Nebivolol Tablets (Bystolic Tablets)
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Nebivolol Tablets (Bystolic Tablets)

BYSTOLIC®
(nebivolol)

DRUG DESCRIPTION

The chemical name for the active ingredient in BYSTOLIC (nebivolol) tablets is (1RS,1'RS)-1,1'-[(2RS,2'SR)bis(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)]-2,2'-iminodiethanol hydrochloride. Nebivolol is a racemate composed of d-Nebivolol and l-Nebivolol with the stereochemical designations of [SRRR]-nebivolol and [RSSS]nebivolol, respectively. Nebivolol's molecular formula is (C22H25F2NO4•HCl) with the following structural formula:

BYSTOLIC® (nebivolol) Structural Formula Illustration

SRRR - or d-nebivolol hydrochloride

BYSTOLIC® (nebivolol) Structural Formula Illustration

RSSS - or l-nebivolol hydrochloride
MW: 441.90 g/mol

Nebivolol hydrochloride is a white to almost white powder that is soluble in methanol, dimethylsulfoxide, and N,N-dimethylformamide, sparingly soluble in ethanol, propylene glycol, and polyethylene glycol, and very slightly soluble in hexane, dichloromethane, and methylbenzene.

BYSTOLIC as tablets for oral administration contains nebivolol hydrochloride equivalent to 2.5, 5, 10, and 20 mg of nebivolol base. In addition, BYSTOLIC contains the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, D&C Red #27 Lake, FD&C Blue #2 Lake, FD&C Yellow #6 Lake, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, pregelatinized starch, polysorbate 80, and sodium lauryl sulfate.

What are the possible side effects of nebivolol (Bystolic)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • feeling short of breath, even with mild exertion;
  • swelling of your ankles or feet;
  • slow or uneven heartbeats; or
  • numbness or cold feeling in your hands and feet.

Less serious side effects may include:

  • headache;
  • tired feeling;
  • nausea, stomach pain;
  • diarrhea; or
  • sleep...

Read All Potential Side Effects and See Pictures of Bystolic Tablets »

What are the precautions when taking nebivolol tablets (Bystolic Tablets)?

Before taking nebivolol, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: history of severe allergic reactions (e.g., anaphylaxis), blood circulation problems (e.g., Raynaud's disease), breathing problems (e.g., asthma, chronic obstructive pulmonary disease-COPD), diabetes, heart problems (e.g., slow or irregular heartbeat, heart failure), kidney disease, liver disease, mental/mood disorders (e.g., depression), a certain muscle disease (myasthenia gravis), overactive thyroid (hyperthyroidism), a...

Read All Potential Precautions of Bystolic Tablets »

Last reviewed on RxList: 1/4/2012
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

Hypertension

BYSTOLIC is indicated for the treatment of hypertension, to lower blood pressure [see Clinical Studies]. BYSTOLIC may be used alone or in combination with other antihypertensive agents [see DRUG INTERACTIONS].

Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes, including the class to which this drug principally belongs. There are no controlled trials demonstrating risk reduction with BYSTOLIC.

Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program's Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).

Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly.

Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.

Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy.

DOSAGE AND ADMINISTRATION

Hypertension

The dose of BYSTOLIC must be individualized to the needs of the patient. For most patients, the recommended starting dose is 5 mg once daily, with or without food, as monotherapy or in combination with other agents. For patients requiring further reduction in blood pressure, the dose can be increased at 2-week intervals up to 40 mg. A more frequent dosing regimen is unlikely to be beneficial.

Renal Impairment

In patients with severe renal impairment (ClCr less than 30 mL/min) the recommended initial dose is 2.5 mg once daily; titrate up slowly if needed. BYSTOLIC has not been studied in patients receiving dialysis [see CLINICAL PHARMACOLOGY].

Hepatic Impairment

In patients with moderate hepatic impairment, the recommended initial dose is 2.5 mg once daily; titrate up slowly if needed. BYSTOLIC has not been studied in patients with severe hepatic impairment and therefore it is not recommended in that population [see CLINICAL PHARMACOLOGY].

Subpopulations

Geriatric Patients

It is not necessary to adjust the dose in the elderly [see Use in Specific Populations].

CYP2D6 Polymorphism

No dose adjustments are necessary for patients who are CYP2D6 poor metabolizers. The clinical effect and safety profile observed in poor metabolizers were similar to those of extensive metabolizers [see CLINICAL PHARMACOLOGY].

HOW SUPPLIED

Dosage Forms And Strengths

BYSTOLIC is available as tablets for oral administration containing nebivolol hydrochloride equivalent to 2.5, 5, 10, and 20 mg of nebivolol.

BYSTOLIC tablets are triangular-shaped, biconvex, unscored, differentiated by color and are engraved with “FL” on one side and the number of mg (2 ½, 5, 10, or 20) on the other side.

Storage And Handling

BYSTOLIC is available as tablets for oral administration containing nebivolol hydrochloride equivalent to 2.5, 5, 10, and 20 mg of nebivolol.

BYSTOLIC tablets are triangular-shaped, biconvex, unscored, differentiated by color and are engraved with “FL” on one side and the number of mg (2 ½, 5, 10, or 20) on the other side. BYSTOLIC tablets are supplied in the following strengths and package configurations:

BYSTOLIC
Tablet Strength Package Configuration NDC # Tablet Color
2.5 mg Bottle of 30 0456-1402-30 Light Blue
Bottle of 100 0456-1402-01
10 x 10 Unit Dose 0456-1402-63
5 mg Bottle of 30 0456-1405-30 Beige
Bottle of 100 0456-1405-01
10 x 10 Unit Dose 0456-1405-63
10 mg Bottle of 30 0456-1410-30 Pinkish-Purple
Bottle of 100 0456-1410-01
10 x 10 Unit Dose 0456-1410-63
20 mg Bottle of 30 0456-1420-30 Light Blue
Bottle of 100 0456-1420-01
10 x 10 Unit Dose 0456-1420-63

Store at 20° to 25°C (68° to 77°F) [see USP for Controlled Room Temperature].

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

Rev. June 2011. Distributed by: Forest Pharmaceuticals, Inc. Subsidiary of Forest Laboratories, Inc. St. Louis, MO 63045, USA.

Last reviewed on RxList: 1/4/2012
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

Clinical Studies Experience

BYSTOLIC has been evaluated for safety in patients with hypertension and in patients with heart failure. The observed adverse reaction profile was consistent with the pharmacology of the drug and the health status of the patients in the clinical trials. Adverse reactions reported for each of these patient populations are provided below. Excluded are adverse reactions considered too general to be informative and those not reasonably associated with the use of the drug because they were associated with the condition being treated or are very common in the treated population.

