Usage
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This combination medication is primarily prescribed for the management of hypertension (high blood pressure). It may also be used to treat angina (chest pain), improve exercise capacity in patients with angina, and reduce the frequency of angina attacks. Furthermore, it can be used in the treatment of heart failure, and after a heart attack to reduce the risk of future heart attacks and strokes.
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Pharmacological Classification: This is a combination product containing a calcium channel blocker (S-Amlodipine) and a beta-blocker (S-Metoprolol Tartrate).
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Mechanism of Action: S-Amlodipine inhibits the influx of calcium ions into vascular smooth muscle cells, leading to vasodilation (widening of blood vessels) and a reduction in blood pressure. S-Metoprolol selectively blocks beta-1 adrenergic receptors in the heart, decreasing heart rate and contractility, which further contributes to lower blood pressure.
Alternate Names
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Levamlodipine + S-Metoprolol Tartrate
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S-Amlodipine besylate + S-Metoprolol succinate
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Brand Names: Actiblok AM 25, Amlodac M, Asomex-M, Eslomet, Metolash AM. Several other brand names likely exist in different markets.
How It Works
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Pharmacodynamics: S-Amlodipine primarily affects the vascular smooth muscle by causing vasodilation, while S-Metoprolol primarily acts on the heart, reducing heart rate and contractility. The combination leads to a synergistic decrease in blood pressure.
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Pharmacokinetics:
- Absorption: Both drugs are orally absorbed. Amlodipine reaches peak plasma levels in 6-12 hours, S-metoprolol in about 1.5 - 2 hours.
- Metabolism: Amlodipine is extensively metabolized by the liver (primarily CYP3A4). Metoprolol is also metabolized in the liver, mainly by the CYP2D6 enzyme.
- Elimination: Amlodipine is eliminated through both renal and hepatic pathways, having a terminal elimination half-life of approximately 30-50 hours. Metoprolol is primarily eliminated by hepatic metabolism.
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Mode of Action: S-Amlodipine blocks L-type calcium channels, leading to a decrease in intracellular calcium concentration in vascular smooth muscle. This decrease in calcium inhibits muscle contraction, resulting in vasodilation. S-Metoprolol selectively blocks beta-1 adrenergic receptors, reducing the effects of sympathetic stimulation on the heart, resulting in a decrease in heart rate and contractility.
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Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: S-Amlodipine acts on L-type calcium channels, and S-Metoprolol acts as a beta-1 adrenergic receptor antagonist.
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Elimination Pathways: Amlodipine is eliminated through both renal and hepatic pathways. Metoprolol is primarily eliminated by hepatic metabolism, mainly via the CYP2D6 enzyme.
Dosage
Standard Dosage
Adults:
- Initial dose: S-Amlodipine 2.5 mg / S-Metoprolol 25 mg once daily.
- Maintenance dose: The dosage may be titrated up based on the patient’s blood pressure response to a maximum of S-Amlodipine 10 mg / S-Metoprolol 200 mg per day. It’s typical to adjust the dose at weekly intervals, or even longer, until optimal response is achieved.
Children:
- This combination is generally not recommended for children under 6 years of age.
- For children older than 6, the dose needs to be individualized and carefully titrated under close medical supervision, starting with a lower dose based on the child’s weight and the specific condition being treated.
Special Cases:
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Elderly Patients: Initiate therapy with lower doses and titrate cautiously due to potential age-related changes in drug clearance and increased sensitivity to side effects.
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Patients with Renal Impairment: Dose adjustments may be required based on the degree of impairment. Close monitoring is essential.
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Patients with Hepatic Dysfunction: Start with lower doses and titrate cautiously due to the potential for altered metabolism. A lower initial dose may be required for patients with hepatic impairment. Consider starting with 2.5 mg/day PO.
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Patients with Comorbid Conditions: Careful evaluation and dose adjustment are crucial for patients with conditions like diabetes, heart failure, or asthma.
Clinical Use Cases
- The sources do not provide specific dosage recommendations for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Dosage should be determined on a case-by-case basis considering the patient’s condition and other medications they are receiving. For a myocardial infarction, after IV administration of metoprolol, an initial dose of 50 mg orally every 6 hours for 48 hours may be given to patients tolerant of the full IV dose. Patients intolerant of the full IV dose may receive 25 or 50mg orally every 6 hours.
Dosage Adjustments
- Dose modifications should be based on patient-specific factors like renal/hepatic dysfunction, other comorbid conditions, and response to therapy. Close monitoring of blood pressure, heart rate, and other relevant clinical parameters is necessary throughout treatment.
Side Effects
Common Side Effects
- Fatigue, dizziness, headache, nausea, peripheral edema (swelling in the ankles or feet), bradycardia (slow heart rate), hypotension (low blood pressure), and shortness of breath.
Rare but Serious Side Effects
- Severe chest pain, difficulty breathing, irregular heartbeat, allergic reactions (skin rash, itching, swelling), and worsening of heart failure.
Long-Term Effects
- Potential long-term effects of this combination may include worsening of pre-existing heart conditions if not properly monitored and managed.
Adverse Drug Reactions (ADR)
- Clinically significant ADRs include severe hypotension, bradycardia, heart block, and bronchospasm (especially in patients with asthma), requiring immediate medical attention.
Contraindications
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Absolute Contraindications: Hypersensitivity to amlodipine, metoprolol, or any component of the formulation; severe bradycardia; second- or third-degree heart block; sick sinus syndrome (unless a pacemaker is present); cardiogenic shock; decompensated heart failure; severe hepatic impairment; severe aortic stenosis; untreated pheochromocytoma.
