Acebutolol Hydrochloride (0002)
[ a-se-byoo'-toe-lole hye-droe-klor'-ide ]
| Ingredients: |
Acebutolol Hydrochloride |
| Indications: |
Arrhythmia, ventricular; Hypertension, essential |
| Pregnancy Category: |
B |
| FDA Approved: |
1984- 12- 01 |
| Classes: |
Antiadrenergics, beta blocking; Antiarrhythmics, class II |
| Brand Names: |
ACB
-
New-zealand, Singapore
;
Acecor
-
Italy
;
Diasectral
-
Denmark, Finland
;
Espesil
-
Finland
;
Flebutol
-
Venezuela
;
Grifobutol
-
Chile
;
Monitan
-
Canada
;
Prent
-
Germany, Italy, Portugal
;
Rhotral
-
Canada
;
Sectral
-
CARIBBEAN, MIDDLEEAST, US; Belgium, Bulgaria, Canada, Czech-republic, England, France, Hong-kong, Ireland, Italy, Malaysia, Netherlands, Poland, South-africa, Spain, Switzerland, Taiwan
;
Sectral LP
-
France
;
|
| DEA schedules: |
(none)
|
| Cost of therapy: |
$40.19
(
Hypertension ;
Generic Capsules (Par) ;
400 mg ;
1 capsule(s)/day ;
30 day supply
)
$100.67
(
Hypertension ;
Sectral ;
400 mg ;
1 capsule(s)/day ;
30 day supply
)
|
DESCRIPTION
|
| |
Acebutolol hydrochloride 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 hydrochloride 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 Butanamide, N- [3- acetyl- 4- [2- hydroxy- 3- [(1- methylethyl)amino]propoxy]phenyl]-
, (±)- or (±)- 3′- Acetyl- 4′- [2- hydroxy- 3- (isopropylamino)propoxy] butyranilide.
|
CLINICAL PHARMACOLOGY
|
| |
Acebutolol HCl is a cardioselective, β- adrenoreceptor blocking agent, which possesses mild intrinsic sympathomimetic activity
(ISA) in its therapeutically effective dose range.
Pharmacodynamics
|
| |
β1 - cardioselectivity has been demonstrated in experimental animal studies. In anesthetized dogs and cats, acebutolol HCl is
more potent in antagonizing isoproterenol- induced tachycardia (β1 ) than in antagonizing isoproterenol- induced vasodilatation (β2 ). In guinea pigs and cats, it is more potent in antagonizing this tachycardia than in antagonizing isoproterenol- induced
bronchodilatation (β2 ). ISA of acebutolol HCl 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 acebutolol
HCl.
Clinical studies have demonstrated β1 - 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; and (d) inhibition of isoproterenol- induced tachycardia.
The β1 - selectivity of acebutolol HCl has also been demonstrated on the basis of the following vascular and bronchial effects:
- Vascular Effects: Acebutolol HCl has less antagonistic effects on peripheral vascular β2 - receptors at rest and after epinephrine stimulation than nonselective β- 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 acebutolol HCl in man, as shown by a slightly smaller (about 3 beats/ min) decrease in resting
heart rate when compared to equivalent β- blocking doses of propranolol, metoprolol or atenolol. Chronic therapy with acebutolol
HCl induced no significant alteration in the blood lipid profile.
Acebutolol HCl 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 acebutolol HCl 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
acebutolol HCl administration with maximal effects occurring between 3 and 8 hours postdosing in normal volunteers. Acebutolol
HCl has demonstrated a significant effect on exercise- induced tachycardia 24- 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 β- blockade of exercise- induced tachycardia.
The antihypertensive effect of acebutolol HCl has been shown in double- blind controlled studies to be superior to placebo
and similar to propranolol and hydrochlorothiazide. In addition, patients responding to acebutolol HCl administered twice
daily had a similar response whether the dosage regimen was changed to once daily administration or continued on a bid regimen.
Most patients responded to 400- 800 mg/ day in divided doses.
