Nebivolol is a prescription beta-blocker used to treat high blood pressure. It is sold in the US as Bystolic and as generic tablets. It blocks β1-adrenergic receptors in the heart, like older drugs such as metoprolol and atenolol, but it also widens blood vessels through the nitric oxide (NO) pathway. That second action sets it apart from classic β1-selective blockers such as atenolol.
The FDA approved nebivolol in 2007 for hypertension only. In the UK it is also licensed for stable chronic heart failure in people aged 70 and over, based on the SENIORS trial. It shows up in discussions of anabolic steroid use because steroid users often have raised blood pressure, but no trial has tested nebivolol in that group.
This page summarizes what the FDA label, the UK product information and clinical trials report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Beta-adrenergic blocker, β1-selective, with NO-mediated vasodilation |
| Brands / approval | Bystolic (NDA 021742, approved December 2007); AB-rated generics |
| Route | Oral tablet |
| Strengths (US) | 2.5, 5, 10 and 20 mg |
| Labeled dose (hypertension) | Usually 5 mg once daily to start; can be raised at 2-week intervals up to 40 mg |
| Half-life (label) | About 12 h for the active d-isomer in most people; about 19 h in CYP2D6 poor metabolizers |
| Selectivity | β1-selective at doses up to 10 mg in most people; also blocks β2 at higher doses and in poor metabolizers |
| US status | Prescription only |
| WADA status | P1 beta-blocker: prohibited in competition in specific sports (e.g. archery, shooting, golf) |
What it is
Nebivolol is a racemic mixture of two mirror-image forms: d-nebivolol (SRRR) and l-nebivolol (RSSS). Its formula is C₂₂H₂₅F₂NO₄, with a molecular weight of 405.4 g/mol for the base and 441.9 g/mol for the hydrochloride salt used in tablets (Bystolic label; PubChem). The US label states that Bystolic is distributed under license from Janssen Pharmaceutica of Beerse, Belgium.
The two isomers do different jobs:
| Isomer | Main action |
|---|---|
| d-nebivolol (SRRR) | β1-receptor blockade. Its β-receptor affinity is over 1,000-fold higher than the l-isomer’s. |
| l-nebivolol (RSSS) | Contributes little β-blockade. In a human forearm study, both isomers dilated blood vessels to a similar degree. |
The nitric oxide effect
Most beta-blockers lower blood pressure mainly by slowing the heart and reducing its force. Nebivolol also relaxes arteries. In a study in 8 healthy volunteers, nebivolol infused into the brachial artery raised forearm blood flow by 91%, while an equal dose of atenolol had no significant effect (Cockcroft et al., JPET 1995). Blocking NO production with L-NMMA cut that response by about 65%, and adding L-arginine restored it. This showed that the vasodilation runs through the L-arginine/NO pathway.
The FDA label lists several possible contributors to the blood pressure effect without naming one as definitive:
- slower heart rate;
- reduced force of heart contraction;
- reduced sympathetic nerve output from the brain;
- lower renin activity;
- vasodilation and lower peripheral vascular resistance.
The UK product information notes that, despite the slower heart rate, the fall in cardiac output may be limited because each heartbeat pumps more blood (UK SmPC). At clinical doses, nebivolol does not block α1 receptors and has no intrinsic sympathomimetic activity.
Pharmacokinetics
Nebivolol’s handling depends strongly on CYP2D6, a liver enzyme whose activity varies by genotype. Most people are “extensive metabolizers”; a minority are “poor metabolizers” who break the drug down much more slowly. In the two main US hypertension trials, 6% of patients were genotyped as poor metabolizers (Bystolic label).
| Parameter | Extensive metabolizers | Poor metabolizers |
|---|---|---|
| Oral bioavailability (UK SmPC) | About 12% | Virtually complete |
| Time to peak | 1.5–4 h | 1.5–4 h |
| d-nebivolol half-life (FDA label) | About 12 h | About 19 h |
| d-nebivolol exposure at the same dose | Reference | About 5× higher peak, 10× higher AUC |
| Urine / feces recovery of a labeled dose | 38% / 44% | 67% / 13% |
Despite the large difference in parent-drug levels, the label does not call for dose changes in poor metabolizers. The hydroxyl metabolites and glucuronides also block β-receptors, and the clinical effect and safety profile were similar in both groups. The UK SmPC reports that when active metabolites are counted, peak levels differ only 1.3–1.4-fold between the groups. It gives a half-life of about 24 h for the hydroxy-metabolites in extensive metabolizers.
