Deprenorm OD, 70 mg 60 pcs

Pharmacodynamics

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

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

The cells in ischemia require less oxygen for energy during glucose oxidation than during beta-oxidation of fatty acids.

The switch of cellular energy metabolism from fatty acid oxidation to glucose oxidation underlies the pharmacological effects of trimetazidine. Under experimental conditions it has been shown that the drug:

-supports energy metabolism of the heart and neurosensory tissues under ischemia;

-reduces the severity of intracellular acidosis and changes in transmembrane ion flow occurring during ischemia;

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

-reduces the size of myocardial damage;

-does not have adverse effects on hemodynamic parameters.

In patients with coronary heart disease, trimetazidine acts as a metabolic agent, maintaining sufficient intracellular high-energy phosphate activity 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 to take short-acting nitroglycerin;

-improves left ventricular contractile function in patients with ischemic dysfunction.

Pharmacokinetics

In oral administration, trimetazidine is rapidly absorbed from the gastrointestinal tract (GIT), with maximum plasma concentration reached in an average of 5 hours. For more than 24 hours, the plasma concentration of trimetazidine is maintained at levels greater than or equal to 75% of maximum.

The equilibrium state of the drug concentration in blood is reached after 60 hours. Food intake has no effect on the pharmacokinetic properties of trimetazidine. The volume of distribution is 4.8 l/kg. The binding to plasma proteins is low and in vitro is 16%.

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

The total renal clearance of trimetazidine directly correlates with creatinine clearance (CK), hepatic clearance decreases with age.

Patients older than 75 years

In patients older than 75 years, an increase in plasma exposure to trimetazidine may be observed as a result of age-related decline in renal function. No differences have been found regarding the safety of the drug in patients over 75 years of age compared to the general population.

Patients with impaired renal function

Trimetazidine plasma exposure was increased approximately 2.4-fold in patients with moderate renal impairment (CKD 30-60 ml/min) and approximately 4-fold in patients with severe renal impairment (CKD less than 30 ml/min) compared with healthy volunteers with normal renal function.

No differences were found regarding the safety of the drug in patients with impaired renal function compared to the general population.

The use in children and adolescents

The pharmacokinetics of trimetazidine in children and adolescents younger than 18 years has not been studied.

Indications

Long-term therapy of coronary heart disease: prevention of attacks of stable angina as part of mono- or combined therapy.

Active ingredient

Trimetazidine

Composition

1 film-coated sustained release tablet contains:

the active ingredient: trimetazidine dihydrochloride 70.00 mg;

excipients: Hypromellose (hydroxypropyl methylcellulose) 171.00 mg; carbomer 10.97 mg; colloidal silica 6.00 mg; magnesium stearate 3.00 mg; microcrystalline cellulose 189.03 mg;

film coating composition: Opadray clear 2.60 mg, including: Hypromellose (hydroxypropyl methylcellulose) 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 [Ponceau 4R] dye 0.2579 mg; indigo carmine dye 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.

How to take, the dosage

Orally, with meals.

Deprenorm® OD is taken as 1 tablet 70 mg once daily (morning). The tablets should be taken whole, without chewing, with water. 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 of the therapy the drug Deprenorm® OD should be discontinued.

The maximum daily dose of trimetazidine is 70 mg.

The use in special clinical groups of patients

In patients with renal impairment

In patients with moderate to severe renal impairment (CKI less than 60 ml/min), the drug is contraindicated because the recommended daily dose of trimetazidine for these patients is 35 mg, Deprenorm® OD tablets have no risk to provide the required dosing regimen.

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 be performed with caution.

Interaction

No cases of drug interactions have been described.

Special Instructions

Trimetazidine is not intended to control angina attacks and is not indicated for initial therapy of unstable angina or myocardial infarction in the pre-hospital phase or in the first days after hospitalization.

In the event of an angina attack, treatment (drug therapy or revascularization procedure) should be reviewed and adapted.

Trimetazidine may cause or worsen symptoms of parkinsonism (tremor, akinesia, increased muscle tone), so close medical monitoring of such patients, especially elderly patients, is required. In doubtful cases patients should be referred to a neurologist for appropriate evaluation.

Trimetazidine should be discontinued if movement disorders occur, such as symptoms of parkinsonism, restless legs, tremor, unsteadiness in the Romberg posture and wobbly gait. These cases are rare and symptoms usually disappear after discontinuation of therapy (in most patients within 4 months of discontinuation).

If symptoms of parkinsonism persist for more than 4 months after discontinuation of the drug, a consultation with a neurologist is necessary. There may be cases of falls associated with unsteadiness in Romberg posture and unsteady gait or marked decrease in blood pressure, especially in patients taking hypotensive medications.

A close medical monitoring is required when trimetazidine is used in patients with severe hepatic impairment and in patients older than 75 years (due to possible increase of its exposure because of age-related decrease of renal function).

In view of possible dizziness and other adverse reactions during the use of the drug, caution should be exercised while driving vehicles and operating machinery as well as during other activities requiring increased concentration and rapid psychomotor reaction.

Contraindications

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

• Parkinson’s disease, Parkinsonian symptoms, tremor, restless legs syndrome, and other related movement disorders;

• Moderate to severe renal impairment (creatinine clearance (CK) less than 60 mL/min);

• pregnancy;

• Breast-feeding period;

• Age

  under 18 years of age (there are no data on the efficacy and safety of trimetazidine in this age group).

With caution:

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

Side effects

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

Blood and lymphatic system disorders

Frequency unknown: agranulocytosis, thrombocytopenia, thrombocytopenic purpura.

Nervous system disorders

Often: dizziness, headache;

Arequent unknown: Parkinsonian symptoms (tremor, akinesia, increased muscle tone, Romberg posture instability and wobbly gait, restless legs syndrome, other related movement disorders, usually reversible after discontinuation of therapy), sleep disorders (insomnia, somnolence).

Hearing and labyrinth disorders

Prevalence unknown: Vertigo.

Cardiac disorders

Rarely: palpitations, extrasystole, tachycardia.

Vascular disorders

Rarely: decreased blood pressure, orthostatic hypotension (may be accompanied by general weakness, dizziness, or loss of balance, especially when concomitant use of hypotensive drugs, flushing of the face.

Gastrointestinal disorders

Often: abdominal pain, diarrhea, dyspepsia, nausea, vomiting;

Prevalence unknown: constipation.

Liver and biliary tract disorders

Often unknown: hepatitis.

Skin and subcutaneous tissue disorders

Often: skin rash, skin itching, urticaria;

Often unknown: acute generalized exanthematous pustulosis, Quincke’s edema.

General disorders and disorders at the site of administration

Often: asthenia.

Overdose

There is limited information about trimetazidine overdose. In case of overdose symptomatic therapy should be administered.

Pregnancy use

The use of trimetazidine during pregnancy is contraindicated. There are no clinical data on the experience of trimetazidine use in pregnant women.

Animal studies have shown no teratogenic effects. The potential risk of trimetazidine use during pregnancy in humans is unknown. It is unknown whether trimetazidine or its metabolites penetrate into breast milk.

The use of trimetazidine during breastfeeding is contraindicated. If it is necessary to use Deprenorm® OD, breastfeeding should be stopped.

Similarities

Predysin, Deprenorm MB, Trimectal MB, Trimetazidine, Antisten MB, Preductal OD , Trimetazidine MB-Teva, Trimetazidine MB, Deprenorm OD