Nebivolol is a beta blocker used to treat hypertension and heart failure.[ It may be used by itself or with other blood pressure medication.][ It is taken by mouth.][
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Common side effects include dizziness, feeling tired, nausea, and headaches.[ Serious side effects may include heart failure and bronchospasm.][ Its use in pregnancy and breastfeeding is not recommended.]
Nebivolol was patented in 1983 and came into medical use in 1997.[ In 2022, it was the 173rd most commonly prescribed medication in the United States, with more than 3million prescriptions.]
Medical uses
It is used to treat hypertension and heart failure.[
Nebivolol is used in the treatment of angina, to decrease the heart rate and contractile force. This is relevant in patients who need to decrease the oxygen demand of the heart so that the blood supplied from stenosed or constricted arteries is adequate.
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ACE inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, and thiazide diuretics are generally preferred over beta blockers for the treatment of primary hypertension in the absence of co-morbidities.
Pharmacology and biochemistry
β1-selectivity
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.
In a laboratory experiment conducted on biopsied heart tissue, nebivolol proved to be the most β1-selective of the beta blockers tested, being approximately 3.5 times more β1-selective than bisoprolol.
Nebivolol
Due to enzymatic inhibition, fluvoxamine increases the exposure to nebivolol and its active hydroxylated metabolite (4-OH-nebivolol) in healthy volunteers.
Vasodilator action
Nebivolol is unique as a beta-blocker.
Nebivolol induces vasodilation by stimulating the production of nitric oxide, a natural blood vessel relaxant. This effect is achieved by activating the endothelial isoform of NO synthase (eNOS) in the cells lining the blood vessels. Unlike traditional β-blockers, nebivolol's unique mechanism of action improves arterial flexibility and reduces peripheral resistance, making it beneficial for hypertensive patients with endothelial dysfunction. The drug's ability to increase NO production persists even after metabolism, offering long-lasting benefits. Nebivolol's distinct approach to promoting NO release has shown promising results in improving endothelial function and managing hypertension in clinical trials.
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.
Antihypertensive effect
Nebivolol lowers blood pressure (BP) by reducing peripheral vascular resistance, and significantly increases stroke volume with preservation of cardiac output.
Pharmacokinetics
Nebivolol plasma protein binding is approximately 98%, mostly to albumin and its half-life of low doses is 12 hours in extensive CYP2D6 metabolizers and 19 hours in poor metabolizers.
Contraindications
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Severe bradycardia
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Heart block greater than first degree
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Patients with cardiogenic shock
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Decompensated cardiac failure
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Sick sinus syndrome (unless a permanent pacemaker is in place)
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Patients with severe hepatic impairment (Child-Pugh class B)
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Patients who are hypersensitive to any component of this product.
Side effects
Side effects might include headache, tiredness, dizziness, lightheadedness, Raynaud syndrome, bradycardia.
Controversies
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.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.
FDA warning letter about advertising claims
In August 2008, the FDA issued a Warning Letter to Forest Laboratories citing exaggerated and misleading claims in their launch journal ad, in particular over claims of superiority and novelty of action.
History
Mylan Laboratories licensed the US 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 Nebula (Zydus Healthcare Ltd), Nebizok (Eris life-sciences), Nebicip (Cipla ltd), Nebilong (Micro Labs), Nebistar (Lupin ltd), Nebicard (Torrent), Nubeta (Abbott Healthcare Pvt Ltd – India), and Nodon (Cadila Pharmaceuticals).
In Greece and Italy, nebivolol is marketed by Menarini as Lobivon.
In Germany it is marketed as Nebilet by Berlin Chemie.
In the Middle East, Russia and Australia, it is marketed under the name Nebilet and in Pakistan it is marketed by The Searle Company Limited as Byscard.
