Atenolol
Tablets USP
Rx only

/Atenolol
Tablets USP
Rx only
Atenolol
Tablets USP
Rx only
2018-09-06T09:12:40+00:00

Prescription Drug Name:

Atenolol
Tablets USP
Rx only

ID:

D18BCF6D-2F2D-4F70-735B-4CAD05CE9AF4

Code:

34391-3

DESCRIPTION


id: 5222D06F-CFAB-F127-6D83-50D41A0DCC23
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Atenolol, a synthetic, beta1-selective (cardioselective) adrenoreceptor blocking agent, may be chemically described as Benzene-acetamide, 4-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]-. The structural formula is represented below:

C14H22N2O3                           M.W. 266.34

It is a relatively polar hydrophilic compound with a water solubility of 26.5 mg/mL at 37°C and a log partition coefficient (octanol/water) of 0.23. It is freely soluble in 1N HCl (300 mg/mL at 25°C) and less soluble in chloroform (3 mg/mL at 25°C).Each tablet, for oral administration, contains 50 mg or 100 mg atenolol. In addition, each tablet contains the following inactive ingredients: magnesium stearate, microcrystalline cellulose, povidone and sodium starch glycolate.

CLINICAL PHARMACOLOGY


id: 61D85DE4-C953-3E30-67B1-D21FB26E1E18
displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1

