Skip to Content


Generic Name: Nebivolol Hydrochloride
Class: beta-Adrenergic Blocking Agents
Chemical Name: (1RS,1′RS)-1,1′-[(2RS,2′SR)-bis(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)]- 2,2′-iminodiethanol hydrochloride
Molecular Formula: C22H25F2NO4•HCl
CAS Number: 152520-56-4

Medically reviewed on Mar 1, 2017


β-adrenergic blocking agent (β-blocker).1 2 3 4 5 6 7 8 9 10 11 20 24

Uses for Bystolic


Management of hypertension (alone or in combination with other classes of antihypertensive agents).1 2 3 4 5 6 10 11 24

β-Blockers generally not preferred for initial management of hypertension, but may be considered in patients who have a compelling indication (e.g., prior MI, ischemic heart disease, heart failure) for their use or as add-on therapy in those who do not respond adequately to the preferred drug classes (ACE inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, or thiazide diuretics).29 501 502 503 504 515 523 524 527 800

Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to β-blockers.21 22 23 500 501 504 However, diminished response to β-blockers is largely eliminated when administered concomitantly with a thiazide diuretic.500

Bystolic Dosage and Administration


  • Individualize dosage according to patient response.1

  • If long-term therapy is discontinued, reduce dosage gradually over a period of about 1–2 weeks.1 (See Abrupt Withdrawal of Therapy under Cautions.)

  • β1-Adrenergic blocking selectivity diminishes as dosage is increased beyond 10 mg.1

BP Monitoring and Treatment Goals

  • Carefully monitor BP during initial titration or subsequent upward adjustment in dosage.500 501

  • When available, use evidence-based dosing information (i.e., dosages shown in randomized controlled trials to reduce complications of hypertension) to determine target dosages; target dosages usually can be achieved within 2–4 weeks but may take up to several months.501

  • Goal is to achieve and maintain optimal control of BP; individualize specific target BP based on consideration of multiple factors, including patient age and comorbidities, and currently available evidence from clinical studies.500 501


Oral Administration

Administer orally once daily without regard to meals.1

Frequent administration (i.e., daily divided doses) unlikely to be more beneficial than once-daily administration.1


Available as nebivolol hydrochloride; dosage expressed in terms of nebivolol.1



Initially, 5 mg once daily, either alone or in combination with other antihypertensives.1 11 24 Increase at 2-week intervals (up to 40 mg daily) in patients whose BP is uncontrolled with the initial dosage.1 11

If intolerable adverse effects occur, consider dosage reduction; if adverse effects worsen or fail to resolve, may need to discontinue and switch to another antihypertensive drug class.501

Prescribing Limits



Maximum 40 mg daily.1

Special Populations

Hepatic Impairment

Initially, 2.5 mg once daily in patients with moderate hepatic impairment (Child-Pugh class B).1 11 Increase dosage carefully, if necessary.1

Contraindicated in patients with severe hepatic impairment (Child-Pugh class C).1 6 (See Contraindications under Cautions.)

Renal Impairment

Initially, 2.5 mg once daily in patients with severe renal impairment (Clcr <30 mL/minute).1 11 Increase dosage carefully, if necessary.1

Geriatric Patients

Dosage adjustment not required.1

Poor CYP2D6 Metabolizers

No dosage adjustment required in poor metabolizers of CYP2D6 substrates.1 7

Cautions for Bystolic


  • Severe bradycardia.1

  • Heart block greater than first degree.1

  • Cardiogenic shock.1

  • Decompensated cardiac failure.1 (See Heart Failure under Cautions.)

