Angimet MR Tablet (Modified Release)

Introduction

Angimet MR Tablet (Modified Release) 35 mg is an anti-ischemic agent primarily used for the treatment of angina pectoris (chest pain) and other conditions related to decreased oxygen supply to the heart. It works by optimizing cellular metabolism during ischemic conditions without affecting hemodynamics (blood flow).

Uses

Angimet MR Tablet (Modified Release) 35 mg is used for:

• Treatment of stable angina pectoris, either alone or in combination with other anti-anginal medications.
• Managing symptoms of inner ear disorders like Ménière’s disease, vertigo, and tinnitus.
• Improving visual disturbances related to retinal vascular disorders.

Mechanism of Action

Trimetazidine works by preserving energy metabolism in cells exposed to hypoxia or ischemia. It selectively inhibits the long-chain 3-ketoacyl-CoA thiolase enzyme in the fatty acid oxidation pathway, leading to increased glucose oxidation. This shift in energy production improves ATP production and helps maintain ion homeostasis in ischemic tissues, particularly in the myocardium (heart muscle).

How Long Does It Take to Work?

Trimetazidine generally begins to work within a few hours of administration, with noticeable clinical effects typically occurring after a few days of continuous use in patients with stable angina.

Absorption

After oral administration, Trimetazidine is rapidly absorbed in the gastrointestinal tract, with peak plasma concentrations (C_max) achieved within 2 hours of ingestion. Its bioavailability is approximately 85%, and food intake has little impact on its absorption.

Route of Elimination

Trimetazidine is predominantly eliminated by the kidneys, with approximately 60% to 75% of the dose excreted unchanged in urine. The remaining portion is metabolized in the liver before renal excretion.

Dosage

The typical dosage for Angimet MR Tablet (Modified Release) 35 mg is:

• Adults (angina pectoris): 35 mg twice daily (extended-release formulation) or 20 mg three times daily (immediate-release formulation).
• Other indications: Doses are typically in the range of 20-35 mg, adjusted based on clinical response.

Administration

Trimetazidine is administered orally, typically with meals to reduce gastrointestinal discomfort. It is available in both immediate-release and extended-release tablet formulations.

Side Effects

Common side effects include:

• Dizziness
• Headache
• Gastrointestinal discomfort (nausea, vomiting, and abdominal pain)
• Fatigue

• Extrapyramidal symptoms (tremors, muscle rigidity, and gait disturbances)
• Allergic skin reactions (rash, itching)

Toxicity

Trimetazidine overdose can lead to increased severity of side effects, particularly neurological symptoms like dizziness and extrapyramidal effects. Supportive treatment and symptomatic care should be provided in case of overdose.

Precautions

• Not recommended for patients with Parkinson’s disease or severe movement disorders due to the risk of worsening motor symptoms.
• Should be used cautiously in elderly patients, as they may be more sensitive to its effects.
• Avoid use in patients with severe renal impairment (creatinine clearance below 30 mL/min).

Interaction

Trimetazidine has minimal drug-drug interaction potential due to its unique mechanism of action. However, caution should be exercised when co-administered with drugs that affect renal function or those with a narrow therapeutic index.

Disease Interaction

• Parkinson’s disease: May worsen motor symptoms.
• Renal impairment: Dosage adjustments are required in patients with moderate renal dysfunction, and it is contraindicated in severe renal impairment.

Drug Interaction

There are no significant interactions reported with other cardiovascular drugs, but caution is advised when used with drugs that influence renal function.

Food Interactions

There are no clinically significant food interactions with Trimetazidine. It can be taken with or without food.

Pregnancy Use

There is limited data on the use of Trimetazidine during pregnancy. It should only be used if the potential benefits justify the risks to the fetus. Animal studies have not shown teratogenic effects, but it is recommended to avoid use during pregnancy unless absolutely necessary.

Lactation Use

It is unknown if Trimetazidine is excreted in human breast milk. Therefore, caution should be exercised, and the drug should only be used in nursing mothers if the potential benefit outweighs the risk to the infant.

Acute Overdose

Symptoms of overdose include exacerbated side effects such as dizziness, headaches, and gastrointestinal symptoms. Neurological symptoms like tremors and rigidity may occur in severe cases. Management of overdose is supportive, with symptomatic treatment as needed.

Contraindication

Trimetazidine is contraindicated in:

• Patients with known hypersensitivity to Trimetazidine or any of its components.
• Patients with Parkinson’s disease or other severe movement disorders.
• Patients with severe renal impairment (creatinine clearance < 30 mL/min).

Use Direction

For angina pectoris, Trimetazidine is usually taken twice a day, with or after meals. The tablets should be swallowed whole, and patients are advised not to chew or crush them.

Storage Conditions

Store at room temperature, between 20°C to 25°C (68°F to 77°F), away from moisture and light. Keep out of reach of children.

Volume of Distribution

Trimetazidine has a moderate volume of distribution of approximately 4.8 L/kg, indicating that it is well distributed in body tissues.

Half Life

The elimination half-life of Trimetazidine is approximately 6 hours, with prolonged clearance in patients with renal impairment.

Clearance

The clearance of Trimetazidine is primarily renal, with a clearance rate of about 250 mL/min in healthy adults. Reduced clearance is observed in elderly patients and those with impaired renal function.

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