The antiarrhythmic effect of acebutolol HCl was compared with placebo, propranolol, and quinidine. Compared with placebo,
acebutolol HCl significantly reduced mean total ventricular ectopic beats (VEB), paired VEB, multiform VEB, R- on- T beats,
and ventricular tachycardia (VT). Both acebutolol HCl and propranolol significantly reduced mean total and paired VEB and
VT. Acebutolol HCl and quinidine significantly reduced resting total and complex VEB; the antiarrhythmic efficacy of acebutolol
HCl was also observed during exercise.
|
Pharmacokinetics and Metabolism
|
| |
Acebutolol HCl 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 acebutolol HCl and in cats is more cardioselective than acebutolol
HCl; therefore, this first- pass phenomenon does not attenuate the therapeutic effect of acebutolol HCl. Food intake does
not have a significant effect on the area under the plasma concentration- time curve (AUC) of acebutolol HCl although the
rate of absorption and peak concentration decreased slightly.
The plasma elimination half- life of acebutolol HCl is approximately 3- 4 hours, while that of its metabolite, diacetolol,
is 8- 13 hours. The time to reach peak concentration for acebutolol HCl is 2.5 hours and for diacetolol, after oral administration
of acebutolol HCl, 3.5 hours.
Within the single oral dose range of 200- 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- 40% and by nonrenal mechanisms 50- 60%, which includes excretion into the bile and direct passage
through the intestinal wall.
Acebutolol HCl has a low binding affinity for plasma proteins (about 26%). Acebutolol HCl 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 acebutolol HCl administration. The kinetics
of acebutolol HCl 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 acebutolol HCl, but there is decreased
elimination of the metabolite, diacetolol, resulting in a 2- to 3- fold increase in its half- life. For this reason, the drug
should be administered with caution in patients with renal insufficiency (see PRECAUTIONS ). Acebutolol HCl and its major metabolite are dialyzable.
Acebutolol HCl crosses the placental barrier and is secreted in breast milk.
In geriatric patients, the bioavailability of acebutolol HCl and its metabolite is increased, approximately 2- fold, probably
due to decreases in the first- pass metabolism and renal function in the elderly.
|
|
INDICATIONS AND USAGE
|
| |
Hypertension
|
| |
Acebutolol HCl 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
|
| |
Acebutolol HCl 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
|
| |
Acebutolol HCl is Contraindicated in:
- Persistently severe bradycardia.
- Second- and third- degree heart block.
- Overt cardiac failure.
- 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 β- adrenergic receptor blockade may precipitate more severe failure. Although β- blockers should be
avoided in overt cardiac failure, acebutolol HCl can be used with caution in patients with a history of heart failure who
are controlled with digitalis and/ or diuretics. Both digitalis and acebutolol HCl impair AV conduction. If cardiac failure
persists, therapy with acebutolol HCl 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 β- 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, acebutolol HCl therapy should be withdrawn.
|
Exacerbation of Ischemic Heart Disease Following Abrupt Withdrawal
|
| |
Following abrupt cessation of therapy with certain β- 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 acebutolol HCl is planned, the patient should be carefully observed, and should be advised to limit
physical activity to a minimum while acebutolol HCl is gradually withdrawn over a period of about 2 weeks. (If therapy with
an alternative β- blocker is desired, the patient may be transferred directly to comparable doses of another agent without
interruption of β- 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 β- 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 β- blocker. Because of its relative β1 - selectivity, however, low doses of acebutolol HCl may be used with caution in patients with bronchospastic disease who do
not respond to, or who cannot tolerate, alternative treatment. Since β1 - selectivity is not absolute and is dose- dependent, the lowest possible dose of acebutolol HCl should be used initially,
preferably in divided doses to avoid the higher plasma levels associated with the longer dose- interval. A bronchodilator,
such as theophylline or a β2 - stimulant, should be made available in advance with instructions concerning its use.
|
Anesthesia and Major Surgery
|
| |
The necessity, or desirability, of withdrawal of a β- blocking therapy prior to major surgery is controversial. β- adrenergic
receptor blockade impairs the ability of the heart to respond to β- 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 acebutolol HCl. Acebutolol HCl, like other β- blockers,
is a competitive inhibitor of β- receptor agonists, and its effect on the heart can be reversed by cautious administration
of such agents ( e.g., dobutamine or isoproterenol, see OVERDOSAGE ).
