Drugs Details

Drugs Info of Zebeta
Drugs Details
  • Drugs Type  : Multum
  • Date : 13th Jul 2015 02:54 am
  • Brand Name : Zebeta
  • Generic Name : bisoprolol (Pronunciation: BIS oh PROE lol)
Descriptions

Zebeta (bisoprolol fumarate) is a synthetic, beta1-selective (cardioselective) adrenoceptor blocking agent. The chemical name for bisoprolol fumarate is (±)-1-[4-[[2-(1-Methylethoxy)ethoxy]methyl]phenoxy]-3[(1-methylethyl)amino]-2-propanol(E)-2-butenedioate (2:1) (salt). It possesses an asymmetric carbon atom in its structure and is provided as a racemic mixture. The S(-) enantiomer is responsible for most of the beta-blocking activity. Its empirical formula is (C18H31NO4)2•C4H4O4 and its structure is:

 

Zebeta®
(Bisoprolol Fumarate) Structural Formula Illustration

Bisoprolol fumarate has a molecular weight of 766.97. It is a white crystalline powder which is approximately equally hydrophilic and lipophilic, and is readily soluble in water, methanol, ethanol, and chloroform.

Zebeta (bisoprolol fumarate) is available as 5 and 10 mg tablets for oral administration.

Inactive ingredients include Colloidal Silicon Dioxide, Corn Starch, Crospovidone, Dibasic Calcium Phosphate, Hypromellose, Magnesium Stearate, Microcrystalline Cellulose, Polyethylene Glycol, Polysorbate 80, and Titanium Dioxide. The 5 mg tablets also contain Red and Yellow Iron Oxide.

What are the possible side effects of bisoprolol (Zebeta)?

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

Call your doctor at once if you have any of these serious side effects:

  • slow, fast, or pounding heartbeats;
  • chest pain, feeling like you might pass out;
  • confusion, hallucinations;
  • feeling short of breath, even with mild exertion;
  • swelling of your ankles or feet;
  • pain or burning when you urinate; or
  • numbness, tingling, or cold feeling in your hands and...

Read All Potential Side Effects and See Pictures of Zebeta »

What are the precautions when taking bisoprolol fumarate (Zebeta)?

Before taking bisoprolol, 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.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: certain types of heart rhythm problems (such as a slow heartbeat, second- or third-degree atrioventricular block), severe heart failure.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: breathing problems (such as asthma, chronic bronchitis, emphysema), kidney disease, liver disease, overactive thyroid disease...

Read All Potential Precautions of Zebeta »

Indications

Zebeta (bisoprolol fumarate) is indicated in the management of hypertension. It may be used alone or in combination with other antihypertensive agents.

Dosage Administration

The dose of Zebeta (bisoprolol fumarate) must be individualized to the needs of the patient. The usual starting dose is 5 mg once daily. In some patients, 2.5 mg may be an appropriate starting dose (see Bronchospastic Disease in WARNINGS). If the antihypertensive effect of 5 mg is inadequate, the dose may be increased to 10 mg and then, if necessary, to 20 mg once daily.

Patients with Renal or Hepatic Impairment

In patients with hepatic impairment (hepatitis or cirrhosis) or renal dysfunction (creatinine clearance less than 40 mL/min), the initial daily dose should be 2.5 mg and caution should be used in dose-titration. Since limited data suggest that bisoprolol fumarate is not dialyzable, drug replacement is not necessary in patients undergoing dialysis.

Geriatric Patients

It is not necessary to adjust the dose in the elderly, unless there is also significant renal or hepatic dysfunction (see above and Geriatric Use in PRECAUTIONS).

Pediatric Patients

There is no pediatric experience with Zebeta (bisoprolol fumarate) .

How Supplied

Zebeta® (bisoprolol fumarate) is supplied as 5 mg and 10 mg tablets.

The 5 mg tablet is pink, heart-shaped, biconvex, film-coated, vertically scored in half on both sides, with an engraved stylized b/stylized b on one side and 6/0 on the reverse side, supplied as follows:

30 Unit-of-use NDC 51285-060-01

The 10 mg tablet is white, heart-shaped, biconvex, film-coated, with an engraved stylized b on one side and 61 on the reverse side, supplied as follows:

30 Unit-of-use NDC 51285-061-01

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

Protect from moisture.

Dispense in tight containers.

Duramed Pharmaceuticals, Inc. Subsidiary of Barr Pharmaceuticals, Inc. Pomona, New York 10970. Revised November 2010

Side Effects

Safety data are available in more than 30,000 patients or volunteers. Frequency estimates and rates of withdrawal of therapy for adverse events were derived from two U.S. placebo-controlled studies.

