Trikat MR (trimetazidine dihydrochloride): Uses, Dosage & Side Effects

What it's for (Indications)

Trimetazidine dihydrochloride is clinically indicated as an add-on therapy for the symptomatic treatment of adult patients with stable angina pectoris.
It is specifically prescribed when existing first-line anti-anginal treatments, such as beta-blockers or calcium channel blockers, are insufficient to control symptoms or when patients demonstrate an intolerance to these conventional therapies.
This medicinal product aims to improve myocardial metabolism under ischemic conditions, thereby reducing the frequency and severity of angina attacks.
Its role is supplementary to standard care, focusing on improving the quality of life for individuals grappling with chronic stable angina by optimizing cellular energy processes within the cardiac muscle.
It is not intended for the initial treatment of angina, nor for the treatment of unstable angina or myocardial infarction.

Dosage Information

Type	Guideline
Standard	The recommended dosage for trimetazidine dihydrochloride is typically 35 mg modified-release tablets, administered orally twice daily, once in the morning and once in the evening, preferably taken with meals. For immediate-release formulations, the standard regimen is 20 mg, taken three times a day. Dosage adjustments are crucial for specific patient populations, particularly those with moderate renal impairment (creatinine clearance 30-60 ml/min), where the recommended dose is one 35 mg modified-release tablet in the morning or 20 mg immediate-release tablets twice daily. Trimetazidine is not recommended for patients with severe renal impairment (creatinine clearance < 30 ml/min) due to increased risk of accumulation. Treatment initiation and subsequent adjustments should always be under the direct supervision and guidance of a healthcare professional, considering individual patient response, tolerance, and renal function.

Type

Guideline

Standard

The recommended dosage for trimetazidine dihydrochloride is typically 35 mg modified-release tablets, administered orally twice daily, once in the morning and once in the evening, preferably taken with meals. For immediate-release formulations, the standard regimen is 20 mg, taken three times a day. Dosage adjustments are crucial for specific patient populations, particularly those with moderate renal impairment (creatinine clearance 30-60 ml/min), where the recommended dose is one 35 mg modified-release tablet in the morning or 20 mg immediate-release tablets twice daily. Trimetazidine is not recommended for patients with severe renal impairment (creatinine clearance < 30 ml/min) due to increased risk of accumulation. Treatment initiation and subsequent adjustments should always be under the direct supervision and guidance of a healthcare professional, considering individual patient response, tolerance, and renal function.

Safety & Warnings

Common Side Effects

Commonly reported side effects of trimetazidine dihydrochloride include gastrointestinal disturbances such as nausea, vomiting, dyspepsia, abdominal pain, and diarrhea.
Other frequently observed adverse reactions may include dizziness, headache, and asthenia (physical weakness or lack of energy).
Less common but significant adverse effects can include skin rashes, pruritus (itching), urticaria (hives), and generalized flushing.
Of serious concern is the potential for developing or exacerbating Parkinsonian symptoms, including tremor, akinesia (loss of voluntary movement), hypertonia (increased muscle tone), and gait instability, particularly in elderly patients.
Other neurological effects like restless leg syndrome, sleep disturbances, and extrapyramidal symptoms have also been reported.
Orthostatic hypotension may occur, especially in patients taking other antihypertensive agents, leading to symptoms like lightheadedness or fainting.
Patients should be advised to report any new or worsening symptoms promptly to their physician.

Serious Warnings

Black Box Warning: **SERIOUS WARNINGS: POTENTIAL FOR NEUROLOGICAL ADVERSE EFFECTS AND RISK OF EXACERBATING MOVEMENT DISORDERS** Trimetazidine dihydrochloride is not approved by the U.S. Food and Drug Administration (FDA) and therefore does not carry an official FDA Black Box Warning. However, based on extensive international regulatory guidance and clinical data, a serious warning is warranted regarding its potential for significant neurological adverse effects. Trimetazidine has been consistently associated with the development or exacerbation of Parkinsonian symptoms (e.g., tremor, akinesia, hypertonia, gait instability), other extrapyramidal symptoms, and restless leg syndrome. These neurological symptoms can manifest at any time during treatment and are generally reversible upon discontinuation of the drug. However, in some instances, these symptoms may persist, necessitating prolonged medical management. The risk of these adverse effects is particularly heightened in elderly patients and those with pre-existing renal impairment. Consequently, trimetazidine is contraindicated in patients with established Parkinson's disease, existing parkinsonian symptoms, tremors, restless leg syndrome, or any other movement disorder. Healthcare professionals must meticulously assess patients for any signs of neurological symptoms before initiating therapy and monitor them closely throughout the course of treatment. If such symptoms develop or worsen, the drug should be immediately and permanently discontinued. Patients must be comprehensively advised about these potential serious risks and instructed to seek prompt medical attention if they experience any new or worsening movement-related issues or any unexplained neurological changes. This medication is not indicated for the acute treatment of angina attacks or unstable angina; its role is solely as an adjunctive therapy for stable angina.
Trimetazidine dihydrochloride is not a treatment for an acute angina attack and should not be prescribed as an initial treatment for unstable angina or myocardial infarction.
It is not indicated as a stand-alone therapy or for immediate symptom relief.
Special caution is warranted in patients with pre-existing Parkinson's disease or other movement disorders, as trimetazidine can induce or worsen these symptoms.
Patients should be thoroughly informed about the potential for neurological side effects, including dizziness and gait disturbance, which may significantly affect their ability to drive or operate machinery safely.
These symptoms are generally reversible upon discontinuation of treatment but may persist in some cases, requiring further medical management.
Dosage adjustment is absolutely necessary for patients with moderate renal impairment, and the drug is strictly contraindicated in severe renal impairment.
Elderly patients are typically more susceptible to adverse effects due to altered pharmacokinetics and should be monitored very closely for any emerging symptoms, especially neurological ones.

How it Works (Mechanism of Action)

Trimetazidine dihydrochloride operates through a distinctive metabolic mechanism, primarily by inhibiting 3-ketoacyl-CoA thiolase (3-KAT), an enzyme involved in the beta-oxidation of long-chain fatty acids within myocardial cells. By partially inhibiting this enzyme, trimetazidine effectively shifts the myocardial energy production from fatty acid oxidation towards glucose oxidation. Glucose oxidation is recognized as a more oxygen-efficient process than fatty acid oxidation, meaning it requires less oxygen to produce the same amount of adenosine triphosphate (ATP). In conditions of myocardial ischemia, where oxygen supply is limited, this metabolic shift helps to preserve cellular ATP levels, reduce the accumulation of harmful byproducts of fatty acid metabolism, and prevent the associated intracellular acidosis and ionic imbalances (e.g., calcium overload). This cytoprotective effect ultimately improves myocardial function, maintains cellular integrity, and reduces the symptoms of angina pectoris without directly altering hemodynamic parameters like heart rate or blood pressure.