Nebivolol (Lexi-Drugs)

Pronunciation

(ne BIV oh lole)

Brand Names: US

Bystolic

Brand Names: Canada

Bystolic

Dosing: Adult

Hypertension (alternative agent): Oral: Initial: 5 mg once daily; titrate as needed at 2-week intervals based on patient response to a maximum dose of 40 mg once daily (ACC/AHA [Whelton 2017]).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

CrCl 50 to 80 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling; however, dose adjustment does not appear necessary. Following a single 5 mg dose in patients with CrCl 50 to 80 mL/minute, nebivolol clearance was unchanged.

CrCl 30 to 50 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling; however, dose adjustment is likely not necessary. Following a single 5 mg dose in patients with moderate impairment, reduction in nebivolol clearance was negligible (~17%) (Shaw 2005).

CrCl <30 mL/minute: Initial: 2.5 mg once daily; if initial response is inadequate, may increase cautiously.

Hemodialysis: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Dosing: Hepatic Impairment: Adult

Mild impairment (Child-Pugh class A): There are no dosage adjustments provided in the manufacturer’s labeling; use caution.

Moderate impairment (Child-Pugh class B): Initial: 2.5 mg once daily; if initial response is inadequate, may increase cautiously

Severe impairment (Child-Pugh class C): Use is contraindicated.

Use: Labeled Indications

Hypertension: Management of hypertension. Note: Beta-blockers are not recommended as first-line therapy (ACC/AHA [Whelton 2017]).

Clinical Practice Guidelines

Coronary Artery Bypass Graft Surgery:

AHA Scientific Statement, “Secondary Prevention After Coronary Artery Bypass Graft Surgery,” February 2015

Hypertension:

“2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults,” November 2017.

AHA/ACC/ASH, “Treatment of Hypertension in Patients with Coronary Artery Disease: A Scientific Statement by the American Heart Association, American College of Cardiology and American Society of Hypertension,” May 2015

“ACCF/AHA Expert Consensus Document on Hypertension in the Elderly,” 2011

AHA/ACC/CDC, “AHA/ACC/CDC Science Advisory: An Effective Approach to High Blood Pressure Control” November 2013

ASH/ISH “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,” January 2014

Eighth Joint National Committee (JNC 8), “2014 Evidence-based Guideline for the Management of High Blood Pressure in Adults,” December 2013

Ischemic Heart Disease:

ACC/AHA/AATS/PCNA/SCAI/STS, “2014 Focused Update of the Guideline for the Diagnosis and Management of Patients with Stable Ischemic Heart Disease,” July 2014

ACCF/AHA/ACP/AATS/PCNA/SCAI/STS, “2012 Guideline for the Diagnosis and Management of Patients with Stable Ischemic Heart Disease,” November 2012

Prevention:

“AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients with Coronary and Other Atherosclerotic Vascular Disease: 2011 Update,” November 2011

Valvular Heart Disease:

AHA/ACC, “2014 AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease,” March 2014

Administration: Oral

May be administered with or without food.

Storage/Stability

Store at 20°C to 25°C (68°F to 77°F). Protect from light.

Medication Patient Education with HCAHPS Considerations

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache or loss of strength and energy. Have patient report immediately to prescriber signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, tachycardia, confusion, increased hunger, or sweating), dizziness, passing out, shortness of breath, excessive weight gain, swelling of arms or legs, or bradycardia (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Contraindications

Hypersensitivity to nebivolol or any component of the formulation; severe bradycardia; heart block greater than first-degree (except in patients with a functioning artificial pacemaker); cardiogenic shock; decompensated heart failure; sick sinus syndrome (unless a permanent pacemaker is in place); severe hepatic impairment (Child-Pugh class C)

Documentation of allergenic cross-reactivity for beta-blockers is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Canadian labeling: Additional contraindications (not in US labeling): Severe peripheral arterial circulatory disorders; sinoatrial block; rare hereditary conditions of Galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactic reactions: Use caution with history of severe anaphylaxis to a variety of allergens; patients taking beta-blockers may become more sensitive to repeated challenges. Treatment of anaphylaxis (eg, epinephrine) in patients taking beta-blockers may be ineffective or promote undesirable effects.

