| 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 |
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| Clinical data | |
| 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 |
| ATC code | C07AB12 |
| PubChem | CID 71301 |
| DrugBank | DB04861 |
| ChemSpider | 64421 |
| UNII | 030Y90569U |
| KEGG | D05127 |
| ChEMBL | CHEMBL434394 |
| Chemical data | |
| Formula | C22H25F2NO4 |
| Mol. mass | 405.435 g/mol |
| SMILES | eMolecules & PubChem |
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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]
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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.
Nebivolol is unique as a beta-blocker.[7] Unlike carvedilol, it has a nitric oxide (NO)-potentiating, vasodilatory effect.[8][9] Along with labetalol and carvedilol, it is one of three 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]
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 US hypertensive population, in Black patients, and in those receiving concurrent treatment with other antihypertensive drugs.[12]
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:
| “ | Bystolic is associated with a number of serious risks. Bystolic is contraindicated in patients with severe bradycardia, heart block greater than first degree, cardiogenic shock, decompensated cardiac failure, sick sinus syndrome (unless a permanent pacemaker is in place), severe hepatic impairment (Child-Pugh > B) and in patients who are hypersensitive to any component of the product. Bystolic therapy is also associated with warnings regarding abrupt cessation of therapy, cardiac failure, angina and acute myocardial infarction, bronchospastic diseases, anesthesia and major surgery, diabetes and hypoglycemia, thyrotoxicosis, peripheral vascular disease, non-dihydropyridine calcium channel blockers use, as well as precautions regarding use with CYP2D6 inhibitors, impaired renal and hepatic function, and anaphylactic reactions. Finally, Bystolic is associated with other risks as described in the Adverse Reactions section of its PI. For example, a number of treatment-emergent adverse events with an incidence greater than or equal to 1 percent in Bystolic-treated patients and at a higher frequency than placebo-treated patients were identified in clinical studies, including headache, fatigue, and dizziness. | ” |
[16]
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]
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 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.
Nebistar (Lupin Ltd)
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