Manifestations of excessive vagal tone ( e.g., profound bradycardia, hypotension) may be corrected with atropine 1- 3 mg IV in divided doses.
|
Diabetes and Hypoglycemia
|
| |
β- 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
|
| |
β- adrenergic blockade may mask certain clinical signs (tachycardia) of hyperthyroidism. Abrupt withdrawal of β- blockade
may precipitate a thyroid storm; therefore, patients suspected of developing thyrotoxicosis from whom acebutolol HCl therapy
is to be withdrawn should be monitored closely.
|
|
PRECAUTIONS
|
| |
Impaired Renal or Hepatic Function
|
| |
Studies on the effect of acebutolol in patients with renal insufficiency have not been performed in the US 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 50 ml/ min and by 75% when it is less than 25 ml/ min. Acebutolol HCl should
be used cautiously in patients with impaired hepatic function.
Acebutolol HCl has been used successfully and without problems in elderly patients in the US clinical trials without specific
adjustment of dosage. However, elderly patients may require lower maintenance doses because the bioavailability of both acebutolol
HCl and its metabolite are approximately doubled in this age group.
|
Information for the Patient
|
| |
Patients, especially those with evidence of coronary artery disease, should be warned against interruption or discontinuation
of acebutolol HCl therapy without a physician's supervision. Although cardiac failure rarely occurs in properly selected patients,
those being treated with β- 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 α- adrenergic stimulants,
such as the nasal decongestants commonly used in OTC cold preparations and nasal drops.
|
Clinical Laboratory Findings
|
| |
Acebutolol HCl, like other β- blockers, has been associated with the development of antinuclear antibodies (ANA). In prospective
clinical trials, patients receiving acebutolol HCl 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.
|
Carcinogenesis, Mutagenesis, and 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 acebutolol HCl. Diacetolol,
the major metabolite of acebutolol HCl in man, was without carcinogenic potential in rats when tested at doses as high as
1800 mg/ kg/ day. Acebutolol HCl and diacetolol were also shown to be devoid of mutagenic potential in the Ames Test. Acebutolol
HCl, 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 Category B
|
| |
Teratogenic Effects
|
| |
Reproduction studies have been performed with acebutolol HCl 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 post-
implantation 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, acebutolol HCl 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- 14 hours, while the half- life of diacetolol was 24- 30 hours for the first
24 hours after birth, followed by a half- life of 12- 16 hours. Adequate facilities for monitoring these infants at birth
should be available.
|
|
Labor and Delivery
|
| |
The effect of acebutolol HCl on labor and delivery in pregnant women is unknown. Studies in animals have not shown any effect
of acebutolol HCl 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 children have not been established.
|
|
DRUG INTERACTIONS
|
| |
Catecholamine- depleting drugs, such as reserpine, may have an additive effect when given with β- blocking agents. Patients
treated with acebutolol HCl 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 β- adrenergic antagonists and
α- adrenergic stimulants, including those contained in proprietary cold remedies and vasoconstrictive nasal drops. Patients
receiving β- 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.
|
ADVERSE REACTIONS
|
| |
Acebutolol HCl 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.
TABLE 1 shows the frequency of treatment- related side effects derived from controlled clinical trials in patients with hypertension,
angina pectoris, and arrhythmia. These patients received acebutolol HCl, propranolol, or hydrochlorothiazide as monotherapy,
or placebo.
| TABLE 1
Total Volunteered and Elicited (US Studies)
|
| |
Acebutolol HCl |
Propranolol |
Hydrochlorothiazide |
Placebo |
| Body System/ Adverse Reaction |
(n=1002) |
(n=424) |
(n=178) |
(n=314) |
| 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 acebutolol HCl 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 acebutolol HCl dose is shown in TABLE 2 . (Data from 266 hypertensive patients treated for 3 months on a constant dose.)
| TABLE 2
|
| |
400 mg/ day |
800 mg/ day |
1200 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 β- blocking agents and should also be
considered as potential adverse effects of acebutolol HCl.
