Nebicard Tablet 5mg

Product Information

NEBICARD

NEBICARD®

Nebivolol

Presentation

Nebicard 2.5 tablet: Pink, round tablet. Each tablet contains Nebivolol Hydrochloride INN equivalent to Nebivolol 2.5mg. Nebicard

5 Tablet: Pink, shield shaped tablet, scored on one side. Each tablet contains Nebivolol Hydrochloride INN equivalent to Nebivolol

5mg.

Nebicard Prescribing Information

Nebivolol is a ß adrenergic receptor blocking agent. Nebivolol inhibits both ß1 and ß2-adrenergic receptors. Nebivolol lacks

intrinsic sympathomimetic and membrane stabilizing activity at therapeutically relevant concentrations. At clinically relevant

doses, Nebicard does not demonstrate ß1-adrenergic receptor blockade activity. Various metabolites, including glucuronides,

contribute to beta-blocking activity.

Pharmacodynamics

Mode of Action of Nebicard 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 resin 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 b blocking activity.

Absorption and Distribution

Absorption of Nebicard is similar to an oral solution. 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. Nebicard may be administered without

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

independent of nebivolol concentrations.

Metabolism and Excretion

Nebivolol is predominantly metabolized via direct glucuronidation of parent and to a lesser extent via N-dealkylation and

oxidation via cytochrome P450 2D6. 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.

Digoxin: Concomitant administration of Nebicard (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. Warfarin: Administration of

Nebicard (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. The starting dose should be reduced in patients with moderate hepatic impairment. No formal studies have been

performed in patients with severe hepatic impairment and nebivolol should be contraindicated for these patients.

Indications and Usage for Nebicard

Hypertension

Treatment of essential hypertension.

Chronic heart failure (CHF)

Treatment of stable mild and moderate chronic heart failure in addition to standard therapies in elderly patients.

Contraindications

Nebicard is contraindicated in patients with severe bradycardia, heart block greater than first degree, cardiogenic shock,

decompensated cardiac failure, sick sinus syndrome (unless a permanent pacemaker is in place), or severe hepatic impairment

(Child-Pugh >B), and in patients who are hypersensitive to any component of this product. Warnings

Abrupt Cessation of Therapy

Patients with coronary artery disease treated with Nebicard should be advised against abrupt discontinuation of therapy. Severe

exacerbation of angina and the occurrence of myocardial infarction and ventricular arrhythmias have been reported in patients with

coronary artery disease following the abrupt discontinuation of therapy with b-blockers. Myocardial infarction and ventricular

arrhythmias may occur with or without preceding exacerbation of the angina pectoris. Even patients without overt coronary artery

disease should be cautioned against interruption or abrupt discontinuation of therapy. As with other ß-blockers, when

discontinuation of Nebicard is planned, patients should be carefully observed and advised to minimize physical activity. Nebicard

should be tapered over 1 to 2 weeks when possible. If the angina worsens or acute coronary insufficiency develops, it is

recommended that Nebicard be promptly reinstituted, at least temporarily.

Cardiac Failure

Sympathetic stimulation is a vital component supporting circulatory function in the setting of congestive heart failure, and

ß-blockade may result in further depression of myocardial contractility and precipitate more severe failure. In patients who have

compensated congestive heart failure, Nebicard should be administered cautiously. If heart failure worsens, discontinuation of

Nebicard should be considered.

Angina and Acute Myocardial Infarction

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

Bronchospastic Diseases

In general, patients with bronchospastc diseases should not receive ß-blockers.

Anesthesia and Major Surgery

If Nebicard is to be continued perioperatively, patients should be closely monitored when anesthetic agents which depress

myocardial function, such as ether, cyclopropane, and trichloroethylene, are used. If ß-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 ß-blocking effects of Nebicard can be reversed by ß-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 ß-blockers.

Diabetes and Hypoglycemia

ß-blockers may mask some of the manifestations of hypoglycemia, particularly tachycardia. Nonselective ß-blockers may potentiate

insulin-induced hypoglycemia and delay recovery of serum glucose levels. It is not known whether nebivolol has these effects.

Patients subject to spontaneous hypoglycemia, or diabetic patients receiving insulin or oral hypoglycemic agents, should be

advised about these possibilities and nebivolol should be used with caution.

Thyrotoxicosis

ß-blockers may mask clinical signs of hyperthyroidism, such as tachycardia. Abrupt withdrawal of ß-blockers may be followed by an

exacerbation of the symptoms of hyperthyroidism or may precipitate a thyroid storm.

Peripheral Vascular Disease

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

should be exercised in these patients.

Non-dihydropyridine Calcium Channel Blockers

Because of significant negative inotropic and chronotropic effects in patients treated with ß-blockers and calcium channel

blockers of the verapamil and diltiazem type, caution should be used in patients treated concomitantly with these agents and ECG

and blood pressure should be monitored.

Precautions

Impaired Renal Function

Nebicard should be used with caution in patients with severe renal impairment because of decreased renal clearance. Nebicard has

not been studied in patients receiving dialysis.

Impaired Hepatic Function

Nebicard should be used with caution in patients with moderate hepatic impairment because of decreased metabolism. Since Nebicard

has not been studied in patients with severe hepatic impairment, Nebicard is contraindicated in this population.

Risk of Anaphylactic Reactions

While taking ß-blockers, patients with a history of severe anaphylactic reactions 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.

Drug Interactions

Nebicard 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 [diltiazerm] classes), or antiarrhythmic agents, such as

disopyramide, are used concurrently. Both digitalis glycosides and ß-blockers slow atrioventricular conduction and decrease heart

rate. Concomitant use can increase the risk of bradycardia.

Nebicard should not be combined with other ß-blockers. Patients receiving catecholamine-depleting drugs, such as reserpine or

guanethidine, should be closely monitored, because the added ß-blocking action of Nebicard may produce excessive reduction of

sympathetic activity. In patients who are receiving Nebicard and clonidine, Nebicard should be discontinued for several days

before the gradual tapering of clonidine.

CYP2D6 Inhibitors: Use caution when Nebicard is co-administered with CYP2D6 inhibitors (quinidine, propafenone, fluoxetine,

paroxetine, etc.)

Adverse Reactions

Headache, nausea and bradycardia.

Nebicard Dosage and Administration

The dose of Nebicard should 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.

Packaging quantites

Nebicard 2.5 tablet: Carton containing 30 tablet in Alu-Alu blister pack.

Nebicard 5 Tablet: Carton containing 30 tablet in Alu-Alu blister pack.

Manufactured by

UniMed & UniHealth Manufacturers Ltd. B. K. Bari, Gazipur, Bangladesh

® Registered Trademark