Usage
- Trimetazidine is prescribed as an add-on therapy for the symptomatic treatment of stable angina pectoris (chest pain due to reduced blood flow to the heart) in adult patients who are inadequately controlled by or intolerant to first-line antianginal therapies.
- Pharmacological Classification: Antianginal agent, metabolic modulator.
- Trimetazidine shifts myocardial energy metabolism from fatty acid oxidation to glucose oxidation, which is more oxygen-efficient. This helps maintain myocardial energy levels during ischemia, reducing angina symptoms without directly affecting hemodynamics.
Alternate Names
- International variations may exist.
- Brand Names: Vastarel MR, Trizedon, RiteMED Trimetazidine, Trimetazidine Stella MR (and others).
How It Works
- Pharmacodynamics: Trimetazidine optimizes myocardial energy metabolism during ischemia by inhibiting long-chain 3-ketoacyl-CoA thiolase, a key enzyme in fatty acid beta-oxidation. This metabolic shift towards glucose oxidation improves the efficiency of ATP production, preserving cellular function and reducing angina symptoms. Trimetazidine does not typically alter heart rate or blood pressure.
- Pharmacokinetics:
- Absorption: Well-absorbed orally. Modified-release formulations provide sustained plasma levels.
- Metabolism: Hepatic metabolism is a minor elimination pathway.
- Elimination: Primarily renal excretion (around 60% unchanged). Elimination half-life is approximately 6 hours.
- Mode of Action: Inhibits long-chain 3-ketoacyl-CoA thiolase, thereby shifting myocardial energy metabolism from fatty acid oxidation towards glucose oxidation. This improves oxygen utilization and reduces lactic acid accumulation during ischemia.
- Receptor binding, enzyme inhibition, or neurotransmitter modulation: Trimetazidine’s primary mechanism is the inhibition of long-chain 3-ketoacyl-CoA thiolase.
- Elimination pathways: Primarily via renal excretion, with some minor hepatic metabolism.
Dosage
Standard Dosage
Adults:
- Conventional Tablets: 20 mg three times daily with meals.
- Modified-Release Tablets: 35 mg twice daily with meals.
- Prolonged-Release Capsules: 80 mg once daily with breakfast.
Children:
- Not recommended for use in children below 18 years of age as safety and efficacy have not been established.
Special Cases:
- Elderly Patients (especially >75 years): May require dose adjustments based on renal function, starting with a lower dose. Titration should be done cautiously.
- Patients with Renal Impairment (CrCl 30-60 mL/min): Reduced dose is recommended. Conventional tablets: 20 mg twice daily. Modified-release tablets: 35 mg once daily. Contraindicated in severe renal impairment (CrCl <30 mL/min).
- Patients with Hepatic Dysfunction: No specific dosage adjustments indicated but caution advised.
- Patients with Comorbid Conditions: Use with caution in patients with diabetes, cardiovascular disease, and other conditions, with dose adjustments as needed based on renal function and overall health.
Clinical Use Cases
- Trimetazidine is not indicated for:
- Acute angina attacks
- Initial treatment of unstable angina
- Myocardial infarction
- Pre-hospital or early hospital phase of acute coronary syndromes
- Its use in settings like intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations involving angina is not routinely recommended.
Dosage Adjustments
- Dose reduction is required in moderate renal impairment and should be considered in elderly patients.
- Dose modifications might be needed for patients with metabolic disorders or genetic polymorphisms affecting drug metabolism, based on individual patient assessment.
Side Effects
Common Side Effects
- Dizziness, headache, gastrointestinal disturbances (nausea, vomiting, abdominal pain, diarrhea, dyspepsia), asthenia, rash, pruritus, urticaria.
Rare but Serious Side Effects
- Parkinsonian symptoms (tremor, akinesia, rigidity), restless legs syndrome, gait disturbances, orthostatic hypotension, blood dyscrasias (agranulocytosis, thrombocytopenia, thrombocytopenic purpura), angioedema, acute generalized exanthematous pustulosis (AGEP), hepatitis.
Long-Term Effects
- Chronic complications from prolonged use are possible, particularly parkinsonian symptoms, which might persist even after discontinuation.
Adverse Drug Reactions (ADR)
- Parkinsonian symptoms, falls (related to gait instability or hypotension), blood dyscrasias, angioedema, acute generalized exanthematous pustulosis (AGEP), hepatitis, significant hypotension.
Contraindications
- Hypersensitivity to trimetazidine.
- Parkinson’s disease, parkinsonian symptoms, tremors, restless legs syndrome, and other related movement disorders.
- Severe renal impairment (CrCl < 30 mL/min).
- Pregnancy and lactation (use with caution, if at all).
Drug Interactions
- No specific CYP450 interactions have been documented, but be cautious when co-administering with:
- Monoamine oxidase inhibitors (MAOIs).
- Certain medications for Parkinson’s disease (e.g., levodopa).
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Data in pregnant women is limited. Animal studies do not show teratogenicity. Avoid use during pregnancy unless absolutely necessary.
- Breastfeeding: It is unknown if trimetazidine is excreted in breast milk. A risk to newborns/infants cannot be excluded. Avoid use during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Inhibits fatty acid oxidation, promotes glucose oxidation in the myocardium, improving energy efficiency during ischemia.
- Side Effects: Dizziness, headache, GI disturbances, asthenia, rash, and rarely, parkinsonian symptoms.
- Contraindications: Hypersensitivity, Parkinson’s disease and related disorders, severe renal impairment.
- Drug Interactions: MAO inhibitors, certain Parkinson’s medications.
- Pregnancy & Breastfeeding: Avoid unless benefits outweigh risks.
- Dosage: Adults: 20 mg TID or 35 mg BID (modified-release) or 80 mg OD (prolonged-release), with meals. Dose adjustments in renal impairment and elderly.
- Monitoring Parameters: Renal function, monitor for parkinsonian symptoms, blood pressure.
Popular Combinations
- Trimetazidine is often used in combination with other antianginal medications such as beta-blockers, calcium channel blockers, and nitrates to optimize angina control.
Precautions
- Assess renal function, especially in elderly patients.
- Screen for parkinsonian symptoms, especially during long-term use.
- Caution in patients with hypotension.
- Advise patients about potential dizziness and its impact on driving/operating machinery.
FAQs (Frequently Asked Questions)
A: Adults: 20 mg three times daily or 35 mg twice daily (modified-release), or 80 mg once daily (prolonged-release), with meals. Dose adjustments needed for renal impairment and in elderly patients. Not recommended for children under 18.
A: It shifts myocardial energy metabolism from fatty acid oxidation to glucose oxidation, leading to better oxygen utilization during ischemia and reduced angina symptoms.
Q3: What are the common side effects?
A: Dizziness, headache, gastrointestinal disturbances, asthenia, rash, itching, hives.
Q4: What are the serious side effects to watch for?
A: Parkinsonian symptoms, orthostatic hypotension, falls, blood dyscrasias, angioedema, acute generalized exanthematous pustulosis (AGEP).
A: Limited data available; avoid use unless absolutely necessary.
A: Dose adjustment required in moderate renal impairment. Contraindicated in severe renal impairment.
A: Use cautiously with MAO inhibitors and some anti-Parkinson’s drugs.
A: The onset of action and duration of effect can vary. The benefit should be assessed after three months of therapy.
A: No, it is not indicated for acute angina attacks.
A: Patients should be informed about potential side effects, including dizziness and the risk of falls, and advised to avoid driving or operating machinery if affected. They should also report any new or worsening neurological symptoms promptly.
