Sectral

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.

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, 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 If cardiac failure persists, therapy with Sectral should be withdrawn.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 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 If cardiac failure continues despite adequate digitalization and/or diuretic, Sectral therapy should be withdrawn.

Exacerbation Of Is Chemic 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 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should be carefully observed, and should be advised to limit physical activity to a minimum while Sectral is gradually withdrawn over a period of about two weeks.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 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 Disease

PATIENTS WITH BRONCHOSPASTIC DISEASE SHOULD, IN GENERAL, NOT RECEIVE A β-BLOCKER. Because of its relative β1 -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 β1-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 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 - blocking therapy prior to major surgery is controversial. -adrenergic receptor blockade impairs the ability of the heart to respond to - 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 -blockers, is a competitive inhibitor of -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

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 Sectral therapy is to be withdrawn should be monitored closely.

Do not stop taking acebutolol without first talking to your doctor. Stopping suddenly may make your condition worse.

If you need to have any type of surgery, you may need to temporarily stop using acebutolol. Be sure the surgeon knows ahead of time that you are using acebutolol.

Acebutolol can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.

Avoid drinking alcohol, which could increase drowsiness and dizziness while you are taking acebutolol.

Acebutolol is only part of a complete program of treatment for hypertension that may also include diet, exercise, and weight control. Follow your diet, medication, and exercise routines very closely if you are being treated for hypertension.

Keep using this medicine as directed, even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

Sectral is a prescription medication used to treat high blood pressure and irregular heartbeat (known medically as ventricular arrhythmia). 

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

• Promius Pharma, LLC

Before taking Sectral, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to any ingredient in Sectral 
• have persistently severe bradycardia
• have second- and third-degree heart block
• have diabetes
• are pregnant or breastfeeding
• have asthma or other lung disease

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Contraindications

• Patients with heart block greater than first degree, severe bradycardia, cardiogenic shock, or overt cardiac failure.1

Warnings/Precautions

Warnings

Possible precipitation of heart failure.1

Avoid use in patients with decompensated heart failure; use cautiously in patients with inadequate myocardial function and, if necessary, in patients with well-compensated heart failure (e.g., those controlled with cardiac glycosides and/or diuretics).1

Adequate treatment (e.g., with a cardiac glycoside and/or diuretic) and close observation recommended if signs or symptoms of impending cardiac failure occur; if cardiac failure continues, discontinue therapy, gradually if possible.1

Possible exacerbated angina symptoms or precipitation of MI in patients with CAD.1 Abrupt discontinuance of therapy is not recommended.1 276 Gradually decrease dosage over a period of about 2 weeks; monitor patients carefully and advise to temporarily limit their physical activity.1 276 If exacerbation of angina occurs, reinstitute therapy promptly and initiate appropriate measures for the management of unstable angina pectoris.1

Possible reduction in cardiac output and precipitation or aggravation of symptoms of arterial insufficiency.1 Use with caution; observe for evidence of disease progression.1

Possible bronchoconstriction.1

Use with caution in patients with bronchospastic disease; administer the lowest effective dosage (initially in divided doses). A bronchodilator (e.g., a β2-adrenergic agonist, theophylline) should be available for immediate use, if necessary.1

Possible risks associated with general anesthesia (e.g., severe hypotension, maintenance of heart beat) due to decreased ability of the heart to respond to reflex β-adrenergic stimuli.1 Use with caution in patients undergoing major surgery involving general anesthesia; anesthetics used should not cause myocardial depression.1

Possible decreased signs and symptoms of hypoglycemia (e.g., tachycardia, palpitation, BP changes, tremor, feelings of anxiety, but not sweating or dizziness) and increased insulin-induced hypoglycemia.1

Use with caution in patients with diabetes mellitus.1

Signs of hyperthyroidism (e.g., tachycardia) may be masked.1 Possible thyroid storm if therapy is abruptly withdrawn; carefully monitor patients having or suspected of developing thyrotoxicosis.1