Disease-related concerns:

• Bronchospastic disease: In general, patients with bronchospastic disease should not receive beta-blockers; for patients with bronchospastic disease who do not respond to or cannot tolerate other therapies, initial low doses of beta1-selective nebivolol may be employed and used cautiously with close monitoring. Ensure patient has an inhaled beta2-agonist immediately available.

• Diabetes: Use with caution in patients with diabetes mellitus; may potentiate hypoglycemia and/or mask signs and symptoms.

• Heart failure (HF): Note: Nebivolol has not been shown to reduce morbidity or mortality in the general HF population; only beta-blockers proven to reduce mortality (ie, bisoprolol, carvedilol, or extended-release metoprolol succinate) should be used in the treatment of heart failure. Use with caution in patients with compensated HF and monitor for a worsening of the condition. If condition worsens, consider temporary discontinuation or dosage reduction of nebivolol. Patients should be stabilized on HF regimen prior to initiation of beta-blocker. Beta-blocker therapy should be initiated at very low doses with gradual and very careful titration. Adjustment of other medications (ACE inhibitors and/or diuretics) may be required.

• Hepatic impairment: Use with caution in patients with hepatic impairment; dosage adjustment required with moderate impairment (Child-Pugh class B). Use is contraindicated in patients with Child-Pugh class C hepatic impairment.

• Myasthenia gravis: Use with caution in patients with myasthenia gravis.

• Peripheral vascular disease (PVD) and Raynaud disease: Can precipitate or aggravate symptoms of arterial insufficiency in patients with PVD and Raynaud disease. Use with caution and monitor for progression of arterial obstruction.

• Pheochromocytoma (untreated): Adequate alpha-blockade is required prior to use of any beta-blocker.

• Psoriasis: Beta-blocker use has been associated with induction or exacerbation of psoriasis, but cause and effect have not been firmly established.

• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment required with severe renal impairment (CrCl <30 mL/minute). Nebivolol has not been evaluated in dialysis-dependent patients.

• Thyroid disease: May mask signs of hyperthyroidism (eg, tachycardia). If thyrotoxicosis is suspected, carefully manage and monitor; abrupt withdrawal may exacerbate symptoms of hyperthyroidism or precipitate thyroid storm.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Bradycardia may be observed more frequently in elderly patients (>65 years of age); dosage reductions may be necessary.

Other warnings/precautions:

• Abrupt withdrawal: Beta-blocker therapy should not be withdrawn abruptly (particularly in patients with coronary artery disease), but gradually tapered over 1-2 weeks to avoid acute tachycardia, hypertension, and/or ischemia. Severe exacerbation of angina, ventricular arrhythmias, and myocardial infarction (MI) have been reported following abrupt withdrawal of beta-blocker therapy. Temporary but prompt resumption of beta-blocker therapy may be indicated with worsening of angina or acute coronary insufficiency.

• Major surgery: Chronic beta-blocker therapy should not be routinely withdrawn prior to major surgery.

Geriatric Considerations

Due to alterations in the beta-adrenergic autonomic nervous system, beta-adrenergic blockade may result in less hemodynamic response than seen in younger adults. Studies indicate that despite decreased sensitivity to the chronotropic effects of beta-blockade with age, there appears to be an increased myocardial sensitivity to the negative inotropic effect during stress (eg, exercise). Controlled trials have shown the overall response rate for propranolol to be only 20% to 50% in elderly populations. Therefore, all beta-adrenergic blocking drugs may result in a decreased response as compared to younger adults.

The AHA/ACC/ASH 2015 scientific statement on the treatment of hypertension in patients with CAD warns to use caution to avoid decreases in DBP <60 mm Hg especially in patients >60 years of age since reduced coronary perfusion may occur. When lowering SBP in older hypertensive patients with wide pulse pressures, very low DBP values (<60 mm Hg) may result. In patients with obstructive CAD, clinicians should lower blood pressure slowly and carefully monitor for any untoward signs or symptoms, especially those resulting from myocardial ischemia and worsening heart failure (AHA/ACC/ASH [Rosendorff 2015]).

