ACEBUTOLOL
DESCRIPTION:
Sectral (acebutolol HCl) is a selective, hydrophilic beta-adrenoreceptor
blocking agent with mild intrinsic sympathomimetic activity for use in treating
patients with hypertension and ventricular arrhythmias. It is marketed in
capsule form for oral administration. Sectral capsules are provided in two
dosage strengths which contain 200 or 400 mg of acebutolol as the hydrochloride
salt. The inactive ingredients present are D&C Red 22, FD&C Blue 1, FD&C Yellow
6, gelatin, povidone, starch, stearic acid, and titanium dioxide. The 200 mg
dosage strength also contains D&C Red 28 and the 400 mg dosage strength also
contains FD&C Red 40.
Acebutolol HCl is a white or slightly off-white powder freely soluble in water,
and less soluble in alcohol. Chemically it is defined as the hydrochloride salt
of(+/)N-(3-Acetyl- 4-(2-hydroxy-3-((1-methylethyl) amino)propoxy)phenyl)
butanamide or (+/-)-3'-Acetyl-4'-(2-hydroxy- 3-(isopropylamino)propoxy)
butyranilide.
ACTIONS/CLINICAL PHARMACOLOGY:
Sectral is a cardioselective, beta-adrenoreceptor blocking agent, which
possesses mild intrinsic sympathomimetic activity (ISA) in its therapeutically
effective dose range.
Pharmacodynamics
Beta1-cardioselectivity has been demonstrated in experimental animal studies. In
anesthetized dogs and cats, Sectral is more potent in antagonizing
isoproterenol-induced tachycardia (beta1) than in antagonizing isoproterenol-
induced vasodilatation (beta2). In guinea pigs and cats, it is more potent in
antagonizing this tachycardia than in antagonizing isoproterenol-induced
bronchodilatation (beta2). ISA of Sectral has been demonstrated in
catecholamine-depleted rats by tachycardia induced by intravenous administration
of this agent. A membrane- stabilizing effect has been detected in animals, but
only with high concentrations of Sectral.
Clinical studies have demonstrated beta1-blocking activity at the recommended
doses by: a) reduction in the resting heart rate and decrease in exercise-
induced tachycardia; b) reduction in cardiac output at rest and after exercise;
c) reduction of systolic and diastolic blood pressures at rest and postexercise;
d) inhibition of isoproterenol-induced tachycardia.
The beta1-selectivity of Sectral has also been demonstrated on the basis of the
following vascular and bronchial effects:
Vascular Effects: Sectral has less antagonistic effects on peripheral vascular
beta2-receptors at rest and after epinephrine stimulation than nonselective
beta-antagonists.
Bronchial Effects: In single-dose studies in asthmatics examining effects of
various beta- blockers on pulmonary function, low doses of acebutolol produce
less evidence of bronchoconstriction and less reduction of beta2 agonist,
bronchodilating effects, than nonselective agents like propranolol but more than
atenolol.
ISA has been observed with Sectral in man, as shown by a slightly smaller (about
3 beats per minute) decrease in resting heart rate when compared to equivalent
beta-blocking doses of propranolol, metoprolol or atenolol. Chronic therapy with
Sectral induced no significant alteration in the blood lipid profile.
Sectral has been shown to delay AV conduction time and to increase the
refractoriness of the AV node without significantly affecting sinus node
recovery time, atrial refractory period, or the HV conduction time. The
membrane-stabilizing effect of Sectral is not manifest at the doses used
clinically.
Significant reductions in resting and exercise heart rates and systolic blood
pressures have been observed 1.5 hours after Sectral administration with maximal
effects occurring between 3 and 8 hours postdosing in normal volunteers. Sectral
has demonstrated a significant effect on exercise-induced tachycardia 24 to 30
hours after drug administration.
There are significant correlations between plasma levels of acebutolol and both
the reduction in resting heart rate and the percent of beta- blockade of
exercise-induced tachycardia.
The antihypertensive effect of Sectral has been shown in double-blind controlled
studies to be superior to placebo and similar to propranolol and
hydrochlorothiazide. In addition, patients responding to Sectral administered
twice daily had a similar response whether the dosage regimen was changed to
once daily administration or continued on a b.i.d. regimen. Most patients
responded to 400 to 800 mg per day in divided doses.