In Study A, doses of 5, 10, and 20 mg bisoprolol fumarate were administered for 4 weeks. In Study B, doses of 2.5, 10, and 40 mg of bisoprolol fumarate were administered for 12 weeks. A total of 273 patients were treated with 5-20 mg of bisoprolol fumarate; 132 received placebo.

Withdrawal of therapy for adverse events was 3.3% for patients receiving bisoprolol fumarate and 6.8% for patients on placebo. Withdrawals were less than 1% for either bradycardia or fatigue/lack of energy.

The following table presents adverse experiences, whether or not considered drug related, reported in at least 1% of patients in these studies, for all patients studied in placebo-controlled clinical trials (2.5-40 mg), as well as for a subgroup that was treated with doses within the recommended dosage range (5-20 mg). Of the adverse events listed in the table, bradycardia, diarrhea, asthenia, fatigue, and sinusitis appear to be dose related.

 

Body System/Adverse Experience All Adverse Experiences (%a) Bisoprolol Fumarate
Placebo
(n=132)
%
5-20 mg
(n=273)
%
2.5-40 mg
(n=404)
%
Skin
  increased sweating 1.5 0.7 1.0
Musculoskeletal
  arthralgia 2.3 2.2 2.7
Central Nervous System
  dizziness 3.8 2.9 3.5
  headache 11.4 8.8 10.9
  hypoaesthesia 0.8 1.1 1.5
Autonomic Nervous System
  dry mouth 1.5 0.7 1.3
Heart Rate/Rhythm
  bradycardia 0 0.4 0.5
Psychiatric
  vivid dreams 0 0 0
  insomnia 2.3 1.5 2.5
  depression 0.8 0 0.2
Gastrointestinal
  diarrhea 1.5 2.6 3.5
  nausea 1.5 1.5 2.2
  vomiting 0 1.1 1.5
Respiratory
  bronchospasm 0 0 0
  cough 4.5 2.6 2.5
  dyspnea 0.8 1.1 1.5
  pharyngitis 2.3 2.2 2.2
  rhinitis 3.0 2.9 4.0
  sinusitis 1.5 2.2 2.2
  URI 3.8 4.8 5.0
Body as a Whole
  asthenia 0 0.4 1.5
  chest pain 0.8 1.1 1.5
  fatigue 1.5 6.6 8.2
  edema (peripheral) 3.8 3.7 3.0
a percentage of patients with event

The following is a comprehensive list of adverse experiences reported with bisoprolol fumarate in worldwide studies, or in postmarketing experience (in italics):

Central Nervous System

Dizziness, unsteadiness, vertigo, syncope, headache, paresthesia, hypoesthesia, hyperesthesia, somnolence, sleep disturbances, anxiety/restlessness, decreased concentration/memory.

Autonomic Nervous System

Dry mouth.

Cardiovascular

Bradycardia, palpitations and other rhythm disturbances, cold extremities, claudication, hypotension, orthostatic hypotension, chest pain, congestive heart failure, dyspnea on exertion.

Psychiatric

Vivid dreams, insomnia, depression.

Gastrointestinal

Gastric/epigastric/abdominal pain, gastritis, dyspepsia, nausea, vomiting, diarrhea, constipation, peptic ulcer.

Musculoskeletal

Muscle/joint pain, arthralgia, back/neck pain, muscle cramps, twitching/tremor.

Skin

Rash, acne, eczema, psoriasis, skin irritation, pruritus, flushing, sweating, alopecia, dermatitis, angioedema, exfoliative dermatitis, cutaneous vasculitis.

Special Senses

Visual disturbances, ocular pain/pressure, abnormal lacrimation, tinnitus, decreased hearing, earache, taste abnormalities.

Metabolic

Gout.

Respiratory

Asthma/bronchospasm, bronchitis, coughing, dyspnea, pharyngitis, rhinitis, sinusitis, URI.

Genitourinary

Decreased libido/impotence, Peyronie's disease, cystitis, renal colic, polyuria.

Hematologic

Purpura.

General

Fatigue, asthenia, chest pain, malaise, edema, weight gain, angioedema.

In addition, a variety of adverse effects have been reported with other beta-adrenergic blocking agents and should be considered potential adverse effects of ZEBETA (bisoprolol fumarate) :

Central Nervous System

Reversible mental depression progressing to catatonia, hallucinations, an acute reversible syndrome characterized by disorientation to time and place, emotional lability, slightly clouded sensorium.

