Acebutolol hydrochloride

372.89

372.181580

251-980-3

757412

DTXSID5045461

White or slightly off-white, crystalline powder|Crystals from anhydrous methanol-anhydrous diethyl ether

2924296000

87.7

3.63140

solid

141-143 °C

564.1ºC at 760 mmHg

>55.9 [ug/mL]

2-8°C

Oral-rat LD50:6620mg/kg;Oral-Mouse LD50: 4050 mg/kg

Flammable; decomposes by heating to release toxic nitrogen oxides and hydrogen chloride fumes

188.3 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

Acebutolol is related structurally to atenolol and metoprolol in that the drugs contain substituents in the para position of the benzene ring; however acebutlol differs from these drugs in that it also contains an acetyl group at position 3 in benzene ring. /Acebutolol/

NONH for all modes of transport

3

20/21/22

36

ES5235000

Xn

Warehouse ventilated, low temperature and dry

P261-P280

H312 + H332

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl acebutolol hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.|Acebutolol used as a beta adrenergic blocking agent was approved by FDA for marketing in the United States 12/84.|Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

|Warning|H312 (47.62%): Harmful in contact with skin [Warning Acute toxicity, dermal]|P201, P260, P261, P263, P264, P270, P271, P272, P280, P302+P352, P304+P312, P304+P340, P305+P351+P338, P308+P313, P312, P321, P322, P333+P313, P337+P313, P363, and P501|Aggregated GHS information provided by 85 companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

moderately toxic

When acebutolol and a catecholamine-depleting drug (eg, reserpine) are administered concomitantly, the effects of the drugs may be additive.|When acebutolol is administered with diuretics or other hypotensive agents, the hypotensive effect may be increased. This effect usually is used to therapeutic advantage, but careful adjustment of dosage is necessary when these drugs are used concomitantly. No substantial pharmacokinetic interactions between acebutolol and hydrochlorothiazide or hydralazine have been observed.|Acebutolol has decreased the hypoglycemic action of glyburide in type II diabetic patients, presumably by decreasing insulin secretion. Nonsteroidal anti-inflammatory agents have blunted the hypotensive effects of beta-adrenergic blocking agents.|A delay in the onset of isoniazid induced convulsions was found in rats pretreated with the beta 2-adrenoceptor blocker, butoxamine, and the nonspecific beta-blocker, propranolol. In these animals the convulsive responses were inhibited in a dose dependent manner. These compounds were found to be effective even after the induction of convulsions. The beta-1-blocker, acebutolol was able to protect rats only when injected prior to the challenge. The anticonvulsant effect of acebutolol and propranolol but not that of butoxamine was found to be enhanced in animals pretreated with a gamma-aminobutyric acid elevating agent, aminooxyacetic acid. The findings indicate that the gamma-aminobutyric acid mediated anticonvulsant action of aminooxyacetic acid seems to be additive with that resulting from beta-1 but not beta-2-blockade.|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 /acebutolol hydrochloride/ administration. The kinetics of sectral were not significantly altered by concomitant administration of hydrochlorothiazide, hydralazine, sulfinpyrazone, or oral contraceptives.

LD50 Rat (male) oral 3.2 g/kg|LD50 Rat (female) oral 5.2 g/kg|LD50 Rat (male) iv 115 mg/kg|LD50 Rat (female) iv 120 mg/kg)

Acebutolol and diacetolol are distributed into milk; the mean acebutolol and diacetolol milk-to-plasma ratios are approximately 7.1 and 12.2, respectively.

Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Antihypertensive Agents; Sympatholytics|Acebutolol ... /is/ indicated in the treatment of classic angina pectoris, also referred to as "effort-associated angina". /NOT included in US product labeling/|Acebutolol /is/ used in the treatment of mitral value prolapse syndrome. /NOT included in US product labeling/|Acebutolol ... /is/ used for thyrotoxicosis. /NOT included in US product labeling/|For more Therapeutic Uses (Complete) data for ACEBUTOLOL HYDROCHLORIDE (10 total), please visit the HSDB record page.

Abrupt withdrawal of acebutolol may exacerbate angina symptoms or precipitate myocardial infarction in patients with corornary artery disease. Therefore, patients receiving acebutolol (especially those with ischemic heart disease) should be warned not to interrupt or discontinue therapy without consulting their physician. When acebutolol therapy is discontinued, patients should be monitored carefully and advised to temporarily limit their physical activity. If exacerbation of angina occurs after acebutolol therapy is interrupted, antianginal therapy should be reinstituted promptly, and appropriate measures for the management of unstable angina pectoris should be initiated. Because coronary artery disease is common and may be unrecognized, it may be prudent not to discontinue acebutolol therapy abruptly, even in patients receiving the drug for conditions other than angina.|Since beta-adrenergic blocking agents may reduce cardiac output and precipitate or aggravate the symptoms of arterial insufficiency in patients with peripheral or mesenteric vascular disease, acebutolol should be used with caution in these patients, and the patients should be observed for evidence of progression of arterial insufficiency.|... It is recommended that acebutolol be used with caution in patients with diabetes mellitus (especially those with labile diabetes) since the drug also may mask signs and symptoms of hypoglycemia (e.g., tachycardia, palpitation, blood pressure changes, tremor, feelings of anxiety, but not sweating) and may potentiate insulin-induced hypoglycemia.|Since beta-adrenergic blocking agents may inhibit bronchodilation produced by endogenous catecholamines, the drugs generally should not be used in patients with bronchospastic disease; however, because of its relative beta 1-selective adrenergic blocking activity, acebutolol may be used with caution in patients with bronchospastic disease who do not respond to or cannot tolerate other hypotensive agents.|For more Drug Warnings (Complete) data for ACEBUTOLOL HYDROCHLORIDE (22 total), please visit the HSDB record page.

