Atenolol tablets

/Atenolol tablets
Atenolol tablets2018-09-06T09:12:40+00:00

Prescription Drug Name:

Atenolol tablets

ID:

f78df56b-0a2e-402a-be14-15350eaf5318

Code:

34391-3

DESCRIPTION


id: 0eb5d354-303b-4921-8731-36a172875158
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Atenolol, a synthetic, beta1-selective (cardioselective)
adrenoreceptor blocking agent, may be chemically described as benzeneacetamide,
4 -[2’-hydroxy-3’-[(1- methylethyl) amino] propoxy]-. The molecular formula is
C14H22N2O3 and its structural formula is: Atenolol (free base) has a molecular weight of 266. 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).
Atenolol tablets, USP are available as 25, 50 and 100 mg tablets for oral
administration.
Inactive Ingredients: colloidal silicon dioxide, corn starch, magnesium
carbonate, magnesium stearate, sodium lauryl sulfate, sodium starch glycolate.

CLINICAL PHARMACOLOGY


id: 3e2621b6-f4d4-4a37-a732-557c348cc9b6
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 Metabolism In 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.)
Pharmacodynamics In 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 less than 50 bpm or systolic blood pressure less than 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 I.V. 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 less than 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 Pharmacology: In 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: e65f73ba-d89c-4222-8aec-05ff29b08917
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9

Hypertension Atenolol is indicated in the management of hypertension. It
may be used alone or concomitantly with other antihypertensive agents,
particularly with a thiazide-type diuretic.
Angina Pectoris Due to Coronary Atherosclerosis Atenolol is indicated for the long-term management of
patients with angina pectoris.
Acute Myocardial Infarction Atenolol is 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: eb3d4b0f-519e-4ca5-84be-c4603fc4f24c
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3

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

WARNINGS


id: d495a0d5-4de8-41b8-a5ee-b059452bec29
displayName: WARNINGS SECTION
FDA Article Code: 34071-1

Cardiac Failure Sympathetic stimulation is necessary in supporting
circulatory function in congestive heart failure, and beta-blockade carries the
potential hazard of further depressing myocardial contractility and
precipitating more severe failure.
In patients with acute myocardial infarction, cardiac failure which is not
promptly and effectively controlled by 80 mg of intravenous furosemide or
equivalent therapy is a contraindication to beta-blocker treatment.
In Patients Without a History of Cardiac Failure Continued depression of the myocardium with beta-blocking
agents over a period of time can, in some cases, lead to cardiac failure. At the
first sign or symptom of impending cardiac failure, patients should be treated
appropriately according to currently recommended guidelines, and the response
observed closely. If cardiac failure continues despite adequate treatment,
atenolol should be withdrawn (see DOSAGE AND
ADMNISTRATION
).

PRECAUTIONS


id: 4e5ab65a-df8c-485b-9f47-d91c17f2d975
displayName: PRECAUTIONS SECTION
FDA Article Code: 42232-9

General Patients already on a beta-blocker must be evaluated
carefully before atenolol is administered. Initial and subsequent atenolol
dosages can be adjusted downward depending on clinical observations including
pulse and blood pressure. Atenolol may aggravate peripheral arterial circulatory
disorders.
Impaired Renal Function The drug should be used with caution in patients with
impaired renal function (see DOSAGE AND
ADMINISTRATION
).

Drug Interactions


id: 9759788f-b721-4f08-be7b-fbbf5fa9d09a
displayName: DRUG INTERACTIONS SECTION
FDA Article Code: 34073-7