Pregnancy Considerations

Adverse events, such as fetal/neonatal bradycardia, hypoglycemia, reduced birth weight, have been observed following in utero exposure to beta-blockers as a class. Adequate facilities for monitoring infants at birth is generally recommended.

Untreated chronic maternal hypertension and preeclampsia are also associated with adverse events in the fetus, infant, and mother (ACOG 2015; Magee 2014). Although beta-blockers may be used when treatment of hypertension in pregnancy is indicated, agents other than nebivolol are preferred (ACOG 2013; Magee 2014; Regitz-Zagrosek 2011).

Breast-Feeding Considerations

It is not known if nebivolol is present in breast milk. Breastfeeding is not recommended by the manufacturer due to the potential for beta-blockers to produce serious effects on breastfed infants, especially bradycardia.

Lexicomp Pregnancy & Lactation, In-Depth
Briggs’ Drugs in Pregnancy & Lactation
Adverse Reactions

1% to 10%:

Cardiovascular: Peripheral edema (1%), bradycardia (≤1%), chest pain (≤1%)

Central nervous system: Headache (6% to 9%), fatigue (dose-related; 2% to 5%), dizziness (2% to 4%), insomnia (1%), paresthesia

Dermatologic: Skin rash (≤1%)

Endocrine & metabolic: Decreased HDL cholesterol, hypercholesterolemia, increased serum triglycerides, increased uric acid

Gastrointestinal: Diarrhea (dose-related; 2% to 3%), nausea (1% to 3%), abdominal pain

Hematologic & oncologic: Decreased platelet count

Neuromuscular & skeletal: Weakness

Renal: Increased blood urea nitrogen

Respiratory: Dyspnea (≤1%)

<1%, postmarketing, and/or case reports: Acute pulmonary edema, acute renal failure, angioedema, atrioventricular block (second and third degree), bronchospasm, claudication, dermatological disease, drowsiness, erectile dysfunction, hepatic insufficiency, hypersensitivity angiitis, hypersensitivity reaction, increased serum ALT, increased serum AST, increased serum bilirubin, myocardial infarction, peripheral ischemia, pruritus, psoriasis, Raynaud’s phenomenon, syncope, thrombocytopenia, urticaria, vertigo, vomiting

Allergy and Idiosyncratic Reactions
Metabolism/Transport Effects

Substrate of CYP2D6 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions 

Acetylcholinesterase Inhibitors: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Alpha1-Blockers: Beta-Blockers may enhance the orthostatic hypotensive effect of Alpha1-Blockers. The risk associated with ophthalmic products is probably less than systemic products. Risk C: Monitor therapy

Alpha2-Agonists: May enhance the AV-blocking effect of Beta-Blockers. Sinus node dysfunction may also be enhanced. Beta-Blockers may enhance the rebound hypertensive effect of Alpha2-Agonists. This effect can occur when the Alpha2-Agonist is abruptly withdrawn. Management: Closely monitor heart rate during treatment with a beta blocker and clonidine. Withdraw beta blockers several days before clonidine withdrawal when possible, and monitor blood pressure closely. Recommendations for other alpha2-agonists are unavailable.Exceptions: Apraclonidine. Risk D: Consider therapy modification

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Risk D: Consider therapy modification

Aminoquinolines (Antimalarial): May decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy

Amiodarone: May enhance the bradycardic effect of Beta-Blockers. Possibly to the point of cardiac arrest. Amiodarone may increase the serum concentration of Beta-Blockers. Risk C: Monitor therapy

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Antipsychotic Agents (Phenothiazines): May enhance the hypotensive effect of Beta-Blockers. Beta-Blockers may decrease the metabolism of Antipsychotic Agents (Phenothiazines). Antipsychotic Agents (Phenothiazines) may decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]).Risk C: Monitor therapy

