Usage
- Nebivolol is primarily prescribed for the management of hypertension (high blood pressure) and chronic heart failure. It may also be used to treat angina (chest pain).
- Pharmacological classification: Beta-1 selective adrenergic blocking agent (beta-blocker).
- Mechanism of Action: Nebivolol primarily blocks beta-1 adrenergic receptors in the heart, leading to decreased heart rate and force of contraction, thus lowering blood pressure. It also exhibits vasodilatory properties, further contributing to blood pressure reduction. It is highly selective for beta-1 receptors at low doses.
Alternate Names
- International variations may exist.
- Brand Names: Bystolic, Nebilet, Nebilong, and others.
How It Works
- Pharmacodynamics: Nebivolol reduces heart rate, myocardial contractility, systolic and diastolic blood pressure. It also inhibits renin release from the kidneys. It may improve left ventricular function in heart failure.
- Pharmacokinetics:
- Absorption: Well-absorbed orally.
- Metabolism: Extensively metabolized by the liver, primarily via CYP2D6. Individuals with reduced CYP2D6 activity (poor metabolizers) have higher plasma concentrations of nebivolol.
- Elimination: Excreted in urine and feces. Half-life is approximately 12-24 hours.
- Mode of Action: Nebivolol binds to and blocks beta-1 adrenergic receptors, inhibiting the effects of catecholamines (like adrenaline and noradrenaline) on the heart, leading to a decrease in heart rate and force of contraction, and a reduction in blood pressure.
- Receptor Binding: Highly selective for beta-1 adrenergic receptors at low doses. Higher doses may affect beta-2 receptors.
- Elimination Pathways: Hepatic metabolism (CYP2D6) followed by renal and fecal excretion.
Dosage
Standard Dosage
Adults:
- Hypertension: Initial dose is 5 mg orally once daily. May be increased to a maximum of 40 mg daily at 2-week intervals based on patient response.
- Chronic Heart Failure: Initial dose is 1.25 mg once daily, up-titrated gradually (every 1-2 weeks) to a maximum of 10 mg daily as tolerated, under close medical supervision.
Children:
- Safety and efficacy not established in pediatric patients. Use is not recommended.
Special Cases:
- Elderly Patients (≥65 years): Initial dose for hypertension is 2.5 mg daily, with cautious up-titration. Initial dose for chronic heart failure (≥70 years) is 1.25 mg daily, with careful titration.
- Patients with Renal Impairment: Initial dose of 2.5 mg daily for mild to moderate impairment (CrCl 30–80 mL/min). Cautious titration if necessary. Not recommended in severe renal impairment (CrCl <30 mL/min).
- Patients with Hepatic Dysfunction: Contraindicated in moderate to severe hepatic impairment (Child-Pugh B or C). Use with caution in mild impairment (Child-Pugh A). Start at 2.5 mg daily and titrate cautiously.
- Patients with Comorbid Conditions: Caution in patients with diabetes, asthma, or peripheral vascular disease. Close monitoring is required.
Clinical Use Cases
- Nebivolol is generally not indicated for acute clinical situations such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations like cardiac arrest. Its primary role is in chronic management of hypertension and heart failure.
Dosage Adjustments
- Dose adjustment is based on patient response, renal function, hepatic function, and the presence of comorbid conditions.
Side Effects
Common Side Effects
- Headache, fatigue, dizziness, nausea, diarrhea, bradycardia (slow heart rate).
Rare but Serious Side Effects
- Severe bradycardia, hypotension (low blood pressure), worsening heart failure, bronchospasm (breathing difficulty), heart block.
Long-Term Effects
- May mask symptoms of hypoglycemia in patients with diabetes.
- Potential for worsening of peripheral vascular disease.
Adverse Drug Reactions (ADR)
- Angioedema (swelling of the face, lips, or tongue), severe allergic reactions.
Contraindications
- Severe bradycardia, second or third-degree heart block (unless paced), sick sinus syndrome, cardiogenic shock, decompensated heart failure, severe hepatic impairment (Child-Pugh C), severe peripheral artery disease, hypersensitivity to nebivolol.
