Nebivolol is indicated for:

• Hypertension
• Treatment of essential hypertension
• Chronic heart failure (CHF)
• Treatment of stable mild to moderate chronic heart failure as an add-on to standard therapy in elderly patients.

Nebivolol is a beta-adrenergic receptor blocking agent that blocks both beta-1 and beta-2 adrenergic receptors. It has no intrinsic sympathomimetic or membrane-stabilizing activity at therapeutic doses. At clinically relevant doses, it primarily acts as a beta-1 selective blocker. Its metabolites, including glucuronides, also contribute to beta-blocking activity.

Its mechanism of action includes

• reduced heart rate,
• decreased myocardial contractility,
• reduced sympathetic outflow from the central nervous system,
• suppression of renin activity,
• and vasodilation leading to decreased peripheral vascular resistance.

Pharmacokinetics Nebivolol is metabolized via glucuronidation and CYP2D6-mediated hydroxylation. The active isomer (d-nebivolol) has a half-life of approximately 12 hours in extensive metabolizers and about 19 hours in poor metabolizers. Food does not affect its absorption, and it may be taken with or without meals. Plasma protein binding is approximately 98%, mainly to albumin.

Metabolism and Excretion Nebivolol undergoes extensive hepatic metabolism mainly through glucuronidation and CYP2D6 pathways. After oral administration, elimination occurs via urine and feces, with variations depending on metabolizer status.

Drug Interactions Digoxin: No significant pharmacokinetic interaction observed with nebivolol. Warfarin: No significant effect on warfarin pharmacokinetics or anticoagulant activity has been observed.

Dose adjustment is required in moderate hepatic impairment. Nebivolol is contraindicated in severe hepatic impairment due to lack of data.

The dose of Nebivolol should be individualized to the needs of the patient. For most patients, the recommended starting dose is 5 mg once daily, with or without food, as monotherapy or in combination with other agents. For patients requiring further reduction in blood pressure, the dose can be increased at 2-week intervals up to 40 mg. A more frequent dosing regimen is unlikely to be beneficial.

Nebivolol should be used with caution when myocardial depressants or AV conduction inhibitors are given concomitantly, such as certain calcium channel blockers (verapamil, diltiazem) and antiarrhythmic agents like disopyramide. Digitalis glycosides and β-blockers both slow AV conduction and heart rate; combined use may increase the risk of bradycardia.

Nebivolol should not be used with other β-blockers. Patients receiving catecholamine-depleting agents such as reserpine or guanethidine should be closely monitored, as excessive reduction of sympathetic activity may occur. When used with clonidine, Nebivolol should be discontinued several days before gradual withdrawal of clonidine.

CYP2D6 inhibitors (e.g., quinidine, propafenone, fluoxetine, paroxetine) may increase nebivolol levels and require caution.

Nebivolol is contraindicated in severe bradycardia, second or higher degree heart block, cardiogenic shock, decompensated heart failure, sick sinus syndrome without a pacemaker, severe hepatic impairment (Child-Pugh > B), and hypersensitivity to any component of the product.

Headache, nausea, and bradycardia.

Abrupt Cessation of Therapy: Patients with coronary artery disease treated with Nebivolol should be advised not to stop therapy suddenly. Abrupt discontinuation of β-blockers has been associated with severe worsening of angina, myocardial infarction, and ventricular arrhythmias. These events may occur with or without prior angina worsening. Even patients without obvious coronary artery disease should avoid sudden interruption of therapy. When discontinuation is necessary, Nebivolol should be tapered gradually over 1–2 weeks with careful monitoring and reduced physical activity. If angina worsens or acute coronary insufficiency develops, Nebivolol should be restarted temporarily if needed.

Cardiac Failure: Sympathetic stimulation is important for maintaining circulation in congestive heart failure. β-blockade may reduce myocardial contractility and worsen heart failure. In compensated heart failure patients, Nebivolol should be used with caution, and discontinuation should be considered if condition deteriorates.

Angina and Acute Myocardial Infarction: Nebivolol has not been adequately studied in patients with angina pectoris or recent myocardial infarction.

Bronchospastic Diseases: Patients with bronchospastic conditions generally should not receive β-blockers.

Anesthesia and Major Surgery: If Nebivolol is continued during surgery, close monitoring is required when using anesthetic agents that depress myocardial function (e.g., ether, cyclopropane, trichloroethylene). Abrupt withdrawal before surgery may increase risk of cardiac complications due to reduced adrenergic response. β-blocking effects can be reversed with β-agonists such as dobutamine or isoproterenol, but this may cause prolonged severe hypotension. Difficulty in restarting or maintaining heart rhythm has also been reported.

Diabetes and Hypoglycemia: β-blockers may mask symptoms of hypoglycemia, especially tachycardia. Nonselective β-blockers may worsen insulin-induced hypoglycemia and delay glucose recovery. It is not fully known whether Nebivolol has these effects. Diabetic patients or those prone to hypoglycemia should use it cautiously and be informed of this risk.

Thyrotoxicosis: β-blockers may mask signs of hyperthyroidism such as tachycardia. Sudden withdrawal may worsen symptoms or trigger thyroid storm.

Peripheral Vascular Disease: β-blockers may worsen arterial insufficiency in patients with peripheral vascular disease; caution is required.

Non-dihydropyridine Calcium Channel Blockers: Concomitant use with verapamil or diltiazem increases the risk of significant negative effects on heart rate and contractility. ECG and blood pressure should be closely monitored in such cases.

Renal impairment: Use with caution in severe renal impairment; not studied in dialysis patients.

Hepatic impairment: Use cautiously in moderate impairment; contraindicated in severe hepatic disease.

Anaphylaxis risk: Patients with history of severe allergic reactions may show increased sensitivity and reduced response to epinephrine.

Beta-adrenoceptor blocking drugs, Beta-blockers

Store below 30°C. Protect from light and moisture. Keep out of reach of children.