Allergic

Fever, combined with aching and sore throat, laryngospasm, respiratory distress.

Hematologic

Agranulocytosis, thrombocytopenia, thrombocytopenic purpura.

Gastrointestinal

Mesenteric arterial thrombosis, ischemic colitis.

Miscellaneous

The oculomucocutaneous syndrome associated with the beta-blocker practolol has not been reported with Zebeta (bisoprolol fumarate) during investigational use or extensive foreign marketing experience.

Laboratory Abnormalities

In clinical trials, the most frequently reported laboratory change was an increase in serum triglycerides, but this was not a consistent finding.

Sporadic liver test abnormalities have been reported. In the U.S. controlled trials experience with bisoprolol fumarate treatment for 4-12 weeks, the incidence of concomitant elevations in SGOT and SGPT from 1 to 2 times normal was 3.9%, compared to 2.5% for placebo. No patient had concomitant elevations greater than twice normal.

In the long-term, uncontrolled experience with bisoprolol fumarate treatment for 6-18 months, the incidence of one or more concomitant elevations in SGOT and SGPT from 1 to 2 times normal was 6.2%. The incidence of multiple occurrences was 1.9%. For concomitant elevations in SGOT and SGPT of greater than twice normal, the incidence was 1.5%. The incidence of multiple occurrences was 0.3%. In many cases these elevations were attributed to underlying disorders, or resolved during continued treatment with bisoprolol fumarate.

Other laboratory changes included small increases in uric acid, creatinine, BUN, serum potassium, glucose, and phosphorus and decreases in WBC and platelets. These were generally not of clinical importance and rarely resulted in discontinuation of bisoprolol fumarate.

As with other beta-blockers, ANA conversions have also been reported on bisoprolol fumarate. About 15% of patients in long-term studies converted to a positive titer, although about one-third of these patients subsequently reconverted to a negative titer while on continued therapy.

Interactions

Zebeta (bisoprolol fumarate) should not be combined with other beta-blocking agents. Patients receiving catecholamine-depleting drugs, such as reserpine or guanethidine, should be closely monitored, because the added beta-adrenergic blocking action of Zebeta (bisoprolol fumarate) may produce excessive reduction of sympathetic activity. In patients receiving concurrent therapy with clonidine, if therapy is to be discontinued, it is suggested that Zebeta (bisoprolol fumarate) be discontinued for several days before the withdrawal of clonidine.

Zebeta (bisoprolol fumarate) should be used with care when 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, are used concurrently.

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

Concurrent use of rifampin increases the metabolic clearance of Zebeta (bisoprolol fumarate) , resulting in a shortened elimination half-life of Zebeta (bisoprolol fumarate) . However, initial dose modification is generally not necessary. Pharmacokinetic studies document no clinically relevant interactions with other agents given concomitantly, including thiazide diuretics and cimetidine. There was no effect of Zebeta (bisoprolol fumarate) on prothrombin time in patients on stable doses of warfarin.

Risk of Anaphylactic Reaction

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

Warnings

Cardiac Failure

Sympathetic stimulation is a vital component supporting circulatory function in the setting of congestive heart failure, and beta-blockade may result in further depression of myocardial contractility and precipitate more severe failure. In general, beta-blocking agents should be avoided in patients with overt congestive failure. However, in some patients with compensated cardiac failure it may be necessary to utilize them. In such a situation, they must be used cautiously.

In Patients Without a History of Cardiac Failure

Continued depression of the myocardium with beta-blockers can, in some patients, precipitate cardiac failure. At the first signs or symptoms of heart failure, discontinuation of Zebeta (bisoprolol fumarate) should be considered. In some cases, beta-blocker therapy can be continued while heart failure is treated with other drugs.

Abrupt Cessation of Therapy

Exacerbation of angina pectoris, and, in some instances, myocardial infarction or ventricular arrhythmia, have been observed in patients with coronary artery disease following abrupt cessation of therapy with beta-blockers. Such patients should, therefore, be cautioned against interruption or discontinuation of therapy without the physician's advice. Even in patients without overt coronary artery disease, it may be advisable to taper therapy with Zebeta (bisoprolol fumarate) over approximately one week with the patient under careful observation. If withdrawal symptoms occur, Zebeta (bisoprolol fumarate) therapy should be reinstituted, at least temporarily.

Peripheral Vascular Disease

Beta-blockers can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease. Caution should be exercised in such individuals.