Catecholamine-depleting drugs (e.g., reserpine) may have an
additive effect when given with beta-blocking agents. Patients treated with
atenolol plus a catecholamine depletor should therefore be closely observed for
evidence of hypotension and/or marked bradycardia which may produce vertigo,
syncope, or postural hypotension.
Calcium channel blockers may also have an additive effect when given with
atenolol (see WARNINGS).
Disopyramide is a Type I antiarrhythmic drug with potent negative inotropic
and chronotropic effects. Disopyramide has been associated with severe
bradycardia, asystole and heart failure when administered with
beta-blockers.
Amiodarone is an antiarrhythmic agent with negative chronotropic properties
that may be additive to those seen with beta-blockers.
Beta-blockers may exacerbate the rebound hypertension which can follow the
withdrawal of clonidine. If the two drugs are coadministered, the beta-blocker
should be withdrawn several days before the gradual withdrawal of clonidine. If
replacing clonidine by beta-blocker therapy, the introduction of beta-blockers
should be delayed for several days after clonidine administration has
stopped.
Concomitant use of prostaglandin synthase inhibiting drugs, e.g.,
indomethacin, may decrease the hypotensive effects of beta-blockers.
Information on concurrent usage of atenolol and aspirin is limited. Data from
several studies, i.e., TIMI-II, ISIS-2, currently do not suggest any clinical
interaction between aspirin and beta-blockers in the acute myocardial infarction
setting.
While taking beta-blockers, patients with a history of anaphylactic reaction
to a variety of allergens may have a more severe reaction on repeated challenge,
either accidental, diagnostic or therapeutic. Such patients may be unresponsive
to the usual doses of epinephrine used to treat the allergic reaction.
Both digitalis glycosides and beta-blockers slow atrioventricular conduction
and decrease heart rate. Concomitant use can increase the risk of
bradycardia.

Carcinogenesis, Mutagenesis, Impairment of Fertility


id: ede1c587-88db-4e81-8765-e086a388678d
displayName: CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION
FDA Article Code: 34083-6

Two long-term (maximum dosing duration of 18 or 24 months)
rat studies and one long-term (maximum dosing duration of 18 months) mouse
study, each employing dose levels as high as 300 mg/kg/day or 150 times the
maximum recommended human antihypertensive dose1, did not
indicate a carcinogenic potential of atenolol. A third (24 month) rat study,
employing doses of 500 and 1,500 mg/kg/day (250 and 750 times the maximum
recommended human antihypertensive dose1) resulted in
increased incidences of benign adrenal medullary tumors in males and females,
mammary fibroadenomas in females, and anterior pituitary adenomas and thyroid
parafollicular cell carcinomas in males. No evidence of a mutagenic potential of
atenolol was uncovered in the dominant lethal test (mouse), in vivo cytogenetics test (Chinese hamster) or Ames test
(S typhimurium).
Fertility of male or female rats (evaluated at dose levels as high as 200
mg/kg/day or 100 times the maximum recommended human dose1) was unaffected by atenolol administration.

Animal Toxicology


id: facf18d8-58a0-4d50-a10f-13546b8529f4
displayName: ANIMAL PHARMACOLOGY & OR TOXICOLOGY SECTION
FDA Article Code: 34091-9

Chronic studies employing oral atenolol performed in animals have revealed the
occurrence of vacuolation of epithelial cells of Brunner’s glands in the
duodenum of both male and female dogs at all tested dose levels of atenolol
(starting at 15 mg/kg/day or 7.5 times the maximum recommended human
antihypertensive dose1) and increased incidence of atrial
degeneration of hearts of male rats at 300 but not 150 mg atenolol/kg/day (150
and 75 times the maximum recommended human antihypertensive dose1, respectively

Usage in Pregnancy


id: 916d2588-d3de-4f21-bd1a-96ca588b952d
displayName: PREGNANCY SECTION
FDA Article Code: 42228-7

Pregnancy Category D See WARNINGS – Pregnancy and Fetal
Injury
.

Nursing Mothers


id: 7596edef-28c0-46da-905a-3923794a6627
displayName: NURSING MOTHERS SECTION
FDA Article Code: 34080-2

Atenolol is excreted in human breast milk at a ratio of 1.5
to 6.8 when compared to the concentration in plasma. Caution should be exercised
when atenolol is administered to a nursing woman. Clinically significant
bradycardia has been reported in breastfed infants. Premature infants, or
infants with impaired renal function, may be more likely to develop adverse
effects.
Neonates born to mothers who are receiving atenolol at parturition or
breastfeeding may be at risk for hypoglycemia and bradycardia. Caution should be
exercised when atenolol is administered during pregnancy or to a woman who is
breastfeeding (see WARNINGS, Pregnancy and
Fetal Injury
).

