increases the coronary reserve, thereby slowing the onset of exercise-induced ischemia, starting from the 15th day of therapy; limits blood pressure fluctuations caused by exercise, without significant changes in heart rate; significantly reduces the frequency of angina attacks and the need for short-acting nitroglycerin; improves left ventricular contractility in patients with ischemic dysfunction.

The results of clinical studies have confirmed the efficacy and safety of trimetazidine in patients with stable angina pectoris, both in monotherapy and in combination therapy with insufficient effect of other antianginal drugs.

In a study involving 426 patients with stable angina, the addition of trimetazidine (60 mg/day) to metoprolol 100 mg/day (50 mg twice daily) therapy for 12 weeks significantly improved exercise test results and clinical symptoms compared to placebo: total duration of exercise tests was +20.1 s, p=0.023, total exercise time +0.54 METs, p=0.001, time to development of ST-segment depression by 1 mm +33.4 s, p=0.003, time to angina attack +33.9 s, p

In a study involving 223 patients with stable angina, the addition of trimetazidine 35 mg (2 times / day) to atenolol 50 mg (1 time/day) therapy for 8 weeks resulted in an increase in the time to development of ST-segment ischemic depression by 1 mm (+34.4 s, p=0.03) during exercise tests in a subgroup of patients (n=173), compared with placebo,12 hours after taking the drug. This difference was also shown for the time of development of angina attacks (p=0.049). There were no significant differences between the groups for other secondary endpoints (total duration of exercise tests, total exercise time, and clinical endpoints).

In a study involving 1,962 patients with stable angina, trimetazidine in two dosages (70 mg/day and 140 mg/day) compared with placebo was added to therapy with atenolol 50 mg / day.

In the general population, including both non-symptomatic and symptomatic angina patients, trimetazidine did not show any benefits in terms of ergometric (total duration of exercise tests, time to 1 mm ST-segment ischemic depression, and time to angina attack) and clinical endpoints. However, in a retrospective analysis in a subset of patients with angina symptoms (n=1574), trimetazidine (140 mg) significantly improved overall exercise test time (+23.8 s compared to +13.1 s for placebo; p=0.001) and time to angina attack (+46.3 s compared to +32.5 for placebo; p=0.005).

Pharmacokinetics

Suction

After oral use of Preduktal® OD trimetazidine capsules, it has a linear pharmacokinetic profile and reaches Cmax in plasma approximately 14 hours after use. In the intervals between doses of the drug (i. e. within 24 hours), the concentration of trimetazidine in blood plasma for 15 hours after taking the drug remains at least 75% of Cmax. The equilibrium state is reached after taking the 3rd dose (after 3 days). Food intake does not affect the bioavailability of trimetazidine when taking Preduktal® OD 80 mg.

The distribution

of Vd is 4.8 l / kg, which indicates a good distribution of trimetazidine in tissues (the degree of binding to plasma proteins is quite low, about 16% in vitro).

Deduction

Trimetazidine is mainly excreted by the kidneys, mainly in unchanged form. T 1/2 in young healthy volunteers is about 7 hours, in patients older than 65 years – about 12 hours.

Renal clearance of trimetazidine is directly correlated with creatinine clearance, and hepatic clearance decreases with age.

Pharmacokinetics in special patient groups

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 when using trimetazidine tablets at a dose of 35 mg 2 times a day. The analysis performed by the kinetic population method showed an average twofold increase in plasma exposure in patients with severe renal insufficiency (creatinine clearance less than 30 ml/min) compared with patients with creatinine clearance more than 60 ml / min.

No safety features were found in patients over 75 years of age compared to the general population.

Trimetazidine exposure was increased on average 2.4 – fold in patients with moderate renal insufficiency (creatinine clearance 30-60 ml/min), and on average 4-fold in patients with severe renal insufficiency (creatinine clearance less than 30 ml/min) compared with healthy volunteers with normal renal function. No safety features were found in this patient population compared to the general population.

The pharmacokinetics of trimetazidine in children and adolescents under 18 years of age have not been studied.

Indications

-long-term therapy of CHD: prevention of stable angina attacks as part of mono-or combination therapy.

Contraindications

— severe renal failure (CC less than 30 ml/min);

Parkinson’s disease, Parkinsonian symptoms, tremors, restless leg syndrome and other related movement disorders;

— intolerance to fructose/sucrose, a syndrome of glucose-galactose malabsorption, and sucrase/isomaltase and other fermentopathy associated with intolerance to sucrose, a part of the drug;

— age up to 18 years (due to lack of sufficient clinical data);

— hypersensitivity to any component of the drug.

With caution, the drug should be prescribed to patients with severe hepatic insufficiency (from 10 to 15 points on the Child-Pugh scale), moderate renal insufficiency (creatinine clearance 30-60 ml / min), patients over 75 years of age (see the sections “Dosage regimen” and “Special instructions”).