The data described below reflect worldwide clinical trial exposure to BYSTOLIC in 6545 patients, including 5038 patients treated for hypertension and the remaining 1507 subjects treated for other cardiovascular diseases. Doses ranged from 0.5 mg to 40 mg. Patients received BYSTOLIC for up to 24 months, with over 1900 patients treated for at least 6 months, and approximately 1300 patients for more than one year.

Hypertension: In placebo-controlled clinical trials comparing BYSTOLIC with placebo, discontinuation of therapy due to adverse reactions was reported in 2.8% of patients treated with nebivolol and 2.2% of patients given placebo. The most common adverse reactions that led to discontinuation of BYSTOLIC were headache (0.4%), nausea (0.2%) and bradycardia (0.2%). Reference ID: 3058093

Table 1 lists treatment-emergent adverse reactions that were reported in three 12-week, placebo-controlled monotherapy trials involving 1597 hypertensive patients treated with either 5 mg, 10 mg, or 20-40 mg of BYSTOLIC and 205 patients given placebo and for which the rate of occurrence was at least 1% of patients treated with nebivolol and greater than the rate for those treated with placebo in at least one dose group.

Table 1: Treatment-Emergent Adverse Reactions with an Incidence (over 6 weeks) ≥ 1% in BYSTOLIC-Treated Patients and at a Higher Frequency than Placebo-Treated Patients

System Organ Class – Preferred Term Placebo
(n = 205)
(%)
Nebivolol 5 mg
(n = 459)
(%)
Nebivolol 10 mg
(n = 461)
(%)
Nebivolol 20-40 mg
(n = 677)
(%)
Cardiac Disorders
Bradycardia 0 0 0 1
Gastrointestinal Disorders
Diarrhea 2 2 2 3
Nausea 0 1 3 2
General Disorders
Fatigue 1 2 2 5
Chest pain 0 0 1 1
Peripheral edema 0 1 1 1
Nervous System Disorders
Headache 6 9 6 7
Dizziness 2 2 3 4
Psychiatric Disorders
Insomnia 0 1 1 1
Respiratory Disorders
Dyspnea 0 0 1 1
Skin and subcutaneous Tissue Disorders
Rash 0 0 1 1

Listed below are other reported adverse reactions with an incidence of at least 1% in the more than 4300 patients treated with BYSTOLIC in controlled or open-label trials except for those already appearing in Table 1, terms too general to be informative, minor symptoms, or adverse reactions unlikely to be attributable to drug because they are common in the population. These adverse reactions were in most cases observed at a similar frequency in placebo-treated patients in the controlled studies.

Body as a Whole: asthenia.

Gastrointestinal System Disorders: abdominal pain

Metabolic and Nutritional Disorders: hypercholesterolemia

Nervous System Disorders: paraesthesia

Laboratory Abnormalities

In controlled monotherapy trials of hypertensive patients, BYSTOLIC was associated with an increase in BUN, uric acid, triglycerides and a decrease in HDL cholesterol and platelet count.

Postmarketing Experience

The following adverse reactions have been identified from spontaneous reports of BYSTOLIC received worldwide and have not been listed elsewhere. These adverse reactions have been chosen for inclusion due to a combination of seriousness, frequency of reporting or potential causal connection to BYSTOLIC. Adverse reactions common in the population have generally been omitted. Because these adverse reactions were reported voluntarily from a population of uncertain size, it is not possible to estimate their frequency or establish a causal relationship to BYSTOLIC exposure: abnormal hepatic function (including increased AST, ALT and bilirubin), acute pulmonary edema, acute renal failure, atrioventricular block (both second and third degree), bronchospasm, erectile dysfunction, hypersensitivity (including urticaria, allergic vasculitis and rare reports of angioedema), myocardial infarction, pruritus, psoriasis, Raynaud's phenomenon, peripheral ischemia/claudication, somnolence, syncope, thrombocytopenia, various rashes and skin disorders, vertigo, and vomiting.

Read the Bystolic Tablets (nebivolol tablets) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

CYP2D6 Inhibitors

Use caution when BYSTOLIC is co-administered with CYP2D6 inhibitors (quinidine, propafenone, fluoxetine, paroxetine, etc.) [see CLINICAL PHARMACOLOGY].

Hypotensive Agents

Do not use BYSTOLIC with other β-blockers. Closely monitor patients receiving catecholamine-depleting drugs, such as reserpine or guanethidine, because the added β-blocking action of BYSTOLIC may produce excessive reduction of sympathetic activity. In patients who are receiving BYSTOLIC and clonidine, discontinue BYSTOLIC for several days before the gradual tapering of clonidine.

Digitalis Glycosides

Both digitalis glycosides and β-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.

Calcium Channel Blockers

BYSTOLIC can exacerbate the effects of myocardial depressants or inhibitors of AV conduction, such as certain calcium antagonists (particularly of the phenylalkylamine [verapamil] and benzothiazepine [diltiazem] classes), or antiarrhythmic agents, such as disopyramide.

Last reviewed on RxList: 1/4/2012
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Abrupt Cessation of Therapy

Do not abruptly discontinue BYSTOLIC therapy in patients with coronary artery disease. Severe exacerbation of angina, myocardial infarction and ventricular arrhythmias have been reported in patients with coronary artery disease following the abrupt discontinuation of therapy with β-blockers. Myocardial infarction and ventricular arrhythmias may occur with or without preceding exacerbation of the angina pectoris. Caution patients without overt coronary artery disease against interruption or abrupt discontinuation of therapy. As with other β-blockers, when discontinuation of BYSTOLIC is planned, carefully observe and advise patients to minimize physical activity. Taper BYSTOLIC over 1 to 2 weeks when possible. If the angina worsens or acute coronary insufficiency develops, re-start BYSTOLIC promptly, at least temporarily.

Angina and Acute Myocardial Infarction

BYSTOLIC was not studied in patients with angina pectoris or who had a recent MI.

Bronchospastic Diseases

In general, patients with bronchospastic diseases should not receive β-blockers.

Anesthesia and Major Surgery

Because beta-blocker withdrawal has been associated with an increased risk of MI and chest pain, patients already on beta-blockers should generally continue treatment throughout the perioperative period. If BYSTOLIC is to be continued perioperatively, monitor patients closely when anesthetic agents which depress myocardial function, such as ether, cyclopropane, and trichloroethylene, are used. If β-blocking therapy is withdrawn prior to major surgery, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures.

The β-blocking effects of BYSTOLIC can be reversed by β-agonists, e.g., dobutamine or isoproterenol. However, such patients may be subject to protracted severe hypotension. Additionally, difficulty in restarting and maintaining the heartbeat has been reported with β-blockers.