The antiarrhythmic effect of Sectral was compared with placebo, propranolol, and
quinidine. Compared with placebo, Sectral significantly reduced mean total
ventricular ectopic beats (VEB), paired VEB, multiform VEB, R-on-T beats, and
ventricular tachycardia (VT). Both Sectral and propranolol significantly reduced
mean total and paired VEB and VT. Sectral and quinidine significantly reduced
resting total and complex VEB; the antiarrhythmic efficacy of Sectral was also
observed during exercise.
Pharmacokinetics and Metabolism
Sectral is well absorbed from the GI tract. It is subject to extensive first-
pass hepatic biotransformation, with an absolute bioavailability of
approximately 40% for the parent compound. The major metabolite, an N- acetyl
derivative (diacetolol), is pharmacologically active. This metabolite is
equipotent to Sectral and in cats is more cardioselective than Sectral;
therefore, this first-pass phenomenon does not attenuate the therapeutic effect
of Sectral. Food intake does not have a significant effect on the area under the
plasma concentration-time curve (AUC) of Sectral although the rate of absorption
and peak concentration decreased slightly.
The plasma elimination half-life of Sectral is approximately 3 to 4 hours, while
that of its metabolite, diacetolol, is 8 to 13 hours. The time to reach peak
concentration for Sectral is 2.5 hours and for diacetolol, after oral
administration of Sectral, 3.5 hours.
Within the single oral dose range of 200 to 400 mg, the kinetics are dose
proportional. However, this linearity is not seen at higher doses, probably due
to saturation of hepatic biotransformation sites. In addition, after multiple
dosing the lack of linearity is also seen by AUC increases of approximately 100%
as compared to single oral dosing. Elimination via renal excretion is
approximately 30% to 40% and by nonrenal mechanisms 50% to 60%, which includes
excretion into the bile and direct passage through the intestinal wall.
Sectral has a low binding affinity for plasma proteins (about 26%). Sectral and
its metabolite, diacetolol, are relatively hydrophilic and, therefore, only
minimal quantities have been detected in the cerebrospinal fluid (CSF).
Drug interaction studies with tolbutamide and warfarin indicated no influence on
the therapeutic effects of these compounds. Digoxin and hydrochlorothiazide
plasma levels were not affected by concomitant Sectral administration. The
kinetics of Sectral were not significantly altered by concomitant administration
of hydrochlorothiazide, hydralazine, sulfinpyrazone, or oral contraceptives.
In patients with renal impairment, there is no effect on the elimination half-
life of Sectral, but there is decreased elimination of the metabolite,
diacetolol, resulting in a two- to three-fold increase in its half-life. For
this reason, the drug should be administered with caution in patients with renal
insufficiency (see "PRECAUTIONS"). Sectral and its major metabolite are
dialyzable.
Sectral crosses the placental barrier and is secreted in breast milk.
In geriatric patients, the bioavailability of Sectral and its metabolite is
increased, approximately two-fold, probably due to decreases in the first-pass
metabolism and renal function in the elderly.
INDICATIONS AND USAGE:
Hypertension
Sectral is indicated for the management of hypertension in adults. It may be
used alone or in combination with other antihypertensive agents, especially
thiazide-type diuretics.
Ventricular Arrhythmias
Sectral is indicated in the management of ventricular premature beats; it
reduces the total number of premature beats, as well as the number of paired and
multiform ventricular ectopic beats, and R-on-T beats.
CONTRAINDICATIONS:
Sectral is contraindicated in:
1) persistently severe bradycardia;
2) second- and third-degree heart block;
3) overt cardiac failure; and
4) cardiogenic shock. (See WARNINGS.)
WARNINGS:
Cardiac Failure
Sympathetic stimulation may be essential for support of the circulation in
individuals with diminished myocardial contractility, and its inhibition by
beta-adrenergic receptor blockade may precipitate more severe failure. Although
beta-blockers should be avoided in overt cardiac failure, Sectral can be used
with caution in patients with a history of heart failure who are controlled with
digitalis and/or diuretics. Both digitalis and Sectral impair AV conduction. If
cardiac failure persists, therapy with Sectral should be withdrawn.
In Patients Without A History Of Cardiac Failure
In patients with aortic or mitral valve disease or compromised left ventricular
function, continued depression of the myocardium with beta- blocking agents over
a period of time may lead to cardiac failure. At the first signs of failure,
patients should be digitalized and/or be given a diuretic and the response
observed closely. If cardiac failure continues despite adequate digitalization
and/or diuretic, Sectral therapy should be withdrawn.