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Relative Contraindications: Conditions like diabetes, asthma, peripheral vascular disease, cerebrovascular disease, and impaired renal or hepatic function may require careful consideration and dose adjustment.
Drug Interactions
- Clinically Significant Drug Interactions: Other antihypertensives (additive hypotensive effects); CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, erythromycin) may increase amlodipine levels; CYP2D6 inhibitors (e.g., fluoxetine, paroxetine) may increase metoprolol levels; beta-blockers (additive bradycardia and hypotension); calcium channel blockers (additive hypotension); digoxin (increased risk of bradycardia); insulin or oral hypoglycemics (masked hypoglycemia); alcohol (increased risk of hypotension and dizziness); grapefruit juice (may inhibit amlodipine metabolism, leading to elevated drug levels); certain NSAIDs (may reduce the antihypertensive effects of the medication).
Pregnancy and Breastfeeding
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Pregnancy: Pregnancy Category C. Use only if clearly needed. Metoprolol may cause intrauterine growth restriction. No adequate and well-controlled studies of amlodipine and metoprolol have been done in pregnant women. Because animal reproduction studies are not always predictive of human response, use this drug combination during pregnancy only if clearly needed.
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Breastfeeding: Metoprolol is excreted in breast milk; amlodipine’s excretion is unknown. It’s recommended to discontinue breastfeeding while taking this medication, considering the potential risks to the infant versus the benefits to the mother.
Drug Profile Summary
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Mechanism of Action: Calcium channel blockade (amlodipine) and beta-1 adrenergic blockade (metoprolol) leading to vasodilation and reduced cardiac output.
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Side Effects: Dizziness, headache, fatigue, nausea, edema, bradycardia, hypotension.
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Contraindications: Severe bradycardia, heart block, cardiogenic shock, decompensated heart failure.
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Drug Interactions: Other antihypertensives, CYP3A4 inhibitors, CYP2D6 inhibitors, digoxin, alcohol, grapefruit juice, certain NSAIDs.
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Pregnancy & Breastfeeding: Category C; use with caution. Generally, breastfeeding is not recommended while taking this medication.
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Dosage: Adults: Start with S-Amlodipine 2.5 mg / S-Metoprolol 25 mg once daily, titrate as needed. Not recommended for children under 6.
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Monitoring Parameters: Blood pressure, heart rate, signs of heart failure, blood glucose levels, and renal/hepatic function tests if indicated.
Popular Combinations
- This combination itself is a common and effective therapy for hypertension. Sometimes, a thiazide diuretic may be added to further enhance blood pressure control.
Precautions
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General Precautions: Monitor blood pressure, heart rate, and ECG. Evaluate hepatic and renal function if necessary before initiating therapy.
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Specific Populations: Exercise caution in patients with diabetes, asthma, peripheral vascular disease, and cerebrovascular disease. Careful monitoring is essential, especially in elderly patients and patients with renal or hepatic impairment.
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Lifestyle Considerations: Patients should limit alcohol intake, avoid smoking, follow a balanced diet (potentially a low-sodium diet), and engage in regular exercise as advised by their physician. Driving or operating heavy machinery should be avoided if dizziness or fatigue occurs.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for S-Amlodipine + S-Metoprolol Tartrate?
A: The initial dose is typically S-Amlodipine 2.5 mg/S-Metoprolol 25 mg once daily. The dose can be titrated up to a maximum of S-Amlodipine 10 mg/S-Metoprolol 200 mg per day, based on the patient’s blood pressure response and tolerability.
Q2: What are the common side effects?
A: Common side effects include fatigue, dizziness, headache, nausea, ankle swelling, slow heart rate, and low blood pressure.
A: Serious side effects include severe chest pain, difficulty breathing, allergic reactions (skin rash, itching, swelling), irregular heartbeat, and worsening of heart failure.
Q4: Can this medication be used during pregnancy or breastfeeding?
A: This medication is generally avoided during pregnancy and breastfeeding due to potential risks to the fetus or infant. Consult a physician for individual guidance.
Q5: What are the contraindications for this medication?
A: This medication is contraindicated in individuals with severe bradycardia, heart block, cardiogenic shock, decompensated heart failure, severe hepatic impairment, severe aortic stenosis, and untreated pheochromocytoma.
Q6: What other medications should be avoided while taking S-Amlodipine + S-Metoprolol Tartrate?
A: Avoid or use with caution medications like other antihypertensives, CYP3A4 inhibitors (e.g., ketoconazole, itraconazole), CYP2D6 inhibitors (e.g., fluoxetine, paroxetine), digoxin, and certain NSAIDs. Inform your doctor about all medications, including over-the-counter drugs and supplements you are taking.
Q7: How does this medication interact with grapefruit juice?
A: Grapefruit juice can inhibit the metabolism of amlodipine, potentially increasing drug levels and side effects. It’s best to avoid grapefruit juice during treatment.
Q8: Are there any dietary restrictions while taking this medication?
A: It’s often recommended to follow a low-sodium diet to help control blood pressure. Limiting alcohol intake is also advised due to the potential for additive hypotensive effects.
Q9: What should I do if I miss a dose?
A: If you miss a dose, take it as soon as you remember. However, if it is close to the time for your next dose, skip the missed dose and continue with your regular dosing schedule. Do not double the dose to catch up.
Q10: How should I store this medication?
A: Store the medication at room temperature, away from moisture, heat, and direct sunlight. Keep it out of the reach of children.