Atenolol is a beta1-selective (cardioselective) beta-adrenergic receptor blocking agent without membrane stabilizing or intrinsic sympathomimetic (partial agonist) activities. This preferential effect is not absolute, however, and at higher doses, atenolol inhibits beta2-adrenoreceptors, chiefly located in the bronchial and vascular musculature.Pharmacokinetics and MetabolismIn man, absorption of an oral dose is rapid and consistent but incomplete. Approximately 50% of an oral dose is absorbed from the gastrointestinal tract, the remainder being excreted unchanged in the feces. Peak blood levels are reached between two (2) and four (4) hours after ingestion. Unlike propranolol or metoprolol, but like nadolol, atenolol undergoes little or no metabolism by the liver, and the absorbed portion is eliminated primarily by renal excretion. Over 85% of an intravenous dose is excreted in urine within 24 hours compared with approximately 50% for an oral dose. Atenolol also differs from propranolol in that only a small amount (6% to 16%) is bound to proteins in the plasma. This kinetic profile results in relatively consistent plasma drug levels with about a fourfold interpatient variation.The elimination half-life of oral atenolol is approximately 6 to 7 hours, and there is no alteration of the kinetic profile of the drug by chronic administration. Following intravenous administration, peak plasma levels are reached within 5 minutes. Declines from peak levels are rapid (5- to 10-fold) during the first 7 hours; thereafter, plasma levels decay with a half-life similar to that of orally administered drug. Following oral doses of 50 mg or 100 mg, both beta blocking and antihypertensive effects persist for at least 24 hours. When renal function is impaired, elimination of atenolol is closely related to the glomerular filtration rate; significant accumulation occurs when the creatinine clearance falls below 35 mL/min/1.73 m2. (See DOSAGE AND ADMINISTRATION.)PharmacodynamicsIn standard animal or human pharmacological tests, beta-adrenoreceptor blocking activity of atenolol has been demonstrated by: (1) reduction in resting and exercise heart rate and cardiac output, (2) reduction of systolic and diastolic blood pressure at rest and on exercise, (3) inhibition of isoproterenol induced tachycardia, and (4) reduction in reflex orthostatic tachycardia.A significant beta blocking effect of atenolol, as measured by reduction of exercise tachycardia, is apparent within one hour following oral administration of a single dose. This effect is maximal at about 2 to 4 hours, and persists for at least 24 hours. Maximum reduction in exercise tachycardia occurs within 5 minutes of an intravenous dose. For both orally and intravenously administered drug, the duration of action is dose related and also bears a linear relationship to the logarithm of plasma atenolol concentration. The effect on exercise tachycardia of a single 10 mg intravenous dose is largely dissipated by 12 hours, whereas beta blocking activity of single oral doses of 50 mg and 100 mg is still evident beyond 24 hours following administration. However, as has been shown for all beta blocking agents, the antihypertensive effect does not appear to be related to plasma level.In normal subjects, the beta1 selectivity of atenolol has been shown by its reduced ability to reverse the beta2-mediated vasodilating effect of isoproterenol as compared to equivalent beta blocking doses of propranolol. In asthmatic patients, a dose of atenolol producing a greater effect on resting heart rate than propranolol resulted in much less increase in airway resistance. In a placebo controlled comparison of approximately equipotent oral doses of several beta blockers, atenolol produced a significantly smaller decrease of FEV1 than nonselective beta blockers such as propranolol and, unlike those agents, did not inhibit bronchodilation in response to isoproterenol.Consistent with its negative chronotropic effect due to beta blockade of the SA node, atenolol increases sinus cycle length and sinus node recovery time. Conduction in the AV node is also prolonged. Atenolol is devoid of membrane stabilizing activity, and increasing the dose well beyond that producing beta blockade does not further depress myocardial contractility. Several studies have demonstrated a moderate (approximately 10%) increase in stroke volume at rest and during exercise.In controlled clinical trials, atenolol, given as a single daily oral dose, was an effective antihypertensive agent providing 24-hour reduction of blood pressure. Atenolol has been studied in combination with thiazide-type diuretics, and the blood pressure effects of the combination are approximately additive. Atenolol is also compatible with methyldopa, hydralazine, and prazosin, each combination resulting in a larger fall in blood pressure than with the single agents. The dose range of atenolol is narrow and increasing the dose beyond 100 mg once daily is not associated with increased antihypertensive effect. The mechanisms of the antihypertensive effects of beta blocking agents have not been established. Several possible mechanisms have been proposed and include: (1) competitive antagonism of catecholamines at peripheral (especially cardiac) adrenergic neuron sites, leading to decreased cardiac output, (2) a central effect leading to reduced sympathetic outflow to the periphery, and (3) suppression of renin activity. The results from long-term studies have not shown any diminution of the antihypertensive efficacy of atenolol with prolonged use.By blocking the positive chronotropic and inotropic effects of catecholamines and by decreasing blood pressure, atenolol generally reduces the oxygen requirements of the heart at any given level of effort, making it useful for many patients in the long-term management of angina pectoris. On the other hand, atenolol can increase oxygen requirements by increasing left ventricular fiber length and end diastolic pressure, particularly in patients with heart failure.In a multicenter clinical trial (ISIS-1) conducted in 16,027 patients with suspected myocardial infarction, patients presenting within 12 hours (mean = 5 hours) after the onset of pain were randomized to either conventional therapy plus atenolol (n = 8,037) or conventional therapy alone (n = 7,990). Patients with a heart rate of < 50 bpm or systolic blood pressure < 100 mm Hg, or with other contraindications to beta blockade, were excluded. Thirty-eight percent of each group were treated within 4 hours of onset of pain. The mean time from onset of pain to entry was 5 ± 2.7 hours in both groups. Patients in the atenolol group were to receive atenolol injection 5 to 10 mg given over 5 minutes plus atenolol tablets 50 mg every 12 hours orally on the first study day (the first oral dose administered about 15 minutes after the IV dose) followed by either atenolol tablets 100 mg once daily or atenolol tablets 50 mg twice daily on days 2 to 7. The groups were similar in demographic and medical history characteristics and in electrocardiographic evidence of myocardial infarction, bundle branch block, and first degree atrioventricular block at entry.During the treatment period (days 0 to 7), the vascular mortality rates were 3.89% in the atenolol group (313 deaths) and 4.57% in the control group (365 deaths). This absolute difference in rates, 0.68%, is statistically significant at the P < 0.05 level. The absolute difference translates into a proportional reduction of 15% (3.89 to 4.57/4.57 = -0.15). The 95% confidence limits are 1% to 27%. Most of the difference was attributed to mortality in days 0 to 1
(atenolol – 121 deaths; control – 171 deaths).
Despite the large size of the ISIS-1 trial, it is not possible to identify clearly subgroups of patients most likely or least likely to benefit from early treatment with atenolol. Good clinical judgment suggests, however, that patients who are dependent on sympathetic stimulation for maintenance of adequate cardiac output and blood pressure are not good candidates for beta blockade. Indeed, the trial protocol reflected that judgment by excluding patients with blood pressure consistently below 100 mm Hg systolic. The overall results of the study are compatible with the possibility that patients with borderline blood pressure (less than 120 mm Hg systolic), especially if over 60 years of age, are less likely to benefit.The mechanism through which atenolol improves survival in patients with definite or suspected acute myocardial infarction is unknown, as is the case for other beta blockers in the postinfarction setting. Atenolol, in addition to its effects on survival, has shown other clinical benefits including reduced frequency of ventricular premature beats, reduced chest pain, and reduced enzyme elevation.Atenolol Geriatric PharmacologyIn general, elderly patients present higher atenolol plasma levels with total clearance values about 50% lower than younger subjects. The half-life is markedly longer in the elderly compared to younger subjects. The reduction in atenolol clearance follows the general trend that the elimination of renally excreted drugs is decreased with increasing age.