Other points from the label:
- Food does not change absorption, so it can be taken with or without meals.
- About 98% is bound to plasma proteins, mainly albumin, so dialysis is not expected to remove it.
- Moderate liver impairment (Child-Pugh B) raised d-nebivolol exposure 10-fold.
- Severe kidney impairment (creatinine clearance under 30 mL/min) cut clearance by 53%.
Approved medical use
Hypertension (US and UK)
The FDA label approves nebivolol to treat hypertension, alone or with other blood pressure drugs (Bystolic label). Labeled dosing:
| Situation | Labeled dose |
|---|---|
| Most adults | Start at 5 mg once daily; can increase at 2-week intervals up to 40 mg |
| Severe kidney impairment (CrCl under 30 mL/min) | Start at 2.5 mg once daily, titrate slowly |
| Moderate liver impairment | Start at 2.5 mg once daily, titrate slowly |
| Severe liver impairment | Not recommended (contraindicated) |
| CYP2D6 poor metabolizers, older adults | No adjustment required |
The label states that no controlled trial has shown that nebivolol itself reduces cardiovascular events. The benefit is inferred from blood pressure lowering, which other drug classes have shown reduces stroke and heart attack.
The UK SmPC uses 5 mg once daily as the standard hypertension dose. It notes that the effect appears after 1–2 weeks, and occasionally only after 4 weeks (UK SmPC).
Chronic heart failure in older adults (UK, not US)
UK product information also licenses nebivolol for “stable mild and moderate chronic heart failure in addition to standard therapies in elderly patients ≥ 70 years.” In heart failure, it is started at 1.25 mg once daily and increased stepwise (2.5, 5, then 10 mg) at 1–2-week intervals, to a maximum of 10 mg. Each step is supervised for at least 2 hours.
Combination product
Byvalson, a fixed combination of nebivolol and valsartan, was approved by FDA in June 2016 and is now listed as discontinued (Drugs@FDA, NDA 206302).
What the research shows
Blood pressure lowering
FDA approval rested on three 12-week, placebo-controlled monotherapy trials in 2,016 patients with mild to moderate hypertension (baseline diastolic 95–109 mmHg). Placebo-subtracted reductions in sitting systolic/diastolic pressure in Study 1 were as follows (Bystolic label):
| Daily dose | Placebo-subtracted change (mmHg) |
|---|---|
| 1.25 mg | −6.6 / −5.1 |
| 2.5 mg | −8.5 / −5.6 |
| 5 mg | −8.1 / −5.5 |
| 10 mg | −9.2 / −6.3 |
| 20 mg | −8.7 / −6.9 |
| 30–40 mg | −11.7 / −8.3 |
All of these differences were statistically significant. The effect appeared within 2 weeks and held over the full 24-hour dosing interval. In a separate trial of 300 Black patients, nebivolol worked, but the effect as monotherapy was somewhat smaller.
One published dose-ranging trial randomized 909 patients to placebo or nebivolol 1.25–40 mg once daily for up to 84 days (Weiss et al., J Clin Hypertens 2007). Trough diastolic pressure fell by 8.0–11.2 mmHg on nebivolol versus 2.9 mmHg on placebo. Overall adverse events were similar: 46.1% on nebivolol versus 40.7% on placebo (p = 0.273).
A 2008 meta-analysis of 12 randomized trials compared nebivolol 5 mg with other drugs (Van Bortel et al., Am J Cardiovasc Drugs 2008). Response rates were similar to other beta-blockers, calcium channel blockers and losartan, and higher than ACE inhibitors (OR 1.92). Adverse events were less frequent than with other beta-blockers (OR 0.56). The authors described the findings as suggestive rather than definitive.
