Usage
Nebivolol + S-Amlodipine is primarily prescribed for the treatment of hypertension (high blood pressure) and chronic stable angina. It is a fixed-dose combination medication containing two distinct antihypertensive agents.
Pharmacological Classification:
- Nebivolol: Cardio-selective beta-1 adrenergic blocker.
- S-Amlodipine: Dihydropyridine calcium channel blocker.
Mechanism of Action: This combination therapy targets two different mechanisms involved in blood pressure regulation. Nebivolol reduces heart rate and myocardial contractility by selectively blocking beta-1 adrenergic receptors, while also promoting vasodilation through nitric oxide release. S-Amlodipine inhibits calcium influx into vascular smooth muscle cells, leading to vasodilation and reduced peripheral vascular resistance. The combined effect results in a significant reduction in blood pressure.
Alternate Names
Several alternate names and brand names exist for this combination, although the generic name “Nebivolol + S-Amlodipine” is most commonly used. Some examples include:
Brand Names: Nebicard-SM, Nebistar-SA, Nebizem SM, Nebivas SA, Nebipril-SA, Nebilong-AM, BEVOS.
How It Works
Pharmacodynamics: Nebivolol exerts its antihypertensive effect through beta-1 adrenergic receptor blockade, reducing heart rate, cardiac output, and renin release. S-Amlodipine, a calcium channel blocker, inhibits calcium ion influx across cell membranes, leading to vasodilation of peripheral arterioles and a decrease in systemic vascular resistance.
Pharmacokinetics:
- Absorption: Both drugs are orally absorbed, with S-amlodipine achieving peak plasma concentration within 6-12 hours, and nebivolol showing somewhat variable absorption.
- Metabolism: Nebivolol is extensively metabolized in the liver, primarily by CYP2D6, producing active metabolites. S-Amlodipine is also extensively metabolized by the liver.
- Elimination: Nebivolol is eliminated through both renal and hepatic routes. S-amlodipine is primarily excreted in the urine and feces as inactive metabolites.
Mode of Action: Nebivolol binds to beta-1 adrenergic receptors in the heart, inhibiting the binding of catecholamines and reducing sympathetic activity. S-Amlodipine binds to L-type calcium channels in vascular smooth muscle, blocking calcium influx and causing vasodilation.
Receptor Binding/Enzyme Inhibition: Nebivolol selectively binds to beta-1 adrenergic receptors. S-Amlodipine inhibits L-type calcium channels.
Elimination Pathways: Both renal and hepatic excretion are involved in the elimination of nebivolol and its metabolites. S-Amlodipine primarily undergoes hepatic metabolism followed by excretion in urine and feces.
Dosage
Standard Dosage
Adults: The usual starting dose is Nebivolol 2.5mg/S-Amlodipine 5mg or Nebivolol 5mg/S-Amlodipine 5mg once daily. The maximum dose is Nebivolol 5mg/S-Amlodipine 10mg once daily.
Children: Not recommended for use in children and adolescents under 18 years old due to insufficient safety and efficacy data.
Special Cases:
- Elderly Patients: Initial dose of Nebivolol 2.5mg/S-Amlodipine 5mg once daily. Titrate cautiously based on patient response.
- Patients with Renal Impairment: Mild to moderate impairment requires no dose adjustment. Severe renal impairment (CrCl < 30 mL/min): Initial dose of Nebivolol 2.5mg/S-Amlodipine 5mg once daily; titrate cautiously.
- Patients with Hepatic Dysfunction: Moderate impairment (Child-Pugh B): Initial dose of Nebivolol 2.5mg/S-Amlodipine 5mg once daily; titrate cautiously. Severe hepatic impairment (Child-Pugh C): Not recommended.
- Patients with Comorbid Conditions: Use with caution in patients with diabetes, thyroid disease, asthma, or peripheral vascular disease. Close monitoring is advised.
Clinical Use Cases
The combination of Nebivolol and S-Amlodipine is generally not indicated for acute clinical situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its primary role is in chronic management of hypertension and stable angina.
Dosage Adjustments
Dose adjustments may be necessary based on individual patient response, renal/hepatic function, and the presence of comorbid conditions. Titration should be done cautiously, especially in elderly patients and those with renal or hepatic impairment.
Side Effects
Common Side Effects:
Headache, dizziness, fatigue, edema (especially of the ankles and feet), nausea, flushing.
Rare but Serious Side Effects:
Bradycardia, hypotension, worsening heart failure, bronchospasm, angioedema, severe allergic reactions.
Long-Term Effects:
Potential long-term effects of this combination are not well-established, but may include worsening of pre-existing conditions like heart failure or peripheral vascular disease if not closely monitored.
Adverse Drug Reactions (ADR):
Angioedema, severe hypotension, bronchospasm, and severe allergic reactions are potentially life-threatening ADRs that require immediate medical intervention.
Contraindications
- Severe bradycardia
- Second or third-degree heart block (without pacemaker)
- Cardiogenic shock
- Decompensated heart failure
- Severe hepatic impairment (Child-Pugh Class C)
- Hypersensitivity to either nebivolol or amlodipine
Drug Interactions
Nebivolol + S-Amlodipine can interact with several medications, including:
- CYP2D6 inhibitors (e.g., fluoxetine, paroxetine): Can increase nebivolol levels.
- CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, erythromycin): Can increase amlodipine levels.
- Other antihypertensive drugs: Additive hypotensive effects.
- Beta-blockers (including ophthalmic preparations): Additive bradycardia and hypotensive effects.
- Calcium channel blockers: Increased risk of hypotension and bradycardia.
- Digoxin: Can increase digoxin levels.
It’s crucial to consider potential interactions with other medications, OTC drugs, supplements, alcohol, and grapefruit juice.
Pregnancy and Breastfeeding
The safety of Nebivolol + S-Amlodipine during pregnancy and breastfeeding has not been fully established. Its use should be avoided unless the potential benefit to the mother clearly outweighs the potential risk to the fetus or infant. Consult with a specialist for individual risk assessment and alternative treatments if necessary.
Drug Profile Summary
- Mechanism of Action: Nebivolol: Beta-1 adrenergic blocker, S-Amlodipine: Calcium channel blocker.
- Side Effects: Headache, dizziness, fatigue, edema, nausea, flushing. Rarely: bradycardia, hypotension, worsening heart failure.
- Contraindications: Severe bradycardia, heart block, cardiogenic shock, decompensated heart failure, severe hepatic impairment, hypersensitivity.
- Drug Interactions: CYP2D6 and CYP3A4 inhibitors, other antihypertensives, beta-blockers, calcium channel blockers, digoxin.
- Pregnancy & Breastfeeding: Use with caution; potential risks to fetus/infant.
- Dosage: Adults: Starting dose 2.5/5mg or 5/5mg once daily; max 5/10mg. Elderly: Start with 2.5/5mg. Renal/Hepatic impairment: Dose adjustment may be needed.
- Monitoring Parameters: Blood pressure, heart rate, signs and symptoms of heart failure, peripheral edema.
Popular Combinations
Nebivolol + S-Amlodipine is itself a combination medication. Further combining it with other antihypertensives should be done with caution and close monitoring for additive effects.
Precautions
- General Precautions: Assess renal and hepatic function, monitor blood pressure and heart rate regularly.
- Specific Populations: Caution in elderly patients, patients with renal/hepatic impairment, asthma, diabetes, and peripheral vascular disease. Avoid in pregnancy/breastfeeding unless clearly necessary.
- Lifestyle Considerations: Encourage lifestyle modifications including a low-sodium diet, regular exercise, limited alcohol intake, and smoking cessation.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Nebivolol + S-Amlodipine?
A: The standard adult starting dose is Nebivolol 2.5mg/S-Amlodipine 5mg or Nebivolol 5mg/S-Amlodipine 5mg once daily, with a maximum dose of Nebivolol 5mg/S-Amlodipine 10mg once daily. Elderly patients should typically start with a lower dose of Nebivolol 2.5mg/S-Amlodipine 5mg once daily. Dosages may need adjustment based on patient response and renal/hepatic function. Pediatric use is not recommended.
Q2: What are the common side effects?
A: Common side effects include headache, dizziness, fatigue, peripheral edema, nausea, and flushing.
Q3: What are the serious side effects I should watch for?
A: Serious side effects include bradycardia, hypotension, worsening heart failure, bronchospasm, angioedema, and severe allergic reactions.
Q4: Can this medication be used during pregnancy?
A: Use during pregnancy is generally not recommended unless the potential benefit to the mother significantly outweighs the risk to the fetus. Consult with a specialist for individualized assessment.
Q5: What if my patient has renal impairment?
A: For mild to moderate renal impairment, no dose adjustment is usually necessary. For severe renal impairment (CrCl < 30 mL/min), start with Nebivolol 2.5mg/S-Amlodipine 5mg once daily and titrate cautiously.
Q6: Can Nebivolol + S-Amlodipine be combined with other antihypertensive medications?
A: While it can be used in combination with other antihypertensives, this should be done cautiously and with close monitoring for additive effects like hypotension.
Q7: What are the contraindications for this combination?
A: Contraindications include severe bradycardia, second or third-degree heart block, cardiogenic shock, decompensated heart failure, severe hepatic impairment, and hypersensitivity to either drug.
Q8: How should I monitor patients on this medication?
A: Monitor blood pressure and heart rate regularly. Also watch for signs and symptoms of heart failure, such as shortness of breath, peripheral edema, and weight gain. Pay attention to any complaints of dizziness or lightheadedness.
Q9: How does this combination work at the cellular level?
A: Nebivolol blocks beta-1 adrenergic receptors in the heart, reducing heart rate and contractility. S-Amlodipine blocks calcium channels in vascular smooth muscle, leading to vasodilation. The combined effect reduces blood pressure through distinct mechanisms.
Q10: What should patients know about lifestyle modifications while taking this medication?
A: Patients should be advised on lifestyle modifications that can complement the medication’s effects, including a low-sodium diet, regular exercise, limiting alcohol consumption, and smoking cessation.
