Usage
This combination is prescribed for stable angina pectoris, particularly in patients inadequately controlled by or intolerant to first-line antianginal therapies. Metoprolol belongs to the beta-adrenergic blocking agent class, while trimetazidine is classified as an anti-ischemic metabolic agent. Metoprolol works by blocking beta-1 adrenergic receptors, reducing heart rate and myocardial contractility, thereby decreasing oxygen demand. Trimetazidine shifts myocardial energy metabolism from fatty acid oxidation to glucose oxidation, improving energy efficiency and reducing ischemia.
Alternate Names
While the combination itself doesn’t have alternative names, the individual components do. Metoprolol succinate may be referred to simply as metoprolol. Trimetazidine is also available as trimetazidine dihydrochloride. Brand names for metoprolol include Lopressor, Toprol XL, and Betaloc. Trimetazidine is marketed under various brand names such as Vastarel, Metacard, and Preductal MR.
How It Works
Metoprolol Succinate:
- Pharmacodynamics: Metoprolol primarily blocks beta-1 adrenergic receptors in the heart, leading to decreased heart rate, contractility, and cardiac output, thus reducing myocardial oxygen demand. It also has some beta-2 blocking activity, particularly at higher doses.
- Pharmacokinetics: Metoprolol succinate is an extended-release formulation, meaning it is absorbed slowly and steadily. It is metabolized primarily by the liver, specifically CYP2D6, and excreted mainly in the urine.
Trimetazidine:
- Pharmacodynamics: Trimetazidine inhibits long-chain 3-ketoacyl CoA thiolase, a key enzyme in fatty acid oxidation. This shifts myocardial energy metabolism towards glucose oxidation, which is more oxygen-efficient. Trimetazidine does not affect hemodynamics.
- Pharmacokinetics: Trimetazidine is well-absorbed orally, reaching peak plasma concentrations in approximately 5 hours for immediate release and a longer time for extended-release formulations. It is excreted primarily unchanged in the urine, with a half-life of about 7 hours (longer in elderly patients).
Combined Mechanism: The combination of metoprolol and trimetazidine provides synergistic anti-ischemic effects. Metoprolol reduces myocardial oxygen demand while trimetazidine optimizes myocardial oxygen utilization.
Dosage
Standard Dosage
Adults:
- Metoprolol Succinate: 25 mg to 200 mg orally once a day, depending on indication and patient response.
- Trimetazidine: 20 mg three times daily (immediate release) or 35 mg twice daily (modified release).
Children:
Use of this combination in children is generally not recommended due to limited safety and efficacy data.
Special Cases:
- Elderly Patients: Start with lower doses of both medications and titrate cautiously. Monitor for side effects.
- Patients with Renal Impairment: Dose adjustment may be necessary for both drugs based on creatinine clearance.
- Patients with Hepatic Dysfunction: Dose adjustment is recommended for metoprolol.
- Patients with Comorbid Conditions: Caution is advised in patients with diabetes, asthma, or peripheral vascular disease.
Clinical Use Cases
The primary use case is chronic stable angina. Dosages for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations would involve individual adjustments for metoprolol or other appropriate agents and not this combination. Trimetazidine is generally not used in these acute settings.
Dosage Adjustments
Dose adjustments are based on individual patient response, renal and hepatic function, and presence of other medical conditions. Careful titration is crucial, especially in elderly and patients with renal or hepatic impairment.
Side Effects
Common Side Effects
- Metoprolol: Fatigue, dizziness, bradycardia, hypotension, diarrhea, nausea, and cold extremities.
- Trimetazidine: Nausea, vomiting, gastrointestinal discomfort, dizziness, headache, and asthenia.
Rare but Serious Side Effects
- Metoprolol: Heart block, bronchospasm, worsening heart failure.
- Trimetazidine: Parkinsonian symptoms, tremors, restless leg syndrome.
Long-Term Effects
Potential long-term effects of metoprolol may include worsening of pre-existing heart failure or bronchospastic disease. Trimetazidine’s long-term effects may include movement disorders, including Parkinsonian symptoms.
