Bisoprolol Fumarate (Page 4 of 4)

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 weeks to 12 weeks, the incidence of concomitant elevations in SGOT and SGPT from 1 time 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 months to 18 months, the incidence of one or more concomitant elevations in SGOT and SGPT from 1 time 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: 2,000 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.

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 (i.e., digitalis, diuretics, inotropic agents, vasodilating agents).

Bronchospasm

Administer bronchodilator therapy such as isoproterenol and/or aminophylline.

Hypoglycemia

Administer IV glucose.

DOSAGE AND ADMINISTRATION

The dose of bisoprolol fumarate tablets, USP 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.

Bisoprolol fumarate tablets, USP 5 mg are light pink to pink colored, round shaped, film-coated tablets, debossed with “111” on one side and scored on the other side, supplied as follows:

NDC 72578-111-06 in bottles of 30 tablets with child-resistant closure.

NDC 72578-111-01 in bottles of 100 tablets with child-resistant closure.

Bisoprolol fumarate tablets, USP 10 mg are white to off white colored with occasional greyish to black speckles, round shaped, film-coated tablets, debossed with “112” on one side and plain on the other side, supplied as follows:

NDC 72578-112-06 in bottles of 30 tablets with child-resistant closure.

NDC 72578-112-01 in bottles of 100 tablets with child-resistant closure.

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature.]

Protect from moisture.

Dispense in a tight, light-resistant container.

Call your doctor for medical advice about side effects. You may report side effects to Viona Pharmaceuticals Inc. at 1-888-304-5011 or FDA at 1-800-FDA-1088.

Manufactured by:

Cadila Healthcare Ltd.

Ahmedabad, India

Distributed by:

Viona Pharmaceuticals Inc.

Cranford, NJ 07016

Rev.: 04/21

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

NDC 72578-111-06

Bisoprolol Fumarate Tablets USP, 5 mg

30 Tablets

Unit-of-Use

Rx only

Viona

NDC 72578-112-06

Bisoprolol Fumarate Tablets USP, 10 mg

30 Tablets

Unit-of-Use

Rx only

Viona

BISOPROLOL FUMARATE bisoprolol fumarate tablet, film coated

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:72578-111 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength BISOPROLOL FUMARATE (BISOPROLOL) BISOPROLOL FUMARATE 5 mg

Inactive Ingredients Ingredient Name Strength ALUMINUM OXIDE ANHYDROUS DIBASIC CALCIUM PHOSPHATE BUTYLATED HYDROXYANISOLE CROSPOVIDONE (12 MPA.S AT 5%) D&C YELLOW NO. 10 ALUMINUM LAKE FD&C RED NO. 40 HYPROMELLOSE 2910 (6 MPA.S) MAGNESIUM STEARATE MICROCRYSTALLINE CELLULOSE POLYETHYLENE GLYCOL 6000 SILICON DIOXIDE TITANIUM DIOXIDE

Product Characteristics Color PINK (light pink to pink) Score 2 pieces Shape ROUND Size 6mm Flavor Imprint Code 111 Contains

Packaging # Item Code Package Description Multilevel Packaging 1 NDC:72578-111-06 30 TABLET, FILM COATED in 1 BOTTLE None 2 NDC:72578-111-01 100 TABLET, FILM COATED in 1 BOTTLE None

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA215680 09/15/2022

BISOPROLOL FUMARATE bisoprolol fumarate tablet, film coated

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:72578-112 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength BISOPROLOL FUMARATE (BISOPROLOL) BISOPROLOL FUMARATE 10 mg

Inactive Ingredients Ingredient Name Strength ANHYDROUS DIBASIC CALCIUM PHOSPHATE BUTYLATED HYDROXYANISOLE CROSPOVIDONE (12 MPA.S AT 5%) HYPROMELLOSE 2910 (6 MPA.S) MAGNESIUM STEARATE MICROCRYSTALLINE CELLULOSE POLYETHYLENE GLYCOL 6000 SILICON DIOXIDE TITANIUM DIOXIDE

Product Characteristics Color WHITE (white to off white colored with occasional greyish) Score no score Shape ROUND Size 7mm Flavor Imprint Code 112 Contains

Packaging # Item Code Package Description Multilevel Packaging 1 NDC:72578-112-06 30 TABLET, FILM COATED in 1 BOTTLE None 2 NDC:72578-112-01 100 TABLET, FILM COATED in 1 BOTTLE None

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA215680 09/15/2022

Labeler — Viona Pharmaceuticals Inc (081468959)

Registrant — Zydus Lifesciences Limited (650199482)

Establishment
Name	Address	ID/FEI	Operations
Zydus Lifesciences Limited		863362789	ANALYSIS (72578-111), ANALYSIS (72578-112), MANUFACTURE (72578-111), MANUFACTURE (72578-112)

Revised: 07/2022 Viona Pharmaceuticals Inc