Barbiturates: May decrease the serum concentration of Beta-Blockers. Risk C: Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Beta2-Agonists: Beta-Blockers (Beta1 Selective) may diminish the bronchodilatory effect of Beta2-Agonists. Of particular concern with nonselective beta-blockers or higher doses of the beta1 selective beta-blockers. Risk C: Monitor therapy

Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Risk C: Monitor therapy

Bretylium: May enhance the bradycardic effect of Bradycardia-Causing Agents. Bretylium may also enhance atrioventricular (AV) blockade in patients receiving AV blocking agents. Risk C: Monitor therapy

Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Bromperidol: Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. Risk X: Avoid combination

Bupivacaine: Beta-Blockers may increase the serum concentration of Bupivacaine. Risk C: Monitor therapy

Calcium Channel Blockers (Nondihydropyridine): May enhance the hypotensive effect of Beta-Blockers. Bradycardia and signs of heart failure have also been reported. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Beta-Blockers. Exceptions: Bepridil. Risk C: Monitor therapy

Cardiac Glycosides: Beta-Blockers may enhance the bradycardic effect of Cardiac Glycosides. Risk C: Monitor therapy

Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Exceptions are discussed in separate monographs. Risk D: Consider therapy modification

Cholinergic Agonists: Beta-Blockers may enhance the adverse/toxic effect of Cholinergic Agonists. Of particular concern are the potential for cardiac conduction abnormalities and bronchoconstriction. Management: Administer these agents in combination with caution, and monitor for conduction disturbances. Avoid methacholine with any beta blocker due to the potential for additive bronchoconstriction. Risk C: Monitor therapy

CYP2D6 Inhibitors (Moderate): May increase the serum concentration of Nebivolol. Risk C: Monitor therapy

CYP2D6 Inhibitors (Strong): May increase the serum concentration of Nebivolol. Risk C: Monitor therapy

Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Dipyridamole: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy

Disopyramide: May enhance the bradycardic effect of Beta-Blockers. Beta-Blockers may enhance the negative inotropic effect of Disopyramide. Risk C: Monitor therapy

Dronedarone: May enhance the bradycardic effect of Beta-Blockers. Dronedarone may increase the serum concentration of Beta-Blockers. This likely applies only to those agents that are metabolized by CYP2D6. Management: Use lower initial beta-blocker doses; adequate tolerance of the combination, based on ECG findings, should be confirmed prior to any increase in beta-blocker dose. Risk D: Consider therapy modification

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy

EPINEPHrine (Nasal): Beta-Blockers (Beta1 Selective) may diminish the therapeutic effect of EPINEPHrine (Nasal). Risk C: Monitor therapy

EPINEPHrine (Oral Inhalation): Beta-Blockers (Beta1 Selective) may diminish the therapeutic effect of EPINEPHrine (Oral Inhalation). Risk C: Monitor therapy

Epinephrine (Racemic): Beta-Blockers (Beta1 Selective) may diminish the therapeutic effect of Epinephrine (Racemic). Risk C: Monitor therapy

EPINEPHrine (Systemic): Beta-Blockers (Beta1 Selective) may diminish the therapeutic effect of EPINEPHrine (Systemic). Risk C: Monitor therapy

Ergot Derivatives: Beta-Blockers may enhance the vasoconstricting effect of Ergot Derivatives. Exceptions: Nicergoline. Risk D: Consider therapy modification

Fingolimod: Beta-Blockers may enhance the bradycardic effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and beta-blockers if possible. If coadministration is necessary, patients should have overnight continuous ECG monitoring conducted after the first dose of fingolimod. Monitor patients for bradycardia. Risk D: Consider therapy modification

Floctafenine: May enhance the adverse/toxic effect of Beta-Blockers. Risk X: Avoid combination

Grass Pollen Allergen Extract (5 Grass Extract): Beta-Blockers may enhance the adverse/toxic effect of Grass Pollen Allergen Extract (5 Grass Extract). More specifically, Beta-Blockers may inhibit the ability to effectively treat severe allergic reactions to Grass Pollen Allergen Extract (5 Grass Extract) with epinephrine. Some other effects of epinephrine may be unaffected or even enhanced (e.g., vasoconstriction) during treatment with Beta-Blockers. Risk D: Consider therapy modification