  • Sick sinus syndrome (unless a functioning permanent pacemaker is present).1

  • Severe hepatic impairment (Child-Pugh class C).1

  • Known hypersensitivity to nebivolol or any ingredient in the formulation.1



Abrupt Withdrawal of Therapy

Abrupt discontinuance of therapy is not recommended as it may exacerbate angina symptoms or precipitate MI and ventricular arrhythmias in patients with CAD.1 Gradually decrease dosage over a period of about 1–2 weeks; monitor patients carefully and advise patients to temporarily limit their physical activity during withdrawal of therapy.1 If exacerbation of angina occurs or acute coronary insufficiency develops, reinstitute therapy (at least temporarily).1

Heart Failure

Possible precipitation of heart failure.1

Avoid use in patients with overt heart failure; use cautiously in patients with inadequate cardiac function and, if necessary, in patients with well-compensated heart failure.1 If heart failure worsens, consider discontinuing therapy.1

Ischemic Heart Disease

Safety and efficacy in patients with angina pectoris or recent MI have not been established.1

Major Surgery

Possible increased risks associated with general anesthesia (e.g., severe hypotension, difficulty in restarting or maintaining a heart beat) have occurred in some patients who received β-blockers.1 Use with caution in patients undergoing major surgery involving general anesthesia, especially with myocardial-depressant anesthetics (e.g., cyclopropane, ether, trichloroethylene).1

Effects of β-blockers can be reversed by administration of β-agonists (e.g., dobutamine, isoproterenol).1

Bronchospastic Disease

Possible bronchospasm.1 Generally should not be used in patients with bronchospastic disease.1 2

Diabetes Mellitus and Hypoglycemia

Possible decreased signs and symptoms of hypoglycemia (e.g., tachycardia) and increased insulin-induced hypoglycemia.1

Use with caution in patients with history of spontaneous hypoglycemia and in patients with diabetes receiving hypoglycemic agents.1


Signs of hyperthyroidism (e.g., tachycardia) may be masked.1 Possible exacerbation of hyperthyroidism or thyroid storm if therapy is abruptly withdrawn.1

Peripheral Vascular Disease

Possible precipitation or aggravation of arterial insufficiency.1 Use with caution.1


Concomitant use with nondihydropyridine calcium-channel blocking agents (e.g. verapamil, diltiazem) requires caution.1 (See Specific Drugs under Interactions.)

General Precautions

Risk of Anaphylactic Reactions

Patients with a history of anaphylactic reactions to a variety of allergens may be more reactive to repeated accidental, diagnostic, or therapeutic challenges with allergens while taking β-blockers.1 Such patients may be unresponsive to usual doses of epinephrine.1


Use with caution in patients suspected of having pheochromocytoma; initiate therapy with α-adrenergic blocking agent before using any β-blocker.1

Specific Populations


Category C.1


Distributed into milk in rats; not known whether distributed into human milk.1 Discontinue nursing or drug.1

Pediatric Use

Safety and efficacy not established in children <18 years of age.1

Geriatric Use

No substantial differences in safety or efficacy relative to younger adults.1

Hepatic Impairment

Decreased clearance in patients with moderate hepatic impairment (Child-Pugh class B); use with caution.1 7 (See Hepatic Impairment under Dosage and Administration.)

Safety and efficacy not established in patients with severe hepatic impairment (Child-Pugh class C); use is contraindicated in these patients.1 (See Contraindications.)

Renal Impairment

Decreased clearance in patients with severe renal impairment (Clcr <30 mL/minute); use with caution.1 7 (See Renal Impairment under Dosage and Administration.)

Not specifically studied in patients undergoing dialysis; use with caution in these patients.1

Common Adverse Effects

Headache,1 2 3 4 5 13 fatigue,1 2 3 4 5 11 13 dizziness,1 2 3 4 5 11 13 diarrhea,1 3 4 nausea.1 3

Interactions for Bystolic

Metabolized by CYP2D6;1 7 11 does not inhibit CYP isoenzymes at clinically relevant concentrations.1

Drugs Affecting Hepatic Microsomal Enzymes

CYP2D6 inhibitors: Potential increased plasma nebivolol concentrations;1 11 monitor patients carefully and adjust dosage according to BP response.1

Specific Drugs




Antiarrhythmic agents (e.g., amiodarone, disopyramide)

Possible conduction disturbances1 2

Use concomitantly with caution1 2 24

Antidiabetic agents (oral)

