Nadolol Tablets, USP

SPL UNCLASSIFIED SECTION

SPL UNCLASSIFIED SECTION

PRODUCT OVERVIEW: Nadalol Tablets USP Rx Only

DESCRIPTION

DESCRIPTION SECTION

Nadolol tablets, USP is a synthetic nonselective beta-adrenergic receptor blocking agent designated chemically as 1-( tert -butyl-amino)-3-[(5,6,7,8-tetrahydro- cis -6,7-dihydroxy-1-naphthyl) oxy]-2-propanol. Structural formula: C 17 H 27 NO 4 MW 309.40 Nadolol is a white crystalline powder. It is freely soluble in ethanol, soluble in hydrochloric acid, slightly soluble in water and in chloroform, and very slightly soluble in sodium hydroxide. Nadolol tablets, USP is available for oral administration as 20 mg, 40 mg, and 80 mg tablets. Inactive ingredients: Microcrystalline Cellulose (Type 101), Dried Maize Starch, FD&C Blue#2, Indigo carmine Aluminum Lake, Copovidone, Citric Acid Monohydrate, Sodium Starch Glycolate, Magnesium Stearate and Purified Water.

CLINICAL PHARMACOLOGY

CLINICAL PHARMACOLOGY SECTION

Nadolol tablets, USP is a nonselective beta-adrenergic receptor blocking agent. Clinical pharmacology studies have demonstrated beta-blocking activity by showing (1) reduction in heart rate and cardiac output at rest and on exercise, (2) reduction of systolic and diastolic blood pressure at rest and on exercise, (3) inhibition of isoproterenol-induced tachycardia, and (4) reduction of reflex orthostatic tachycardia. Nadolol tablets, USP specifically competes with beta-adrenergic receptor agonists for available beta receptor sites; it inhibits both the beta 1 receptors located chiefly in cardiac muscle and the beta 2 receptors located chiefly in the bronchial and vascular musculature, inhibiting the chronotropic, inotropic, and vasodilator responses to beta-adrenergic stimulation proportionately. CORGARD has no intrinsic sympathomimetic activity and, unlike some other beta-adrenergic blocking agents, nadolol has little direct myocardial depressant activity and does not have an anesthetic-like membrane- stabilizing action. Animal and human studies show that CORGARD slows the sinus rate and depresses AV conduction. In dogs, only minimal amounts of nadolol were detected in the brain relative to amounts in blood and other organs and tissues. CORGARD has low lipophilicity as determined by octanol/water partition coefficient, a characteristic of certain beta-blocking agents that has been correlated with the limited extent to which these agents cross the blood-brain barrier, their low concentration in the brain, and low incidence of CNS-related side effects. In controlled clinical studies, Nadolol tablets, USP at doses of 40 to 320 mg/day has been shown to decrease both standing and supine blood pressure, the effect persisting for approximately 24 hours after dosing. The mechanism of the antihypertensive effects of beta-adrenergic receptor blocking agents has not been established; however, factors that may be involved include (1) competitive antagonism of catecholamines at peripheral (non-CNS) adrenergic neuron sites (especially cardiac) leading to decreased cardiac output, (2) a central effect leading to reduced tonic-sympathetic nerve outflow to the periphery, and (3) suppression of renin secretion by blockade of the beta-adrenergic receptors responsible for renin release from the kidneys. While cardiac output and arterial pressure are reduced by nadolol therapy, renal hemodynamics are stable, with preservation of renal blood flow and glomerular filtration rate. By blocking catecholamine-induced increases in heart rate, velocity and extent of myocardial contraction, and blood pressure, Nadolol tablets, USP generally reduces the oxygen requirements of the heart at any given level of effort, making it useful for many patients in the long-term management of angina pectoris. On the other hand, nadolol can increase oxygen requirements by increasing left ventricular fiber length and end diastolic pressure, particularly in patients with heart failure. Although beta-adrenergic receptor blockade is useful in treatment of angina and hypertension, there are also situations in which sympathetic stimulation is vital. For example, in patients with severely damaged hearts, adequate ventricular function may depend on sympathetic drive. Beta-adrenergic blockade may worsen AV block by preventing the necessary facilitating effects of sympathetic activity on conduction. Beta 2 -adrenergic blockade results in passive bronchial constriction by interfering with endogenous adrenergic bronchodilator activity in patients subject to bronchospasm and may also interfere with exogenous bronchodilators in such patients. Absorption of nadolol after oral dosing is variable, averaging about 30 percent. Peak serum concentrations of nadolol usually occur in three to four hours after oral administration and the presence of food in the gastrointestinal tract does not affect the rate or extent of nadolol absorption. Approximately 30 percent of the nadolol present in serum is reversibly bound to plasma protein. Unlike many other beta-adrenergic blocking agents, nadolol is not metabolized by the liver and is excreted unchanged, principally by the kidneys. The half-life of therapeutic doses of nadolol is about 20 to 24 hours, permitting once-daily dosage. Because nadolol is excreted predominantly in the urine, its half-life increases in renal failure (see PRECAUTIONS and DOSAGE AND ADMINISTRATION ). Steady-state serum concentrations of nadolol are attained in six to nine days with once-daily dosage in persons with normal renal function. Because of variable absorption and different individual responsiveness, the proper dosage must be determined by titration. Exacerbation of angina and, in some cases, myocardial infarction and ventricular dysrhythmias have been reported after abrupt discontinuation of therapy with beta-adrenergic blocking agents in patients with coronary artery disease. Abrupt withdrawal of these agents in patients without coronary artery disease has resulted in transient symptoms, including tremulousness, sweating, palpitation, headache, and malaise. Several mechanisms have been proposed to explain these phenomena, among them increased sensitivity to catecholamines because of increased numbers of beta receptors.