Pediatric Use


id: e4b0d1ec-226d-4a95-a719-2b43bd00f97b
displayName: PEDIATRIC USE SECTION
FDA Article Code: 34081-0

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use


id: 56eeafa9-5e6d-4156-ac50-6846b48cbe08
displayName: GERIATRIC USE SECTION
FDA Article Code: 34082-8

Hypertension and Angina Pectoris Due to Coronary
Atherosclerosis:
Clinical studies of atenolol did not include sufficient number of patients
aged 65 and over to determine whether they respond differently from younger
subjects. Other reported clinical experience has not identified differences in
responses between the elderly and younger patients. In general, dose selection
for an elderly patient should be cautious, usually starting at the low end of
the dosing range, reflecting the greater frequency of decreased hepatic, renal,
or cardiac function, and of concomitant disease or other drug therapy.
Acute Myocardial Infarction: Of the 8,037 patients with suspected acute myocardial infarction randomized
to atenolol in the ISIS-1 trial (see CLINICAL
PHARMACOLOGY
),
33% (2,644) were 65 years of age and older. It was not
possible to identify significant differences in efficacy and safety between
older and younger patients; however, elderly patients with systolic blood
pressure less than 120 mm Hg seemed less likely to benefit (see INDICATIONS AND USAGE).
In general, dose selection for an elderly patient should be cautious, usually
starting at the low end of the dosing range, reflecting greater frequency of
decreased hepatic, renal, or cardiac function, and of concomitant disease or
other drug therapy. Evaluation of patients with hypertension or myocardial
infarction should always include assessment of renal function.

ADVERSE REACTIONS


id: 3ea560f9-5033-4ede-908c-1fbf88c13956
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 (U.S. 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.

Volunteered
(U.S. Studies)
Total – Volunteered
and Elicited
(Foreign + U.S. Studies)
Atenolol
(n = 164)
%
Placebo
(n = 206)
%
Atenolol
(n = 399)
%
Placebo
(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
Lightheadedness 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
Acute Myocardial Infarction In a series of investigations in the treatment of acute
myocardial infarction, bradycardia and hypotension occurred more commonly, as
expected for any beta-blocker, in atenolol-treated patients than in control
patients. However, these usually responded to atropine and/or to withholding
further dosage of atenolol. The incidence of heart failure was not increased by
atenolol. Inotropic agents were infrequently used. The reported frequency of
these and other events occurring during these investigations is given in the
following table.
In a study of 477 patients, the following adverse events were reported during
either intravenous and/or oral atenolol administration:
Conventional Therapy
Plus Atenolol
(n = 244)
Conventional
Therapy Alone
(n = 233)
Bradycardia 43 (18%) 24 (10%)
Hypotension 60 (25%) 34 (15%)
Bronchospasm 3 (1.2%) 2 (0.9%)
Heart Failure 46 (19%) 56 (24%)
Heart Block 11 (4.5%) 10 (4.3%)
BBB + Major
Axis Deviation
16 (6.6%) 28 (12%)
Supraventricular Tachycardia 28 (11.5%) 45 (19%)
Atrial Fibrillation 12 (5%) 29 (11%)
Atrial Flutter 4 (1.6%) 7 (3%)
Ventricular Tachycardia 39 (16%) 52 (22%)
Cardiac Reinfarction 0 (0%) 6 (2.6%)
Total Cardiac Arrests 4 (1.6%) 16 (6.9%)
Nonfatal Cardiac Arrests 4 (1.6%) 12 (5.1%)
Deaths 7 (2.9%) 16 (6.9%)
Cardiogenic Shock 1 (0.4%) 4 (1.7%)
Development of Ventricular
Septal Defect
0 (0%) 2 (0.9%)
Development of Mitral
Regurgitation
0 (0%) 2 (0.9%)
Renal Failure 1 (0.4%) 0 (0%)
Pulmonary Emboli 3 (1.2%) 0 (0%)
In the subsequent International Study of Infarct Survival
(ISIS-1) including over 16,000 patients of whom 8,037 were randomized to receive
atenolol treatment, the dosage of intravenous and subsequent oral atenolol was
either discontinued or reduced for the following reasons:
Reasons 
for 
Reduced 
Dosage