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Insulins: Beta-Blockers may enhance the hypoglycemic effect of Insulins. Risk C: Monitor therapy

Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Risk C: Monitor therapy

Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Risk C: Monitor therapy

Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy

Lidocaine (Systemic): Beta-Blockers may increase the serum concentration of Lidocaine (Systemic). Risk C: Monitor therapy

Lidocaine (Topical): Beta-Blockers may increase the serum concentration of Lidocaine (Topical). Risk C: Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Mepivacaine: Beta-Blockers may increase the serum concentration of Mepivacaine. Risk C: Monitor therapy

Methacholine: Beta-Blockers may enhance the adverse/toxic effect of Methacholine. Risk X: Avoid combination

Methoxyflurane: May enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

NIFEdipine: May enhance the hypotensive effect of Beta-Blockers. NIFEdipine may enhance the negative inotropic effect of Beta-Blockers. Risk C: Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Beta-Blockers. Risk C: Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification

Opioids (Anilidopiperidine): May enhance the bradycardic effect of Beta-Blockers. Opioids (Anilidopiperidine) may enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Propafenone: May increase the serum concentration of Beta-Blockers. Propafenone possesses some independent beta blocking activity. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Regorafenib: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy

Reserpine: May enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy

Rifamycin Derivatives: May decrease the serum concentration of Beta-Blockers. Exceptions: Rifabutin. Risk C: Monitor therapy

Rivastigmine: May enhance the bradycardic effect of Beta-Blockers. Risk X: Avoid combination

Ruxolitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Management: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible. Risk C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: May increase the serum concentration of Beta-Blockers. Exceptions: Citalopram; Escitalopram; FluvoxaMINE. Risk C: Monitor therapy

Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia.Risk D: Consider therapy modification

Sulfonylureas: Beta-Blockers may enhance the hypoglycemic effect of Sulfonylureas. Cardioselective beta-blockers (eg, acebutolol, atenolol, metoprolol, and penbutolol) may be safer than nonselective beta-blockers. All beta-blockers appear to mask tachycardia as an initial symptom of hypoglycemia. Ophthalmic beta-blockers are probably associated with lower risk than systemic agents. Risk C: Monitor therapy

Terlipressin: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Theophylline Derivatives: Beta-Blockers (Beta1 Selective) may diminish the bronchodilatory effect of Theophylline Derivatives. Management: Monitor for reduced theophylline efficacy during concomitant use with any beta-blocker. Beta-1 selective agents are less likely to antagonize theophylline than nonselective agents, but selectivity may be lost at higher doses. Risk C: Monitor therapy

Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Test Interactions

May lead to false-positive aldosterone/renin ratio (ARR) (Funder 2016)

Monitoring Parameters

Blood pressure, ECG; serum glucose (in diabetic patients)

Hypertension: The 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults (ACC/AHA [Whelton 2017]):

Confirmed hypertension and known CVD or 10-year ASCVD risk ≥10%: Target blood pressure <130/80 mm Hg is recommended.

Confirmed hypertension without markers of increased ASCVD risk: Target blood pressure <130/80 mm Hg may be reasonable.

Advanced Practitioners Physical Assessment/Monitoring

Monitor therapeutic response, especially pulse rate and blood pressure, prior to initiation and periodically thereafter. Obtain ECG. Advise patients with diabetes to monitor glucose levels closely.

Nursing Physical Assessment/Monitoring

Monitor therapeutic response, especially pulse rate and blood pressure, prior to initiation and periodically thereafter. Taper dosage slowly when discontinuing. Advise patients with diabetes to monitor glucose levels closely; beta-blockers may alter glucose tolerance.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Bystolic: 2.5 mg, 5 mg, 10 mg, 20 mg [contains fd&c blue #2 aluminum lake, fd&c yellow #6 aluminum lake]

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Bystolic: 2.5 mg, 5 mg, 10 mg, 20 mg [contains FD&C BLUE #2 ALUMINUM LAKE, FD&C YELLOW #6 ALUMINUM LAKE]

Anatomic Therapeutic Chemical (ATC) Classification
  • C07AB12
Generic Available (US)

No

Pricing: US

Tablets (Bystolic Oral)

2.5 mg (per each): $5.73

5 mg (per each): $5.73

10 mg (per each): $5.73

20 mg (per each): $5.73

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer’s AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

Highly-selective inhibitor of beta1-adrenergic receptors; at doses ≤10 mg nebivolol preferentially blocks beta1-receptors. Nebivolol, unlike other beta-blockers, also produces an endothelium-derived nitric oxide-dependent vasodilation resulting in a reduction of systemic vascular resistance.