Side effects

Adverse reactions defined as adverse events that are at least potentially relevant to trimetazidine treatment are listed in the following gradation: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10,000, <1/1000); very rare (

From the central nervous system:  often – dizziness, headache; unspecified frequency – symptoms of Parkinsonism (tremor, akinesia, increased tone), ” shaky ” gait, restless legs syndrome, and other associated motor disorders, usually reversible after discontinuation of therapy. Sleep disorders (insomnia, drowsiness).

From the cardiovascular system: rarely – palpitation, extrasystole, tachycardia, marked decrease in blood pressure, orthostatic hypotension, which may be accompanied by general weakness, dizziness or loss of balance, especially with the simultaneous use of antihypertensive drugs, “flushes” of blood to the skin of the face.

From the digestive system: often – abdominal pain, diarrhea, dyspepsia, nausea, vomiting; unspecified frequency-constipation.

From the liver and biliary tract: unspecified frequency-hepatitis.

From the hematopoietic system: unspecified frequency – agranulocytosis, thrombocytopenia, thrombocytopenic purpura.

From the side of the skin and subcutaneous fat: often – skin rash, pruritus, urticaria; unspecified frequency-angioedema, acute generalized exanthematous pustulosis.

Common disorders: often-asthenia.

Interaction

Not observed. The patient should inform the doctor about all medications taken.

How to take, course of use and dosage

The drug is taken orally,1 capsule 1 time/day, in the morning during breakfast. Capsules should be taken whole, without chewing, washed down with water.

Evaluation of the benefit of treatment can be carried out after 3 months of using the drug. If there is no improvement during this time, use Preduktal® ML should be discontinued.

The duration of treatment is determined by the doctor.

In patients with moderate renal insufficiency (creatinine clearance 30-60 ml/min) (see sections “Pharmacokinetics” and “Special instructions”), a dose reduction is recommended, i. e. 1 tablet containing 35 mg of trimetazidine per day.

Caution should be exercised in the treatment of patients with severe hepatic insufficiency (see section “Special instructions”) due to the fact that the available data are limited and do not allow us to completely exclude the absence of an effect of impaired liver function on the metabolism of trimetazidine.

Patients over 75 years of age may experience increased exposure to trimetazidine due to age-related decline in renal function (see section “Pharmacokinetics”). In patients with moderate renal insufficiency (creatinine clearance 30-60 ml/min), a dose reduction is recommended, i. e. 1 tablet containing 35 mg of trimetazidine per day. Dose selection in patients over 75 years of age should be carried out with caution (see section “Special instructions”).

The safety and efficacy of trimetazidine in patients under 18 years of age have not been established. No data available.

Overdose

There is only very limited information about trimetazidine overdose.

Treatment: in case of overdose, symptomatic therapy should be performed.

Special instructions

Preduktal® OD is not intended for the management of angina attacks and is not indicated for the initial course of treatment of unstable angina or myocardial infarction at the prehospital stage or in the first days of hospitalization.

If an angina attack develops, treatment should be reviewed and adapted (drug therapy or revascularization procedures). Preduktal ® OD may cause or worsen the symptoms of Parkinsonism (tremor, akinesia, increased tone), so patients, especially the elderly, should be regularly monitored. In case of doubt, the patient should be referred to a neurologist for an appropriate examination.

When motor disorders occur, such as Parkinsonism symptoms, restless legs syndrome, tremor, ” shaky ” gait, Preduktal® The ML should be permanently canceled. Such cases are rare and symptoms usually resolve after discontinuation of therapy: in most patients – within 4 months after discontinuation of the drug. If symptoms of parkinsonism persist for more than 4 months after discontinuation of the drug, you should consult a neurologist.

There may be cases of falls associated with instability in the Romberg position and “unsteadiness” of gait or a marked decrease in blood pressure, especially in patients taking antihypertensive drugs (see the section “Side effects”).

Caution should be exercised when prescribing Preductal® OD to patients who may have increased exposure to it:

– in patients with moderate renal insufficiency (see sections “Pharmacological action” and “Dosage regimen”);

– in elderly patients over 75 years of age (see section “Dosage regimen”).

The drug contains sucrose, so the drug is not recommended for patients with fructose intolerance, glucose-galactose malabsorption syndrome and sucrose-isomaltase deficiency.

Influence on the ability to drive motor vehicles and manage mechanisms

In clinical studies, no effect of trimetazidine on hemodynamic parameters was detected, however, cases of dizziness and drowsiness were observed during post-marketing use (see the section “Side effects”). These symptoms can affect the ability to drive vehicles and perform work that requires an increased rate of physical and mental reactions.

Form of production

Capsules with a prolonged release, solid gelatin, No. 2, with a white body and an orange-red lid;

the company logo and the inscription “80” are printed on the lid in white*; the contents of the capsule are spherical granules of white or almost white color.

Active ingredient

Trimetazidine

Conditions of release from pharmacies

By prescription

Dosage form

long-acting capsules

Purpose

For adults as directed by your doctor

Indications

Vascular diseases of the eyes, Angina Pectoris