May mask symptoms of hypoglycemia (e.g., tachycardia)1

Use concomitantly with caution1


Possible additive effects1

Concomitant use with other β-blockers not recommended1

Calcium-channel blocking agents, nondihydropyridine (e.g., diltiazem, verapamil)

Possible conduction disturbances1 2 27 28

Use concomitantly with caution;1 2 24 27 28 monitor BP and ECG with concomitant use1

Catecholamine-depleting agents (e.g., guanethidine, reserpine)

Potential additive effects (e.g., hypotension, bradycardia)1 26

Monitor closely for symptoms (e.g., vertigo, syncope, postural hypotension)1 26

Charcoal (activated)

Pharmacokinetic interaction unlikely1


Potential increased plasma nebivolol concentrations1 2 7 20 24

No apparent change in pharmacodynamics of nebivolol (e.g., BP, heart rate)2 7 20


Potential for increased rebound hypertension following discontinuance of clonidine25

If used concurrently, discontinue nebivolol therapy several days before clonidine therapy is to be gradually discontinued1 25


Possible additive negative effects on AV conduction and heart rate;1 increased risk of bradycardia1

Concomitant use did not affect pharmacokinetics of digoxin or nebivolol1 7 24

Use concomitantly with caution2

Diuretics (e.g., furosemide, hydrochlorothiazide, spironolactone)

Pharmacokinetic interactions unlikely1 7 24


Potential increased plasma nebivolol concentrations 1 11

Use concomitantly with caution1


May mask symptoms of hypoglycemia (e.g., tachycardia)1

Use concomitantly with caution1


Pharmacokinetic interaction unlikely1 7 24

Myocardial-depressant general anesthetics (e.g., cyclopropane, ether, trichloroethylene)

Increased risk of hypotension and difficulty in restarting or maintaining heartbeat1

Closely monitor with concomitant use1


Potential increased plasma nebivolol concentrations 1

Use concomitantly with caution1


Potential increased plasma nebivolol concentrations1

Use concomitantly with caution1


Potential increased plasma nebivolol concentrations1

Use concomitantly with caution1


Pharmacokinetic interaction unlikely1 7 24


Pharmacokinetic interaction unlikely; no apparent change in pharmacodynamics of nebivolol (e.g., BP, heart rate) 1 7 20 24


Additive effects on BP and pulse1

Potential decreased peak plasma concentrations of sildenafil; modest effect on peak plasma concentration and AUC of d-nebivolol1


No effect on PT or warfarin pharmacokinetics observed1 7 24

Bystolic Pharmacokinetics



Absolute bioavailability not determined.1

Following oral administration, mean peak plasma concentrations occur within approximately 1.5–4 hours.1


Food does not alter pharmacokinetics; however, may slightly reduce nebivolol glucuronides.1



Distributed into milk in rats; not known whether distributed into human milk.1

Plasma Protein Binding

Approximately 98% (mainly albumin).1



Undergoes first-pass metabolism in the liver mainly via glucuronidation of the parent drug and, to a lesser extent, via N-dealkylation and oxidation by CYP2D6.1 2 7 11

Elimination Route

Excreted in urine (38%) and feces (44%), principally as metabolites;1 <0.5% eliminated in urine and feces as unchanged drug.7 11


12 hours for d-nebivolol.1

Special Populations

Poor CYP2D6 metabolizers: Eliminated in urine (67%) and feces (13%), principally as metabolites.1 7 Half-life is 19 hours.1

Decreased clearance in patients with moderate hepatic impairment (Child-Pugh class B) or with severe renal impairment (Clcr <30 mL/minute).1 7





Tight, light-resistant containers at 20–25° C.1


  • Inhibits response to adrenergic stimuli by competitively blocking β1-adrenergic receptors within the myocardium in extensive CYP2D6 metabolizers and at doses ≤10 mg.1 Blocks both β1- and β2-adrenergic receptors in poor CYP2D6 metabolizers and at doses >10 mg.1

  • Exhibits vasodilatory effects through stimulation of endothelial nitric oxide activity;2 7 8 9 10 24 precise mechanism of this effect not fully elucidated.7 9