Adverse Drug Reactions (ADR)
ADRs needing immediate intervention include severe bradycardia, hypotension, bronchospasm (metoprolol) and extrapyramidal symptoms (trimetazidine).
Contraindications
- Metoprolol: Bradycardia, heart block, decompensated heart failure, severe peripheral vascular disease.
- Trimetazidine: Parkinson’s disease, Parkinsonian symptoms, restless legs syndrome, tremors, severe renal impairment. Concurrent use of dopamine agonists is also contraindicated.
Drug Interactions
- Metoprolol: Interacts with calcium channel blockers, digoxin, insulin, and other beta-blockers. Cimetidine may increase metoprolol levels.
- Trimetazidine: Although few drug interactions have been reported, caution is advised with other medications metabolized by the liver.
Pregnancy and Breastfeeding
- Metoprolol: Metoprolol crosses the placenta and is present in breast milk. It is generally considered safe during pregnancy and breastfeeding, but monitoring is necessary.
- Trimetazidine: Data on trimetazidine use during pregnancy is limited. Its presence in breast milk is unknown. Use during pregnancy and breastfeeding should be avoided unless clearly needed.
Drug Profile Summary
- Mechanism of Action: Metoprolol: Beta-blocker; Trimetazidine: Anti-ischemic metabolic agent.
- Side Effects: See detailed side effects section.
- Contraindications: See detailed contraindications section.
- Drug Interactions: See detailed drug interactions section.
- Pregnancy & Breastfeeding: Metoprolol: Generally safe with monitoring; Trimetazidine: Avoid.
- Dosage: See detailed dosage section.
- Monitoring Parameters: Heart rate, blood pressure, electrocardiogram (ECG), signs of heart failure, blood glucose levels (for diabetics).
Popular Combinations
Metoprolol and trimetazidine are frequently combined with other antianginal drugs like nitrates and calcium channel blockers.
Precautions
See sections on contraindications, drug interactions, and pregnancy/breastfeeding. Monitor heart rate, blood pressure, and ECG. Screen for pre-existing conditions.
FAQs (Frequently Asked Questions)
A: Metoprolol Succinate: 25 mg to 200 mg once daily; Trimetazidine: 20 mg thrice daily (immediate release) or 35 mg twice daily (modified release). Dosage adjustments are based on individual patient response and comorbidities.
Q2: What are the key differences between Metoprolol Tartrate and Metoprolol Succinate?
A: Metoprolol tartrate is immediate-release, while metoprolol succinate is extended-release. Succinate offers once-daily dosing and more stable plasma levels.
A: It optimizes myocardial energy metabolism by shifting from fatty acid oxidation to glucose oxidation, which requires less oxygen.
Q4: What are the contraindications for using this combination?
A: Contraindications include severe bradycardia, heart block, decompensated heart failure, Parkinson’s disease, Parkinsonian symptoms, and severe renal impairment.
Q5: Can this combination be used in patients with diabetes?
A: Caution is advised in patients with diabetes as metoprolol can mask symptoms of hypoglycemia. Careful monitoring of blood glucose is essential.
Q6: What are the potential drug interactions with this combination?
A: Metoprolol interacts with calcium channel blockers, digoxin, and cimetidine. Trimetazidine has few documented drug interactions but caution is advised with hepatic metabolized medications.
Q7: What are the monitoring parameters for this drug combination?
A: Monitor heart rate, blood pressure, ECG, symptoms of heart failure, and blood glucose levels (for patients with diabetes).
Q8: Is it safe to use this combination during pregnancy?
A: Metoprolol is generally considered safe, but trimetazidine should be avoided unless clearly necessary due to limited safety data.
Q9: Can this combination be used in patients with renal impairment?
A: Dose adjustments are necessary for both drugs in patients with renal impairment, depending on the severity of the impairment.
A: Trimetazidine inhibits long-chain 3-ketoacyl CoA thiolase, shifting myocardial energy metabolism from fatty acid oxidation to glucose oxidation. This improves oxygen utilization by the heart.
