Triductan

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT TRIDUCTANE (TRIDUCTANE)

Composition:

Active substance: trimetazidine;

1 tablet contains 20 mg of trimetazidine dihydrochloride;

Excipients: maize starch, mannitol (E 421), polyvinylpyrrolidone, talc, magnesium stearate, film coating Opadry II Red (talc, polyethylene glycol, indigo carmine (E 132), polyvinyl alcohol, titanium dioxide (E 171), Ponceau 4R (E 124), "Sunset Yellow" (E 110)).

Pharmaceutical form. Film-coated tablets.

Main physicochemical characteristics: round, biconvex film-coated tablets of red color.

Pharmacotherapeutic group. Cardiology agents. ATC code C01EB15.

Pharmacological properties.

Pharmacodynamics.

Mechanism of action.

By preserving cellular energy metabolism under conditions of hypoxia or ischemia, trimetazidine prevents the decrease in intracellular ATP levels, thereby maintaining proper functioning of ionic pumps and transmembrane sodium-potassium flux, preserving cellular homeostasis.

Trimetazidine inhibits fatty acid β-oxidation by blocking long-chain 3-ketoacyl-CoA thiolase (3-KAT), thus enhancing glucose oxidation. In ischemic cells, energy production via glucose oxidation requires less oxygen compared to energy production through β-oxidation of fatty acids. Enhanced glucose oxidation optimizes cellular energy processes and consequently supports energy metabolism under ischemic conditions.

Pharmacodynamic effects.

In patients with ischemic heart disease, trimetazidine acts as a metabolic agent, preserving intracellular levels of high-energy phosphates in the myocardium. These effects are achieved without concomitant hemodynamic changes.

Clinical efficacy and safety.

Clinical studies have demonstrated the efficacy and safety of trimetazidine in the treatment of patients with stable angina, both as monotherapy and as an add-on to other antianginal drugs in cases of insufficient efficacy.

Pharmacokinetics.

After oral administration, trimetazidine is rapidly absorbed from the gastrointestinal tract. Maximum plasma concentration is reached within less than 2 hours and amounts to 55 ng/mL after a single 20 mg dose. Steady-state plasma concentration is achieved within 24–36 hours after initiation of treatment. The volume of distribution is 4.8 L/kg. Plasma protein binding is low, approximately 16%, based on in vitro measurements. Trimetazidine is primarily excreted in urine, mostly in unchanged form. Elimination half-life is approximately 6 hours.

Special patient groups.

Elderly patients. In elderly patients, increased trimetazidine concentrations may occur due to age-related decline in renal function.

Renal impairment. Trimetazidine blood concentrations are increased in patients with moderate renal impairment (creatinine clearance 30–60 mL/min) and in patients with severe renal impairment (creatinine clearance < 30 mL/min).

Clinical characteristics.

Indications.

For symptomatic treatment of adult patients with stable angina when first-line antianginal medications are insufficiently effective or not tolerated.

Contraindications.

Hypersensitivity to trimetazidine or to any of the excipients.

Parkinson's disease, symptoms of parkinsonism, tremor, restless legs syndrome, and other movement disorders related to the above.

Severe renal impairment (creatinine clearance < 30 mL/min).

Interaction with other medicinal products and other forms of interaction.

No interactions of the drug Triductan with other medicinal products leading to adverse effects have been described.

The use of Triductan in combination with nitrates, β-blockers, or calcium antagonists provides an additional therapeutic effect in patients with angina.

Trimetazidine may be administered in combination with heparin, vitamin K antagonists (without potentiation of their effect), as well as with ACE inhibitors, oral lipid-lowering agents, and acetylsalicylic acid.

Special precautions for use.

The drug should not be used to relieve angina attacks. It should not be prescribed for unstable angina or myocardial infarction as initial therapy at the pre-hospital stage or during the first days of hospitalization.

If an attack of unstable angina occurs during ongoing treatment, the patient's condition should be reassessed and treatment adjusted (medication therapy and possibility of revascularization).

Trimetazidine may induce or worsen symptoms of parkinsonism (tremor, akinesia, muscle hypertonia), which should be regularly monitored, especially in elderly patients. In doubtful cases, patients should be referred to a neurologist for appropriate evaluation.

If motor disorders occur, such as parkinsonism symptoms, tremor, restless legs syndrome, or gait instability, the drug should be discontinued. These events are rare and usually resolve after stopping treatment; in most patients, within 4 months after discontinuation of trimetazidine. If parkinsonism symptoms persist for more than 4 months after stopping the drug, consultation with a neurologist is required.