Exacerbation Of Ischemic Heart Disease Following Abrupt Withdrawal
Following abrupt cessation of therapy with certain beta-blocking agents in
patients with coronary artery disease, exacerbation of angina pectoris and, in
some cases, myocardial infarction and death have been reported. Therefore, such
patients should be cautioned against interruption of therapy without a
physician's advice. Even in the absence of overt ischemic heart disease, when
discontinuation of Sectral is planned, the patient should be carefully observed,
and should be advised to limit physical activity to a minimum while Sectral is
gradually withdrawn over a period of about two weeks. (If therapy with an
alternative beta-blocker is desired, the patient may be transferred directly to
comparable doses of another agent without interruption of beta- blocking
therapy.) If an exacerbation of angina pectoris occurs, antianginal therapy
should be restarted immediately in full doses and the patient hospitalized until
his condition stabilizes.
Peripheral Vascular Disease
Treatment with beta-antagonists reduces cardiac output and can precipitate or
aggravate the symptoms of arterial insufficiency in patients with peripheral or
mesenteric vascular disease. Caution should be exercised with such patients, and
they should be observed closely for evidence of progression of arterial
obstruction.
Bronchospastic Diseases
PATIENTS WITH BRONCHOSPASTIC DISEASE SHOULD, IN GENERAL, NOT RECEIVE A BETA-
BLOCKER. Because of its relative beta1-selectivity, however, low doses of
Sectral may be used with caution in patients with bronchospastic disease who do
not respond to, or who cannot tolerate, alternative treatment. Since beta1-
selectivity is not absolute and is dose-dependent, the lowest possible dose of
Sectral should be used initially, preferably in divided doses to avoid the
higher plasma levels associated with the longer dose-interval. A bronchodilator,
such as a theophylline or a beta2-stimulant, should be made available in advance
with instructions concerning its use.
Anesthesia And Major Surgery
The necessity, or desirability, of withdrawal of a beta-blocking therapy prior
to major surgery is controversial. Beta-adrenergic receptor blockade impairs the
ability of the heart to respond to beta-adrenergically mediated reflex stimuli.
While this might be of benefit in preventing arrhythmic response, the risk of
excessive myocardial depression during general anesthesia may be enhanced and
difficulty in restarting and maintaining the heart beat has been reported with
beta-blockers. If treatment is continued, particular care should be taken when
using anesthetic agents which depress the myocardium, such as ether,
cyclopropane and trichlorethylene, and it is prudent to use the lowest possible
dose of Sectral. Sectral, like other beta-blockers, is a competitive inhibitor
of beta-receptor agonists, and its effect on the heart can be reversed by
cautious administration of such agents (e.g., dobutamine or isoproterenol--see
OVERDOSE).
Manifestations of excessive vagal tone (e.g., profound bradycardia, hypotension)
may be corrected with atropine 1 to 3 mg IV in divided doses.
Diabetes And Hypoglycemia
Beta-blockers may potentiate insulin-induced hypoglycemia and mask some of its
manifestations such as tachycardia; however, dizziness and sweating are usually
not significantly affected. Diabetic patients should be warned of the
possibility of masked hypoglycemia.
Thyrotoxicosis
Beta-adrenergic blockade may mask certain clinical signs (tachycardia) of
hyperthyroidism. Abrupt withdrawal of beta-blockade may precipitate a thyroid
storm; therefore, patients suspected of developing thyrotoxicosis from whom
Sectral therapy is to be withdrawn should be monitored closely.
PRECAUTIONS:
Risk of Anaphylactic Reaction
While taking beta-blockers, patients with a history of severe anaphylactic
reaction 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 reaction.
Impaired Renal Or Hepatic Function
Studies on the effect of acebutolol in patients with renal insufficiency have
not been performed in the U.S. Foreign published experience shows that
acebutolol has been used successfully in chronic renal insufficiency. Acebutolol
is excreted through the GI tract, but the active metabolite, diacetolol, is
eliminated predominantly by the kidney. There is a linear relationship between
renal clearance of diacetolol and creatinine clearance. Therefore, the daily
dose of acebutolol should be reduced by 50% when the creatinine clearance is
less than 50mL/min and by 75% when it is less than 25 mL/min. Sectral should be
used cautiously in patients with impaired hepatic function.
