Hyporetic

Uses

Nebivolol is used for the treatment of essential hypertension and adjunct in stable mild to moderate heart failure in patients over 70 years.

Hyporetic is also used to associated treatment for these conditions: High Blood Pressure (Hypertension)

How Hyporetic works

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.

Dosage

Hyporetic dosage

Adults: 5 mg daily, maximum recommended dose 40 mg once daily.

Renal Impairment: In patients with severe renal impairment the recommended initial dose is 2.5 mg once daily; titrate up slowly if needed.

Hepatic Impairment: In patients with moderate hepatic impairment, the recommended initial dose is 2.5 mg once daily; titrate up slowly if needed.

Geriatric Patients: It is not necessary to adjust the dose in the elderly.

Pediatric Use: Safety and effectiveness of Nebivolol in pediatric patients have not been established.

Side Effects

The most common side effects are headache, nausea and bradycardia.

Toxicity

Patients experiencing an overdose may present with bradycardia, hypotension, cardiac failure, dizziness, hypoglycemia, fatigue, vomiting, bronchospasm and heart block. Treat overdose with general supportive measures including intravenous atropine for bradycardia, vasopressors and intravenous fluids for hypotension, isoproterenol infusion for heart block, digitalis glycosides and diuretics for congestive heart failure, bronchodilators for bronchospasm, and intravenous glucose for hypoglycemia.

Precaution

Patients with inadequate cardiac function, well-compensated heart failure, myasthenia gravis. Patients undergoing major surgery involving general anaesth. May mask signs and symptoms of hypoglycaemia and hyperthyroidism. Abrupt withdrawal may exacerbate angina symptoms and/or precipitate MI and ventricular arrhythmias in patients with coronary artery disease. Pregnancy and lactation.

Interaction

Use caution when Nebivolol is co-administered with CYP2D6 inhibitors (quinidine, propafenone, fluoxetine, paroxetine, etc.), Do not use Nebivolol with other β-blockers, both digitalis glycosides and β-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia, Nebivolol can exacerbate the effects of myocardial depressants or inhibitors of AV conduction, such as certain calcium antagonists (verapamil and diltiazem), or antiarrhythmic agents, such as disopyramide.

Volume of Distribution

For a 20mg dose, d-nebivolol has an apparent volume of distribution of 10,290.81±3911.72L, l-nebivolol has an apparent volume of distribution of 8,066.66±4,055.50L, and both enantiomers together have a volume of distribution of 10,423.42±6796.50L.

Elimination Route

The absorption of nebivolol is not affected by food. Nebivolol has a T_max of 1.5-4 hours. Bioavailability can range from 12-96% for extensive to poor CYP2D6 metabolizers. For a 20mg dose, d-nebivolol has a C_max of 2.75±1.55ng/mL, l-nebivolol has a C_max of 5.29±2.06ng/mL, both enantiomers have a C_max of 8.02±3.47ng/mL, and nebivolol glucuronides have a C_max of 68.34±44.68ng/mL. For a 20mg dose, d-nebivolol has an AUC of 13.78±15.27ng*h/mL, l-nebivolol has an AUC of 27.72±15.32ng*h/mL, both enantiomers have an AUC of 41.50±29.76ng*h/mL, and nebivolol glucuronides have an AUC of 396.78±297.94ng*h/mL.

Half Life

d-nebivolol has a half life of 12 hours in CYP2D6 extensive metabolizers and 19 hours in poor metabolizers.

Clearance

For a 20mg dose, the clearance of d-nebivolol is 1241.63±749.77L/h, l-nebivolol is 435.53±180.93L/h, and both enantiomers is 635.31±300.25L/h.

Elimination Route

In extensive CYP2D6 metabolizers, 38% is eliminated in the urine and 44% in the feces. In poor CYP2D6 metabolizers, 67% is eliminated in the urine and 13% in the feces. 5

Pregnancy & Breastfeeding use

Pregnancy category C and not recommended during nursing.

Contraindication

Nebivolol is contraindicated in the following conditions: severe bradycardia, heart block greater than first degree, patients with cardiogenic shock, decompensated cardiac failure, sick sinus syndrome, patients with severe hepatic impairment, patients who are hypersensitive to any component of this product.

Acute Overdose

Symptoms: Bradycardia, hypotension, cardiac failure, dizziness, fatigue, hypoglycaemia, vomiting, bronchospasm, heart block.

Management: Symptomatic and supportive treatment. IV atropine may be given for bradycardia, if it persists, admin IV isoproterenol cautiously. For hypotension, admin IV fluids and vasopressors. IV glucagon may also be useful. A β2-agonist and/or aminophylline for bronchospasm. Admin IV glucose for hypoglycaemia and an IV cardiac glycoside and diuretic may be used for CHF.

Storage Condition

Store between 20-25° C. Protect from light. Keep out of the reach of children.

Innovators Monograph

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