Diabetes and Hypoglycemia

β-blockers may mask some of the manifestations of hypoglycemia, particularly tachycardia. Nonselective βblockers may potentiate insulin-induced hypoglycemia and delay recovery of serum glucose levels. It is not known whether nebivolol has these effects. Advise patients subject to spontaneous hypoglycemia and diabetic patients receiving insulin or oral hypoglycemic agents about these possibilities.

Thyrotoxicosis

β-blockers may mask clinical signs of hyperthyroidism, such as tachycardia. Abrupt withdrawal of β-blockers may be followed by an exacerbation of the symptoms of hyperthyroidism or may precipitate a thyroid storm.

Peripheral Vascular Disease

β-blockers can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease.

Non-dihydropyridine Calcium Channel Blockers

Because of significant negative inotropic and chronotropic effects in patients treated with β-blockers and calcium channel blockers of the verapamil and diltiazem type, monitor the ECG and blood pressure in patients treated concomitantly with these agents.

Use with CYP2D6 Inhibitors

Nebivolol exposure increases with inhibition of CYP2D6 [see DRUG INTERACTIONS]. The dose of BYSTOLIC may need to be reduced.

Impaired Renal Function

Renal clearance of nebivolol is decreased in patients with severe renal impairment. BYSTOLIC has not been studied in patients receiving dialysis [see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION].

Impaired Hepatic Function

Metabolism of nebivolol is decreased in patients with moderate hepatic impairment. BYSTOLIC has not been studied in patients with severe hepatic impairment [see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION].

Risk of Anaphylactic Reactions

While taking β-blockers, patients with a history of severe anaphylactic reactions to a variety of allergens may be more reactive to repeated accidental, diagnostic, or therapeutic challenge. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reactions.

Pheochromocytoma

In patients with known or suspected pheochromocytoma, initiate an α-blocker prior to the use of any βblocker.

Patient Counseling Information

See FDA-Approved Patient Labeling.

Patient Advice

Advise patients to take BYSTOLIC regularly and continuously, as directed. BYSTOLIC can be taken with or without food. If a dose is missed, take the next scheduled dose only (without doubling it). Do not interrupt or discontinue BYSTOLIC without consulting the physician.

Patients should know how they react to this medicine before they operate automobiles, use machinery, or engage in other tasks requiring alertness.

Advise patients to consult a physician if any difficulty in breathing occurs, or if they develop signs or symptoms of worsening congestive heart failure such as weight gain or increasing shortness of breath, or excessive bradycardia.

Caution patients subject to spontaneous hypoglycemia, or diabetic patients receiving insulin or oral hypoglycemic agents, that β-blockers may mask some of the manifestations of hypoglycemia, particularly tachycardia.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

In a two-year study of nebivolol in mice, a statistically significant increase in the incidence of testicular Leydig cell hyperplasia and adenomas was observed at 40 mg/kg/day (5 times the maximally recommended human dose of 40 mg on a mg/m² basis). Similar findings were not reported in mice administered doses equal to approximately 0.3 or 1.2 times the maximum recommended human dose. No evidence of a tumorigenic effect was observed in a 24-month study in Wistar rats receiving doses of nebivolol 2.5, 10 and 40 mg/kg/day (equivalent to 0.6, 2.4, and 10 times the maximally recommended human dose). Co-administration of dihydrotestosterone reduced blood LH levels and prevented the Leydig cell hyperplasia, consistent with an indirect LH-mediated effect of nebivolol in mice and not thought to be clinically relevant in man.

A randomized, double-blind, placebo- and active-controlled, parallel-group study in healthy male volunteers was conducted to determine the effects of nebivolol on adrenal function, luteinizing hormone, and testosterone levels. This study demonstrated that 6 weeks of daily dosing with 10 mg of nebivolol had no significant effect on ACTH-stimulated mean serum cortisol AUC0-120 min, serum LH, or serum total testosterone.

Effects on spermatogenesis were seen in male rats and mice at ≥ 40 mg/kg/day (10 and 5 times the MRHD, respectively). For rats the effects on spermatogenesis were not reversed and may have worsened during a four week recovery period. The effects of nebivolol on sperm in mice, however, were partially reversible.

Mutagenesis: Nebivolol was not genotoxic when tested in a battery of assays (Ames, in vitro mouse lymphoma TK+/, in vitro human peripheral lymphocyte chromosome aberration, in vivo Drosophila melanogaster sex-linked recessive lethal, and in vivo mouse bone marrow micronucleus tests).

Use In Specific Populations

Pregnancy

Teratogenic Effects: Category C

Decreased pup body weights occurred at 1.25 and 2.5 mg/kg in rats, when exposed during the perinatal period (late gestation, parturition and lactation). At 5 mg/kg and higher doses (1.2 times the MRHD), prolonged gestation, dystocia and reduced maternal care were produced with corresponding increases in late fetal deaths and stillbirths and decreased birth weight, live litter size and pup survival. Insufficient numbers of pups survived at 5 mg/kg to evaluate the offspring for reproductive performance.

In studies in which pregnant rats were given nebivolol during organogenesis, reduced fetal body weights were observed at maternally toxic doses of 20 and 40 mg/kg/day (5 and 10 times the MRHD), and small reversible delays in sternal and thoracic ossification associated with the reduced fetal body weights and a small increase in resorption occurred at 40 mg/kg/day (10 times the MRHD). No adverse effects on embryo-fetal viability, sex, weight or morphology were observed in studies in which nebivolol was given to pregnant rabbits at doses as high as 20 mg/kg/day (10 times the MRHD).

Labor and Delivery

Nebivolol caused prolonged gestation and dystocia at doses ≥ 5 mg/kg in rats (1.2 times the MRHD). These effects were associated with increased fetal deaths and stillborn pups, and decreased birth weight, live litter size and pup survival rate, events that occurred only when nebivolol was given during the perinatal period (late gestation, parturition and lactation).

No studies of nebivolol were conducted in pregnant women. Use BYSTOLIC during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Studies in rats have shown that nebivolol or its metabolites cross the placental barrier and are excreted in breast milk. It is not known whether this drug is excreted in human milk.

Because of the potential for β-blockers to produce serious adverse reactions in nursing infants, especially bradycardia, BYSTOLIC is not recommended during nursing.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established. Pediatric studies in ages newborn to 18 years old have not been conducted because of incomplete characterization of developmental toxicity and possible adverse effects on long-term fertility [see Nonclinical Toxicology].

Geriatric Use

Of the 2800 patients in the U.S. sponsored placebo-controlled clinical hypertension studies, 478 patients were 65 years of age or older. No overall differences in efficacy or in the incidence of adverse events were observed between older and younger patients.

Heart Failure

In a placebo-controlled trial of 2128 patients (1067 BYSTOLIC, 1061 placebo) over 70 years of age with chronic heart failure receiving a maximum dose of 10 mg per day for a median of 20 months, no worsening of heart failure was reported with nebivolol compared to placebo. However, if heart failure worsens consider discontinuation of BYSTOLIC.