  • Precise mechanism of hypotensive action not fully elucidated;1 may reduce BP by decreasing heart rate, myocardial contractility, and sympathetic outflow from the CNS; suppressing renin activity; and/or decreasing peripheral vascular resistance as a result of its vasodilating effects.1 11

  • Does not exhibit intrinsic sympathomimetic (β1-agonist) activity, membrane-stabilizing (local anesthetic) activity, or α1-adrenergic blocking activity at clinically relevant concentrations.1 7

  • Racemic mixture: d-isomer has substantial β-adrenergic blocking activity; l-isomer appears to be pharmacologically active, but precise contribution to pharmacologic effects not fully established.2 7

Advice to Patients

  • Importance of taking nebivolol exactly as prescribed.1

  • Importance of not interrupting or discontinuing therapy without consulting a clinician;1 patients should temporarily limit physical activity when discontinuing therapy.1

  • If a dose is missed, importance of patient taking only the next scheduled dose (i.e., the next dose should not be doubled).1

  • Importance of avoiding some activities (e.g., driving, operating machinery) until effects on the patient are known.1

  • Importance of warning patients receiving insulin or oral hypoglycemic agents and those subject to spontaneous hypoglycemia that β-blockers can mask some symptoms of hypoglycemia (e.g., tachycardia).1

  • Importance of immediately informing clinician at the first sign or symptom (e.g., weight gain, shortness of breath) of CHF.1

  • Importance of patients informing their anesthesiologist or dentist about nebivolol therapy before undergoing major surgery.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Nebivolol Hydrochloride


Dosage Forms


Brand Names




2.5 mg (of nebivolol)



5 mg (of nebivolol)



10 mg (of nebivolol)



20 mg (of nebivolol)



AHFS DI Essentials. © Copyright 2019, Selected Revisions March 1, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.


1. Forest Laboratories, Inc. Bystolic (nebivolol) tablets prescribing information. St. Louis, MO; 2008 Aug.

2. Veverka A, Nuzum DS, Jolly JL. Nebivolol: A third-generation β-adrenergic blocker. Ann Pharmacother. 2006; 40:1353-60.

3. 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 β-blocker, in patients with mild to moderate hypertension. J Clin Hypertens. 2007; 9:667-76.

4. Saunders E, Smith WB, DeSalvo KB et al. The efficacy and tolerability of nebivolol in hypertensive African American patients. J Clin Hypertens. 2007; 9:866-75.

5. Gradman AH. Addition of the β-blocker nebivolol to ongoing therapy in the management of mild-moderate hypertension. Poster presentation from American Society of Hypertension 22nd Annual Meeting; Chicago, IL; May 19-22, 2007.

6. Forest Laboratories, Inc., St. Louis, MO: Personal communication.

7. Prisant LM. Nebivolol: pharmacologic profile of an ultraselective, vasodilatory β1-blocker. J Clin Pharmacol. 2008; 48:225-39.

8. Mason RP, Kalinowski L, Jacob RF et al. Nebivolol reduces nitroxidative stress and restores nitric oxide bioavailability in endothelium of black Americans. Circulation. 2005; 112:3795-801.

9. Dessy C, Saliez J, Ghisdal P et al. Endothelial B3-adrenoreceptors mediate nitric oxide-dependent vasorelaxation of coronary microvessels in response to the third-generation β-blocker nebivolol. Circulation. 2005; 112:1198-205.

10. Rosei EA, Rizzoni D. Metabolic profile of nebivolol, a β-adrenoceptor antagonist with unique characteristics. Drugs. 2007; 67:1097-107.

11. Anon. Nebivolol (Bystolic) for hypertension. Med Lett Drugs Ther. 2008; 50:17-9.

13. Van Nueten L, Taylor FR, Robertson JL.. Nebivolol vs. atenolol and placebo in essential hypertension: a double-blind randomised trial. J Hum Hypertens. 1998; 12:135-40.