INDICATIONS AND USAGE


id: 90C909BD-E91F-F636-E9D4-04117CBB3719
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9

HypertensionAtenolol tablets are indicated in the management of hypertension. They may be used alone or concomitantly with other antihypertensive agents, particularly with a thiazide-type diuretic.Angina Pectoris Due to Coronary AtherosclerosisAtenolol tablets are indicated for the long-term management of patients with angina pectoris.Acute Myocardial InfarctionAtenolol tablets are indicated in the management of hemodynamically stable patients with definite or suspected acute myocardial infarction to reduce cardiovascular mortality. Treatment can be initiated as soon as the patient’s clinical condition allows. (See DOSAGE AND ADMINISTRATION, CONTRAINDICATIONS, and WARNINGS.) In general, there is no basis for treating patients like those who were excluded from the ISIS-1 trial (blood pressure less than 100 mm Hg systolic, heart rate less than 50 bpm) or have other reasons to avoid beta blockade. As noted above, some subgroups (e.g., elderly patients with systolic blood pressure below 120 mm Hg) seemed less likely to benefit.

CONTRAINDICATIONS


id: E4EA168D-907C-6B29-C9E7-9695FDAD497B
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3

Atenolol tablets are contraindicated in sinus bradycardia, heart block greater than first degree, cardiogenic shock, and overt cardiac failure. (See WARNINGS.)Atenolol tablets are contraindicated in those patients with a history of hypersensitivity to the atenolol or any of the drug product’s components.

ADVERSE REACTIONS


id: 5C583739-3240-D2D6-A278-D017F607E831
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4

Most adverse effects have been mild and transient.The frequency estimates in the following table were derived from controlled studies in hypertensive patients in which adverse reactions were either volunteered by the patient (US studies) or elicited, e.g., by checklist (foreign studies). The reported frequency of elicited adverse effects was higher for both atenolol and placebo-treated patients than when these reactions were volunteered. Where frequency of adverse effects of atenolol and placebo is similar, causal relationship to atenolol is uncertain.

Total-Volunteered
Volunteered (US Studies) and Elicited
(Foreign + US Studies)
Atenolol Placebo Atenolol Placebo
(n = 164) (n = 206) (n = 399) (n = 407)
% % % %
CARDIOVASCULAR
Bradycardia 3 0 3 0
Cold Extremities 0 0.5 12 5
Postural Hypotension 2 1 4 5
Leg Pain 0 0.5 3 1
CENTRAL NERVOUS
SYSTEM/NEUROMUSCULAR
Dizziness 4 1 13 6
Vertigo 2 0.5 2 0.2
Light-headedness 1 0 3 0.7
Tiredness 0.6 0.5 26 13
Fatigue 3 1 6 5
Lethargy 1 0 3 0.7
Drowsiness 0.6 0 2 0.5
Depression 0.6 0.5 12 9
Dreaming 0 0 3 1
GASTROINTESTINAL
Diarrhea 2 0 3 2
Nausea 4 1 3 1
RESPIRATORY
(see WARNINGS)
Wheeziness 0 0 3 3
Dyspnea 0.6 1 6 4

POTENTIAL ADVERSE EFFECTS


id: 7C647CF3-D334-8098-290B-7462EB048095
displayName: SPL UNCLASSIFIED SECTION
FDA Article Code: 42229-5

In addition, a variety of adverse effects have been reported with other beta-adrenergic blocking agents, and may be considered potential adverse effects of atenolol.

OVERDOSAGE


id: 22B3E29D-9C40-B4B0-3C13-30DB7E29B0E8
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5

Overdosage with atenolol has been reported with patients surviving acute doses as high as 5 g. One death was reported in a man who may have taken as much as 10 g acutely.The predominant symptoms reported following atenolol overdose are lethargy, disorder of respiratory drive, wheezing, sinus pause and bradycardia. Additionally, common effects associated with overdosage of any beta-adrenergic blocking agent and which might also be expected in atenolol overdose are congestive heart failure, hypotension, bronchospasm and/or hypoglycemia.Treatment of overdose should be directed to the removal of any unabsorbed drug by induced emesis, gastric lavage, or administration of activated charcoal. Atenolol can be removed from the general circulation by hemodialysis. Other treatment modalities should be employed at the physician’s discretion and may include:

HOW SUPPLIED


id: 908B72CD-E7A2-DA6C-7E24-5895F382A538
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Atenolol Tablets USP, 50 mg are 9/32”, scored, round, white tablets imprinted DAN 50 and 5777 supplied in bottles of 100 and 1000.Atenolol Tablets USP, 100 mg are 11/32”, unscored, round, white tablets imprinted 5778 and DAN 100 supplied in bottles of 100.Dispense in a well-closed, light-resistant container with child-resistant closure.Store at 20°-25°C (68°-77°F). [See USP controlled room temperature.]Watson Laboratories, Inc.
Corona, CA 92880 USA