BISOPROLOL FUMARATE tablet, film coated

United States - English - NLM (National Library of Medicine)

Buy It Now

Active ingredient:
BISOPROLOL FUMARATE (UNII: UR59KN573L) (BISOPROLOL - UNII:Y41JS2NL6U)
Available from:
ORIT LABORATORIES LLC
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Bisoprolol fumarate  is indicated in the management of hypertension. It may be used alone or in combination with other antihypertensive agents. Bisoprolol fumarate  is contraindicated in patients with cardiogenic shock, overt cardiac failure, second or third degree AV block, and marked sinus bradycardia.
Product summary:
Bisoprolol Fumarate Tablets, USP is supplied as 5 mg and 10 mg tablets. The 5 mg tablet is white, round, biconvex, film-coated, scored and debossed with “S5” on one side NDC 15955-373-30 bottles of 30 NDC 15955-373-50 bottles of 500 The 10 mg tablet is white, round, biconvex, film-coated and debossed with “S10” on one side NDC 15955-374-30 bottles of 30 NDC 15955-374-50 bottles of 500 Dispense in a tight, light-resistant container as defined in the USP with a child-resistant closure, as required. Store at 20º to 25ºC (68º to 77ºF) [See USP Controlled Room Temperature].   Protect from light and moisture. KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.   Manufactured for: Orit Laboratories LLC West Caldwell, NJ 07006 Manufactured by: Aenova France SAS Saint-Quentin-Fallavier, France Rev. 07/13
Authorization status:
Abbreviated New Drug Application
Authorization number:
15955-373-30, 15955-373-50, 15955-374-30, 15955-374-50

BISOPROLOL FUMARATE - bisoprolol fumarate tablet, film coated

ORIT LABORATORIES LLC

----------

Bisoprolol Fumarate Tablets, USP

Rx only

DESCRIPTION

Bisoprolol fumarate is a synthetic, beta -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 (C

H NO ) C H O and its structure is:

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.

Bisoprolol Fumarate Tablets, USP is available as 5 and 10 mg tablets for oral administration.

Inactive ingredients include colloidal silicon dioxide, partially pregelatinized starch, crospovidone,

anhydrous dibasic calcium phosphate, hypromellose, magnesium stearate, microcrystalline cellulose,

polyethylene glycol, titanium dioxide and talc.

CLINICAL PHARMACOLOGY

Bisoprolol fumarate is a beta -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 beta -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 to 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 to 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 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 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 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, bisoprolol fumarate therapy resulted in a reduction of exercise- and

isoproterenol-induced tachycardia. The maximal effect occurred within 1 to 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 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.

Beta -selectivity of bisoprolol fumarate has been demonstrated in both animal and human studies. No

effects at therapeutic doses on beta -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 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.

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.

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 (Δ ) After 3 to 4

Weeks

Study A

Bisoprolol Fumarate

Placebo

5 mg

10 mg

20 mg

Total ΔBP (mm Hg)

5.4/3.2

10.4/8.0

11.2/10.9

12.8/11.9

Drug Effect*

5.0/4.8

5.8/7.7

7.4/8.7

Total ΔHR (bpm)

11.3

Drug Effect*

10.8

Study B

Bisoprolol Fumarate

Placebo

2.5 mg

10 mg

Total ΔBP (mm Hg)

3.0/3.7

7.6/8.1

13.5/11.2

Drug Effect*

4.6/4.4

10.5/7.5

Total ΔHR (bpm)

10.7

Drug Effect*

* 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.

INDICATIONS AND USAGE

Bisoprolol fumarate is indicated in the management of hypertension. It may be used alone or in

combination with other antihypertensive agents.

CONTRAINDICATIONS

Bisoprolol fumarate is contraindicated in patients with cardiogenic shock, overt cardiac failure, second

or third degree AV block, and marked sinus bradycardia.

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 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 bisoprolol fumarate over approximately one week with the patient

under careful observation. If withdrawal symptoms occur, 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 beta -selectivity, however, 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 beta -selectivity is not absolute, the

lowest possible dose of bisoprolol fumarate should be used, with therapy starting at 2.5 mg. A

beta 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

1

1

2

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 beta -selectivity, this is less likely with 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.

Thyrotoxicos is

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 bisoprolol fumarate in patients with renal or hepatic impairment

(see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION).

Drug Interactions

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 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 bisoprolol fumarate be discontinued for several days before the

withdrawal of clonidine.

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 bisoprolol fumarate , resulting in a

shortened elimination half-life of 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 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.

Information for Patients

Patients, especially those with coronary artery disease, should be warned about discontinuing use of

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.

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. 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

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.

ADVERSE REACTIONS

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 to 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

to 40 mg), as well as for a subgroup that was treated with doses within the recommended dosage range

(5 to 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

(%*) Bisoprolol Fumarate

Placebo (n=132)

5-20

mg (n=273)

2.5-40

mg (n=404)

Skin

increased sweating

Musculoskeletal

arthralgia

Central Nervous System

dizziness

headache

11.4

10.9

hypoaesthesia

Autonomic Nervous System

dry mouth

Heart Rate/Rhythm

Heart Rate/Rhythm

bradycardia

Psychiatric

vivid dreams

insomnia

depression

Gastrointestinal

diarrhea

nausea

vomiting

Respiratory

bronchospasm

cough

dyspnea

pharyngitis

rhinitis

sinusitis

Body as a Whole

asthenia

chest pain

fatigue

edema (peripheral)

* 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.

Cardiovas cular

Bradycardia, palpitations and other rhythm disturbances, cold extremities, claudication, hypotension,

orthostatic hypotension, chest pain, congestive heart failure, dyspnea on exertion.