14. Uhlir O, Feifusa M, Havanek K et al. Nebivolol versus metoprolol in the treatment of hypertension. Drug Invest. 1991; 3(Suppl):107.

15. Rosei EA, Rizzoni D, Comini S et al. Evaluation of the efficacy and tolerability of nebivolol versus lisinopril in the treatment of essential arterial hypertension: a randomized, multicentre, double-blind study. Blood Pressure 2003; (Suppl 1): 30-35.

16. Van Bortel LM, Bulpitt CJ, Fici F. Quality of life and antihypertensive effect with nebivolol and losartan. Am J Hypertens. 2005; 18:1060-6.

17. Van Nueten LM. , Schelling A, Verommen C et al. Nebivolol vs enalapril in the treatment of essential hypertension: a double-blind randomised trial. J Hum Hypertens. 1997; 11:813-9.

18. Van Nueten LM. , Lacouriere Y, Vyssoulis G et al. Nebivolol versus nifedipine in the treatment of essential hypertension: A double-blind, randomized, comparative trial. Am J Ther. 1998; 5:237-43.

19. Mazza A. , Gil-Extremera B, Maldonato A et al. Nebivolol vs amlodipine as first-line treatment of essential arterial hypertension in the elderly. Blood Press. 2002; 11:182-8.

20. Kamali F, Howes A, Thomas SH et al. A pharmacokinetic and pharmacodynamic interaction study between nebivolol and the H2-receptor antagonists cimetidine and ranitidine. Br J Clin Pharmacol. 1997; 43:201-4.

21. Douglas JG, Bakris GL, Epstein M et al. Management of high blood pressure in African Americans: Consensus statement of the Hypertension in African Americans Working Group of the International Society on Hypertension in Blacks. Arch Intern Med. 2003; 163:525-41.

22. Wright JT, Dunn JK, Cutler JA et al. Outcomes in hypertensive black and nonblack patients treated with chlorthalidone, amlodipine, and lisinopril. JAMA. 2005; 293:595-607.

23. Neaton JD, Kuller LH. Diuretics are color blind. JAMA. 2005; 293:1663-6.

24. Gray CL, Ndefo UA. Nebivolol: a new antihypertensive agent. Am J Health-Syst Pharm. 2008; 65:1125-33.

25. Boehringer Ingelheim. Catapres (clonidine hydrochloride) tablets prescribing information. Ridgefield, CT; 2007 Jan 5.

26. King Pharmaceuticals, Inc. Corgard (nadolol) tablets prescribing information. Bristol, TN; 2007 Jul.

27. Biovail Pharmaceuticals, Inc. Cardizem (diltiazem hydrochloride) capsules prescribing information. Bridgewater, NJ; 2001 Aug.

28. Pfizer. Calan (verapamil hydrochloride) tablets prescribing information. New York, NY; 2006 May.

29. Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint Reduction in Hypertension Study (LIFE). Lancet. 2002;359:995-1003.

500. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7). Bethesda, MD: National Institutes of Health; 2004 Aug. (NIH publication No. 04-5230.)

501. James PA, Oparil S, Carter BL et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014; 311:507-20.

502. Mancia G, Fagard R, Narkiewicz K et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013; 31:1281-357.

503. Go AS, Bauman MA, Coleman King SM et al. An effective approach to high blood pressure control: a science advisory from the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention. Hypertension. 2014; 63:878-85.

504. Weber MA, Schiffrin EL, White WB et al. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hypertens (Greenwich). 2014; 16:14-26.

515. Thomas G, Shishehbor M, Brill D et al. New hypertension guidelines: one size fits most?. Cleve Clin J Med. 2014; 81:178-88.

523. Fihn SD, Gardin JM, Abrams J et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2012; 126:e354-471.

524. WRITING COMMITTEE MEMBERS, Yancy CW, Jessup M et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013; 128:e240-327.

527. O'Gara PT, Kushner FG, Ascheim DD et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013; 127:e362-425.

800. Yancy CW, Jessup M, Bozkurt B et al. 2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2016; :.