Heart failure in older adults: SENIORS
SENIORS randomized 2,128 patients aged 70 or older with heart failure to nebivolol (titrated to 10 mg) or placebo, regardless of ejection fraction (Flather et al., Eur Heart J 2005). Mean follow-up was 21 months, mean age 76, and the mean maintenance dose 7.7 mg.
| Outcome | Nebivolol | Placebo | Hazard ratio (95% CI) |
|---|---|---|---|
| Death or cardiovascular hospital admission (primary) | 31.1% | 35.3% | 0.86 (0.74–0.99) |
| Death from any cause | 15.8% | 18.1% | 0.88 (0.71–1.08), not significant |
The UK SmPC adds that sudden death occurred in 4.1% on nebivolol versus 6.6% on placebo. The FDA label notes that heart failure did not worsen on nebivolol compared with placebo in this trial, but heart failure is not a US indication.
Metabolic effects compared with metoprolol
Older beta-blockers can worsen insulin sensitivity. In a 12-week randomized trial in 46 people with metabolic syndrome, nebivolol 5 mg/day and metoprolol 100 mg/day lowered blood pressure and heart rate equally (Ayers et al., Hypertension 2012). Metoprolol reduced insulin sensitivity and raised plasminogen activator inhibitor-1 (a clotting-balance marker); nebivolol did not change either. This was a small trial of surrogate markers, not clinical outcomes.
The FDA label does report some lab shifts on nebivolol in its hypertension trials: increases in BUN, uric acid and triglycerides, and decreases in HDL cholesterol and platelet count.
Erectile function
Erectile dysfunction is a known complaint with beta-blockers. Two small randomized trials compared nebivolol with other beta-blockers in hypertensive men:
| Trial | Design | Finding |
|---|---|---|
| Boydak et al., Clin Drug Investig 2005 | 131 men, 12 weeks; nebivolol 5 mg vs atenolol 50 mg ± chlorthalidone | Satisfactory intercourse per month fell on atenolol (7.0 to 3.7) and atenolol + chlorthalidone (6.4 to 2.8); unchanged on nebivolol (6.4 to 6.0) |
| Brixius et al., Clin Exp Pharmacol Physiol 2007 | Crossover, men aged 40–55; nebivolol 5 mg vs metoprolol succinate 95 mg, 12 weeks each | Metoprolol lowered the IIEF erectile function score by 0.92; nebivolol did not |
These trials were small, and the FDA label still lists erectile dysfunction among postmarketing reports.
Hormones and fertility
Because steroid users often ask about this, the label’s hormone data are worth noting. In a randomized, placebo-controlled study in healthy men, 10 mg/day for 6 weeks had no significant effect on LH, total testosterone or stimulated cortisol (Bystolic label).
The animal findings are different:
- In mice, 40 mg/kg/day for two years (5 times the maximum human dose by body surface area) increased testicular Leydig cell hyperplasia and adenomas. Giving DHT prevented this, pointing to an indirect, LH-driven effect that the label says is not thought to be relevant in humans.
- In rats and mice, doses of 40 mg/kg/day or more impaired sperm production. In rats this did not reverse over a 4-week recovery period.
Use alongside anabolic steroids
Nebivolol appears in steroid-user discussions mainly as a blood pressure drug. The concern is real. In a Danish cross-sectional study of men in recreational strength training, current steroid users had higher 24-hour systolic pressure than controls, 132 versus 124 mmHg (Rasmussen et al., J Hypertens 2018). Systolic hypertension was present in 51% of current users versus 17% of controls, and both current and former users had stiffer aortas.
A US study of 140 experienced weightlifters found lower heart pumping function in long-term steroid users: mean left ventricular ejection fraction 52% versus 63% in non-users (Baggish et al., Circulation 2017). Users also had more coronary plaque.
What the evidence does not show:
- No trial has tested nebivolol, or any beta-blocker, for blood pressure or heart outcomes in people using anabolic steroids.
- Nebivolol’s lack of effect on testosterone and LH was measured in healthy men not taking steroids.