Sensitivity Reactions

Patients with a history of anaphylactic reactions to a variety of allergens may be more reactive to repeated accidental, diagnostic, or therapeutic challenges with such allergens while taking β-blocking agents.1 Such patients may be unresponsive to usual doses of epinephrine.1

Specific Populations

Category B.1

Distributed into milk in higher concentrations than in maternal plasma.1 2 105 Use not recommended by manufacturer.1

Safety and efficacy not established in children <12 years of age.1 268

Insufficient experience in patients >65 years of age to determine whether geriatric patients respond differently than younger adults.1 However, reduction of maintenance dosage may be necessary,1 2 since bioavailability of acebutolol and diacetolol (active metabolite) may be increased compared with that in younger adults.1 2 122 (See Geriatric Patients under Dosage and Administration.)

Use with caution.1 2 Cirrhosis does not appear to substantially affect the pharmacokinetics of acebutolol or diacetolol; however, the effects of hepatic impairment on elimination of the drug have not been fully evaluated.128

Use with caution; dosage should be reduced based on the degree of renal impairment.1 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Fatigue, dizziness, headache, dyspnea, constipation, diarrhea, dyspepsia, nausea, flatulence, insomnia, increased micturition, chest pain, edema, depression, abnormal dreams, rash, arthralgia, myalgia, cough, rhinitis, abnormal vision.1

Absorption

Bioavailability

Well absorbed from the GI tract following oral administration;1 2 4 11 91 109 undergoes extensive first-pass metabolism in the liver.1 2 97 99 109 122 124

Peak plasma acebutolol and diacetolol concentrations occur within 2–2.5 hours (range: 1–4 hours) and 4 hours (range: 2.4–5 hours), respectively, in healthy individuals1 2 94 95 97 98 99 126 135 or patients with hypertension91 or arrhythmias.2 90 137

Absolute bioavailability is approximately 35–50%.1 4 94 97 102

Food

Food may slightly decrease the rate of absorption and peak plasma concentrations of acebutolol and its major metabolite (diacetolol), but the extent of absorption is not substantially affected.1 2 101

Onset

Effect on resting, reflex, or exercise-induced heart rate and systolic BP begins within 1–1.5 hours,1 3 21 91 100 in healthy1 21 98 100 or hypertensive91 individuals.

Duration

Effect may persist for up to 24 hours or longer.1 3 91 98 100

Special Populations

In geriatric patients, peak plasma concentrations and AUCs of acebutolol and diacetolol are increased twofold compared with those observed in younger patients.1 2 122

Distribution

Extent

Acebutolol and diacetolol readily cross the placenta1 2 105 106 107 and can accumulate in the fetus.105 106 107

Acebutolol and diacetolol are distributed into milk at concentrations higher than those in maternal plasma. (See Lactation under Cautions.)1 2 105 106

Plasma Protein Binding

Approximately 11–25% (acebutolol) and 6–9% (diacetolol).2 93 103 Approximately 50% bound to erythrocytes.4 125

Elimination

Metabolism

Rapidly and extensively metabolized in the liver2 110 113 to metabolites (acetolol and diacetolol).2 4 6 99 108 109 110 113

Elimination Route

Acebutolol and its metabolites are excreted in feces and urine.1 87 92 109 111 123

Half-life

About 3 hours in the initial distribution phase (t½α) 95 and about 11 hours (range: 6–12 hours) in the terminal phase (t½β).95 125 About 7.5 (range: 7–11 hours) and 3 hours, respectively, for diacetolol and acetolol following a single oral dose.101 108 125

Special Populations

Renal impairment may reduce clearances of acebutolol and diacetolol.125 Acebutolol and diacetolol are removed by hemodialysis.1 125 127

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• Very bad dizziness or passing out.
• Shortness of breath, a big weight gain, or swelling in the arms or legs.
• Slow heartbeat.
• A heartbeat that does not feel normal.

Catecholamine-depleting drugs, such as reserpine, may have an additive effect when given with β-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 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.

Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.

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.

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.

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.

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.