Metazine MR

• Approved Indications:
• Adjunctive treatment of stable angina pectoris to reduce the frequency of angina attacks and improve exercise tolerance, particularly when standard antianginal therapies are insufficient or contraindicated.
• Management of ischemic heart disease symptoms by improving myocardial metabolism.
• Off-label Uses:
• Treatment of vertigo and tinnitus associated with inner ear disorders.
• Occasionally used for management of certain cardiomyopathies and peripheral arterial disease symptoms.

• Adults:
• Oral dose: 20 mg to 35 mg taken two to three times daily with meals.
• Extended-release formulations: 35 mg twice daily.
• Duration is usually long-term, based on clinical response and physician assessment.
• Elderly:
• No specific dosage adjustment recommended; caution advised due to potential renal impairment.
• Pediatrics:
• Safety and efficacy not established in children; use not recommended.
• Special Populations:
• Use with caution in patients with renal impairment; dose adjustment may be necessary depending on severity.
• Not recommended in severe hepatic impairment.
• Administration:
• Oral tablets taken with meals to improve absorption and reduce gastrointestinal side effects.

Trimetazidine is a metabolic agent that improves myocardial glucose utilization by inhibiting mitochondrial long-chain 3-ketoacyl-CoA thiolase (an enzyme involved in fatty acid β-oxidation). This inhibition shifts cardiac energy metabolism from fatty acid oxidation to more oxygen-efficient glucose oxidation, thereby enhancing myocardial energy production during ischemia. By optimizing cardiac metabolism, trimetazidine reduces cellular ischemic injury and improves myocardial tolerance to hypoxia without affecting hemodynamics or coronary blood flow.

• Absorption: Rapidly absorbed from the gastrointestinal tract with peak plasma concentrations reached within 1 to 2 hours post-dose.
• Bioavailability: Approximately 90%.
• Distribution: Widely distributed; low plasma protein binding (~16%).
• Metabolism: Minimally metabolized by the liver.
• Elimination: Mainly excreted unchanged via the kidneys.
• Half-life: Approximately 6 hours.
• Onset of Action: Clinical effects may begin within a few days of treatment, with maximum benefits seen over weeks.

• Pregnancy:
• FDA pregnancy category not assigned. Limited data in humans; animal studies do not indicate direct teratogenic effects. Use only if clearly needed.
• Lactation:
• It is unknown whether trimetazidine is excreted in human milk. Caution is advised; breastfeeding is generally not recommended during treatment.

• Primary Class: Metabolic agent
• Subclass: Anti-ischemic metabolic modulator

• Known hypersensitivity to trimetazidine or any excipients.
• Parkinson’s disease or other movement disorders.
• Severe renal impairment (creatinine clearance <30 mL/min).
• Pregnancy and lactation unless benefits outweigh risks.

• Use with caution in patients with renal impairment; dosage adjustment recommended.
• Rarely associated with extrapyramidal symptoms such as Parkinsonism, tremors, and gait disturbances—monitor closely and discontinue if such symptoms develop.
• Not recommended in patients with movement disorders.
• Monitor for neurological symptoms during therapy.
• Avoid abrupt discontinuation unless adverse neurological effects occur.

• Common:
• Headache, dizziness.
• Gastrointestinal disturbances (nausea, vomiting, abdominal discomfort).
• Serious/Rare:
• Extrapyramidal symptoms (tremor, rigidity, bradykinesia).
• Allergic reactions including rash and pruritus.
• Very rare cases of thrombocytopenia or hypersensitivity reactions.
• Side effects may appear weeks to months after treatment initiation and are usually reversible upon discontinuation.

• No significant drug interactions have been reported.
• Caution when used concomitantly with other drugs that may cause extrapyramidal symptoms.
• No known CYP450 enzyme involvement; low potential for pharmacokinetic interactions.

• Continued recommendation as adjunctive therapy in stable angina by various cardiovascular societies.
• Warnings regarding potential movement disorder side effects have been emphasized, leading to updated prescribing information in some regions.
• No major recent changes in dosing guidelines.
• Ongoing evaluation of its role in microvascular angina and metabolic cardiomyopathies.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep in a tightly closed container.
• Do not freeze.
• Keep out of reach of children.