Deprenorm OD sustained release pills 70mg, 60pcs

Composition

1 film-coated extended-release tablet contains:

Active ingredient:  trimetazidine dihydrochloride 70,00 mg;

excipients:  hypromellose (hydroxypropylmethylcellulose) 171.00 mg; carbomer 10.97 mg; colloidal silicon dioxide 6.00 mg; magnesium stearate 3.00 mg; microcrystalline cellulose 189.03 mg;

film shell composition:  Opadray transparent 2.60 mg, including: hypromellose (hydroxypropylmethylcellulose) 2.08 mg; macrogol-4000 (polyethylene glycol-4000) 0.52 mg;

Opadray II pink 12.40 mg, including: sunset yellow dye 0.3150 mg; crimson dye [Ponceau 4R] 0.2579 mg;  dye Indigo Carmine 0.1798 mg; polyvinyl alcohol 4.9600 mg; macrogol-4000 (polyethylene glycol-4000) 2.5048 mg; talc 1.8352 mg, titanium dioxide 2.3473 mg

Pharmacological action

Pharmacodynamics

Trimetazidine under conditions of ischemia and hypoxia prevents an intracellular decrease in the activity of adenosine triphosphatase( ATP), preserving energy metabolism and ensuring cell homeostasis by ensuring the normal functioning of ion channels of cell membranes and transmembrane sodium-potassium flow.

It inhibits beta-oxidation of fatty acids by selectively blocking the enzyme 3-ketoacyl-CoA-thiolase, which increases glucose oxidation.

Cells in a state of ischemia require less oxygen to produce energy during the oxidation of glucose than during the beta-oxidation of fatty acids.

Switching the energy metabolism of cells from fatty acid oxidation to glucose oxidation underlies the pharmacological effects of trimetazidine. In experimental conditions, it was shown that the drug:

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

– reduces the severity of intracellular acidosis and changes in the transmembrane ion flux that occur during ischemia;

– reduces the migration and infiltration of polynuclear neutrophils in ischemic and reperfused heart tissues;

– reduces the size of myocardial damage;

– does not adversely affect hemodynamic parameters.

In patients with coronary artery disease, trimetazidine acts as a metabolic agent, preserving sufficient intracellular activity of high-energy phosphates in the myocardium. The anti-ischemic effect is achieved without affecting hemodynamics.

In patients with angina trimetazidine:

-increases coronary reserve, thereby slowing the onset of ischemia caused by physical activity, starting from the 15th day of therapy;

it limits the fluctuations in blood pressure, caused by physical activity, without significant changes in heart rate;

-reduces the frequency of angina attacks and the need for

taking a short-acting nitroglycerin;

-improves contractile function of the left ventricle in patients with coronary dysfunction.

Pharmacokinetics

When taken orally, trimetazidine is rapidly absorbed from the gastrointestinal tract (GIT), its maximum concentration in blood plasma is reached in an average of 5 hours. For more than 24 hours, the concentration of trimetazidine in blood plasma is maintained at levels exceeding or equal to 75% of the maximum.

The equilibrium state of the drug concentration in the blood is reached after 60 hours. Food intake does not affect the pharmacokinetic properties of trimetazidine. The volume of distribution is 4.8 l/kg. The binding to plasma proteins is low and amounts to 16% in vitro.

Trimetazidine is mainly excreted by the kidneys, mainly in unchanged form. When taken orally at a dose of 35 mg, the half-life in young healthy volunteers is on average 7 hours, in patients older than 65 years-12 hours.

Total renal clearance of trimetazidine is directly correlated with creatinine clearance (CC), and hepatic clearance decreases with age.

Patients over 75 years of age

Patients over 75 years of age may experience increased plasma exposure to trimetazidine as a result of age-related decline in renal function. No features were found regarding the safety of using the drug in patients over 75 years of age compared to the general population.

Patients with impaired renal function

Plasma exposure to trimetazidine was increased approximately 2.4 – fold in patients with moderate renal impairment (creatinine clearance 30-60 ml/min), and approximately 4-fold in patients with severe renal impairment (creatinine clearance less than 30 ml/min) compared to healthy volunteers with normal renal function.

No features were found regarding the safety of the drug in patients with impaired renal function 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 coronary heart disease: prevention of stable angina attacks as part of mono-or combination therapy.

Use during pregnancy and lactation

The use of trimetazidine during pregnancy is contraindicated. There are no clinical data on the experience of using trimetazidine in pregnant women. Animal studies have not revealed the presence of teratogenic effects. The potential risk of using trimetazidine during pregnancy in humans is unknown. It is not known whether trimetazidine or its metabolites pass into breast milk. The use of trimetazidine during breastfeeding is contraindicated. If it is necessary to use Deprenorm® OD – breast-feeding should be discontinued.