Last reviewed on RxList: 1/4/2012
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

In clinical trials and worldwide postmarketing experience there were reports of BYSTOLIC overdose. The most common signs and symptoms associated with BYSTOLIC overdosage are bradycardia and hypotension. Other important adverse reactions reported with BYSTOLIC overdose include cardiac failure, dizziness, hypoglycemia, fatigue and vomiting. Other adverse reactions associated with β-blocker overdose include bronchospasm and heart block.

The largest known ingestion of BYSTOLIC worldwide involved a patient who ingested up to 500 mg of BYSTOLIC along with several 100 mg tablets of acetylsalicylic acid in a suicide attempt. The patient experienced hyperhydrosis, pallor, depressed level of consciousness, hypokinesia, hypotension, sinus bradycardia, hypoglycemia, hypokalemia, respiratory failure and vomiting. The patient recovered.

Because of extensive drug binding to plasma proteins, hemodialysis is not expected to enhance nebivolol clearance.

If overdose occurs, provide general supportive and specific symptomatic treatment. Based on expected pharmacologic actions and recommendations for other β-blockers, consider the following general measures, including stopping BYSTOLIC, when clinically warranted:

Bradycardia: Administer IV atropine. If the response is inadequate, isoproterenol or another agent with positive chronotropic properties may be given cautiously. Under some circumstances, transthoracic or transvenous pacemaker placement may be necessary.

Hypotension: Administer IV fluids and vasopressors. Intravenous glucagon may be useful.

Heart Block (second or third degree): Monitor and treat with isoproterenol infusion. Under some circumstances, transthoracic or transvenous pacemaker placement may be necessary.

Congestive Heart Failure: Initiate therapy with digitalis glycoside and diuretics. In certain cases, consider the use of inotropic and vasodilating agents.

Bronchospasm: Administer bronchodilator therapy such as a short acting inhaled β2-agonist and/or aminophylline.

Hypoglycemia: Administer IV glucose. Repeated doses of IV glucose or possibly glucagon may be required.

Supportive measures should continue until clinical stability is achieved. The half-life of low doses of nebivolol is 12-19 hours.

Call the National Poison Control Center (800-222-1222) for the most current information on β-blocker overdose treatment. Reference ID: 3058093

CONTRAINDICATIONS

BYSTOLIC is contraindicated in the following conditions:

  • Severe bradycardia
  • Heart block greater than first degree
  • Patients with cardiogenic shock
  • Decompensated cardiac failure
  • Sick sinus syndrome (unless a permanent pacemaker is in place)
  • Patients with severe hepatic impairment (Child-Pugh > B)
  • Patients who are hypersensitive to any component of this product.

Last reviewed on RxList: 1/4/2012
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Nebivolol is a β-adrenergic receptor blocking agent. In extensive metabolizers (most of the population) and at doses less than or equal to 10 mg, nebivolol is preferentially β1 selective. In poor metabolizers and at higher doses, nebivolol inhibits both β1 - and β2 - adrenergic receptors. Nebivolol lacks intrinsic sympathomimetic and membrane stabilizing activity at therapeutically relevant concentrations. At clinically relevant doses, BYSTOLIC does not demonstrate α1-adrenergic receptor blockade activity. Various metabolites, including glucuronides, contribute to β-blocking activity.

Mechanism of Action

The mechanism of action of the antihypertensive response of BYSTOLIC has not been definitively established. Possible factors that may be involved include: (1) decreased heart rate, (2) decreased myocardial contractility, (3) diminution of tonic sympathetic outflow to the periphery from cerebral vasomotor centers, (4) suppression of renin activity and (5) vasodilation and decreased peripheral vascular resistance.

Pharmacokinetics

Nebivolol is metabolized by a number of routes, including glucuronidation and hydroxylation by CYP2D6. The active isomer (d-nebivolol) has an effective half-life of about 12 hours in CYP2D6 extensive metabolizers (most people), and 19 hours in poor metabolizers and exposure to d-nebivolol is substantially increased in poor metabolizers. This has less importance than usual, however, because the metabolites, including the hydroxyl metabolite and glucuronides (the predominant circulating metabolites), contribute to β-blocking activity. Reference ID: 3058093

Plasma levels of d–nebivolol increase in proportion to dose in EMs and PMs for doses up to 20mg. Exposure to l-nebivolol is higher than to d-nebivolol but l-nebivolol contributes little to the drug's activity as d-nebivolol's beta receptor affinity is > 1000-fold higher than l-nebivolol. For the same dose, PMs attain a 5-fold higher Cmax and 10-fold higher AUC of d-nebivolol than do EMs. d-Nebivolol accumulates about 1.5-fold with repeated once-daily dosing in EMs.

Absorption

Absorption of BYSTOLIC is similar to an oral solution. The absolute bioavailability has not been determined.

Mean peak plasma nebivolol concentrations occur approximately 1.5 to 4 hours post-dosing in EMs and PMs.

Food does not alter the pharmacokinetics of nebivolol. Under fed conditions, nebivolol glucuronides are slightly reduced. BYSTOLIC may be administered without regard to meals.

Distribution

The in vitro human plasma protein binding of nebivolol is approximately 98%, mostly to albumin, and is independent of nebivolol concentrations.

Metabolism

Nebivolol is predominantly metabolized via direct glucuronidation of parent and to a lesser extent via Ndealkylation and oxidation via cytochrome P450 2D6. Its stereospecific metabolites contribute to the pharmacologic activity [see DRUG INTERACTIONS].

Elimination

After a single oral administration of 14C-nebivolol, 38% of the dose was recovered in urine and 44% in feces for EMs and 67% in urine and 13% in feces for PMs. Essentially all nebivolol was excreted as multiple oxidative metabolites or their corresponding glucuronide conjugates.

Pharmacokinetics in Special Populations

Hepatic Disease

d-Nebivolol peak plasma concentration increased 3-fold, exposure (AUC) increased 10-fold, and the apparent clearance decreased by 86% in patients with moderate hepatic impairment (Child-Pugh Class B). No formal studies have been performed in patients with severe hepatic impairment and nebivolol should be contraindicated for these patients [see DOSAGE AND ADMINISTRATION].

Renal Disease

The apparent clearance of nebivolol was unchanged following a single 5 mg dose of BYSTOLIC in patients with mild renal impairment (ClCr 50 to 80 mL/min, n=7), and it was reduced negligibly in patients with moderate (ClCr 30 to 50 mL/min, n=9), but clearance was reduced by 53% in patients with severe renal impairment (ClCr < 30 mL/min, n=5). No studies have been conducted in patients on dialysis [see DOSAGE AND ADMINISTRATION].

