Brand Name

Nadolol

View Brand Information
FDA approval date: February 23, 2016
Classification: beta-Adrenergic Blocker
Form: Tablet

What is Nadolol?

Angina Pectoris Nadolol tablets, USP are indicated for the long-term management of patients with angina pectoris. Hypertension Nadolol tablets, USP is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs. There are no controlled trials demonstrating risk reduction with Nadolol. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program's Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure . Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension , and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects in black patients, and many antihypertensive drugs have additional approved indications and effects . These considerations may guide selection of therapy. Nadolol may be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics.

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Brand Information

Nadolol (Nadolol)
1DESCRIPTION
Nadolol tablets, USP is a synthetic nonselective beta-adrenergic receptor blocking agent designated chemically as 1-(
C17H27NO4             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.
2CLINICAL PHARMACOLOGY
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
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
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
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.
3CONTRAINDICATIONS
Nadolol is contraindicated in bronchial asthma, sinus bradycardia and greater than first degree conduction block, cardiogenic shock, and overt cardiac failure (see
4ADVERSE REACTIONS
Most adverse effects have been mild and transient and have rarely required withdrawal of therapy.
4.1Cardiovascular
Bradycardia with heart rates of less than 60 beats per minute occurs commonly, and heart rates below 40 beats per minute and/or symptomatic bradycardia were seen in about 2 of 100 patients. Symptoms of peripheral vascular insufficiency, usually of the Raynaud type, have occurred in approximately 2 of 100 patients. Cardiac failure, hypotension, and rhythm/conduction disturbances have each occurred in about 1 of 100 patients. Single instances of first degree and third degree heart block have been reported; intensification of AV block is a known effect of beta-blockers (see also
4.2Central Nervous System
Dizziness or fatigue has been reported in approximately 2 of 100 patients; paresthesias, sedation, and change in behavior have each been reported in approximately 6 of 1000 patients.
4.3Respiratory
Bronchospasm has been reported in approximately 1 of 1000 patients (see
4.4Gastrointestinal
Nausea, diarrhea, abdominal discomfort, constipation, vomiting, indigestion, anorexia, bloating, and flatulence have been reported in 1 to 5 of 1000 patients.
4.5Miscellaneous
Each of the following has been reported in 1 to 5 of 1000 patients: rash; pruritus; headache; dry mouth, eyes, or skin; impotence or decreased libido; facial swelling; weight gain; slurred speech; cough; nasal stuffiness; sweating; tinnitus; blurred vision. Reversible alopecia has been reported infrequently.
The following adverse reactions have been reported in patients taking nadolol and/or other beta-adrenergic blocking agents, but no causal relationship to nadolol has been established.
4.6Central Nervous System
Reversible mental depression progressing to catatonia; visual disturbances; hallucinations; an acute reversible syndrome characterized by disorientation for time and place, short-term memory loss, emotional lability with slightly clouded sensorium, and decreased performance on neuropsychometrics.
4.7Gastrointestinal
Mesenteric arterial thrombosis; ischemic colitis; elevated liver enzymes.
4.8Hematologic
Agranulocytosis; thrombocytopenic or nonthrombocytopenic purpura.
4.9Allergic
Fever combined with aching and sore throat; laryngospasm; respiratory distress.
4.10Miscellaneous
Pemphigoid rash; hypertensive reaction in patients with pheochromocytoma; sleep disturbances; Peyronie's disease.
The oculomucocutaneous syndrome associated with the beta-blocker practolol has not been reported with nadolol.

To report SUSPECTED ADVERSE REACTIONS, contact Beximco Pharmaceuticals USA Inc. at 877-372-6093 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
5OVERDOSAGE
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.
5.1Excessive Bradycardia
Administer atropine (0.25 to 1.0 mg). If there is no response to vagal blockade, administer isoproterenol cautiously.
5.2Cardiac Failure
Administer a digitalis glycoside and diuretic. It has been reported that glucagon may also be useful in this situation.
5.3Hypotension
Administer vasopressors, e.g., epinephrine or levarterenol. (There is evidence that epinephrine may be the drug of choice.)
5.4Bronchospasm
Administer a beta2-stimulating agent and/or a theophylline derivative.
6DOSAGE AND ADMINISTRATION
DOSAGE MUST BE INDIVIDUALIZED. NADOLOL TABLETS, USP MAY BE ADMINISTERED WITHOUT REGARD TO MEALS.
6.1Angina Pectoris
The usual initial dose is 40 mg Nadolol Tablets once daily. Dosage may be gradually increased in 40 to 80 mg increments at 3 to 7 day intervals until optimum clinical response is obtained or there is pronounced slowing of the heart rate. The usual maintenance dose is 40 or 80 mg administered once daily. Doses up to 160 or 240 mg administered once daily may be needed.
The usefulness and safety in angina pectoris of dosage exceeding 240 mg per day have not been established. If treatment is to be discontinued, reduce the dosage gradually over a period of one to two weeks (see
6.2Hypertension
The usual initial dose is 40 mg Nadolol Tablets once daily, whether it is used alone or in addition to diuretic therapy. Dosage may be gradually increased in 40 to 80 mg increments until optimum blood pressure reduction is achieved. The usual maintenance dose is 40 or 80 mg administered once daily. Doses up to 240 or 320 mg administered once daily may be needed.
6.3Dosage Adjustment in Renal Failure
Absorbed nadolol is excreted principally by the kidneys and, although nonrenal elimination does occur, dosage adjustments are necessary in patients with renal impairment. The following dose intervals are recommended:
7HOW SUPPLIED
All tablets are blue color with mottling, round, biconvex, having a score line on one side and debossed with the product code on the other.
Nadolol Tablets are available in the following strengths:
7.1STORAGE
Store at room temperature; avoid excessive heat. Protect from light. Keep bottle tightly closed.
8PRINCIPAL DISPLAY PANEL - 20 mg Tablet Bottle Label
NDC 76385-
Nadolol Tablets, USP
20 mg
Bayshore
100 Tablets
9PRINCIPAL DISPLAY PANEL - 40 mg Tablet Bottle Label
NDC 76385-
Nadolol Tablets, USP
40 mg
Bayshore
100 Tablets
10PRINCIPAL DISPLAY PANEL - 80 mg Tablet Bottle Label
NDC 76385-
Nadolol Tablets, USP
80 mg
Bayshore
100 Tablets