DESCRIPTION

Inderal® (propranolol hydrochloride)is a synthetic beta-adrenergic receptor-blocking agent chemicallydescribed as 2-Propanol, 1-[(1-methylethyl)amino]-3-(1-naphthalenyloxy)-,hydrochloride,(±)-. Its molecular and structural formulae are:

Image from Drug Label Content

C16H21NO2 · HCl

Propranolol hydrochlorideis a stable, white, crystalline solid which is readily soluble inwater and ethanol. Its molecular weight is 295.80.

Inderal LA is formulated to provide a sustained release of propranololhydrochloride. Inderal LA is available as 60mg, 80mg,120mg, and 160mg capsules for oral administration.

The inactive ingredients containedin Inderal LA capsules are: cellulose, ethylcellulose, gelatin capsules,hypromellose, and titanium dioxide. In addition, Inderal LA 60mg,80mg, and 120mg capsules contain D&C Red No.28and FD&C Blue No.1; Inderal LA 160mg capsules containFD&C Blue No.1.

These capsules comply with USP Dissolution Test 1.

CLINICAL PHARMACOLOGY

General

Propranololis a nonselective, beta-adrenergic receptor-blocking agent possessingno other autonomic nervous system activity. It specifically competeswith beta-adrenergic receptor-stimulating agents for available receptorsites. When access to beta-receptor sites is blocked by propranolol,the chronotropic, inotropic, and vasodilator responses to beta-adrenergicstimulation are decreased proportionately. At dosages greater thanrequired for beta blockade, propranolol also exerts a quinidine-likeor anesthetic-like membrane action, which affects the cardiac actionpotential. The significance of the membrane action in the treatmentof arrhythmias is uncertain.

Inderal LA should not be considered a simple mg-for-mg substitutefor conventional propranolol and the blood levels achieved do notmatch (are lower than) those of two to four times daily dosing withthe same dose (see DOSAGE AND ADMINISTRATION). When changing toInderal LA from conventional propranolol, a possible need for retitrationupwards should be considered, especially to maintain effectivenessat the end of the dosing interval. In most clinical settings, however,such as hypertension or angina where there is little correlation betweenplasma levels and clinical effect, Inderal LA has been therapeuticallyequivalent to the same mg dose of conventional Inderal as assessedby 24-hour effects on blood pressure and on 24-hour exercise responsesof heart rate, systolic pressure, and rate pressure product.

Mechanism of Action

The mechanism of the antihypertensive effect of propranololhas not been established. Among the factors that may be involved incontributing to the antihypertensive action include: (1)decreasedcardiac output, (2)inhibition of renin release by the kidneys,and (3)diminution of tonic sympathetic nerve outflow from vasomotorcenters in the brain. Although total peripheral resistance may increaseinitially, it readjusts to or below the pretreatment level with chronicuse of propranolol. Effec