Ps ychiatric

Vivid dreams, insomnia, depression.

Gas trointes tinal

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

ulcer.

Mus culos keletal

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.

Res piratory

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 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.

Gas trointes tinal

Mesenteric arterial thrombosis, ischemic colitis.

Mis cellaneous

The oculomucocutaneous syndrome associated with the beta-blocker practolol has not been reported

with 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 to 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 to 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.

OVERDOSAGE

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, 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.

Hypotens ion

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).

Bronchos pas m

Administer bronchodilator therapy such as isoproterenol and/or aminophylline.

Hypoglycemia

Administer IV glucose.

DOSAGE AND ADMINISTRATION

The dose of 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 bisoprolol fumarate .

HOW SUPPLIED

Bisoprolol Fumarate Tablets, USP is supplied as 5 mg and 10 mg tablets.

The 5 mg tablet is white, round, biconvex, film-coated, scored and debossed with “S5” on one side

NDC15955-373-30 bottles of 30

NDC15955-373-50 bottles of 500

The 10 mg tablet is white, round, biconvex, film-coated and debossed with “S10” on one side

NDC15955-374-30 bottles of 30

NDC15955-374-50 bottles of 500

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

as required.

Store at 20º to 25ºC (68º to 77ºF) [See USP Controlled Room Temperature].

Protect from light and moisture.

KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

Manufactured for:

Orit Laboratories LLC

West Caldwell, NJ 07006

Manufactured by:

Aenova France SAS

Saint-Quentin-Fallavier, France

Rev. 07/13

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 5 mg

NDC 15955-373-30

Bis oprolol

Fumarate

Tablets, USP

5 mg

Rx only

30 Tablets

ORIT

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 10 mg

NDC 15955-374-30

Bisoprolol

Fumarate

Tablets, USP

10 mg

Rx only

30 Tablets

ORIT

BISOPROLOL FUMARATE

bisoprolol fumarate tablet, film coated

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:159 55-373

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

BISO PRO LO L FUMARATE (UNII: UR59 KN573L) (BISOPROLOL - UNII:Y41JS2NL6 U)

BISOPROLOL FUMARATE

5 mg

Inactive Ingredients

Ingredient Name

Stre ng th

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

STARCH, CO RN (UNII: O8 232NY3SJ)

CRO SPO VIDO NE ( 15 MPA.S AT 5%) (UNII: 6 8 40 19 6 0 MK)

CALCIUM PHO SPHATE, DIBASIC, ANHYDRO US (UNII: L11K75P9 2J)

HYPRO MELLO SE, UNSPECIFIED (UNII: 3NXW29 V3WO)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

MICRO CRYSTALLINE CELLULO SE (UNII: OP1R32D6 1U)

PO LYETHYLENE GLYCO L, UNSPECIFIED (UNII: 3WJQ0 SDW1A)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

TALC (UNII: 7SEV7J4R1U)

Product Characteristics

Color

WHITE

S core

2 pieces

S hap e

ROUND (BICONVEX)

S iz e

Flavor

Imprint Code

Contains

Packag ing

#

Item Code

Package Description

Marketing Start

Date

Marketing End

Date

1

NDC:159 55-373-

30 in 1 BOTTLE, PLASTIC; Type 0 : No t a Co mbinatio n

Pro duc t

0 9 /11/20 19

2

NDC:159 55-373-

50 0 in 1 BOTTLE, PLASTIC; Type 0 : No t a Co mbinatio n

Pro duc t

0 9 /11/20 19

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA20 48 9 1

0 9 /11/20 19

BISOPROLOL FUMARATE

bisoprolol fumarate tablet, film coated

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:159 55-374

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

BISO PRO LO L FUMARATE (UNII: UR59 KN573L) (BISOPROLOL - UNII:Y41JS2NL6 U)

BISOPROLOL FUMARATE

10 mg

Inactive Ingredients

Ingredient Name

Stre ng th

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

STARCH, CO RN (UNII: O8 232NY3SJ)

CRO SPO VIDO NE ( 15 MPA.S AT 5%) (UNII: 6 8 40 19 6 0 MK)

CALCIUM PHO SPHATE, DIBASIC, ANHYDRO US (UNII: L11K75P9 2J)

HYPRO MELLO SE, UNSPECIFIED (UNII: 3NXW29 V3WO)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

MICRO CRYSTALLINE CELLULO SE (UNII: OP1R32D6 1U)

PO LYETHYLENE GLYCO L, UNSPECIFIED (UNII: 3WJQ0 SDW1A)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

TALC (UNII: 7SEV7J4R1U)

Product Characteristics

Color

WHITE

S core

no sco re

S hap e

ROUND (BICONVEX)

S iz e

ORIT LABORATORIES LLC

S hap e

S iz e

Flavor

Imprint Code

Contains

Packag ing

#

Item Code

Package Description

Marketing Start

Date

Marketing End

Date

1

NDC:159 55-374-

30 in 1 BOTTLE, PLASTIC; Type 0 : No t a Co mbinatio n

Pro duc t

0 9 /11/20 19

2

NDC:159 55-374-

50 0 in 1 BOTTLE, PLASTIC; Type 0 : No t a Co mbinatio n

Pro duc t

0 9 /11/20 19

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA20 48 9 1

0 9 /11/20 19

Labeler -

ORIT LABORAT ORIES LLC (167618912)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Skyepharma Pro ductio n S.A.S.

38 36 30 456

MANUFACTURE(159 55-373, 159 55-374)

Revised: 9/2019

Similar products

Search alerts related to this product

View documents history

Share this information