Drug-Drug Interactions

Drugs that inhibit CYP2D6 can be expected to increase plasma levels of nebivolol. When BYSTOLIC is coadministered with an inhibitor or an inducer of this enzyme, monitor patients closely and adjust the nebivolol dose according to blood pressure response. In vitro studies have demonstrated that at therapeutically relevant concentrations, d- and l-nebivolol do not inhibit any cytochrome P450 pathways.

Digoxin: Concomitant administration of BYSTOLIC (10 mg once daily) and digoxin (0.25 mg once daily) for 10 days in 14 healthy adult individuals resulted in no significant changes in the pharmacokinetics of digoxin or nebivolol [see DRUG INTERACTIONS].

Warfarin: Administration of BYSTOLIC (10 mg once daily for 10 days) led to no significant changes in the pharmacokinetics of nebivolol or R- or S-warfarin following a single 10 mg dose of warfarin. Similarly, nebivolol has no significant effects on the anticoagulant activity of warfarin, as assessed by Prothrombin time and INR profiles from 0 to 144 hours after a single 10 mg warfarin dose in 12 healthy adult volunteers. Reference ID: 3058093

Diuretics: No pharmacokinetic interactions were observed in healthy adults between nebivolol (10 mg daily for 10 days) and furosemide (40 mg single dose), hydrochlorothiazide (25 mg once daily for 10 days), or spironolactone (25 mg once daily for 10 days).

Ramipril: Concomitant administration of BYSTOLIC (10 mg once daily) and ramipril (5 mg once daily) for 10 days in 15 healthy adult volunteers produced no pharmacokinetic interactions.

Losartan: Concomitant administration of BYSTOLIC (10 mg single dose) and losartan (50 mg single dose) in 20 healthy adult volunteers did not result in pharmacokinetic interactions.

Fluoxetine: Fluoxetine, a CYP2D6 inhibitor, administered at 20 mg per day for 21 days prior to a single 10 mg dose of nebivolol to 10 healthy adults, led to an 8-fold increase in the AUC and 3-fold increase in Cmax for dnebivolol [see DRUG INTERACTIONS].

Histamine-2 Receptor Antagonists: The pharmacokinetics of nebivolol (5 mg single dose) were not affected by the co-administration of ranitidine (150 mg twice daily). Cimetidine (400 mg twice daily) causes a 23% increase in the plasma levels of d-nebivolol.

Charcoal: The pharmacokinetics of nebivolol (10 mg single dose) were not affected by repeated coadministration (4, 8, 12, 16, 22, 28, 36, and 48 hours after nebivolol administration) of activated charcoal (Actidose-Aqua®).

Sildenafil: The co-administration of nebivolol and sildenafil decreased AUC and Cmax of sildenafil by 21 and 23% respectively. The effect on the Cmax and AUC for d-nebivolol was also small ( < 20%). The effect on vital signs (e.g., pulse and blood pressure) was approximately the sum of the effects of sildenafil and nebivolol.

Other Concomitant Medications: Utilizing population pharmacokinetic analyses, derived from hypertensive patients, the following drugs were observed not to have an effect on the pharmacokinetics of nebivolol: acetaminophen, acetylsalicylic acid, atorvastatin, esomeprazole, ibuprofen, levothyroxine sodium, metformin, sildenafil, simvastatin, or tocopherol.

Protein Binding: No meaningful changes in the extent of in vitro binding of nebivolol to human plasma proteins were noted in the presence of high concentrations of diazepam, digoxin, diphenylhydantoin, enalapril, hydrochlorothiazide, imipramine, indomethacin, propranolol, sulfamethazine, tolbutamide, or warfarin. Additionally, nebivolol did not significantly alter the protein binding of the following drugs: diazepam, digoxin, diphenylhydantoin, hydrochlorothiazide, imipramine, or warfarin at their therapeutic concentrations.

Clinical Studies

Hypertension

The antihypertensive effectiveness of BYSTOLIC as monotherapy has been demonstrated in three randomized, double-blind, multi-center, placebo-controlled trials at doses ranging from 1.25 to 40 mg for 12 weeks (Studies 1, 2, and 3). A fourth placebo-controlled trial demonstrated additional antihypertensive effects of BYSTOLIC at doses ranging from 5 to 20 mg when administered concomitantly with up to two other antihypertensive agents (ACE inhibitors, angiotensin II receptor antagonists, and thiazide diuretics) in patients with inadequate blood pressure control.

The three monotherapy trials included a total of 2016 patients (1811 BYSTOLIC, 205 placebo) with mild to moderate hypertension who had baseline diastolic blood pressures (DBP) of 95 to 109 mmHg. Patients received either BYSTOLIC or placebo once daily for twelve weeks. Two of these monotherapy trials (Studies 1 and 2) studied 1716 patients in the general hypertensive population with a mean age of 54 years, 55% males, 26% non-Caucasians, 7% diabetics and 6% genotyped as PMs. The third monotherapy trial (Study 3) studied 300 Black patients with a mean age of 51 years, 45% males, 14% diabetics, and 3% as PMs.

Placebo-subtracted blood pressure reductions by dose for each study are presented in Table 2. Most studies showed increasing response to doses above 5 mg.

Table 2: Placebo-Subtracted Least-Square Mean Reductions in Trough Sitting Systolic/Diastolic Blood Pressure (SiSBP/SiDBP mmHg) by Dose in Studies with Once Daily BYSTOLIC

  Nebivolol dose (mg)
1.25 2.5 5.0 10 20 30-40
Study 1 -6.6*/-5.1* -8.5*/-5.6* -8.1*/-5.5* -9.2*/-6.3* -8.7*/-6.9* -11.7*/-8.3*
Study 2     -3.8/-3.2* -3.1/-3.9* -6.3*/-4.5*  
Study 3¶   -1.5/-2.9 -2.6/-4.9* -6.0*/-6.1* -7.2*/-6.1* -6.8*/-5.5*
Study 4^     -5.7*/-3.3* -3.7*/-3.5* -6.2*/-4.6*  
* p < 0.05 based on pair-wise comparison vs. placebo
¶ Study enrolled only African Americans.
^ Study on top of one or two other antihypertensive medications.

Study 4 enrolled 669 patients with a mean age of 54 years, 55% males, 54% Caucasians, 29% Blacks, 15% Hispanics, 1% Asians, 14% diabetics, and 5% PMs. BYSTOLIC, 5 mg to 20 mg, administered once daily concomitantly with stable doses of up to two other antihypertensive agents (ACE inhibitors, angiotensin II receptor antagonists, and thiazide diuretics) resulted in significant additional antihypertensive effects over placebo compared to baseline blood pressure.