Bronchospastic Disease

PATIENTS WITH BRONCHOSPASTIC DISEASE SHOULD, IN GENERAL, NOT RECEIVE BETA-BLOCKERS. Because of its relative beta1-selectivity, however, Zebeta (bisoprolol fumarate) may be used with caution in patients with bronchospastic disease who do not respond to, or who cannot tolerate other antihypertensive treatment. Since beta1-selectivity is not absolute, the lowest possible dose of Zebeta (bisoprolol fumarate) should be used, with therapy starting at 2.5 mg. A beta2 agonist (bronchodilator) should be made available.

Major Surgery

Chronically administered beta-blocking therapy should not be routinely withdrawn prior to major surgery; however, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures.

Diabetes and Hypoglycemia

Beta-blockers may mask some of the manifestations of hypoglycemia, particularly tachycardia. Nonselective beta-blockers may potentiate insulin-induced hypoglycemia and delay recovery of serum glucose levels. Because of its beta1-selectivity, this is less likely with Zebeta (bisoprolol fumarate) . However, patients subject to spontaneous hypoglycemia, or diabetic patients receiving insulin or oral hypoglycemic agents, should be cautioned about these possibilities and bisoprolol fumarate should be used with caution.

Thyrotoxicosis

Beta-adrenergic blockade may mask clinical signs of hyperthyroidism, such as tachycardia. Abrupt withdrawal of beta-blockade may be followed by an exacerbation of the symptoms of hyperthyroidism or may precipitate thyroid storm.

Precautions

Impaired Renal or Hepatic Function

Use caution in adjusting the dose of Zebeta (bisoprolol fumarate) in patients with renal or hepatic impairment (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION).

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies were conducted with oral bisoprolol fumarate administered in the feed of mice (20 and 24 months) and rats (26 months). No evidence of carcinogenic potential was seen in mice dosed up to 250 mg/kg/day or rats dosed up to 125 mg/kg/day. On a body weight basis, these doses are 625 and 312 times, respectively, the maximum recommended human dose (MRHD) of 20 mg, (or 0.4 mg/kg/day based on a 50 kg individual); on a body surface area basis, these doses are 59 times (mice) and 64 times (rats) the MRHD. The mutagenic potential of bisoprolol fumarate was evaluated in the microbial mutagenicity (Ames) test, the point mutation and chromosome aberration assays in Chinese hamster V79 cells, the unscheduled DNA synthesis test, the micronucleus test in mice, and the cytogenetics assay in rats. There was no evidence of mutagenic potential in these in vitro and in vivo assays.

Reproduction studies in rats did not show any impairment of fertility at doses up to 150 mg/kg/day of bisoprolol fumarate, or 375 and 77 times the MRHD on the basis of body weight and body surface area, respectively.

Pregnancy Category C

In rats, bisoprolol fumarate was not teratogenic at doses up to 150 mg/kg/day which is 375 and 77 times the MRHD on the basis of body weight and body surface area, respectively. Bisoprolol fumarate was fetotoxic (increased late resorptions) at 50 mg/kg/day and maternotoxic (decreased food intake and body weight gain) at 150 mg/kg/day. The fetotoxicity in rats occurred at 125 times the MRHD on a body weight basis and 26 times the MRHD on the basis of body surface area. The maternotoxicity occurred at 375 times the MRHD on a body weight basis and 77 times the MRHD on the basis of body surface area. In rabbits, bisoprolol fumarate was not teratogenic at doses up to 12.5 mg/kg/day, which is 31 and 12 times the MRHD based on body weight and body surface area, respectively, but was embryolethal (increased early resorptions) at 12.5 mg/kg/day.

There are no adequate and well-controlled studies in pregnant women. Zebeta (bisoprolol fumarate) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Small amounts of bisoprolol fumarate ( < 2% of the dose) have been detected in the milk of lactating rats. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk caution should be exercised when bisoprolol fumarate is administered to nursing women.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Zebeta (bisoprolol fumarate) has been used in elderly patients with hypertension. Response rates and mean decreases in systolic and diastolic blood pressure were similar to the decreases in younger patients in the U.S. clinical studies. Although no dose response study was conducted in elderly patients, there was a tendency for older patients to be maintained on higher doses of bisoprolol fumarate.

Observed reductions in heart rate were slightly greater in the elderly than in the young and tended to increase with increasing dose. In general, no disparity in adverse experience reports or dropouts for safety reasons was observed between older and younger patients. Dose adjustment based on age is not necessary.

OverDose

The most common signs expected with overdosage of a beta-blocker are bradycardia, hypotension, congestive heart failure, bronchospasm, and hypoglycemia. To date, a few cases of overdose (maximum: 2000 mg) with bisoprolol fumarate have been reported. Bradycardia and/or hypotension were noted. Sympathomimetic agents were given in some cases, and all patients recovered.