Death occurred after an 8.8 g overdose, whereas survival occurred with 7.6 and 9.6 g overdoses.

Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade. (See all compounds classified as Anti-Arrhythmia Agents.)|Drugs that mimic the effects of stimulating postganglionic adrenergic sympathetic nerves. Included here are drugs that directly stimulate adrenergic receptors and drugs that act indirectly by provoking the release of adrenergic transmitters. (See all compounds classified as Sympathomimetics.)|Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS. (See all compounds classified as Antihypertensive Agents.)|Drugs that bind to and block the activation of ADRENERGIC BETA-1 RECEPTORS. (See all compounds classified as Adrenergic beta-1 Receptor Antagonists.)

Distribution of acebutolol hydrochloride into body tissue and fluids has not been fully characterized. Following IV administration in rats, acebutolol is distributed extensively into many tissues, including heart, liver, kidneys, lungs, intestines, stomach, and salivary glands, but only minimally into CSF or testes. Following oral administration of acebutolol hydrochloride in healthy individuals, acebutolol and, to a lesser extent, diacetolol, are distributed into saliva and minimally into CSF. Following oral administration of a single 300-mg dose of acebutolol hydrochloride, about 3-9% of the dose is distributed into bile within 24 hours, in approximately equivalent amounts as acebutolol and diacetolol. Peak biliary concentrations of acebutolol are approximately 60-100 times greater than peak plasma concentrations.|Acebutolol and diacetolol readily cross the placenta and can accumulate in the fetus. In pregnant women receiving acebutolol, the mean acebutolol and diacetolol ratios of umbilical venous to maternal venous plasma concentrations were 0.8 (range: 0.5-1) and 0.6 (range: 0.3-0.8), respectively.|Following IV administration, acebutolol is rapidly and widely distributed into the extravascular space and the apparent volume of distribution of the drug in healthy adults is approximately 1.6-3 l/kg (range: 1-3.8 l/kg). In healthy individuals, the volume of distribution in the central compartment and at steady state averages 0.16-0.22 and approximately 1.2 l/kg, respectively, following IV administration. The apparent volume distribution may be decreased in geriatric patients.|In vitro, acebutolol and diacetolol are approximately 11-35 and 6-9% bound, respectively, to plasma proteins at plasma acebutolol concentrations of 20-9,000 ng/ml. Acebutolol is approximately 50% bound to erythrocytes.|For more Absorption, Distribution and Excretion (Complete) data for ACEBUTOLOL HYDROCHLORIDE (16 total), please visit the HSDB record page.

Acebutolol is rapidly and extensively metabolized in the liver. Acebutolol undergoes extensive hydrolysis of the butyramide group to form the desbutyl primary amine, acetolol, which is almost completely converted via N-acetylation to diacetolol. The extent of metabolism of acebutolol to diacetolol appears to be independent of the genetic acetylator phenotype of the patient. Diacetolol is equipotent to acebutolol and has a similar pharmacologic profile.

Following single or mutiple oral doses of acebutolol hydrochloride, the elimination half-life of diacetolol reportedly averages 21.5 hours (range: 11-49 hours) or 32 hours (range: 17-54 hours) in patients with creatinine clearances of 6-56 or less than 5 ml/minute, respectively.|Following a single oral dose in healthy adults, the half-life of acebutolol in the initial distrubution phase (t1/2 alpha) is about 3 hours and the half-life in the terminal phase (t1/2 beta) has been reported to average 11 hours (range: 6-12 hours). The half-lives of the two identified metabolites, diacetolol and acetolol, average 7.5 (range: 7-11 hours) and 3 hours, respectively, following a single oral dose of the drug. The half-life of acebutolol tends to be slightly prolonged following multiple rather than single doses. Following multiple-dose oral administration of acebutolol hyrochloride in healthy individuals (400 mg twice daily for 56 days), the elimination half-life of acebutolol average 13 hours (range: 9-20 hours). The elimination half-lives of acebutolol and diacetolol may be slightly iincreased in geriatric patients.|The plasma elimination half-lives of acebutolol and diacetolol in neonates born to women receiving the drug during pregnancy ranged from 6-14 and from 24-30 hours, respectively, in the first 24 hours after birth; the half-life of diacetolol decreased to 12-16 hours during the second day. Neonatal urinary excretion of the drug and diacetolol was maximal during the first 24 hours after birth.

