Nadolol Information
Nadolol () Description
Nadolol () is a synthetic nonselective beta-adrenergic receptor blocking agent designated chemically as 1-(-butylamino)-3-[(5,6,7,8-tetrahydro--6,7-dihydroxy-1-naphthyl)oxy]-2-propanol. Its structural formula is:
Nadolol () , USP 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.
Each tablet for oral administration contains 20 mg, 40 mg or 80 mg of Nadolol () , USP and the following inactive ingredients: anhydrous lactose, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, sodium lauryl sulfate, and D&C Yellow No. 10 Aluminum Lake.
Nadolol () Clinical Pharmacology
Nadolol () 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 () specifically competes with beta-adrenergic receptor agonists for available beta receptor sites; it inhibits both the beta receptors located chiefly in cardiac muscle and the beta receptors located chiefly in the bronchial and vascular musculature, inhibiting the chronotropic, inotropic, and vasodilator responses to beta-adrenergic stimulation proportionately. Nadolol () 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 Nadolol () 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. Nadolol () 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 () 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 () 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-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%. Peak serum concentrations of Nadolol () usually occur in 3 to 4 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% 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 and ). Steady-state serum concentrations of Nadolol () are attained in 6 to 9 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.
Nadolol () Contraindications
Nadolol () tablets are contraindicated in bronchial asthma, sinus bradycardia and greater than first-degree conduction block, cardiogenic shock, and overt cardiac failure (see ).
Nadolol () Warnings
Sympathetic stimulation may be a vital component supporting circulatory function in patients with congestive heart failure, and its inhibition by beta-blockade may precipitate more severe failure. Although beta-blockers should be avoided in overt congestive heart failure, if necessary, they can be used with caution in patients with a history of failure who are well compensated, usually with digitalis and diuretics. Beta-adrenergic blocking agents do not abolish the inotropic action of digitalis on heart muscle.
IN PATIENTS WITHOUT A HISTORY OF HEART FAILURE, continued use of beta-blockers can, in some cases, lead to cardiac failure. Therefore, at the first sign or symptom of heart failure, the patient should be digitalized and/or treated with diuretics, and the response observed closely, or Nadolol () should be discontinued (gradually, if possible).
Nadolol () Precautions
When administered concurrently, the following drugs may interact with beta-adrenergic receptor blocking agents:
WARNINGS, Major Surgery
WARNINGS, Diabetes and Hypoglycemia
Nadolol () Adverse Reactions
Most adverse effects have been mild and transient and have rarely required withdrawal of therapy.
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.
The oculomucocutaneous syndrome associated with the beta-blocker practolol has not been reported with Nadolol () .
Nadolol () Overdosage
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 () .
Nadolol () Dosage And Administration
DOSAGE MUST BE INDIVIDUALIZED. Nadolol () TABLETS MAY BE ADMINISTERED WITHOUT REGARD TO MEALS.
The usual initial dose is 40 mg Nadolol () once daily. Dosage may be gradually increased in 40 mg 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 mg or 80 mg administered once daily. Doses up to 160 mg or 240 mg administered once daily may be needed.
The usefulness and safety in angina pectoris of dosages exceeding 240 mg per day have not been established. If treatment is to be discontinued, reduce the dosage gradually over a period of 1 to 2 weeks (see ).
Nadolol () How Supplied:
Nadolol () Tablets, USP are available containing 20 mg or 40 mg of Nadolol () , USP.
The 20 mg tablets are yellow round, scored tablets debossed with above the score and below the score on one side of the tablet and blank on the other side. They are available as follows:
NDC 51079-812-20 - Unit dose blister packages of 100 (10 cards of 10 tablets each).
The 40 mg tablets are yellow round, scored tablets debossed with above the score and below the score on one side of the tablet and blank on the other side. They are available as follows:
NDC 51079-813-20 - Unit dose blister packages of 100 (10 cards of 10 tablets each).
Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]
Protect from light.
Manufactured by:Mylan Pharmaceuticals Inc.Morgantown, WV 26505
Distributed by:UDL Laboratories, Inc.Rockford, IL 61103
S-5465 R105/10
Nadolol ()
NDC 51079-812-20
100 Tablets (10 x 10)
Each tablet contains:Nadolol () , USP 20 mg
Store at 20° to 25°C (68° to 77°F).[See USP for Controlled RoomTemperature.]
Protect from light.
S-5458 R5
Packaged and Distributed by:
UDL LABORATORIES, INC.
ROCKFORD, IL 61103
This unit dose package is not child resistant.
For institutional use only.
Keep this and all drugs out of the reach of children.
This container provides light-resistance.
See window for lot number and expiration date.
Nadolol ()
NDC 51079-813-20
100 Tablets (10 x 10)
Each tablet contains:Nadolol () , USP 40 mg
Store at 20° to 25°C (68° to 77°F).[See USP for Controlled RoomTemperature.]
Protect from light.
S-5459 R5
Packaged and Distributed by:
UDL LABORATORIES, INC.
ROCKFORD, IL 61103
This unit dose package is not child resistant.
For institutional use only.
Keep this and all drugs out of the reach of children.
This container provides light-resistance.
See window for lot number and expiration date.