Falls may occur due to gait instability or arterial hypotension, particularly in patients receiving antihypertensive agents.

The drug should be used with caution in:

• patients with moderate renal impairment;
• patients aged over 75 years.

The presence of colorants "sunset yellow" (E 110) and ponceau 4R (E 124) in the formulation may provoke allergic-type reactions.

Athletes. This medicinal product contains an active substance that may result in a positive anti-doping test.

Severe skin adverse reactions. Severe skin adverse reactions have been reported with trimetazidine use, including drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) and acute generalized exanthematous pustulosis, which may be life-threatening or lead to fatal outcomes (see section "Adverse reactions"). When prescribing the drug, patients should be informed about the signs and symptoms of severe skin reactions, and careful monitoring of patients should be performed during treatment. If signs indicating such reactions occur, trimetazidine should be immediately discontinued and alternative treatment considered (if necessary).

Use during pregnancy or breastfeeding.

There are no data available on use in pregnant women. It is unknown whether trimetazidine and its metabolites are excreted in breast milk. Trimetazidine is not recommended during pregnancy or breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

Trimetazidine does not affect hemodynamics. Cases of dizziness and somnolence have been reported, which may impair the ability to drive or operate machinery.

Dosage and method of administration.

Triductan should be administered orally, 1 tablet three times a day during meals.

After 3 months of treatment, the therapeutic response should be evaluated, and if no effect is observed, trimetazidine should be discontinued.

Special patient groups.

Patients with renal impairment.

For patients with moderate renal impairment (creatinine clearance 30–60 mL/min), the recommended dosage is 1 tablet twice daily: in the morning and in the evening, during meals.

Elderly patients.

Elderly patients are more sensitive to the effects of trimetazidine due to age-related decline in renal function. For elderly patients with moderate renal impairment (creatinine clearance 30–60 mL/min), the recommended dosage is 1 tablet twice daily: in the morning and in the evening, during meals.

Dosage titration in elderly patients should be performed with caution.

Children.

The safety and efficacy of trimetazidine in children have not been established. Data are lacking.

Overdose.

Data regarding trimetazidine overdose are limited.

Treatment is symptomatic.

Adverse Reactions

Adverse reactions identified as adverse effects possibly related to trimetazidine use are listed below with their defined frequency: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000); frequency not known (cannot be estimated based on available data):

Nervous system disorders: common – headache, dizziness; uncommon – paraesthesia; frequency not known – possible development of parkinsonism symptoms (tremor, akinesia, muscle hypertonia), gait instability, restless legs syndrome, and other movement disorders related to the above, which are reversible after discontinuation of the drug; sleep disorders (insomnia, somnolence).

Ear and labyrinth disorders: frequency not known – vertigo.

Cardiac disorders: rare – palpitations, extrasystoles, tachycardia.

Vascular disorders: rare – arterial hypotension, orthostatic hypotension which may be associated with malaise, dizziness or falls (particularly in patients taking antihypertensive agents), facial flushing.

Gastrointestinal disorders: common – abdominal pain, dyspepsia, diarrhoea, nausea, vomiting; frequency not known – constipation.

Hepatobiliary disorders: frequency not known – hepatitis.

Skin and subcutaneous tissue disorders: common – rash, pruritus, urticaria; frequency not known – drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis (see section "Special precautions").

Blood and lymphatic system disorders: frequency not known – agranulocytosis, thrombocytopenia, thrombocytopenic purpura.

General disorders: common – asthenia.

Shelf life.

3 years.

Storage conditions.

Store in the original packaging, protected from light, in a place inaccessible to children, at a temperature not exceeding 25 °C.

Packaging.

10 film-coated tablets in a blister; 3 or 6 blisters in a cardboard pack.

30 film-coated tablets in a blister; 1, 2, or 3 blisters in a cardboard pack.

Prescription status.

Prescription only.

Manufacturer.

LLC "Pharma Start".

Manufacturer's address and location of business activity.

8 Vatslava Havela Boulevard, Kyiv, 03124, Ukraine.

In case of adverse effects or questions regarding the safety of the medicinal product, please contact the Pharmacovigilance Department of LLC "ASINO UKRAINA" at 8 Vatslava Havela Boulevard, Kyiv, 03124, tel/fax: +38 044 281 2333.