Nebivolol
Encyclopedia
Nebivolol is a β1 receptor blocker
with nitric oxide
-potentiating vasodilatory effect used in treatment of hypertension
and, in Europe, also for left ventricular failure. It is highly cardioselective under certain circumstances but has less robust evidence of survival benefit than other beta-blockers
In a laboratory experiment conducted on biopsied heart tissue, nebivolol proved to be the most β1-selective of the β-blockers tested, being approximately 3.5 times more β1-selective than bisoprolol
. However, the drug's receptor selectivity in humans is more complex and depends on the drug dose and the genetic profile of the patient taking the medication. The drug is highly cardioselective at 5 mg. However, at doses above 10 mg, nebivolol loses its cardioselectivity and blocks both β1 and β2 receptors. (While the recommended starting dose of nebivolol is 5 mg, sufficient control of blood pressure may require doses up to 40 mg). Furthermore, nebivolol is also not cardioselective when taken by patients with a genetic makeup that makes them "poor metabolizers" of nebivolol (and other drugs). As many as 1 in 10 Whites and even more Blacks are poor CYP2D6 metabolizers and therefore might benefit less from nebivolol's cardioselectivity although currently there are no directly comparable studies.
and carvedilol
, it is one of three beta blockers to cause dilation of blood vessels in addition to effects on the heart. However, recent studies question the clinical relevance of this property to Nebivolol's efficacy.
with preservation of cardiac output. The net hemodynamic effect of nebivolol is the result of a balance between the depressant effects of beta-blockade and an action that maintains cardiac output. Antihypertensive responses were significantly higher with nebivolol than with placebo in trials enrolling patient groups considered representative of the US hypertensive population, in Black patients, and in those receiving concurrent treatment with other antihypertensive drugs.
, bradycardia
, or impotence. However, according to the FDA:
to Forest Laboratories citing exaggerated and misleading claims in their sales force's promotional materials, in particular over claims of superiority and novelty of action.
N.V. in 2001. Nebivolol is already registered and successfully marketed in more than 50 other countries, including the US
. It is marketed under the brand name Nebilet. Nebivolol is manufactured by Forest Laboratories, Inc. In India, Nebivolol is available as Nebilong 5 mg (Micro Labs) Nebicard-5 (Torrent), Nubeta (Abbott Healthcare Pvt Ltd -India) and Nodon (Cadila Pharmaceuticals). In Greece and Italy, Nebivolol is marketed under the name Lobivon from Menarini pharmaceutical. In the middle east and in Australia it is marketed under the name Nebilet . In the US, it is marketed under the brand name Bystolic from Mylan Laboratories and Forest Laboratories.
Beta blocker
Beta blockers or beta-adrenergic blocking agents, beta-adrenergic antagonists, beta-adrenoreceptor antagonists or beta antagonists, are a class of drugs used for various indications. They are particularly for the management of cardiac arrhythmias, cardioprotection after myocardial infarction ,...
with nitric oxide
Nitric oxide
Nitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...
-potentiating vasodilatory effect used in treatment of hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
and, in Europe, also for left ventricular failure. It is highly cardioselective under certain circumstances but has less robust evidence of survival benefit than other beta-blockers
β1 Selectivity
Beta blockers help patients with cardiovascular disease by blocking β1 receptors, while many of the side-effects of these medications are caused by their blockade of β2 receptors. For this reason, beta blockers that selectively block β1 receptors (termed cardioselective or β1-selective beta blockers) produce fewer adverse effects (for instance, bronchoconstriction) than those drugs that non-selectively block both β1 and β2 receptors. Nebilovol has been marketed by Micro Labs under the brand name Nebilong; by Forest Laboratories under the name Bystolic; and by Menarini under the names Hypoloc, Lobivon, Nebilet, Nebilox, Nobiten, and Temerit. Micro Labs further ventured into providing a combination with diuretic (hydrochlorothiazide) marketed under the trade name Nebilong-H.In a laboratory experiment conducted on biopsied heart tissue, nebivolol proved to be the most β1-selective of the β-blockers tested, being approximately 3.5 times more β1-selective than bisoprolol
Bisoprolol
Bisoprolol is a drug belonging to the group of beta blockers, a class of drugs used primarily in cardiovascular diseases. More specifically, it is a selective type β1 adrenergic receptor blocker. The FDA approved Duramed Pharmaceutical's application for Zebeta Oral Tablets as a new molecular...