Drug Interactions
- CYP2D6 Inhibitors: (e.g., fluoxetine, paroxetine, quinidine) significantly increase nebivolol levels. Dose adjustment may be necessary.
- Other Beta-Blockers: Additive effects on heart rate and blood pressure. Avoid combined use.
- Calcium Channel Blockers (e.g., verapamil, diltiazem): Additive effects on heart rate. Monitor closely.
- Class I Antiarrhythmics (e.g., disopyramide): Additive effects on cardiac conduction. Use with caution.
- Clonidine, Reserpine: Increased risk of bradycardia and hypotension.
- Digoxin: Additive effects on slowing heart rate.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C. Use only if clearly needed and if benefits outweigh risks. Beta-blockers can cause fetal bradycardia, hypoglycemia, and respiratory depression.
- Breastfeeding: Nebivolol is excreted in breast milk. Use is not recommended. Consider alternative antihypertensives.
Drug Profile Summary
- Mechanism of Action: Beta-1 selective adrenergic blocking agent with vasodilatory properties.
- Side Effects: Headache, fatigue, dizziness, nausea, bradycardia. Rarely, severe bradycardia, hypotension, worsening heart failure.
- Contraindications: Severe bradycardia, heart block, decompensated heart failure, severe hepatic impairment.
- Drug Interactions: CYP2D6 inhibitors, other beta-blockers, calcium channel blockers.
- Pregnancy & Breastfeeding: Use with caution in pregnancy only if benefits outweigh risks. Not recommended during breastfeeding.
- Dosage: 5 mg daily for hypertension (initial 2.5 mg in elderly or renal impairment), 1.25 mg daily for heart failure, titrated to a maximum of 10 mg.
- Monitoring Parameters: Blood pressure, heart rate, ECG, signs of heart failure exacerbation.
Popular Combinations
- Hydrochlorothiazide: Combined with nebivolol for enhanced antihypertensive effects.
Precautions
- General Precautions: Monitor heart rate and blood pressure. Assess for history of respiratory or peripheral vascular disease.
- Specific Populations: See Special Cases under Dosage.
- Lifestyle Considerations: Alcohol may enhance hypotensive effects.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Nebivolol?
A: For hypertension, the initial dose is 5 mg once daily, which can be increased to a maximum of 40 mg daily. For heart failure, the initial dose is 1.25 mg daily, titrated to a maximum of 10 mg daily.
Q2: How should Nebivolol be administered?
A: Orally, once daily, with or without food.
Q3: What are the common side effects of Nebivolol?
A: Headache, fatigue, dizziness, nausea, and bradycardia are common side effects.
Q4: What are the contraindications to using Nebivolol?
A: Contraindications include severe bradycardia, heart block, cardiogenic shock, and decompensated heart failure.
Q5: Does Nebivolol interact with other medications?
A: Yes, clinically significant interactions can occur with CYP2D6 inhibitors (e.g., fluoxetine, paroxetine), other beta-blockers, and calcium channel blockers.
Q6: Can Nebivolol be used during pregnancy or breastfeeding?
A: Nebivolol should be used during pregnancy only if clearly needed and benefits outweigh risks. It is not recommended during breastfeeding.
Q7: How does Nebivolol work in heart failure?
A: Nebivolol reduces heart rate and improves cardiac output, potentially improving left ventricular function in heart failure patients.
Q8: How long does it take for Nebivolol to take effect?
A: The blood pressure-lowering effect is typically evident within 1-2 weeks, with optimal effects sometimes taking up to 4 weeks.
Q9: What should patients be monitored for while taking Nebivolol?
A: Monitor blood pressure, heart rate, and ECG regularly. Watch for signs of worsening heart failure, such as shortness of breath and edema. In diabetic patients, monitor blood glucose carefully.
Q10: Can Nebivolol be stopped abruptly?
A: No, abrupt discontinuation should be avoided, especially in patients with coronary artery disease. Taper the dose gradually under medical supervision.