Pharmacodynamics/Kinetics

Absorption: Rapid

Distribution: Vd: 8 to 12 L/kg

Protein binding: ~98%, primarily to albumin

Metabolism: Hepatic; via glucuronidation and CYP2D6; extensive first-pass metabolism to multiple active metabolites with variable activity

Bioavailability: ~12% (extensive metabolizers); 96% (poor metabolizers) (Mangrella 1998)

Half-life elimination: Terminal: 12 hours (extensive metabolizers) or 19 hours (poor metabolizers); up to 32 hours has been reported in poor metabolizers (Mangrella 1998)

Time to peak, plasma: 1.5 to 4 hours

Excretion: Urine (extensive metabolizers: 38%; poor metabolizers: 67%; <0.5% of total dose as unchanged drug); feces (extensive metabolizers: 44%; poor metabolizers: 13%; <0.5% of total dose as unchanged drug)

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment: Clearance was unchanged in patients with mild renal impairment and was reduced negligibly in patients with moderate renal impairment. However, clearance was reduced by 53% in patients with severe renal impairment.

Hepatic function impairment: Cmax increases 3-fold, AUC increases 10-fold, and apparent clearance decreases 86% in patients with moderate hepatic impairment.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

Nebivolol is a cardioselective beta-blocker. Local anesthetic with vasoconstrictor can be safely used in patients medicated with nebivolol. Nonselective beta-blockers (ie, propranolol, nadolol) enhance the pressor response to epinephrine, resulting in hypertension and bradycardia; this has not been reported for nebivolol. Many nonsteroidal anti-inflammatory drugs, such as ibuprofen and indomethacin, can reduce the hypotensive effect of beta-blockers after 3 or more weeks of therapy with the NSAID. Short-term NSAID use (ie, 3 days) requires no special precautions in patients taking beta-blockers.

Effects on Bleeding

No information available to require special precautions

Index Terms

Nebivolol Hydrochloride

FDA Approval Date
December 17, 2007
References

American College of Obstetricians and Gynecologists (ACOG), Committee on Obstetric Practice. Committee Opinion No. 623: emergent therapy for acute-onset, severe hypertension during pregnancy and the postpartum period. Obstet Gynecol. 2015;125(2):521-525.[PubMed 25611642 ]

American College of Obstetricians and Gynecologists (ACOG), Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013;122(5):1122-1131.[PubMed 24150027 ]

Brauchli YB, Jick SS, Curtin F, et al, “Association Between Beta-Blockers, Other Antihypertensive Drugs and Psoriasis: Population-Based Case-Control Study,” Br J Dermatol, 2008, 158(6):1299-307.[PubMed 18410416]

Brixius K, Bundkirchen A, Bolck B, et al, “Nebivolol, Bucindolol, Metoprolol and Carvedilol are Devoid of Intrinsic Sympathomimetic Activity in Human Myocardium,” Br J Pharmacol, 20, 133(8):1330-8.[PubMed 11498519]

