Tri-Plus

Each hard gelatin capsule contains: Trimetazidine Hydrochloride BP 60 mg (As sustained release pellets).
Approved colours used in hard gelatin capsules shells.

Pharmacotherapeutic group: Other cardiovascular antianginal drug. ATC code: C01EB15 (C: cardiovascular system).
Pharmacology: Pharmacodynamics: Mechanism of action: Trimetazidine inhibits B-oxidation of fatty acids by blocking long-chain 3-ketoacyl-CoA thilase, which enhances glucose oxidation. In an ischaemic cell, energy obtained during glucose oxidation requires less oxygen consumption than in B-oxidation process. Potentiation of glucose oxidation optimizes cellular energy processes, thereby maintaining proper energy metabolism during ischaemia.
Pharmacodynamic effects: In patients with ischaemic heart disease, trimetazidine acts as a metabolic agent, preserving the myocardial high-energy phosphatase intracellular levels. Anti-ischaemic effects are achieved without concomitant haemodynamic effects.
Clinical efficacy and safety: Clinical studies have demonstrated the efficacy and safety of trimetazidine in the treatment of patients with chronic angina, either alone or when the benefit from other antianginal medicinal products was insufficient.
In a 426-patients randomized, double blind, placebo controlled study (Trimpol-II), trimetazidine (60 mg/day) added to metoprolol 100 mg daily (50 mg b.i.d.) for 12 weeks significantly improved statistically exercise tests parameters and clinical symptoms as compared to placebo: total exercise duration +20.1a, p=0.023, total workload +0.54 METs, p=0.001, time to onset of angina +33.9 s, <0.001, angina attacks/week -0.73, p=0.014 and short acting nitrates consumption/week, -0.63, p=0.032, without haemodynamic changes. In a 223 patients randomized, double blind, placebo-controlled study (Sellier), one 35 mg trimetazidine modified release tablet (b.i.d.) added to 50 mg atenolol (o.d.) for 8 weeks produced a significant increase (+34.4 s, p=0.03) in the time to 1-mm ST-segment depression in exercise tests, in a sub-group of patients (n=173), when compared to placebo, 12 hours after taking the drug. A significant difference was also evidenced for the time to onset of angina pectoris (p=0.049). No significant difference between groups could be found for the other secondary endpoints (total exercise duration, total workload and clinical endpoints).
In a 1962 patients three-month randomised, double-blinded study (Vasco study) on top of atenolol 50 mg/day, two dosages of trimetazidine (70 mg/day and 140 mg/day) were tested versus placebo. In the overall population, including both asymptomatic and symptomatic patients, trimetazidine failed to demonstrate a benefit on both ergometric (total exercise duration, time to onset of 1 mm ST and time to onset angina) and clinical endpoints. However, in the subgroup of symptomatic patients (n=1574) defined in a post-hoc analysis, trimetazidine (140 mg) significantly improved total exercise duration (+23.8 s versus +13.1 s placebo; p=0.001) and time onset of angina (+46.3 s versus +32.5 s placebo; p=0.005).
Pharmacokinetics: It is well absorbed and metabolised in the liver to inactive metabolites, then excreted in urine with a T% of 5-6 hours.

Trimetazidine is indicated in adults as add-on therapy for the symptomatic treatment of patients with stable angina pectoris who are inadequately controlled by or intolerant to first-line anti-anginal therapies.

Oral administration: The dose is one capsule of 60 mg trimetazidine once a day during meals.
Elderly patients: Elderly patients may have increased trimetazidine exposure due to age-related decrease in renal function. Dose titration in elderly patients should be exercised with caution.
Paediatric population: The safety and efficacy of trimetazidine in children aged below 18 years have not been established. No data are available.

Every limited information is available on trimetazidine overdosage.
Treatment should be symptomatic.

Hypersensitivity to the active substance or to any of the excipients.
Parkinson's disease, parkinsonian symptoms, tremors, restless leg syndrome, and other related movement disorders.
Severe renal impairment (creatinine clearance <30 mL/min).

This drug is not a curative treatment for angina attacks, nor is indicated as an initial treatment for unstable angina, or myocardial infarction. It should not be used in the prehospital phase nor during the first days of hospitalization.
In the event of an angina attack, angina pectoris disease should be reevaluated and an adaptation of the treatment considered.
Trimetazidine can cause or worsen parkinsonian symptoms (tremor, akinesia, hypertonia), which should be regularly investigated, especially in elderly patients. In doubtful cases, patients should be referred to a neurologist for appropriate investigations.
The occurrence of movement disorders such as parkinsonian symptoms, restless leg syndrome, tremors, gait instability should lead to definitive withdrawal of trimetazidine.
These cases have a low incidence and are usually reversible after treatment discontinuation. The majority of the patients recovered within 4 months after trimetazidine withdrawal. If parkinsonian symptoms persist more than 4 months after drug discontinuation, a neurologist opinion should be sought.
Falls may occur, related to gait instability or hypotension, in particular in patients taking antihypertensive treatment.

Trimetazidine may cause the following undesirable effects ranked under the following frequency.
Very common (>1/10); common (>1/100, <1/10); uncommon (>1/1000, <1/100); rare (>1/10000, <1/1000); very rare (<1/10000), not known (cannot be estimated from the available data). (See table.)

Click on icon to see table/diagram/image

No drug interactions have been identified.

Store at temperatures not exceeding 30°C.

Anti-Anginal Drugs

C01EB15 - trimetazidine ; Belongs to the class of other cardiac preparations.

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