NEBUNTA 5

Indications

• Essential hypertension
• Migraine prophylaxis
• Hypertension in patients with renal impairment
• Adjunct treatment in stable mild to moderate heart failure
• Management of arrhythmias during anesthesia

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations.

Adults: Initially 5 mg once daily, with a maximum of 40 mg daily depending on clinical response and tolerance.

Mechanism of action

Nebivolol selectively antagonizes beta-1 adrenergic receptors, leading to decreased heart rate, myocardial contractility, and blood pressure. Additionally, it stimulates beta-3 adrenergic receptors, causing increased nitric oxide production and subsequent vasodilation. This reduces vascular resistance and enhances cardiac output while minimizing adverse effects commonly associated with non-selective beta blockers.

Pharmacodynamics

Nebivolol decreases vascular resistance and increases stroke volume and cardiac output without negatively impacting left ventricular function. Its effects can persist for up to 48 hours after discontinuation of the drug. It possesses a wide therapeutic window, with typical doses ranging from 5 to 40 mg daily. Patients, especially those with coronary artery disease, should not stop treatment abruptly as this may exacerbate their condition. Additionally, diabetic patients should monitor blood glucose levels, as nebivolol may mask hypoglycemic symptoms.

Pharmacokinetics

Nebivolol is well absorbed and undergoes extensive first-pass metabolism. It has a half-life that allows for once-daily dosing, making it convenient for patient adherence. The drug is primarily metabolized by the liver, and its elimination is influenced by renal function. The pharmacokinetic profile supports its use in various patient populations, including the elderly, who may require dose adjustments.

Contra-indications

• Acute or decompensated heart failure requiring intravenous inotropes
• Severe bradycardia
• Heart block (greater than first degree) unless a functioning pacemaker is present
• Cardiogenic shock
• Severe hepatic impairment

Adverse effects

• Constipation
• Oedema
• Postural hypotension
• Dyspepsia
• Flatulence
• Skin reactions
• Palpitations
• Alopecia
• Arrhythmia
• Conjunctivitis
• Dry eyes
• Fatigue
• Thrombocytopenia
• Sexual dysfunction

Interactions

• Propafenone: Severe (increases exposure)
• Dacomitinib: Severe (increases exposure)
• Berotralstat: Moderate (increases exposure)
• Fedratinib: Moderate (increases exposure)
• Givosiran: Moderate (increases exposure)
• Panobinostat: Moderate (increases exposure)
• Bupropion: Unknown (increases exposure)
• Cinacalcet: Unknown (increases exposure)
• Terbinafine: Unknown (increases exposure)
• Ropeginterferonalfa: Unknown (increases exposure)

Precautions

• Use with caution in patients with diabetes, as beta-blockers may mask signs of hypoglycemia
• Monitor blood pressure and heart rate regularly
• Taper off the medication gradually to avoid exacerbation of coronary artery disease
• Caution in patients with a history of bronchospastic disease

Pregnancy

Use only if the benefits outweigh the risks, as safety in pregnancy has not been established.

Breast-feeding

Manufacturers advise avoidance due to potential effects on the infant.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Nebivolol 1.25 mg tablet
• Nebivolol 5 mg tablet
• Nebivolol 10 mg tablet
• Nebivolol solution for injection

Mechanism of action

Nebivolol is a highly selective beta-1 adrenergic receptor antagonist with weak beta-2 adrenergic receptor antagonist activity. Blocking beta-1 adrenergic receptors by d-nebivolol leads to decreased resting heart rate, exercise heart rate, myocardial contracility, systolic blood pressure, and diastolic blood pressure. The selectivity of d-nebivolol limits the magnitude of beta blocker adverse effects in the airways or relating to insulin sensitivity. Nebivolol also inhibits aldosterone, and beta-1 antagonism in the juxtaglomerular apparatus also inhibits the release of renin. Decreased aldosterone leads to decreased blood volume, and decreased renin leads to reduced vasoconstriction. l-nebivolol is responsible for beta-3 adrenergic receptor agonist activity that stimulates endothelial nitric oxide synthase, increasing nitric oxide levels; leading to vasodilation, decreased peripheral vascular resistance, increased stroke volume, ejection fraction, and cardiac output. The vasodilation, reduced oxidative stress, and reduced platelet volume and aggregation of nebivolol may lead to benefits in heart failure patients.

Pharmacodynamics

Nebivolol is a selective beta-1 adrenergic receptor antagonist that decreases vascular resistance, increases stroke volume and cardiac output, and does not negatively affect left ventricular function. It has a long duration of action as effects can be seen 48 hours after stopping the medication and a wide therapeutic window as patients generally take 5-40mg daily. Patients should not abruptly stop taking this medication as this may lead to exacerbation of coronary artery disease. Diabetic patients should monitor their blood glucose levels as beta blockers may mask signs of hypoglycemia.