Effectiveness was similar in subgroups analyzed by age and sex. Effectiveness was established in Blacks, but as monotherapy the magnitude of effect was somewhat less than in Caucasians.

The blood pressure lowering effect of BYSTOLIC was seen within two weeks of treatment and was maintained over the 24-hour dosing interval.

There are no trials of BYSTOLIC demonstrating reductions in cardiovascular risk in patients with hypertension, but at least one pharmacologically similar drug has demonstrated such benefits.

Last reviewed on RxList: 1/4/2012
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

BYSTOLIC®
(bi-STOL-ik)
(nebivolol) Tablets

Read the Patient Information that comes with BYSTOLIC before you start taking it and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment. If you have any questions about BYSTOLIC, ask your doctor or pharmacist.

WHAT IS BYSTOLIC?

BYSTOLIC is a kind of prescription medicine called a “beta-blocker”. BYSTOLIC treats:

BYSTOLIC can lower blood pressure when used by itself and with other medicines.

BYSTOLIC is not approved for children less than 18 years of age.

WHO SHOULD NOT TAKE BYSTOLIC?

Do not take BYSTOLIC if you:

  • Have heart failure and are in the ICU or need medicines to keep up your blood circulation
  • Have a slow heartbeat or your heart skips beats (irregular heartbeat)
  • Have severe liver damage
  • Are allergic to any ingredient in BYSTOLIC. The active ingredient is nebivolol. See the end of this leaflet for a list of ingredients.

WHAT SHOULD I TELL MY DOCTOR BEFORE TAKING BYSTOLIC?

  • Tell your doctor about all of your medical problems, including if you:
  • Have asthma or other lung problems (such as bronchitis or emphysema)
  • Have problems with blood flow in your feet and legs (peripheral vascular disease) BYSTOLIC can make symptoms of blood flow problems worse.
  • Have diabetes and take medicine to control blood sugar
  • Have thyroid problems
  • Have liver or kidney problems
  • Had allergic reactions to medications or have allergies
  • Have a condition called pheochromocytoma
  • Are pregnant or trying to become pregnant. It is not known if BYSTOLIC is safe for your unborn baby. Talk with your doctor about the best way to treat high blood pressure while you are pregnant.
  • Are breastfeeding. It is not known if BYSTOLIC passes into your breast milk. You should not breastfeed while using BYSTOLIC.
  • Are scheduled for surgery and will be given anesthetic agents

Tell your doctor about all the medicines you take. Include prescription and non-prescription medicines, vitamins, and herbal products. BYSTOLIC and certain other medicines can affect each other and cause serious side effects.

Keep a list of all the medicines you take. Show this list to your doctor and pharmacist before you start a new medicine.

HOW SHOULD I TAKE BYSTOLIC?

  • Do not suddenly stop taking BYSTOLIC. You could have chest pain or a heart attack. If your doctor decides to stop BYSTOLIC, your doctor may slowly lower your dose over time before stopping it completely.
  • Take BYSTOLIC every day exactly as your doctor tells you. Your doctor will tell you how much BYSTOLIC to take and how often. Your doctor may start with a low dose and raise it over time.
  • Do not stop taking BYSTOLIC or change your dose without talking with your doctor.
  • Take BYSTOLIC with or without food.
  • If you miss a dose, take your dose as soon as you remember, unless it is close to the time to take your next dose. Do not take 2 doses at the same time. Take your next dose at the usual time.
  • If you take too much BYSTOLIC, call your doctor or poison control center right away.

WHAT ARE POSSIBLE SIDE EFFECTS OF BYSTOLIC?

  • Low blood pressure and feeling dizzy. If you feel dizzy, sit or lie down and tell your doctor right away.
  • Tiredness
  • Slow heartbeat
  • Headache
  • Leg swelling due to fluid retention (edema). Tell your doctor if you gain weight or have trouble breathing while taking BYSTOLIC.

Tell your doctor if you have any side effects that bother you or don't go away.

HOW SHOULD I STORE BYSTOLIC?

  • Store BYSTOLIC between 68° to 77°F (20° - 25°C).
  • Safely throw away BYSTOLIC that is out of date or no longer needed.
  • Keep BYSTOLIC and all medicines out of the reach of children.

GENERAL INFORMATION ABOUT BYSTOLIC

Doctors sometimes prescribe medicines for conditions not included in the patient information leaflets.

  • Only use BYSTOLIC for the medical problem it was prescribed for.
  • Do not give BYSTOLIC to other people, even if they have the same symptoms. It may harm them.

This leaflet summarizes the most important information about BYSTOLIC. For more information:

  • Talk with your doctor.
  • Ask your doctor or pharmacist for information about BYSTOLIC that is written for healthcare professionals.
  • Visit www.BYSTOLIC.com on the web or call 1-800-678-1605.

WHAT IS IN BYSTOLIC?

Active Ingredient: Nebivolol

Inactive Ingredients: colloidal silicon dioxide, croscarmellose sodium, D&C Red #27 Lake, FD&C Blue #2 Lake, FD&C Yellow #6 Lake, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, pregelatinized starch, polysorbate 80, and sodium lauryl sulfate

WHAT IS HIGH BLOOD PRESSURE (HYPERTENSION)?

Blood pressure is the force in your blood vessels when your heart beats and when your heart rests. You have high blood pressure when the force is too great.

High blood pressure makes the heart work harder to pump blood through the body and causes damage to the blood vessels. BYSTOLIC tablets can help your blood vessels relax so your blood pressure is lower. Medicines that lower your blood pressure lower your chance of having a stroke or heart attack.

Last reviewed on RxList: 1/4/2012
This monograph has been modified to include the generic and brand name in many instances.

>

PATIENT INFORMATION

BYSTOLIC®
(bi-STOL-ik)
(nebivolol) Tablets

Read the Patient Information that comes with BYSTOLIC before you start taking it and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment. If you have any questions about BYSTOLIC, ask your doctor or pharmacist.

WHAT IS BYSTOLIC?

BYSTOLIC is a kind of prescription medicine called a “beta-blocker”. BYSTOLIC treats:

BYSTOLIC can lower blood pressure when used by itself and with other medicines.

BYSTOLIC is not approved for children less than 18 years of age.

WHO SHOULD NOT TAKE BYSTOLIC?

Do not take BYSTOLIC if you:

  • Have heart failure and are in the ICU or need medicines to keep up your blood circulation
  • Have a slow heartbeat or your heart skips beats (irregular heartbeat)
  • Have severe liver damage
  • Are allergic to any ingredient in BYSTOLIC. The active ingredient is nebivolol. See the end of this leaflet for a list of ingredients.

WHAT SHOULD I TELL MY DOCTOR BEFORE TAKING BYSTOLIC?