Sectral has been used successfully and without problems in elderly patients in
the U.S. clinical trials without specific adjustment of dosage. However, elderly
patients may require lower maintenance doses because the bioavailability of both
Sectral and its metabolite are approximately doubled in this age group.
Information For Patients
Patients, especially those with evidence of coronary artery disease, should be
warned against interruption or discontinuation of Sectral therapy without a
physician's supervision. Although cardiac failure rarely occurs in properly
selected patients, those being treated with beta-adrenergic blocking agents
should be advised to consult a physician if they develop signs or symptoms
suggestive of impending CHF, or unexplained respiratory symptoms.
Patients should also be warned of possible severe hypertensive reactions from
concomitant use of alpha-adrenergic stimulants, such as the nasal decongestants
commonly used in OTC cold preparations and nasal drops.
Clinical Laboratory Findings
Sectral, like other beta-blockers, has been associated with the development of
antinuclear antibodies (ANA). In prospective clinical trials, patients receiving
Sectral had a dose-dependent increase in the development of positive ANA titers,
and the overall incidence was higher than that observed with propranolol.
Symptoms (generally persistent arthralgias and myalgias) related to this
laboratory abnormality were infrequent (less than 1% with both drugs). Symptoms
and ANA titers were reversible upon discontinuation of treatment.
Drug Interactions
Catecholamine-depleting drugs, such as reserpine, may have an additive effect
when given with beta- blocking agents. Patients treated with Sectral plus
catecholamine depletors should, therefore, be observed closely for evidence of
marked bradycardia or hypotension which may present as vertigo, syncope/
presyncope, or orthostatic changes in blood pressure without compensatory
tachycardia. Exaggerated hypertensive responses have been reported from the
combined use of beta- adrenergic antagonists and alpha-adrenergic stimulants,
including those contained in proprietary cold remedies and vasoconstrictive
nasal drops. Patients receiving beta-blockers should be warned of this potential
hazard.
Blunting of the antihypertensive effect of beta- adrenoceptor blocking agents by
nonsteroidal anti-inflammatory drugs has been reported.
No significant interactions with digoxin, hydrochlorothiazide, hydralazine,
sulfinpyrazone, oral contraceptives, tolbutamide, or warfarin have been
observed.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Chronic oral toxicity studies in rats and mice, employing dose levels as high as
300 mg/kg/day, which is equivalent to 15 times the maximum recommended (60 kg)
human dose, did not indicate a carcinogenic potential for Sectral. Diacetolol,
the major metabolite of Sectral in man, was without carcinogenic potential in
rats when tested at doses as high as 1800 mg/kg/day. Sectral and diacetolol were
also shown to be devoid of mutagenic potential in the Ames Test. Sectral,
administered orally to two generations of male and female rats at doses of up to
240 mg/kg/day (equivalent to 12 times the maximum recommended therapeutic dose
in a 60-kg human) and diacetolol, administered to two generations of male and
female rats at doses of up to 1000 mg/kg/day, had no significant impact on
reproductive performance or fertility.
Pregnancy
Teratogenic Effects
Pregnancy Category B: Reproduction studies have been performed with Sectral in
rats (up to 630 mg/kg/day) and rabbits (up to 135 mg/kg/day). These doses are
equivalent to approximately 31.5 and 6.8 times the maximum recommended
therapeutic dose in a 60-kg human, respectively. The compound was not
teratogenic in either species. In the rabbit, however, doses of 135 mg/kg/day
caused slight fetal growth retardation; this effect was considered to be a
result of maternal toxicity, as evidenced by reduced food intake, a lowered rate
of body weight gain, and mortality. Studies have also been performed in these
species with diacetolol (at doses of up to 450 mg/kg/day in rabbits and up to
1800 mg/kg/day in rats.) Other than a significant elevation in postimplantation
loss with 450 mg/kg/day diacetolol, a level at which food consumption and body
weight gain were reduced in rabbit dams and a nonstatistically significant
increase in incidence of bilateral cataract in rat fetuses from dams treated
with 1800 mg/kg/day diacetolol, there was no evidence of harm to the fetus.
There are no adequate and well-controlled trials in pregnant women. Because
animal teratology studies are not always predictive of the human response,
Sectral should be used during pregnancy only if the potential benefit justifies
the risk to the fetus.
