Nebivolol for the treatment of heart failure

Riva, Nicoletta; Lip, Gregory Y.H.

doi:10.1517/13543784.2011.625011

Cited by 10 publications

(4 citation statements)

References 80 publications

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“…The (+)‐isomer provides the β1 blocking property, and both (+)‐ and mainly (‐)‐nebivolol have an endothelial NO‐dependent vasodilating effect by the l ‐arginine/NO pathway . (‐)‐Nebivolol increases the activity of the endothelial isoform of NO synthase (NOS) through a direct β3‐adrenoceptor agonistic effect .…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of nebivolol in the rat: low oral absorption, loss in the gut and systemic stereoselectivity

Sanaee

Neves

Lanchote

et al. 2013

Biopharm & Drug Disp

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Nebivolol is a third-generation β1-adrenoceptor blocker with β3 agonistic properties (AR). It has a low oral bioavailability that is speculated to be due to its hepatic first-pass metabolism. Inflammation is known to suppress the clearance of drugs with efficient hepatic metabolism. However, inflammation does not influence nebivolol clearance. Therefore, we looked into the mechanism involved in the drug's low bioavailability and stereoselectivity. Single 1 mg/kg i.v. or intraperitoneal (i.p.) or 2 mg/kg oral doses were administered to male Sprague-Dawley rats and the plasma nebivolol concentration was measured using chiral and achiral assays. The passage of nebivolol enantiomers through the gut was also measured using everted rat sacs. The serum protein binding of the enantiomers was studied in vitro using the ultrafiltration method. Plasma nebivolol concentrations were significantly lower after p.o., but not after i.p., compared with i.v. doses suggesting the gut as the site of pre-systemic loss. Approximately 50% of the enantiomers were lost during 90 min incubation in the presence of gut. Only 0.1% of the added drug crossed the gut wall with no evidence of stereoselectivity. Thus stereoselectivity in the pharmacokinetics of nebivolol (+ > -) is likely at the level of plasma protein binding. The low nebivolol bioavailability is due to its loss in the gut as well as its limited permeability through the intestinal wall.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of nebivolol in the rat: low oral absorption, loss in the gut and systemic stereoselectivity

Sanaee

Neves

Lanchote

et al. 2013

Biopharm & Drug Disp

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“…To determine the target ADR for analysis, we searched the most common ADRs based on literature and the label from the FDA official website. The most common AEs were headache, dizziness, nausea, diarrhea, tiredness, and bradycardia, of which bradycardia, nausea, and headache may lead to discontinuation ( Riva and Lip, 2011 ; Hanif et al, 2023 ). We mapped the above ADRs to their primary system organ class (SOC) according to MedDRA 26.0, mainly involving nervous system disorders, gastrointestinal disorders, and cardiac disorders.…”

Section: Methodsmentioning

confidence: 99%

Contrastive analysis on the safety of brand and generic nebivolol: a real-world pharmacovigilance study based on the FDA adverse event reporting system

Wang,

Zhong,

et al. 2024

Front. Pharmacol.

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Background: The equivalence of generic drugs to their brand-name counterparts is a controversial issue. Current literature indicates disparities between the generic nebivolol (GN) and the brand nebivolol (BN).Aim: The study is designed to investigate the safety difference between GN and BN and provide reference information for clinical practice.Methods: We reviewed adverse event (AE) reports that recorded nebivolol as the primary suspect drug in the FDA Adverse Event Reporting System (FAERS) database from 2004 to 2022, conducted a disproportional analysis to detect signals for the GN and BN respectively, and compared the AE heterogeneity between them using the Breslow-Day test.Results: A total of 2613 AE reports of nebivolol were recorded in the FAERS database from 2004 to 2022, of which 2,200 were classified as BN, 346 as GN, and 67 unclassifiable AE reports were excluded. The signals of 37 AEs distributed in cardiac, gastrointestinal, psychiatric, and nervous systems were detected in disproportional analysis. 33 out of 37 AEs were positive signals, with 21 not previously listed on the drug label, indicating an unrecognized risk with nebivolol. In the heterogeneity analysis of AE signals between GN and BN, the GN generally showed a higher AE signal value than BN, especially 15 AEs distributed in the cardiac, neurological, and psychiatric systems that showed statistically significantly higher risk by taking GN.Conclusion: Our study shows some previously overlooked adverse effects of nebivolol. It suggests that the risk of GN’s adverse effects may be higher than those in BN, which deserves further attention and investigation by healthcare professionals, regulators, and others.