In general, if overdose occurs, Zebeta (bisoprolol fumarate) therapy should be stopped and supportive and symptomatic treatment should be provided. Limited data suggest that bisoprolol fumarate is not dialyzable. Based on the expected pharmacologic actions and recommendations for other beta-blockers, the following general measures should be considered 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, transvenous pacemaker insertion may be necessary.

Hypotension

IV fluids and vasopressors should be administered. Intravenous glucagon may be useful.

Heart Block (second or third degree)

Patients should be carefully monitored and treated with isoproterenol infusion or transvenous cardiac pacemaker insertion, as appropriate.

Congestive Heart Failure

Initiate conventional therapy (ie, digitalis, diuretics, inotropic agents, vasodilating agents).

Bronchospasm

Administer bronchodilator therapy such as isoproterenol and/or aminophylline.

Hypoglycemia

ContrainDications

Zebeta (bisoprolol fumarate) is contraindicated in patients with cardiogenic shock, overt cardiac failure, second or third degree AV block, and marked sinus bradycardia.

Clinical Pharamacology

Zebeta (bisoprolol fumarate) is a beta1-selective (cardioselective) adrenoceptor blocking agent without significant membrane stabilizing activity or intrinsic sympathomimetic activity in its therapeutic dosage range. Cardioselectivity is not absolute, however, and at higher doses ( ≥ 20 mg) bisoprolol fumarate also inhibits beta2-adrenoceptors, chiefly located in the bronchial and vascular musculature; to retain selectivity it is therefore important to use the lowest effective dose.

Pharmacokinetics and Metabolism

The absolute bioavailability after a 10 mg oral dose of bisoprolol fumarate is about 80%. Absorption is not affected by the presence of food. The first pass metabolism of bisoprolol fumarate is about 20%.

Binding to serum proteins is approximately 30%. Peak plasma concentrations occur within 2-4 hours of dosing with 5 to 20 mg, and mean peak values range from 16 ng/mL at 5 mg to 70 ng/mL at 20 mg. Once daily dosing with bisoprolol fumarate results in less than twofold intersubject variation in peak plasma levels. The plasma elimination half-life is 9-12 hours and is slightly longer in elderly patients, in part because of decreased renal function in that population. Steady state is attained within 5 days of once daily dosing. In both young and elderly populations, plasma accumulation is low; the accumulation factor ranges from 1.1 to 1.3, and is what would be expected from the first order kinetics and once daily dosing. Plasma concentrations are proportional to the administered dose in the range of 5 to 20 mg. Pharmacokinetic characteristics of the two enantiomers are similar.

Bisoprolol fumarate is eliminated equally by renal and non-renal pathways with about 50% of the dose appearing unchanged in the urine and the remainder appearing in the form of inactive metabolites. In humans, the known metabolites are labile or have no known pharmacologic activity. Less than 2% of the dose is excreted in the feces. Bisoprolol fumarate is not metabolized by cytochrome P450 II D6 (debrisoquin hydroxylase).

In subjects with creatinine clearance less than 40 mL/min, the plasma half-life is increased approximately threefold compared to healthy subjects.

In patients with cirrhosis of the liver, the elimination of Zebeta (bisoprolol fumarate) (bisoprolol fumarate) is more variable in rate and significantly slower than that in healthy subjects, with plasma half-life ranging from 8.3 to 21.7 hours.

Pharmacodynamics

The most prominent effect of Zebeta (bisoprolol fumarate) is the negative chronotropic effect, resulting in a reduction in resting and exercise heart rate. There is a fall in resting and exercise cardiac output with little observed change in stroke volume, and only a small increase in right atrial pressure, or pulmonary capillary wedge pressure at rest or during exercise.

Findings in short-term clinical hemodynamics studies with Zebeta (bisoprolol fumarate) are similar to those observed with other beta-blocking agents.

The mechanism of action of its antihypertensive effects has not been completely established. Factors which may be involved include:

  1. Decreased cardiac output,
  2. Inhibition of renin release by the kidneys,
  3. Diminution of tonic sympathetic outflow from the vasomotor centers in the brain.

In normal volunteers, Zebeta (bisoprolol fumarate) therapy resulted in a reduction of exercise- and isoproterenol-induced tachycardia. The maximal effect occurred within 1-4 hours post-dosing. Effects persisted for 24 hours at doses equal to or greater than 5 mg.