  • Tell your doctor about all of your medical problems, including if you:
  • Have asthma or other lung problems (such as bronchitis or emphysema)
  • Have problems with blood flow in your feet and legs (peripheral vascular disease) BYSTOLIC can make symptoms of blood flow problems worse.
  • Have diabetes and take medicine to control blood sugar
  • Have thyroid problems
  • Have liver or kidney problems
  • Had allergic reactions to medications or have allergies
  • Have a condition called pheochromocytoma
  • Are pregnant or trying to become pregnant. It is not known if BYSTOLIC is safe for your unborn baby. Talk with your doctor about the best way to treat high blood pressure while you are pregnant.
  • Are breastfeeding. It is not known if BYSTOLIC passes into your breast milk. You should not breastfeed while using BYSTOLIC.
  • Are scheduled for surgery and will be given anesthetic agents

Tell your doctor about all the medicines you take. Include prescription and non-prescription medicines, vitamins, and herbal products. BYSTOLIC and certain other medicines can affect each other and cause serious side effects.

Keep a list of all the medicines you take. Show this list to your doctor and pharmacist before you start a new medicine.

HOW SHOULD I TAKE BYSTOLIC?

  • Do not suddenly stop taking BYSTOLIC. You could have chest pain or a heart attack. If your doctor decides to stop BYSTOLIC, your doctor may slowly lower your dose over time before stopping it completely.
  • Take BYSTOLIC every day exactly as your doctor tells you. Your doctor will tell you how much BYSTOLIC to take and how often. Your doctor may start with a low dose and raise it over time.
  • Do not stop taking BYSTOLIC or change your dose without talking with your doctor.
  • Take BYSTOLIC with or without food.
  • If you miss a dose, take your dose as soon as you remember, unless it is close to the time to take your next dose. Do not take 2 doses at the same time. Take your next dose at the usual time.
  • If you take too much BYSTOLIC, call your doctor or poison control center right away.

WHAT ARE POSSIBLE SIDE EFFECTS OF BYSTOLIC?

  • Low blood pressure and feeling dizzy. If you feel dizzy, sit or lie down and tell your doctor right away.
  • Tiredness
  • Slow heartbeat
  • Headache
  • Leg swelling due to fluid retention (edema). Tell your doctor if you gain weight or have trouble breathing while taking BYSTOLIC.

Tell your doctor if you have any side effects that bother you or don't go away.

HOW SHOULD I STORE BYSTOLIC?

  • Store BYSTOLIC between 68° to 77°F (20° - 25°C).
  • Safely throw away BYSTOLIC that is out of date or no longer needed.
  • Keep BYSTOLIC and all medicines out of the reach of children.

GENERAL INFORMATION ABOUT BYSTOLIC

Doctors sometimes prescribe medicines for conditions not included in the patient information leaflets.

  • Only use BYSTOLIC for the medical problem it was prescribed for.
  • Do not give BYSTOLIC to other people, even if they have the same symptoms. It may harm them.

This leaflet summarizes the most important information about BYSTOLIC. For more information:

  • Talk with your doctor.
  • Ask your doctor or pharmacist for information about BYSTOLIC that is written for healthcare professionals.
  • Visit www.BYSTOLIC.com on the web or call 1-800-678-1605.

WHAT IS IN BYSTOLIC?

Active Ingredient: Nebivolol

Inactive Ingredients: colloidal silicon dioxide, croscarmellose sodium, D&C Red #27 Lake, FD&C Blue #2 Lake, FD&C Yellow #6 Lake, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, pregelatinized starch, polysorbate 80, and sodium lauryl sulfate

WHAT IS HIGH BLOOD PRESSURE (HYPERTENSION)?

Blood pressure is the force in your blood vessels when your heart beats and when your heart rests. You have high blood pressure when the force is too great.

High blood pressure makes the heart work harder to pump blood through the body and causes damage to the blood vessels. BYSTOLIC tablets can help your blood vessels relax so your blood pressure is lower. Medicines that lower your blood pressure lower your chance of having a stroke or heart attack.

Last reviewed on RxList: 1/4/2012
This monograph has been modified to include the generic and brand name in many instances.

Disclaimer

Bystolic Tablets Consumer

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

NEBIVOLOL - ORAL

(ne-BIV-oh-lole)

COMMON BRAND NAME(S): Bystolic

WARNING: Do not stop taking this medication without consulting your doctor. Some conditions may become worse when you suddenly stop this drug. Some people who have suddenly stopped taking similar drugs have had chest pain, heart attack, and irregular heartbeat. If your doctor decides you should no longer use this drug, he or she may direct you to gradually decrease your dose over 1 to 2 weeks.

When gradually stopping this medication, it is recommended that you temporarily limit physical activity to decrease strain on the heart. Seek immediate medical attention if you develop chest pain/tightness/pressure, chest pain spreading to the jaw/neck/arm, unusual sweating, trouble breathing, or fast/irregular heartbeat.

USES: Nebivolol is used to treat high blood pressure. Lowering high blood pressure helps prevent strokes, heart attacks, kidney problems, and decreased sexual ability.

This drug belongs to a class of medications called beta blockers. It works by preventing a certain natural substance made by the body (adrenaline) from acting on the heart and blood vessels. This effect reduces your blood pressure, lowers your pulse (number of times the heart beats in 1 minute), and lessens strain on the heart.

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This drug may also be used to treat certain heart conditions such as angina or coronary artery disease.

HOW TO USE: Take this medication by mouth, usually once daily with or without food or as directed by your doctor.

The dosage is based on your medical condition and response to treatment.

Use this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day. It is important to continue taking this medication even if you feel well. Most people with high blood pressure do not feel sick. It may take up to 2 weeks before you get the full benefit of this drug.

Do not stop taking this medication without your doctor's approval. Some conditions may become worse when this drug is suddenly stopped. Your dose may need to be gradually decreased. (See also the Warning section.)

Tell your doctor if your condition does not improve or if it worsens (e.g., your blood pressure readings remain high or increase).

Disclaimer

Bystolic Tablets Consumer (continued)

SIDE EFFECTS: Headache, dizziness, tiredness, nausea, slow heartbeat, and trouble sleeping may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

To lower your risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

This drug may reduce blood flow to your hands and feet, causing them to feel cold. Smoking may worsen this effect. Dress warmly and avoid tobacco use.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if you notice any of the following unlikely but serious side effects: swelling ankles/feet, severe tiredness, unexplained/sudden weight gain, symptoms of asthma (e.g., feeling of tightness in the chest, shortness of breath, cough, wheezing).