Nonteratogenic Effects
Studies in humans have shown that both acebutolol and diacetolol cross the
placenta. Neonates of mothers who have received acebutolol during pregnancy have
reduced birth weight, decreased blood pressure, and decreased heart rate. In the
newborn the elimination half-life of acebutolol was 6 to 14 hours, while the
half-life of diacetolol was 24 to 30 hours for the first 24 hours after birth,
followed by a half-life of 12 to 16 hours. Adequate facilities for monitoring
these infants at birth should be available.
Labor And Delivery
The effect of Sectral on labor and delivery in pregnant women is unknown.
Studies in animals have not shown any effect of Sectral on the usual course of
labor and delivery.
Nursing Mothers
Acebutolol and diacetolol also appear in breast milk with a milk:plasma ratio of
7.1 and 12.2, respectively. Use in nursing mothers is not recommended.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
DRUG INTERACTIONS:
Catecholamine-depleting drugs, such as reserpine, may have an additive effect
when given with beta- blocking agents. Patients treated with Sectral plus
catecholamine depletors should, therefore, be observed closely for evidence of
marked bradycardia or hypotension which may present as vertigo,
syncope/presyncope, or orthostatic changes in blood pressure without
compensatory tachycardia. Exaggerated hypertensive responses have been reported
from the combined use of beta- adrenergic antagonists and alpha-adrenergic
stimulants, including those contained in proprietary cold remedies and
vasoconstrictive nasal drops. Patients receiving beta-blockers should be warned
of this potential hazard.
Blunting of the antihypertensive effect of beta- adrenoceptor blocking agents by
nonsteroidal anti-inflammatory drugs has been reported.
No significant interactions with digoxin, hydrochlorothiazide, hydralazine,
sulfinpyrazone, oral contraceptives, tolbutamide, or warfarin have been
observed.
(See Also WARNINGS and PRECAUTIONS)
ADVERSE REACTIONS:
Sectral is well tolerated in properly selected patients. Most adverse reactions
have been mild, not required discontinuation of therapy, and tended to decrease
as duration of treatment increases.
The following table shows the frequency of treatment-related side effects
derived from controlled clinical trials in patients with hypertension, angina
pectoris, and arrhythmia. These patients received Sectral, propranolol, or
hydrochlorothiazide as monotherapy, or placebo.
TOTAL VOLUNTEERED AND ELICITED (U.S. STUDIES)
HYDROCHLORO-
SECTRAL PROPRANOLOL THIAZIDE PLACEBO
BODY SYSTEM/ (N=1002) (N=424) (N=178) (N=314)
ADVERSE REACTION % % % %
Cardiovascular
Chest Pain 2 4 4 1
Edema 2 2 4 1
Central Nervous System
Depression 2 1 3 1
Dizziness 6 7 12 2
Fatigue 11 17 10 4
Headache 6 9 13 4
Insomnia 3 6 5 1
Abnormal dreams 2 3 0 1
Dermatologic
Rash 2 2 4 1
Gastrointestinal
Constipation 4 2 7 0
Diarrhea 4 5 5 1
Dyspepsia 4 6 3 1
Flatulence 3 4 7 1
Nausea 4 6 3 0
Genitourinary
Micturition (frequency) 3 1 9 <1
Musculoskeletal
Arthralgia 2 1 3 2
Myalgia 2 1 4 0
Respiratory
Cough 1 1 2 0
Dyspnea 4 6 4 2
Rhinitis 2 1 4 <1
Special Senses
Abnormal Vision 2 2 3 0
The following selected (potentially important) side effects were seen in up to
2% of Sectral patients:
Cardiovascular: hypotension, bradycardia, heart failure.
Central Nervous System: anxiety, hyper/hypoesthesia, impotence.
Dermatological: pruritus.
Gastrointestinal: vomiting, abdominal pain.
Genitourinary: dysuria, nocturia.
Liver And Biliary System: A small number of cases of liver abnormalities
(increased SGOT, SGPT, LDH) have been reported in association with acebutolol
therapy. In some cases increased bilirubin or alkaline phosphatase, fever,
malaise, dark urine, anorexia, nausea, headache, and/or other symptoms have been
reported. In some of the reported cases, the symptoms and signs were confirmed
by rechallenge with acebutolol. The abnormalities were reversible upon cessation
of acebutolol therapy.