- 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 β- blocker practolol has not
been reported with acebutolol HCl during investigational use and extensive foreign clinical experience.
|
|
OVERDOSAGE
|
| |
No specific information on emergency treatment of overdosage is available for acebutolol HCl. However, overdosage with other
β- 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 acebutolol HCl overdose is not available, on the basis of the
pharmacological actions and the observations in treating overdoses with other β- blockers, the following general measures
should be considered:
- 1. Empty stomach by emesis or lavage.
- 2. Bradycardia: IV atropine (1- 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 β2 - 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.
Acebutolol HCl is dialyzable.
|
DOSAGE AND ADMINISTRATION
|
| |
Hypertension
|
| |
The initial dosage of acebutolol HCl 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- 800 mg/ day, although some patients have been maintained on as little
as 200 mg/ day. Patients with more severe hypertension or who have demonstrated inadequate control may respond to a total
of 1200 mg daily (administered bid), or to the addition of a second antihypertensive agent. Beta- 1 selectivity diminishes
as dosage is increased.
|
Ventricular Arrythmia
|
| |
The usual initial dose of acebutolol HCl is 400 mg daily given as 200 mg bid. Dosage should be increased gradually until an
optimal clinical response is obtained, generally at 600- 1200 mg/ day. If treatment is to be discontinued, the dosage should
be reduced gradually over a period of about 2 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.
|
|
HOW SUPPLIED
|
| |
Sectral is available in the following dosage strengths:
- 200 mg: Opaque purple and orange capsule marked "WYETH 4177" and "Sectral 200".
- 400 mg: Opaque brown and orange capsule marked "WYETH 4179" and "Sectral 400".
Storage: Keep tightly closed. Store at room temperature, approx. 25°C (77°F). Dispense in a tight container. Use carton to protect
contents from light.
|
PRODUCT IDENTIFICATION
|
| |
None Available |
PRODUCT LISTING - RATED THERAPEUTICALLY EQUIVALENT
|
| |
| capsule - oral - 200 mg -
|
| 100.0 |
$29.72 |
GENERIC
Par Pharmaceutical Inc
|
49884058701 |
| 100.0 |
$100.73 |
GENERIC
Mylan Pharmaceuticals Inc
|
00378120001 |
| 100.0 |
$113.10 |
GENERIC
Watson Pharmaceuticals
|
00591043701 |
| 100.0 |
$252.38 |
Sectral
ESP Pharma Inc
|
67286417701 |
| 100.0 |
$252.38 |
Sectral
ESP Pharma Inc
|
00008417701 |
| capsule - oral - 400 mg -
|
| 100.0 |
$44.29 |
GENERIC
Par Pharmaceutical Inc
|
49884058801 |
| 100.0 |
$133.97 |
GENERIC
Mylan Pharmaceuticals Inc
|
00378140001 |
| 100.0 |
$150.43 |
GENERIC
Watson Pharmaceuticals
|
00591043801 |
|
PRODUCT LISTING - EQUIVALENTS NOT AVAILABLE
|
| |
| capsule - oral - 400 mg -
|
| 100.0 |
$279.63 |
Sectral
ESP Pharma Inc
|
00008417901 |
| powder - compounding - 100% -
|
| 25.0 gm |
$145.00 |
GENERIC
Medisca Inc
|
38779048925 |
| 25.0 gm |
$177.00 |
GENERIC
Meridian Pharmaceutical Inc
|
62991100101 |
| 100.0 gm |
$462.50 |
GENERIC
Medisca Inc
|
38779048910 |
| 500.0 gm |
$1900.00 |
GENERIC
Medisca Inc
|
38779048950 |
|
|