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“…Less blockade of peripheral β 2 -adrenoceptors with a selective agent reduces the likelihood feelings of cold in the extremities [16][17][18] Controlled clinical trials of bisoprolol (vs. lisinopril [19]) and nebivolol (vs. metoprolol [20]) have demonstrated effective BP lowering, and no cause for concern regarding worsening of limb ischaemia Glycaemic control Many reports have described a worsening of glycaemic control during treatment with a β-blocker and use of a cardioselective agent helps to minimise these effects [17,18] The clinical significance of this phenomenon may have been overrated, however, worsened glycaemia may be unrelated to β-blockade [21],,and use of a β-blocker in a large diabetes prevention trial was not associated with increased risk of diabetes [22] Bisoprolol or nebivolol has not been associated with worsening of glycaemia [7,[23][24][25][26][27][28][29] Asthma and COPD Bronchospasm in patients with COPD or asthma may be exacerbated by blockade of β 2 -adrenoceptors in the smooth muscle of the airways [30] Non-selective β 1 -blockers, but not β 1 -selective agents, increase the risk of asthma exacerbations [31] A recent (2020) randomised, double-blind, crossover study confirmed that the bronchodilatory effects of bisoprolol were non-inferior during treatment with bisoprolol vs. placebo [32] Such findings have led to a reappraisal of the use of selective β 1 -blockers in patients with asthma or COPD [30,33]; β 1selective agents are no contraindicated in Europe only for "severe bronchial asthma" Erectile function β-blockers, have been associated with new or exacerbated erectile dysfunction [34], although neither bisoprolol nor nebivolol were associated with sexual dysfunction [35][36][37] Nebivolol improved erectile function vs. metoprolol [38,39], or atenolol (± chlorthalidone) [40] Another study demonstrated fewer patients reporting vs. not reporting sexual dysfunction on nebivolol vs. other β-blockers…”

Section: Peripheral Vasoconstriction and Pvdmentioning

confidence: 99%

“…β-blockers, have been associated with new or exacerbated erectile dysfunction [ 34 ], although neither bisoprolol nor nebivolol were associated with sexual dysfunction [ 35 – 37 ]…”

Section: Properties Of Bisoprolol and Nebivololmentioning

confidence: 99%

Therapeutic Properties of Highly Selective β-blockers With or Without Additional Vasodilator Properties: Focus on Bisoprolol and Nebivolol in Patients With Cardiovascular Disease

AlHabeeb

Mrabeti²,

Abdelsalam

2021

Cardiovasc Drugs Ther

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Bisoprolol and nebivolol are highly selective β1-adrenoceptor antagonists, with clinical indications in many countries within the management of heart failure with reduced left ventricular ejection fraction (HFrEF), ischaemic heart disease (IHD), and hypertension. Nebivolol has additional vasodilator actions, related to enhanced release of NO in the vascular wall. In principle, this additional mechanism compared with bisoprolol might lead to more potent vasodilatation, which in turn might influence the effectiveness of nebivolol in the management of HFrEF, IHD and hypertension. In this article, we review the therapeutic properties of bisoprolol and nebivolol, as representatives of “second generation” and “third generation” β-blockers, respectively. Although head-to-head trials are largely lacking, there is no clear indication from published studies of an additional effect of nebivolol on clinical outcomes in patients with HFrEF or the magnitude of reductions of BP in patients with hypertension.

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Nebivolol for the treatment of heart failure

Abstract: Nebivolol is a β-blocker with distinctive characteristics. Initiated at 1.25 mg and titrated up to 10 mg/day, it has shown safety and efficacy in one large outcome trial, when added to standard medical therapy, in elderly patients (≥ 70 years) affected by HF.

Cited by 10 publications

References 80 publications

Pharmacokinetics of nebivolol in the rat: low oral absorption, loss in the gut and systemic stereoselectivity

Pharmacokinetics of nebivolol in the rat: low oral absorption, loss in the gut and systemic stereoselectivity

Contrastive analysis on the safety of brand and generic nebivolol: a real-world pharmacovigilance study based on the FDA adverse event reporting system

Therapeutic Properties of Highly Selective β-blockers With or Without Additional Vasodilator Properties: Focus on Bisoprolol and Nebivolol in Patients With Cardiovascular Disease

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