Musculoskeletal: back pain, joint pain.
Respiratory: pharyngitis, wheezing.
Special Senses: conjunctivitis, dry eye, eye pain.
Autoimmune: In extremely rare instances, systemic lupus erythematosus has been
reported.
The incidence of drug-related adverse effects (volunteered and solicited)
according to Sectral dose is shown below. (Data from 266 hypertensive patients
treated for 3 months on a constant dose.)
--------------------------------------------------
400 800 1200
MG/DAY MG/DAY MG/DAY
BODY SYSTEM (N=132) (N=63) (N=71)
--------------------------------------------------
Cardiovascular 5% 2% 1%
Gastrointestinal 3% 3% 7%
Musculoskeletal 2% 3% 4%
Central Nervous
System 9% 13% 17%
Respiratory 1% 5% 6%
Skin 1% 2% 1%
Special Senses 2% 2% 6%
Genitourinary 2% 3% 1%
--------------------------------------------------
Potential Adverse Effects
In addition, certain adverse effects not listed above have been reported with
other beta-blocking agents and should also be considered as potential adverse
effects of Sectral.
Central Nervous System: Reversible mental depression progressing to catatonia
(an acute syndrome characterized by disorientation for time and place), short-
term memory loss, emotional lability, slightly clouded sensorium, and decreased
performance (neuropsychometrics).
Cardiovascular: Intensification of AV block (see CONTRAINDICATIONS).
Allergic: Erythematous rash, fever combined with aching and sore throat,
laryngospasm, and respiratory distress.
Hematologic: Agranulocytosis, nonthrombocytopenic, and thrombocytopenic purpura.
Gastrointestinal: Mesenteric arterial thrombosis and ischemic colitis.
Miscellaneous: Reversible alopecia and Peyronie's disease. The
oculomucocutaneous syndrome associated with the beta-blocker practolol has not
been reported with Sectral during investigational use and extensive foreign
clinical experience.
OVERDOSAGE:
No specific information on emergency treatment of overdosage is available for
Sectral. However, overdosage with other beta-blocking agents has been
accompanied by extreme bradycardia, advanced atrioventricular block,
intraventricular conduction defects, hypotension, severe congestive heart
failure, seizures, and in susceptible patients, bronchospasm and hypoglycemia.
Although specific information on the emergency treatment of Sectral overdose is
not available, on the basis of the pharmacological actions and the observations
in treating overdoses with other beta-blockers, the following general measures
should be considered:
1. Empty stomach by emesis or lavage.
2. Bradycardia: IV atropine (1 to 3 mg in divided doses). If antivagal response
is inadequate, administer isoproterenol cautiously since larger than usual doses
of isoproterenol may be required.
3. Persistent hypotension in spite of correction of bradycardia: Administer
vasopressor (e.g., epinephrine, levarterenol, dopamine, or dobutamine) with
frequent monitoring of blood pressure and pulse rate.
4. Bronchospasm: A theophylline derivative, such as aminophylline and/or
parenteral beta2-stimulant, such as terbutaline.
5. Cardiac failure: Digitalize the patient and/or administer a diuretic. It has
been reported that glucagon is useful in this situation.
Sectral is dialyzable.
DOSAGE AND ADMINISTRATION:
Hypertension
The initial dosage of Sectral in uncomplicated mild-to-moderate hypertension is
400 mg. This can be given as a single daily dose, but in occasional patients
twice daily dosing may be required for adequate 24-hour blood-pressure control.
An optimal response is usually achieved with dosages of 400 to 800 mg per day,
although some patients have been maintained on as little as 200 mg per day.
Patients with more severe hypertension or who have demonstrated inadequate
control may respond to a total of 1200 mg daily (administered b.i.d.), or to the
addition of a second antihypertensive agent. Beta-1 selectivity diminishes as
dosage is increased.
Ventricular Arrhythmia
The usual initial dose of Sectral is 400 mg daily given as 200 mg b.i.d. Dosage
should be increased gradually until an optimal clinical response is obtained,
generally at 600 to 1200 mg per day. If treatment is to be discontinued, the
dosage should be reduced gradually over a period of about two weeks.
Use In Older Patients
Older patients have an approximately 2-fold increase in bioavailability and may
require lower maintenance doses. Doses above 800 mg/day should be avoided in the
elderly.