Acebutolol is a beta-selective adrenergic blocking agent and has pharmacologic actions similar to those of other beta-adrenergic blocking agents. At low dosages, acebutolol selectively inhibits response to adrenergic stimuli by competively blocking cardiac beta1-adrenergic receptors, while having little effect on the beta2-adrenergic receptors of bronchial and vascular smooth muscle. At high dosages (eg, greater than 80 mg daily), the selectively of acebutolol for beta-1-adrenergic receptors usually diminishes, and the drug will competively inhibit beta-1- and beta-2-adrenergic receptors. The beta1-selective blocking activity of acebutolol appears to be more pronounced in animals than in humans. In vivo studies in animals and humans indicate that the relative beta-1-adrenergic blocking activity of acebutolol, on a weight basis, is approximately 10-30% that of propranolol, as determined by inhibition of reflex tachycardia in animals or inhibition of exercise or tilt-induced or reflex tachycardia in healthy individuals.|In addition to inhibiting access of physiologic or synthetic catecholamines to beta-adrenergic receptors, acebutolol exhibits mild intrinsic sympathomimetic activity (partial beta-agonist activity). Acebutolol also has a membrane-stabilizing effect on the heart, which is similar to that of quinidine but occurs only at high plasma concentrations and usually is not apparent at dosages used clinically.|The pharmacologic effects of acebutolol results from both the unchanged drug and its major metabolite, diacetolol. Diacetolol is equipotent to acebutolol and, in animals, has greater beta-selective adrenergic blocking activity than the parent drug. Diacetolol also has weak intrinsic sympathomimetic activity but does not have substantial membrane-stabilizing activity. Diacetolol may contribute substantially to the observed effects of acebutolol, since plasma concentrations of the metabolite are consistently higher than those of the parent during acebutolol therapy.

Emergency and supportive measures. 1. Maintain an open airway and assist ventilation if necessary. 2. Treat coma, seizures, hypotension, hyperkalemia, and hypoglycemia if they occur. 3. Treat bradycardia with atropine, ... ; isoproterenol ... ; or cardiac pacing. 4. Treat bronchospasm with nebulized bronchodilators. 5. Continuously monitor the vital signs and ECG for at least 6 hours after ingestion. /Acebutolol, Beta-adrenergic blockers/|Specific drugs and antidotes. 1. Bradycardia and hypotension resistant to ... /normal/ measures should be treated with glucagon, ... IV bolus, repeated as needed and followed by an infusion of 1-5 mg/hr. Epinephrine (intravenous) infusion ... and titrating to effect. 2. Wide complex conduction defects caused by membrane-depressant poisoning may respond to sodium bicarbonate, ... , as given for tricyclic antidepressant overdose. 3. Torsades de pointes polymorphous ventricular tachycardia associated with QT prolongation resulting from sotalol poisoning can be treated with isoproterenol infusion, magnesium, or overdrive pacing. Correction of hypokalemia may also be useful. /Acebutolol, Beta-adrenergic blockers/|Decontamination. 1. Prehospital. Administer activated charcoal if available. 2. Hospital. Administer activated charcoal. Consider gastric lavage for large ingestions, especially involving propranolol. Gastric emptying is not necessary for small ingestions if activated charcoal can be given promptly. /Acebutolol, Beta-adrenergic blockers/|Enhanced elimination. Most beta blockers, especially the more toxic drugs such as propranolol, are highly lipophillic and have a large volume of distribution (Vd). For those with a relatively small volume of distribution coupled with a long half-life or low intrinsic clearance (eg, acebutolol, atenolol, nadolol, or sotalol), hemoperfusion, hemodialysis, or repeat-dose charcoal may be effective. /Acebutolol, Beta-adrenergic blockers/|For more Antidote and Emergency Treatment (Complete) data for ACEBUTOLOL HYDROCHLORIDE (6 total), please visit the HSDB record page.

Acebutolol

Oral capsules 200 mg, 400 mg, Sectral (with povidone)|Formulation Names: Acecor; Acetanol; Neptal; Prent

Analyte: acebutolol hydrochloride; matrix: chemical purity; procedure: liquid chromatography with detection at 254 nm and comparison to standards|Analyte: acebutolol hydrochloride; matrix: chemical identification; procedure: thin-layer chromatography with comparison to standards|Analyte: acebutolol hydrochloride; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards|Analyte: acebutolol hydrochloride; matrix: pharmaceutical preparation (capsules); procedure: retention time of liquid chromatogram with comparison to standards (chemical identification)|Analyte: acebutolol hydrochloride; matrix: pharmaceutical preparation (capsules); procedure: liquid chromatography with detection at 275 nm and comparison to standards (assay purity)

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