Electrophysiology studies in man have demonstrated that Zebeta (bisoprolol fumarate) significantly decreases heart rate, increases sinus node recovery time, prolongs AV node refractory periods, and, with rapid atrial stimulation, prolongs AV nodal conduction.

Beta1-selectivity of Zebeta (bisoprolol fumarate) has been demonstrated in both animal and human studies. No effects at therapeutic doses on beta2-adrenoceptor density have been observed. Pulmonary function studies have been conducted in healthy volunteers, asthmatics, and patients with chronic obstructive pulmonary disease (COPD). Doses of Zebeta (bisoprolol fumarate) ranged from 5 to 60 mg, atenolol from 50 to 200 mg, metoprolol from 100 to 200 mg, and propranolol from 40 to 80 mg. In some studies, slight, asymptomatic increases in airways resistance (AWR) and decreases in forced expiratory volume (FEV1) were observed with doses of bisoprolol fumarate 20 mg and higher, similar to the small increases in AWR also noted with the other cardioselective beta-blockers. The changes induced by beta-blockade with all agents were reversed by bronchodilator therapy.

Zebeta (bisoprolol fumarate) had minimal effect on serum lipids during antihypertensive studies. In U.S. placebo-controlled trials, changes in total cholesterol averaged +0.8% for bisoprolol fumarate-treated patients, and +0.7% for placebo. Changes in triglycerides averaged +19% for bisoprolol fumarate-treated patients, and +17% for placebo.

Zebeta (bisoprolol fumarate) has also been given concomitantly with thiazide diuretics. Even very low doses of hydrochlorothiazide (6.25 mg) were found to be additive with bisoprolol fumarate in lowering blood pressure in patients with mild-to-moderate hypertension.

Clinical Studies

In two randomized double-blind placebo-controlled trials conducted in the U.S., reductions in systolic and diastolic blood pressure and heart rate 24 hours after dosing in patients with mild-to-moderate hypertension are shown below. In both studies, mean systolic/diastolic blood pressures at baseline were approximately 150/100 mm Hg, and mean heart rate was 76 bpm. Drug effect is calculated by subtracting the placebo effect from the overall change in blood pressure and heart rate.

Sitting Systolic/Diastolic Pressure (BP) and Heart Rate (HR) Mean Decrease (D) After 3 to 4 Weeks

Study A Bisoprolol Fumarate
Placebo 5 mg 10 mg 20 mg
n = 61 61 61 61
Total BP (mm Hg) 5.4/3.2 10.4/8.0 11.2/10.9 12.8/11.9
Drug Effecta - 5.0/4.8 5.8/7.7 7.4/8.7
Total HR (bpm) 0.5 7.2 8.7 11.3
Drug Effecta - 6.7 8.2 10.8
Study B Bisoprolol Fumarate
Placebo 2.5 mg 10 mg  
n = 56 59 62  
Total BP (mm Hg) 3.0/3.7 7.6/8.1 13.5/11.2  
Drug Effecta - 4.6/4.4 10.5/7.5  
Total HR (bpm) 1.6 3.8 10.7  
Drug Effecta - 2.2 9.1  
a Observed total change from baseline minus placebo.

Blood pressure responses were seen within one week of treatment and changed little thereafter. They were sustained for 12 weeks and for over a year in studies of longer duration. Blood pressure returned to baseline when bisoprolol fumarate was tapered over two weeks in a long-term study.

Overall, significantly greater blood pressure reductions were observed on bisoprolol fumarate than on placebo regardless of race, age, or gender. There were no significant differences in response between black and nonblack patients.

Patient Information

Patients, especially those with coronary artery disease, should be warned about discontinuing use of Zebeta (bisoprolol fumarate) without a physician's supervision. Patients should also be advised to consult a physician if any difficulty in breathing occurs, or if they develop signs or symptoms of congestive heart failure or excessive bradycardia.

Patients subject to spontaneous hypoglycemia, or diabetic patients receiving insulin or oral hypoglycemic agents, should be cautioned that beta-blockers may mask some of the manifestations of hypoglycemia, particularly tachycardia, and bisoprolol fumarate should be used with caution.

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

Consumer Overview Uses

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.

 

BISOPROLOL - ORAL

 

(BIS-oh-PROE-lol)

 

COMMON BRAND NAME(S): Zebeta

 

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: Bisoprolol is used with or without other medications to treat high blood pressure (hypertension). Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems.

This medication belongs to a class of drugs known as beta blockers. It works by blocking the action of certain natural chemicals in your body such as epinephrine on the heart and blood vessels. This effect lowers the heart rate, blood pressure, and 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 mild to moderate heart failure.