- No study has examined whether treating blood pressure in steroid users changes the heart-muscle or plaque findings described above.
Other drugs on this site that act on blood pressure include telmisartan, hydrochlorothiazide and spironolactone. The label found no pharmacokinetic interaction between nebivolol and hydrochlorothiazide, spironolactone or furosemide.
Side effects and risks
Common side effects
In three 12-week placebo-controlled trials (1,597 patients on nebivolol, 205 on placebo), these were among the reactions more frequent than placebo (Bystolic label):
| Reaction | Placebo | 5 mg | 10 mg | 20–40 mg |
|---|---|---|---|---|
| Headache | 6% | 9% | 6% | 7% |
| Fatigue | 1% | 2% | 2% | 5% |
| Dizziness | 2% | 2% | 3% | 4% |
| Nausea | 0% | 1% | 3% | 2% |
| Bradycardia (slow heart rate) | 0% | 0% | 0% | 1% |
Discontinuation due to side effects was 2.8% on nebivolol versus 2.2% on placebo. Postmarketing reports include heart block, low blood pressure, fainting, bronchospasm, erectile dysfunction and abnormal liver tests; their frequency is unknown.
Stopping suddenly
The label warns against abrupt discontinuation in people with coronary artery disease. Severe worsening of angina, heart attack and ventricular arrhythmias have been reported after beta-blockers were stopped suddenly. The label advises tapering over 1–2 weeks when possible.
Masking of low blood sugar and thyroid overactivity
Beta-blockers can hide warning signs such as a racing heart:
- Hypoglycemia. They may mask early signs and increase the risk of severe or prolonged low blood sugar, especially in people with diabetes or who are fasting.
- Thyrotoxicosis. They may mask a fast heart rate from excess thyroid hormone, and abrupt withdrawal may trigger a thyroid storm. This is relevant to anyone taking thyroid hormone such as T3.
Lungs and β2-agonists
The label states that people with bronchospastic disease, such as asthma, should generally not receive beta-blockers. Nebivolol’s β1-selectivity is lost at higher doses and in poor metabolizers, when it also blocks β2 receptors, the receptors that drugs such as albuterol and clenbuterol act on. The label notes that β-agonists can reverse nebivolol’s β-blocking effects.
Interactions
| Drug or class | Effect (FDA label) |
|---|---|
| CYP2D6 inhibitors (fluoxetine, paroxetine, quinidine, propafenone) | Fluoxetine raised d-nebivolol AUC 8-fold and peak 3-fold; dose may need reduction |
| Other beta-blockers | Should not be combined |
| Verapamil- or diltiazem-type calcium channel blockers | Excess slowing of heart rate, lower blood pressure and weaker contraction; monitor ECG and blood pressure |
| Digoxin | Added risk of slow heart rate |
| Clonidine, reserpine | Excess reduction of sympathetic activity; stop nebivolol several days before tapering clonidine |
| Sildenafil | Sildenafil AUC fell 21% and peak 23%; blood pressure effects roughly added together |
| Warfarin, diuretics, ramipril, losartan | No significant pharmacokinetic interaction |
For PDE5 inhibitors, see also sildenafil and tadalafil.
Who should not use it
The label contraindicates nebivolol in people with:
- severe bradycardia;
- heart block greater than first degree;
- cardiogenic shock;
- decompensated heart failure;
- sick sinus syndrome, unless a pacemaker is in place;
- severe liver impairment (worse than Child-Pugh B);
- hypersensitivity to any ingredient.
It has not been studied in angina or after a recent heart attack. Its safety and effectiveness in people under 18 have not been established. Breastfeeding is not recommended. In people with pheochromocytoma, an α-blocker should be started first.
Overdose
The most common signs of overdose are slow heart rate and low blood pressure. The largest known ingestion was up to 500 mg; that patient developed low blood pressure, slow heart rate, low blood sugar and respiratory failure, and recovered.
Legal status and anti-doping
In the US, nebivolol is a prescription drug, available as Bystolic and generics (Drugs@FDA, NDA 021742).
