Description
Deprenorm Pharmacodynamics
Trimetazidine prevents the intracellular decrease of adenosine triphosphatase (ATP) activity under ischemia and hypoxia, preserving the energy metabolism and providing
cell homeostasis by ensuring normal functioning of cell membrane ion channels and transmembrane sodium-potassium flux. It inhibits beta-oxidation of
fatty acids by selectively blocking the enzyme 3-ketoacyl-CoAthiolase, which enhances glucose oxidation. Cells in ischemia require less oxygen for energy during the oxidation of
glucose requires less oxygen than fatty acid beta-oxidation.
The switch of cellular energy metabolism from fatty acid oxidation to glucose oxidation underlies the pharmacological effects of trimetazidine. Under experimental conditions, the drug has been shown to:
-supports energy metabolism of the heart and neurosensory tissues under ischemic conditions;
-Reduces the severity of intracellular acidosis and changes in the transmembrane flux of ions that occur in ischemia;
-Reduces 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 ischemic heart 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 pectoris, trimetazidine:
-increases coronary reserve, thereby delaying the onset of exercise-induced ischemia beginning on day 15 of therapy;
-limits exercise-induced blood pressure fluctuations without significant changes in heart rate;
-reduces the frequency of angina attacks and the need for short-acting nitroglycerin;
-improves left ventricular contractile function in patients with coronary dysfunction.
Indications
Long-term therapy of coronary heart disease: prevention of attacks of stable angina as part of mono- or combined therapy.
Contraindications
-Hypersensitivity to trimetazidine or any of the excipients of the drug;
-Parkinson’s disease, parkinsonian symptoms, tremor, restless legs syndrome and other related motor disorders;
-moderate to severe renal insufficiency (creatinine clearance (CK) less than 60 ml/min);
-pregnancy;
Breast-feeding period;
-under 18 years of age (there are no data on the efficacy and safety of trimetazidine in this age group).
Caution
In patients with severe hepatic impairment and in patients aged over 75 years (due to possible increased exposure to trimetazidine).
Administration 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
animal studies have not shown the presence of teratogenic effects. The potential risk of trimetazidine use during pregnancy in humans is unknown. It is not known whether trimetazidine or its
metabolites into breast milk. The use of trimetazidine during breastfeeding is contraindicated. If it is necessary to use the drug Deprenorm OD –
breastfeeding should be discontinued.
Dosage and administration.
- Inside, with a meal.
- Deprenorm® OD is taken as 1 tablet 70 mg 1 time per day (in the morning). the tablets should be taken in whole, without chewing, with water. The duration of therapy is determined by
the doctor. Effectiveness of therapy is evaluated after 3 months of using the drug. If there is no effect of the current therapy, Deprenorm®OD should be discontinued. - The maximum daily dose of trimetazidine is 70 mg.
- Use in special clinical groups of patients
In patients with renal insufficiency. - In patients with moderate to severe renal insufficiency (CKD less than 60 ml/min) the drug is contraindicated because the recommended daily
daily dose of trimetazidine for such patients is 35 mg, Deprenorm OD tablets have no risk to provide the required dosing regimen. - In patients over 75 years of age
- Patients over 75 years of age may have increased exposure to trimetazidine due to age-related decreases in renal function. Dose selection in patients over 75 years of age should
should be performed with caution.
