Nebivolol

Nebivolol

Systematic (IUPAC) name
1-(6-fluorochroman-2-yl)-{[2-(6-fluorochroman-2-yl)-2-hydroxy-ethyl]amino}ethanol OR 2,2'-azanediylbis(1-(6-fluorochroman-2-yl)ethanol) OR 1-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)-2-{[2-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)-2-hydroxyethyl]amino}ethan-1-ol
Clinical data
Trade names	Nebilet, Bystolic
AHFS/Drugs.com	monograph
MedlinePlus	a608029
Licence data	US FDA:link
Pregnancy cat.	C (US)
Legal status	POM (UK) ℞-only (US)
Routes	Oral
Pharmacokinetic data
Protein binding	98%
Metabolism	Hepatic (CYP2D6-mediated)
Half-life	10 hours
Excretion	Renal and fecal
Identifiers
CAS number	99200-09-6 N
ATC code	C07AB12
PubChem	CID 71301
DrugBank	DB04861
ChemSpider	64421 Y
UNII	030Y90569U Y
KEGG	D05127 Y
ChEMBL	CHEMBL434394 Y
Chemical data
Formula	C22H25F2NO4
Mol. mass	405.435 g/mol
SMILES	eMolecules & PubChem
InChI InChI=1S/C22H25F2NO4/c23-15-3-7-19-13(9-15)1-5-21(28-19)17(26)11-25-12-18(27)22-6-2-14-10-16(24)4-8-20(14)29-22/h3-4,7-10,17-18,21-22,25-27H,1-2,5-6,11-12H2 Y Key:KOHIRBRYDXPAMZ-UHFFFAOYSA-N Y
N (what is this?)  (verify)

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.^[1] It is highly cardioselective under certain circumstances^[1] but has less robust evidence of survival benefit than other beta-blockers.^[2]

Pharmacology and biochemistry

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.^[3] 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.^[4] 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.^[5] The drug is highly cardioselective at 5 mg.^[6] However, at doses above 10 mg, nebivolol loses its cardioselectivity and blocks both β1 and β2 receptors.^[5] (While the recommended starting dose of nebivolol is 5 mg, sufficient control of blood pressure may require doses up to 40 mg).^[5] Furthermore, nebivolol is also not cardioselective when taken by patients with a genetic makeup that makes them "poor metabolizers" of nebivolol (and other drugs).^[5] 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.^{[citation needed]}

Vasodilator action

Nebivolol is unique as a beta-blocker.^[7] Unlike carvedilol, it has a nitric oxide (NO)-potentiating, vasodilatory effect.^[8][9] Along with labetalol, celiprolol and carvedilol, it is one of four beta blockers to cause dilation of blood vessels in addition to effects on the heart.^[9] However, recent studies question the clinical relevance of this property to Nebivolol's efficacy.^[2]

Antihypertensive effect

Nebivolol lowers blood pressure (BP) by reducing peripheral vascular resistance, and significantly increases stroke volume with preservation of cardiac output.^[10] 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.^[11] Antihypertensive responses were significantly higher with nebivolol than with placebo in trials enrolling patient groups considered representative of the U.S. hypertensive population, in Black patients, and in those receiving concurrent treatment with other antihypertensive drugs.^[12]

Pharmacology of side-effects

Several studies have suggested that nebivolol has reduced typical beta-blocker-related side effects, such as fatigue, clinical depression, bradycardia, or impotence.^[13][14][15] However, according to the FDA^[16]

FDA warning letter about advertising claims

In late August 2008, the FDA issued a Warning Letter 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.^[16]

Contraindications

This unreferenced section requires citations to ensure verifiability.

• Hepatic insufficiency
• Children
• Pregnancy
• Lactation

Adverse drug reactions

This unreferenced section requires citations to ensure verifiability.

• Headache
• Parasthesia
• Dizziness

History

Mylan Laboratories licensed the U.S. and Canadian rights to nebivolol from Janssen Pharmaceutica N.V. in 2001. Nebivolol is already registered and successfully marketed in more than 50 countries, including the United States where it is marketed under the brand name Bystolic from Mylan Laboratories and Forest Laboratories. Nebivolol is manufactured by Forest Laboratories.

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 by Menarini as Lobivon. In the Middle East and in Australia, it is marketed under the name Nebilet, and in Pakistan, it is marketed by Searle Pakistan Limited as Byscard.

References

Nebistar (Lupin Ltd)

External links

• Prescribing Information for BYSTOLIC