Contraindications

• Hypersensitivity to Trimetazidine or any of the excipients of the drug;

• Parkinson’s disease, Parkinsonian symptoms, tremors, a syndrome of “restless legs” and other related movement disorders;

• renal failure of moderate severity and severe (creatinine clearance (CC) of less than 60 ml/min);

• pregnancy;

• breastfeeding;

• age to 18 years (there are no data on the efficacy and safety of the use of Trimetazidine in this age category).

With caution: In patients with severe hepatic insufficiency and patients over 75 years of age (due to possible increased exposure to trimetazidine).

Side effects

The following criteria were used to assess the frequency of adverse reactions: very common (≥1/10); common (≥1/100, ≤1/10); uncommon (≥1/1000, ≤1/100); rare (≥1/10000, ≤1/1000); very rare (≤1/10000), the frequency is unknown – based on the available data, it is not possible to estimate the frequency.

Disorders of the blood and lymphatic system

Frequency unknown: agranulocytosis, thrombocytopenia, thrombocytopenic purpura.

Nervous system disorders

are Common:  dizziness, headache;

Frequency unknown: symptoms of Parkinsonism (tremor, akinesia, increased muscle tone), instability in the Romberg position and unsteady gait, restless legs syndrome, other associated motor disorders, usually reversible after discontinuation of therapy), sleep disorders (insomnia, drowsiness).

Hearing disorders and labyrinth disorders

Frequency unknown: vertigo.

Cardiac disorders

Rarely:  palpitation, extrasystole, tachycardia.

Vascular disorders

Rarely:  low blood pressure, orthostatic hypotension (may be accompanied by general weakness, dizziness or loss of balance, especially when taking antihypertensive drugs at the same time, flushes of blood to the face.

Gastrointestinal disorders

are Common:  abdominal pain, diarrhea, dyspepsia, nausea, vomiting;

Frequency unknown: constipation.

Liver and biliary tract

disorders Frequency unknown: hepatitis.

Skin and subcutaneous tissue disorders

are common:  skin rash, pruritus, urticaria;

Frequency unknown: acute generalized exanthematous pustulosis, angioedema.

General disorders and disorders at the injection site

Often:  asthenia.

Interaction

Cases of drug interaction are not described.

How to take, course of use and dosage

Inside, while eating.

Deprenorm ® OD is taken 1 tablet of 70 mg once a day (in the morning). Tablets should be taken whole, without chewing,

washed down with water. The duration of therapy is determined by the doctor. The effectiveness of therapy is evaluated after 3 months of using the drug. If there is no effect from the therapy, take Deprenorm® ML should be discontinued.

The maximum daily dose of trimetazidine is 70 mg.

Application in special clinical groups of patients

In patients with renal insufficiency

In patients with moderate to severe renal insufficiency (creatinine clearance less than 60 ml/min), the use of the drug is contraindicated, since the recommended daily dose of trimetazidine for such patients is 35 mg, in tablets of Deprenorm® However, there is no risk to ensure the required dosage regimen.

In 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. Dose selection in patients over 75 years of age should be carried out with caution.

Overdose

There is limited information on trimetazidine overdose. In case of overdose, symptomatic therapy should be performed.

Special instructions

Trimetazidine is not intended for the relief 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 after the patient’s hospitalization.

If an angina attack develops, treatment should be reviewed and adapted (drug therapy or revascularization procedures).

Trimetazidine can cause or worsen the symptoms of parkinsonism (tremor, akinesia, increased muscle tone), so careful medical supervision of such patients, especially the elderly, is required. In doubtful cases, patients should be referred to a neurologist for an appropriate examination.

If motor disorders such as

Parkinsonism symptoms, restless legs syndrome, tremor, instability in the Romberg position and unsteadiness of gait occur, trimetazidine should be discontinued. 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, a neurologist should be consulted. There may be cases of falls associated with instability in the Romberg position and unsteady gait, or a marked decrease in blood pressure, especially in patients taking antihypertensive medications.

Careful medical supervision is required when using trimetazidine in patients with severe hepatic insufficiency and in patients over 75 years of age (due to the possible increase in its exposure due to age-related decline in renal function).

Influence on the ability to drive vehicles and mechanisms

Due to the possible development of dizziness and other adverse reactions while taking the drug, caution should be exercised when driving vehicles and mechanisms, as well as engaging in other activities that require increased concentration of attention and speed of psychomotor reactions.

Storage conditions

At a temperature of not more than 25 C in a secondary package (cardboard pack). Keep out of reach of children.

Shelf

life is 3 years.

Active ingredient

Trimetazidine

Conditions of release from pharmacies

By prescription

Dosage form

long-acting tablets