WADA lists nebivolol by name under P1, beta-blockers (WADA 2026 Prohibited List). Beta-blockers are banned in competition only in particular sports: archery, automobile racing, billiards, darts, golf, mini-golf, shooting and some underwater sports. In archery, shooting and the listed underwater disciplines they are also banned out of competition. All beta-blockers are Specified Substances.
Key takeaways
- A beta-blocker with a vasodilating twist. Nebivolol blocks β1 receptors and also relaxes arteries through the nitric oxide pathway, which most beta-blockers do not.
- Approved for hypertension in the US. The labeled dose is 5–40 mg once daily. The UK also licenses it for heart failure in people 70 and older, based on SENIORS.
- Half-life depends on genotype. About 12 hours for the active isomer in most people and about 19 hours in CYP2D6 poor metabolizers, but active metabolites even out the clinical effect.
- Fewer metabolic and sexual side effects in small trials. It did not reduce insulin sensitivity or erectile function in comparisons with metoprolol and atenolol, but these trials were small.
- No data in steroid users. Anabolic steroid use is linked to higher blood pressure and heart changes, but nebivolol has never been tested in that group.
- Do not stop abruptly and watch for masking. The label warns about withdrawal in coronary disease, and beta-blockers can hide signs of low blood sugar and thyroid overactivity.
Sources
- AbbVie / Allergan. Bystolic (nebivolol) tablets, prescribing information. DailyMed; Drugs@FDA, NDA 021742.
- Food and Drug Administration. Byvalson (nebivolol and valsartan) tablets, NDA 206302. Drugs@FDA.
- Milpharm Ltd. Nebivolol 5 mg tablets, Summary of Product Characteristics (UK), revised April 2025. emc.
- National Center for Biotechnology Information. Nebivolol, PubChem CID 71301. PubChem.
- Cockcroft JR, Chowienczyk PJ, Brett SE, et al. Nebivolol vasodilates human forearm vasculature: evidence for an L-arginine/NO-dependent mechanism. J Pharmacol Exp Ther. 1995;274(3):1067–1071. PubMed.
- Weiss RJ, Weber MA, Carr AA, et al. A randomized, double-blind, placebo-controlled parallel-group study to assess the efficacy and safety of nebivolol, a novel beta-blocker, in patients with mild to moderate hypertension. J Clin Hypertens (Greenwich). 2007;9(9):667–676. PubMed.
- Van Bortel LM, Fici F, Mascagni F. Efficacy and tolerability of nebivolol compared with other antihypertensive drugs: a meta-analysis. Am J Cardiovasc Drugs. 2008;8(1):35–44. PubMed.
- Flather MD, Shibata MC, Coats AJ, et al. Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J. 2005;26(3):215–225. PubMed.
- Ayers K, Byrne LM, DeMatteo A, Brown NJ. Differential effects of nebivolol and metoprolol on insulin sensitivity and plasminogen activator inhibitor in the metabolic syndrome. Hypertension. 2012;59(4):893–898. PubMed.
- Boydak B, Nalbantgil S, Fici F, et al. A randomised comparison of the effects of nebivolol and atenolol with and without chlorthalidone on the sexual function of hypertensive men. Clin Drug Investig. 2005;25(6):409–416. PubMed.
- Brixius K, Middeke M, Lichtenthal A, et al. Nitric oxide, erectile dysfunction and beta-blocker treatment (MR NOED study): benefit of nebivolol versus metoprolol in hypertensive men. Clin Exp Pharmacol Physiol. 2007;34(4):327–331. PubMed.
- Rasmussen JJ, Schou M, Madsen PL, et al. Increased blood pressure and aortic stiffness among abusers of anabolic androgenic steroids: potential effect of suppressed natriuretic peptides in plasma? J Hypertens. 2018;36(2):277–285. PubMed.
- Baggish AL, Weiner RB, Kanayama G, et al. Cardiovascular toxicity of illicit anabolic-androgenic steroid use. Circulation. 2017;135(21):1991–2002. PubMed.
- World Anti-Doping Agency. The 2026 Prohibited List, P1 Beta-blockers. WADA 2026 Prohibited List.