 

HOW TO USE: See also Warning section.

Take this medication by mouth with or without food, usually once a day or as directed by your doctor.

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.

For the treatment of high blood pressure, it may take several weeks before you get the full benefit of this drug. It is important to continue taking this medication even if you feel well. Most people with high blood pressure do not feel sick.

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

Consumer Overview Side Effect

SIDE EFFECTS: See also Warning and Precautions sections.

Tiredness, slow heartbeat, diarrhea, and dizziness 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 any of these unlikely but serious side effects occur: very slow heartbeat, severe dizziness, fainting, blue fingers/toes, trouble breathing, mental/mood changes (such as confusion, mood swings, depression).

Although this medication may be used to treat heart failure, some people may rarely develop new or worsening symptoms of heart failure. Tell your doctor immediately if you experience any of these unlikely but serious side effects: swelling ankles/feet, severe tiredness, shortness of breath, unexplained/sudden weight gain.

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 Zebeta (bisoprolol fumarate) Side Effects Center for a complete guide to possible side effects

Learn More »

PRECAUTIONS: Before taking bisoprolol, 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.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: certain types of heart rhythm problems (such as a slow heartbeat, second- or third-degree atrioventricular block), severe heart failure.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: breathing problems (such as asthma, chronic bronchitis, emphysema), kidney disease, liver disease, overactive thyroid disease (hyperthyroidism), serious allergic reactions including those needing treatment with epinephrine, blood circulation problems (such as Raynaud's disease, peripheral vascular disease), mental/mood disorders (such as depression), a certain muscle disease (myasthenia gravis).

If you have diabetes, this product may prevent the fast/pounding heartbeat you would usually feel when your blood sugar level falls too low (hypoglycemia). Other symptoms of a low blood sugar level, such as dizziness and sweating, are unaffected by this drug. This product may also make it harder to control your blood sugar levels. Check your blood sugar levels regularly as directed by your doctor. Tell your doctor immediately if you have symptoms of high blood sugar such as increased thirst/urination. Your diabetes medication or diet may need to be adjusted.

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.

During pregnancy, this medication should be used only when clearly needed. It may harm an unborn baby. Discuss the risks and benefits with your doctor.

It is unknown if this medication passes into breast milk or if it may harm a nursing infant. Discuss the risks and benefits with your doctor before breast-feeding.

Consumer Overview Missed Dose

DRUG INTERACTIONS: See also Precautions section.

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, especially of: fingolimod.

Check the labels on all your medicines (such as 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 heart rate. 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 a poison control center or emergency room immediately. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: very slow heartbeat, severe dizziness, severe weakness, fainting, trouble breathing.

 

NOTES: Do not share this medication with others.

Talk with your doctor about making changes to your lifestyle that may help this medication work better (such as stress reduction programs, exercise, and dietary changes).

Have your blood pressure and pulse (heart rate) checked regularly while taking this medication. Learn how to check your own blood pressure and pulse at home, and share the results with your doctor.

Laboratory and/or medical tests should be performed periodically 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.

 

Information last revised April 2015. Copyright(c) 2015 First Databank, Inc.

Patient Detailed Side Effect

Brand Names: Zebeta

Generic Name: bisoprolol (Pronunciation: BIS oh PROE lol)

  • What is bisoprolol (Zebeta)?
  • What are the possible side effects of bisoprolol (Zebeta)?
  • What is the most important information I should know about bisoprolol (Zebeta)?
  • What should I discuss with my healthcare provider before taking bisoprolol (Zebeta)?
  • How should I take bisoprolol (Zebeta)?
  • What happens if I miss a dose (Zebeta)?
  • What happens if I overdose (Zebeta)?
  • What should I avoid while taking bisoprolol (Zebeta)?
  • What other drugs will affect bisoprolol (Zebeta)?
  • Where can I get more information?

What is bisoprolol (Zebeta)?

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

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

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

Bisoprolol 10 mg-MYL

round, white, imprinted with M, 524

What are the possible side effects of bisoprolol (Zebeta)?

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

Call your doctor at once if you have any of these serious side effects:

  • slow, fast, or pounding heartbeats;
  • chest pain, feeling like you might pass out;
  • confusion, hallucinations;
  • feeling short of breath, even with mild exertion;
  • swelling of your ankles or feet;
  • pain or burning when you urinate; or
  • numbness, tingling, or cold feeling in your hands and feet.