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Brand Names: International

Bipinor (BD, LK); Hypoloc (BE, DK, NL, SE); Ivolol (BD); Lobivon (CR, DO, ES, GR, GT, HN, IT, NI, NL, PA, SV, TR); Lovispes (EE); Mavilor (EG); Nabila (EC, PE); Nebasco (EG); Nebican (KR); Nebicar (PH); Nebicard (IN, PH); Nebicard-5 (ET, TZ, ZW); Nebiem (ZW); Nebiem 5 (ZW); Nebil (PH); Nebilet (AE, AR, AU, BG, BR, CH, CL, CO, CZ, DE, EE, EG, ES, FI, GB, HK, HR, ID, IE, JO, KR, KW, LB, LT, LV, MT, MY, NL, PE, PH, PL, PT, RO, RU, SA, SE, SG, SI, SK, TH, UA, VE, VN, ZA); Nebilong (UA); Nebilox (FR); Nebimel (IE); Nebinorm (RO); Nebiphar (LV); Nebistar (IN); Nebistol (KR); Nebita (BD); Nebitlol (KR); Nebitrend (UA); Nebival (UA); Nebivas (BD); Nebivel (LK); Neblock (BR); Nebol (IE); Nebyol (HR); Nelet (IE); Nepvol (EG); Nerispes (EE); Nevetrol (KR); Neviolet (KR); Nevodio (ID); Nevol (LK); Nevolmin (KR); Nobiten (BE); Nodon (TZ); Pertium (EC); Silostar (ES); Temerit (CR, DO, FR, GT, HN, NI, PA, SV); Toricard-5 (PH); Volone (HR); Zinebi (IN)

Nebivolol (Patient Education – Adult Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(ne BIV oh lole)

Brand Names: US

Bystolic

Brand Names: Canada

Bystolic

What is this drug used for?
  • It is used to treat high blood pressure.
  • It may be given to you for other reasons. Talk with the doctor.
What do I need to tell my doctor BEFORE I take this drug?
  • If you have an allergy to nebivolol or any other part of this drug.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have any of these health problems: Asthma or other lung or breathing problems that cause shortness of breath or wheezing, heart failure (weak heart), certain types of abnormal heartbeats called heart block or sick sinus syndrome, or a slow heartbeat.
  • If you have liver disease.
  • If you are using another drug like this one.
  • If you are breast-feeding. Do not breast-feed while you take this drug.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
What are some things I need to know or do while I take this drug?
  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how this drug affects you.
  • To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
  • Check blood pressure and heart rate as the doctor has told you. Talk with the doctor.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • This drug may affect certain lab tests. Tell all of your health care providers and lab workers that you take this drug.
  • Talk with your doctor before you drink alcohol.
  • This drug may hide the signs of low blood sugar. Talk with the doctor.
  • If you have high blood sugar (diabetes), you will need to watch your blood sugar closely.
  • Talk with your doctor before using OTC products that may raise blood pressure. These include cough or cold drugs, diet pills, stimulants, ibuprofen or like products, and some natural products or aids.
  • Do not stop taking this drug all of a sudden. If you do, chest pain that is worse and in some cases heart attack may occur. The risk may be greater if you have certain types of heart disease. To avoid side effects, you will want to slowly stop this drug as ordered by your doctor. Call your doctor right away if you have new or worse chest pain or if other heart problems occur.
  • If you have had a very bad allergic reaction, talk with your doctor. You may have a chance of an even worse reaction if you come into contact with what caused your allergy. If you use epinephrine to treat very bad allergic reactions, talk with your doctor. Epinephrine may not work as well while you are taking this drug.
  • This drug may make it harder to tell if you have signs of an overactive thyroid like fast heartbeat. If you have an overactive thyroid and stop taking this drug all of a sudden, it may get worse and could be life-threatening. Talk with your doctor.
  • This drug may cause harm to the unborn baby if you take it while you are pregnant. If you are pregnant or you get pregnant while taking this drug, call your doctor right away.
What are some side effects that I need to call my doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of low blood sugar like dizziness, headache, feeling sleepy, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating.
  • Dizziness or passing out.
  • Shortness of breath, a big weight gain, or swelling in the arms or legs.
  • Slow heartbeat.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
  • Headache.
  • Feeling tired or weak.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best taken?
  • Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.
  • Take with or without food.
  • To gain the most benefit, do not miss doses.
  • Keep taking this drug as you have been told by your doctor or other health care provider, even if you feel well.
What do I do if I miss a dose?
  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
How do I store and/or throw out this drug?
  • Store at room temperature.
  • Protect from light.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.