. However, the drug's receptor selectivity in humans is more complex and depends on the drug dose and the genetic profile of the patient taking the medication. The drug is highly cardioselective at 5 mg. However, at doses above 10 mg, nebivolol loses its cardioselectivity and blocks both β1 and β2 receptors. (While the recommended starting dose of nebivolol is 5 mg, sufficient control of blood pressure may require doses up to 40 mg). Furthermore, nebivolol is also not cardioselective when taken by patients with a genetic makeup that makes them "poor metabolizers" of nebivolol (and other drugs). As many as 1 in 10 Whites and even more Blacks are poor CYP2D6 metabolizers and therefore might benefit less from nebivolol's cardioselectivity although currently there are no directly comparable studies.
Vasodilator action
Nebivolol is unique as a beta-blocker. Unlike carvedilol, it has a nitric oxide (NO)-potentiating, vasodilatory effect. Along with labetalolLabetalol
Labetalol is a mixed alpha/beta adrenergic antagonist, which is used to treat high blood pressure.-Indications:...
and carvedilol
Carvedilol
Carvedilol is a non-selective beta blocker/alpha-1 blocker indicated in the treatment of mild to moderate congestive heart failure . It is marketed under various trade names including Carvil , Coreg , Dilatrend , Eucardic , and Carloc as a generic drug ., and as a...
, it is one of three beta blockers to cause dilation of blood vessels in addition to effects on the heart. However, recent studies question the clinical relevance of this property to Nebivolol's efficacy.
Antihypertensive effect
Nebivolol lowers blood pressure (BP) by reducing peripheral vascular resistance, and significantly increases stroke volumeStroke volume
In cardiovascular physiology, stroke volume is the volume of blood pumped from one ventricle of the heart with each beat. SV is calculated using measurements of ventricle volumes from an echocardiogram and subtracting the volume of the blood in the ventricle at the end of a beat from the volume...
with preservation of cardiac output. The net hemodynamic effect of nebivolol is the result of a balance between the depressant effects of beta-blockade and an action that maintains cardiac output. Antihypertensive responses were significantly higher with nebivolol than with placebo in trials enrolling patient groups considered representative of the US hypertensive population, in Black patients, and in those receiving concurrent treatment with other antihypertensive drugs.
Pharmacology of side-effects
Several studies have suggested that nebivolol has reduced typical beta-blocker-related side effects, such as fatigue, clinical depressionClinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
, bradycardia
Bradycardia
Bradycardia , in the context of adult medicine, is the resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. It may cause cardiac arrest in some patients, because those with bradycardia may not be pumping enough oxygen to their heart...
, or impotence. However, according to the FDA:
FDA warning letter about advertising claims
In late August 2008, the FDA issued a Warning LetterFDA Warning Letter
The United States Food and Drug Adminstration defines a Warning Letter as "...a correspondence that notifies regulated industry about violations that FDA has documented during its inspections or investigations...
to Forest Laboratories citing exaggerated and misleading claims in their sales force's promotional materials, in particular over claims of superiority and novelty of action.
Contraindications
- Hepatic insufficiency
- Children
- Pregnancy
- Lactation
Adverse drug reactions
- Headache
- Parasthesia
- Dizziness
History
Mylan Laboratories licensed the U.S. and Canadian rights to nebivolol from Janssen PharmaceuticaJanssen Pharmaceutica
Janssen Pharmaceutica is pharmaceutical company, established in Belgium in 1953 by Paul Janssen. Its headquarters are located in Beerse, in the Campine region of the province of Antwerp, Belgium. It was created not as a subsidiary of a chemical factory but solely with the aim of conducting...
N.V. in 2001. Nebivolol is already registered and successfully marketed in more than 50 other countries, including the US
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
. It is marketed under the brand name Nebilet. Nebivolol is manufactured by Forest Laboratories, Inc. In India, Nebivolol is available as Nebilong 5 mg (Micro Labs) Nebicard-5 (Torrent), Nubeta (Abbott Healthcare Pvt Ltd -India) and Nodon (Cadila Pharmaceuticals). In Greece and Italy, Nebivolol is marketed under the name Lobivon from Menarini pharmaceutical. In the middle east and in Australia it is marketed under the name Nebilet . In the US, it is marketed under the brand name Bystolic from Mylan Laboratories and Forest Laboratories.