INDICATIONS AND USAGE

INDICATIONS & USAGE SECTION

CONTRAINDICATIONS

CONTRAINDICATIONS SECTION

Nadolol is contraindicated in bronchial asthma, sinus bradycardia and greater than first degree conduction block, cardiogenic shock, and overt cardiac failure (see WARNINGS ).

WARNINGS

WARNINGS SECTION

PRECAUTIONS

PRECAUTIONS SECTION

ADVERSE REACTIONS

ADVERSE REACTIONS SECTION

Most adverse effects have been mild and transient and have rarely required withdrawal of therapy.

OVERDOSAGE

OVERDOSAGE SECTION

Nadolol can be removed from the general circulation by hemodialysis. In addition to gastric lavage, the following measures should be employed, as appropriate. In determining the duration of corrective therapy, note must be taken of the long duration of the effect of nadolol.

DOSAGE AND ADMINISTRATION

DOSAGE & ADMINISTRATION SECTION

DOSAGE MUST BE INDIVIDUALIZED. NADOLOL TABLETS, USP MAY BE ADMINISTERED WITHOUT REGARD TO MEALS.

HOW SUPPLIED

HOW SUPPLIED SECTION

Nadolol Tablets are available in the following strengths: 80 mg tablets NDC: 71335-2131-1: 30 Tablets in a BOTTLE NDC: 71335-2131-2: 28 Tablets in a BOTTLE NDC: 71335-2131-3: 90 Tablets in a BOTTLE STORAGE Store at room temperature; avoid excessive heat. Protect from light. Keep bottle tightly closed. Repackaged/Relabeled by: Bryant Ranch Prepack Burbank, CA 91504

SPL UNCLASSIFIED SECTION

SPL UNCLASSIFIED SECTION

Manufactured for Beximco Pharmaceuticals USA Inc. Suwanee, GA 30024, USA Manufactured by BEXIMCO PHARMACEUTICALS LTD. 126, Kathaldia, Tongi, Gazipur, 1711, Bangladesh Distributed by Bayshore Pharmaceuticals LLC Short Hills, NJ 07078 Revised: 11/2018

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

Nadolol 80mg Tablet