Less serious side effects may include:

  • dry mouth, nausea, vomiting, stomach pain;
  • diarrhea, constipation, increased urination;
  • runny or stuffy nose, ringing in your ears;
  • feeling tired or weak;
  • sleep problems (insomnia);
  • drowsiness, dizziness, spinning sensation;
  • depression, anxiety, restless feeling;
  • joint or muscle pain;
  • mild itching or skin rash; or
  • loss of interest in sex.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

Read the Zebeta (bisoprolol fumarate) Side Effects Center for a complete guide to possible side effects

Learn More »

What is the most important information I should know about bisoprolol (Zebeta)?

Do not skip doses or stop taking bisoprolol without first talking to your doctor. Stopping suddenly may make your condition worse or cause other serious heart problems.

If you need to have any type of surgery, tell the surgeon ahead of time that you are using bisoprolol.

Bisoprolol can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.

Avoid drinking alcohol. It can increase some of the side effects of bisoprolol.

Bisoprolol is only part of a complete program of treatment for hypertension that may also include diet, exercise, and weight control. Follow your diet, medication, and exercise routines very closely if you are being treated for hypertension.

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.

Patient Detailed How Take

What should I discuss with my healthcare provider before taking bisoprolol (Zebeta)?

You should not use this medication if you are allergic to bisoprolol, or if you have certain serious heart conditions such as"AV block" or slow heart rhythm.

If you have certain conditions, you may need a dose adjustment or special tests to safely use this medication. Before you take bisoprolol, tell your doctor if you have:

  • asthma, bronchitis, emphysema;
  • diabetes (taking bisoprolol can make it harder for you to tell when you have low blood sugar);
  • a heart problem such as angina, heart block, slow heart rhythm, or congestive heart failure;
  • liver or kidney disease;
  • a thyroid disorder; or
  • problems with circulation (such as Raynaud's syndrome).

FDA pregnancy category C. It is not known whether bisoprolol is harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether bisoprolol 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 bisoprolol (Zebeta)?

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

Take this medication with a full glass of water.

Take bisoprolol at the same time every day.

Your doctor may occasionally change your dose to make sure you get the best results from this medication.

Do not skip doses or stop taking bisoprolol without first talking to your doctor. Stopping suddenly may make your condition worse or cause other serious heart problems.

To be sure this medication is helping your condition, your blood pressure will need to be checked on a regular basis. Do not miss any scheduled appointments.

If you need to have any type of surgery, tell the surgeon ahead of time that you are using bisoprolol.

Bisoprolol is only part of a complete program of treatment for hypertension that may also include diet, exercise, and weight control. Follow your diet, medication, and exercise routines very closely if you are being treated for hypertension.

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 bisoprolol at room temperature away from moisture and heat.

Patient Detailed Avoid Taking

What happens if I miss a dose (Zebeta)?

Take the missed dose as soon as you remember. If your next dose is less than 4 hours away, skip the missed dose and take the medicine at the next regularly scheduled time. Do not take extra medicine to make up the missed dose.

What happens if I overdose (Zebeta)?

Seek emergency medical attention if you think you have used too much of this medicine.

Overdose symptoms may include slow heart rate, wheezing or shortness of breath, dizziness, anxiety, confusion, nausea, sweating, pale skin, fainting, and seizure (convulsions).

What should I avoid while taking bisoprolol (Zebeta)?

Bisoprolol can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Avoid drinking alcohol. It can increase some of the side effects of bisoprolol.

What other drugs will affect bisoprolol (Zebeta)?

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

  • clonidine (Catapres);
  • digitalis (digoxin, Lanoxin);
  • disopyramide (Norpace);
  • guanethidine (Ismelin);
  • rifampin (Rifadin, Rifater, Rifamate);
  • insulin or diabetes medication you take by mouth;
  • another beta-blocker such as atenolol (Tenormin), carvedilol (Coreg), labetalol (Normodyne, Trandate), metoprolol (Lopressor, Toprol), nadolol (Corgard), propranolol (Inderal, InnoPran), sotalol (Betapace), and others;
  • a heart medication such as nifedipine (Procardia, Adalat), reserpine (Serpasil), verapamil (Calan, Verelan, Isoptin), or diltiazem (Cartia, Cardizem); or
  • medicine for asthma or other breathing disorders, such as albuterol (Ventolin, Proventil), bitolterol (Tornalate), metaproterenol (Alupent), pirbuterol (Maxair), terbutaline (Brethaire, Brethine, Bricanyl), and others.

This list is not complete and there may be other drugs that can interact with bisoprolol. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about bisoprolol.


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.

Rx Scoops
Featured Topics
Advertisements
Copyrights ©2014: Rx Scoops - Designed & Developed By - GOIGI