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the Bystolic Tablets (nebivolol tablets) Side Effects Center for a complete guide to possible side effects »

PRECAUTIONS: Before taking nebivolol, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: history of severe allergic reactions (e.g., anaphylaxis), blood circulation problems (e.g., Raynaud's disease), breathing problems (e.g., asthma, chronic obstructive pulmonary disease-COPD), diabetes, heart problems (e.g., slow or irregular heartbeat, heart failure), kidney disease, liver disease, mental/mood disorders (e.g., depression), a certain muscle disease (myasthenia gravis), overactive thyroid (hyperthyroidism), a certain type of tumor (pheochromocytoma).

Before having surgery, tell your doctor or dentist that you are taking this medication.

This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

If you have diabetes, this medication may mask the fast/pounding heartbeat you would usually feel when your blood sugar falls too low (hypoglycemia). Other symptoms of low blood sugar such as dizziness or sweating are unaffected by this drug.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known whether this medication passes into breast milk. However, similar drugs pass into breast milk and may have undesirable effects on a nursing infant (e.g., slow heartbeat). Discuss the risks and benefits with your doctor before breast-feeding.

Disclaimer

Bystolic Tablets Consumer (continued)

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use.

Other medications can affect the removal of nebivolol from your body, which may affect how nebivolol works. Examples include amiodarone, cimetidine, propafenone, quinidine, rifampin, ritonavir, SSRI antidepressants such as fluoxetine and paroxetine, among others.

Check the labels on all your medicines (e.g., cough-and-cold products, diet aids, nonsteroidal anti-inflammatory drugs-NSAIDs such as ibuprofen for pain/fever reduction) because they may contain ingredients that could increase your blood pressure or pulse. Ask your pharmacist about using those products safely.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a local poison control center. Symptoms of overdose may include: fainting, very slow heartbeat, severe dizziness.

NOTES: Do not share this medication with others.

Talk with your doctor about making changes to your lifestyle that may increase the effectiveness of this medication (e.g., stress reduction programs, exercise, and dietary changes).

Have your blood pressure checked regularly while taking this medication. Learn how to monitor your own blood pressure at home, and share the results with your doctor.

Laboratory and/or medical tests (e.g., kidney or liver function tests) may be performed regularly to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 68-77 degrees F (20-25 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised May 2010. Copyright(c) 2010 First Databank, Inc.

Bystolic Tablets Patient Information Including Side Effects

Brand Names: Bystolic

Generic Name: nebivolol (Pronunciation: ne BIV oh lol)

What is nebivolol (Bystolic Tablets)?

Nebivolol is in a group of drugs called beta-blockers. Beta-blockers affect the heart and circulation (blood flow through arteries and veins).

Nebivolol is used to treat hypertension (high blood pressure).

Nebivolol may also be used for other purposes not listed in this medication guide.

Bystolic 10 mg

triangular, purple, imprinted with FL, 10

Bystolic 5 mg

triangular, beige, imprinted with FL, 5

What are the possible side effects of nebivolol (Bystolic Tablets)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • feeling short of breath, even with mild exertion;
  • swelling of your ankles or feet;
  • slow or uneven heartbeats; or
  • numbness or cold feeling in your hands and feet.

Less serious side effects may include:

  • headache;
  • tired feeling;
  • nausea, stomach pain;
  • diarrhea; or
  • sleep problems (insomnia).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Bystolic Tablets (nebivolol tablets) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about nebivolol (Bystolic Tablets)?

Do not skip doses or stop taking nebivolol without first talking to your doctor. Stopping suddenly may make your condition worse or cause other serious heart problems such as severe chest pain or heart attack. You may need to use less and less before you stop the medication completely.

If you need surgery, tell the surgeon ahead of time that you are using nebivolol.

Nebivolol may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Nebivolol is only part of a complete program of treatment that also includes diet, exercise, and weight control. Follow your diet, medication, and exercise routines very closely.

Keep using this medicine as directed, even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

Side Effects Centers

Bystolic Tablets Patient Information including How Should I Take

What should I discuss with my healthcare provider before taking nebivolol (Bystolic Tablets)?

You should not take nebivolol if you are allergic to it, or if you have:

  • severe liver disease; or
  • a heart problem such as heart block, sick sinus syndrome, slow heart rate, or heart failure.

If you have any of these other conditions, you may need a nebivolol dose adjustment or special tests:

  • asthma, bronchitis, emphysema;
  • liver or kidney disease;
  • diabetes;
  • a thyroid disorder;
  • a history of allergies;
  • problems with circulation (such as Raynaud's syndrome);
  • pheochromocytoma (tumor of the adrenal gland); or
  • if you have recently had a heart attack.

FDA pregnancy category C. It is not known whether nebivolol will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

It is not known whether nebivolol passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take nebivolol (Bystolic Tablets)?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Take nebivolol at the same time every day. You may take the medication with or without food.

Do not skip doses or stop taking nebivolol without first talking to your doctor. Stopping suddenly may make your condition worse or cause other serious heart problems such as severe chest pain or heart attack. You may need to use less and less before you stop the medication completely.

Your blood pressure will need to be checked often. Visit your doctor regularly.

If you need surgery, tell the surgeon ahead of time that you are using nebivolol.

Nebivolol is only part of a complete program of treatment that also includes diet, exercise, and weight control. Follow your diet, medication, and exercise routines very closely.

Keep using this medicine as directed, even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

Store at room temperature away from moisture and heat.

Side Effects Centers

Bystolic Tablets Patient Information including If I Miss a Dose

What happens if I miss a dose (Bystolic Tablets)?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose (Bystolic Tablets)?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include slow heart rate, dizziness, vomiting, trouble breathing, or feeling like you might pass out.

What should I avoid while taking nebivolol (Bystolic Tablets)?

Nebivolol may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

What other drugs will affect nebivolol (Bystolic Tablets)?

Tell your doctor about all other medicines you use, especially:

  • digitalis (digoxin, Lanoxin);
  • clonidine (Catapres);
  • reserpine;
  • a heart or blood pressure medication such as diltiazem (Cartia, Cardizem), felodipine (Plendil), nifedipine (Nifedical, Procardia), verapamil (Calan, Covera, Isoptin, Verelan), and others;
  • heart rhythm medicine such as amiodarone (Cordarone, Pacerone), quinidine (Quin-G), procainamide (Pronestyl), disopyramide (Norpace), flecaininde (Tambocor), mexiletine (Mexitil), propafenone, (Rythmol), and others;
  • an antidepressant such as fluoxetine (Prozac), paroxetine (Paxil), and others; or
  • another beta-blocker such as atenolol (Tenormin, Tenoretic), carvedilol (Coreg), labetalol (Normodyne, Trandate), metoprolol (Lopressor, Toprol), nadolol (Corgard), propranolol (Inderal, InnoPran), sotalol (Betapace), and others.

This list is not complete and other drugs may interact with nebivolol. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about nebivolol.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 2.02. Revision date: 12/15/2010.

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