            IV Atenolol
           Reduced Dose
            (less than 5 mg)*
               Oral Partial
                   Dose
Hypotension/Bradycardia      105 (1.3%)            1168 (14.5%)
Cardiogenic Shock          4 (0.04%)               35 (0.44%)
Reinfarction          0 (0%)                5 (0.06%)
Cardiac Arrest          5 (0.06%)              28 (0.34%)
Heart Block (> first degree)          5 (0.06%)            143 (1.7%)
Cardiac Failure          1 (0.01%)            233 (2.9%)
Arrhythmias          3 (0.04%)              22 (0.27%)
Bronchospasm          1 (0.01%)              50 (0.62%)
*Full dosage was 10 mg and some patients received less than
10 mg but more than 5 mg.
During postmarketing experience with atenolol, the following have been
reported in temporal relationship to the use of the drug: elevated liver enzymes
and/or bilirubin, hallucinations, headache, impotence, Peyronie’s disease,
postural hypotension which may be associated with syncope, psoriasiform rash or
exacerbation of psoriasis, psychoses, purpura, reversible alopecia,
thrombocytopenia, visual disturbance, sick sinus syndrome, and dry mouth.
Atenolol, like other beta-blockers, has been associated with the development of
antinuclear antibodies (ANA), lupus syndrome, and Raynaud’s phenomenon.
POTENTIAL ADVERSE EFFECTS 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.
Hematologic: Agranulocytosis. Allergic: Fever, combined with aching and sore
throat, laryngospasm, and respiratory distress.
Central Nervous System: Reversible mental depression
progressing to catatonia; an acute reversible syndrome characterized by
disorientation of time and place; short-term memory loss; emotional lability
with slightly clouded sensorium; and, decreased performance on
neuropsychometrics.
Gastrointestinal: Mesenteric arterial thrombosis,
ischemic colitis.
Other: Erythematous rash. Miscellaneous: There have been reports of skin rashes
and/or dry eyes associated with the use of beta-adrenergic blocking drugs. The
reported incidence is small, and in most cases, the symptoms have cleared when
treatment was withdrawn. Discontinuance of the drug should be considered if any
such reaction is not otherwise explicable. Patients should be closely monitored
following cessation of therapy (see INDICATIONS
AND USAGE
).
The oculomucocutaneous syndrome associated with the beta-blocker practolol
has not been reported with atenolol. Furthermore, a number of patients who had
previously demonstrated established practolol reactions were transferred to
atenolol therapy with subsequent resolution or quiescence of the reaction.

OVERDOSAGE


id: 9db4e16f-f2f6-4318-87c4-26d16565f6cc
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:
BRADYCARDIA: Atropine intravenously. If there is no response to vagal
blockade, give isoproterenol cautiously. In refractory cases, a transvenous
cardiac pacemaker may be indicated.
HEART BLOCK (SECOND OR THIRD DEGREE): Isoproterenol or transvenous cardiac
pacemaker.
CARDIAC FAILURE: Digitalize the patient and administer a diuretic. Glucagon
has been reported to be useful.
HYPOTENSION: Vasopressors such as dopamine or norepinephrine (levarterenol).
Monitor blood pressure continuously.
BRONCHOSPASM: A beta2 stimulant such as isoproterenol
or terbutaline and/or aminophylline.
HYPOGLYCEMIA: Intravenous glucose. Based on the severity of symptoms, management may require intensive support
care and facilities for applying cardiac and respiratory support.

DOSAGE AND ADMINISTRATION


id: c74123cc-a24f-4564-8d77-b704d0b53cf6
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7

