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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
Brands: Bystolic


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

Uses for Nebivolol Hydrochloride


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

One of several preferred initial therapies in hypertensive patients with heart failure, postmyocardial infarction, high CHD risk, and/or diabetes mellitus.12

Can be used as monotherapy for initial management of uncomplicated hypertension; however, thiazide diuretics are preferred by JNC 7.12

Nebivolol Hydrochloride 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


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.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

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

CYP2D6 Metabolizers

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

Cautions for Nebivolol Hydrochloride


  • Severe bradycardia.1

  • Heart block greater than first degree.1

  • Cardiogenic shock.1

  • Decompensated cardiac failure.1 (See Cardiac 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

Cardiac Failure

Possible precipitation of CHF.1

Avoid use in patients with overt CHF; 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-adrenergic blocking agents.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-adrenergic blocking agents 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-adrenergic blocking agents.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-adrenergic blocking agent.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 Nebivolol Hydrochloride

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

β-Adrenergic blocking agents

Possible additive effects1

Concomitant use with other β-adrenergic blocking agents 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

Nebivolol Hydrochloride 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-adrenergic blocking agents 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.

Nebivolol Hydrochloride


Dosage Forms


Brand Names




2.5 mg (of nebivolol)



5 mg (of nebivolol)



10 mg (of nebivolol)



20 mg (of nebivolol)



Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Bystolic 10MG Tablets (FOREST): 30/$71.99 or 90/$199.96

Bystolic 2.5MG Tablets (FOREST): 30/$73.19 or 90/$201.92

Bystolic 20MG Tablets (FOREST): 30/$74.51 or 90/$199.49

Bystolic 5MG Tablets (FOREST): 30/$71.99 or 90/$207.98

AHFS DI Essentials. © Copyright, 2004-2016, Selected Revisions July 1, 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.


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