Hypertension The initial dose of atenolol is 50 mg given as one tablet a
day either alone or added to diuretic therapy. The full effect of this dose will
usually be seen within one to two weeks. If an optimal response is not achieved,
the dosage should be increased to atenolol 100 mg given as one tablet a day.
Increasing the dosage beyond 100 mg a day is unlikely to produce any further
benefit.
Atenolol may be used alone or concomitantly with other antihypertensive
agents including thiazide-type diuretics, hydralazine, prazosin, and
alpha-methyldopa.
Angina Pectoris The initial dose of atenolol is 50 mg given as one tablet a
day. If an optimal response is not achieved within one week, the dosage should
be increased to atenolol 100 mg given as one tablet a day. Some patients may
require a dosage of 200 mg once a day for optimal effect.
Twenty-four hour control with once daily dosing is achieved by giving doses
larger than necessary to achieve an immediate maximum effect. The maximum early
effect on exercise tolerance occurs with doses of 50 to 100 mg, but at these
doses the effect at 24 hours is attenuated, averaging about 50% to 75% of that
observed with once a day oral doses of 200 mg.
Acute Myocardial Infarction In patients with definite or suspected acute myocardial
infarction, treatment with atenolol I.V. Injection should be initiated as soon
as possible after the patient’s arrival in the hospital and after eligibility is
established. Such treatment should be initiated in a coronary care or similar
unit immediately after the patient’s hemodynamic condition has stabilized.
Treatment should begin with the intravenous administration of 5 mg atenolol over
5 minutes followed by another 5 mg intravenous injection 10 minutes later.
Atenolol I.V. Injection should be administered under carefully controlled
conditions including monitoring of blood pressure, heart rate, and
electrocardiogram. Dilutions of atenolol I.V. Injection in Dextrose Injection
USP, Sodium Chloride Injection USP, or Sodium Chloride and Dextrose Injection
may be used. These admixtures are stable for 48 hours if they are not used
immediately.
In patients who tolerate the full intravenous dose (10 mg), atenolol tablets
50 mg should be initiated 10 minutes after the last intravenous dose followed by
another 50 mg oral dose 12 hours later. Thereafter, atenolol can be given orally
either 100 mg once daily or 50 mg twice a day for a further 6 to 9 days or until
discharge from the hospital. If bradycardia or hypotension requiring treatment
or any other untoward effects occur, atenolol should be discontinued. (See full
prescribing information prior to initiating therapy with atenolol tablets.)
Data from other beta-blocker trials suggest that if there is any question
concerning the use of IV beta-blocker or clinical estimate that there is a
contraindication, the IV beta-blocker may be eliminated and patients fulfilling
the safety criteria may be given atenolol tablets 50 mg twice daily or 100 mg
once a day for at least seven days (if the IV dosing is excluded).
Although the demonstration of efficacy of atenolol is based entirely on data
from the first seven postinfarction days, data from other beta-blocker trials
suggest that treatment with beta-blockers that are effective in the
postinfarction setting may be continued for one to three years if there are no
contraindications.
Atenolol is an additional treatment to standard coronary care unit
therapy.
Elderly Patients or Patients with Renal Impairment Atenolol is excreted by the kidneys; consequently dosage
should be adjusted in cases of severe impairment of renal function. In general,
dose selection for an elderly patient should be cautious, usually starting at
the low end of the dosing range, reflecting greater frequency of decreased
hepatic, renal, or cardiac function, and of concomitant disease or other drug
therapy. Evaluation of patients with hypertension or myocardial infarction
should always include assessment of renal function. Atenolol excretion would be
expected to decrease with advancing age.
No significant accumulation of atenolol occurs until creatinine clearance
falls below 35 mL/min/1.73 m2. Accumulation of atenolol
and prolongation of its half-life were studied in subjects with creatinine
clearance between 5 and 105 mL/min. Peak plasma levels were significantly
increased in subjects with creatinine clearances below 30 mL/min.
The following maximum oral dosages are recommended for elderly,
renally-impaired patients and for patients with renal impairment due to other
causes:

Creatinine Clearance
(mL/min/1.73 m2)
Atenolol
Elimination Half-Life
(h)
Maximum Dosage
15 to 35 16 to 27 50 mg daily
less than 15 > 27 25 mg daily
Some renally-impaired or elderly patients being treated for
hypertension may require a lower starting dose of atenolol: 25 mg given as one
tablet a day. If this 25 mg dose is used, assessment of efficacy must be made
carefully. This should include measurement of blood pressure just prior to the
next dose (“trough” blood pressure) to ensure that the treatment effect is
present for a full 24 hours.
Although a similar dosage reduction may be considered for elderly and/or
renally-impaired patients being treated for indications other than hypertension,
data are not available for these patient populations.
Patients on hemodialysis should be given 25 mg or 50 mg after each dialysis;
this should be done under hospital supervision as marked falls in blood pressure
can occur.
Cessation of Therapy in Patients with Angina Pectoris If withdrawal of atenolol therapy is planned, it should be
achieved gradually and patients should be carefully observed and advised to
limit physical activity to a minimum.

HOW SUPPLIED


id: 1602d96d-7be1-4c4f-a8f2-984462d69e1a
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Each 100 mg atenolol tablet, USP is available as white to off-white round,
flat face, beveled edge tablet, debossed with ‘RE 21’ on one side and plain on
the other side. They are supplied as follows:
NDC 67296-0676-1                   Bottles of 30 Store at 20 – 25°C (68 – 77°F). (See USP Controlled Room Temperature). Dispense in well-closed, light-resistant containers. Call your doctor for medical advice about side effects. You may report side
effects to FDA at 1-800-FDA-1088.
Manufactured for: Ranbaxy Pharmaceuticals Inc. Jacksonville, FL 32257 USA by: Ipca Laboratories Limited 48, Kandivli Ind. Estate, Mumbai 400 067, India April 2009

Package Label


id: 9726cd98-c0c8-4983-8ead-d3b3aebd42b9
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4

copy of label