Prescription Drug Name:
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:
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
carbonate, magnesium stearate, sodium lauryl sulfate, sodium starch glycolate.
displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1
(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.
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
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.
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
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.
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
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.
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
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
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
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).
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.
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
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
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9
may be used alone or concomitantly with other antihypertensive agents,
particularly with a thiazide-type diuretic.
patients with angina pectoris.
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
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.
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3
block greater than first degree, cardiogenic shock, and overt cardiac failure
hypersensitivity to the atenolol or any of the drug product’s components.
displayName: WARNINGS SECTION
FDA Article Code: 34071-1
circulatory function in congestive heart failure, and beta-blockade carries the
potential hazard of further depressing myocardial contractility and
precipitating more severe failure.
promptly and effectively controlled by 80 mg of intravenous furosemide or
equivalent therapy is a contraindication to beta-blocker treatment.
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
displayName: PRECAUTIONS SECTION
FDA Article Code: 42232-9
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
impaired renal function (see
displayName: DRUG INTERACTIONS SECTION
FDA Article Code: 34073-7
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.
and chronotropic effects. Disopyramide has been associated with severe
bradycardia, asystole and heart failure when administered with
that may be additive to those seen with beta-blockers.
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
indomethacin, may decrease the hypotensive effects of beta-blockers.
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
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.
and decrease heart rate. Concomitant use can increase the risk of
Carcinogenesis, Mutagenesis, Impairment of Fertility
displayName: CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION
FDA Article Code: 34083-6
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),
mg/kg/day or 100 times the maximum recommended human dose1) was unaffected by atenolol administration.
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
displayName: PREGNANCY SECTION
FDA Article Code: 42228-7
displayName: NURSING MOTHERS SECTION
FDA Article Code: 34080-2
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
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
displayName: PEDIATRIC USE SECTION
FDA Article Code: 34081-0
Safety and effectiveness in pediatric patients have not been established.
displayName: GERIATRIC USE SECTION
FDA Article Code: 34082-8
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.
to atenolol in the ISIS-1 trial (see
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
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.
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4
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.
|Total – Volunteered
(Foreign + U.S. Studies)
(n = 164)
(n = 206)
(n = 399)
(n = 407)
|CENTRAL NERVOUS SYSTEM/
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
either intravenous and/or oral atenolol administration:
(n = 244)
(n = 233)
|BBB + Major
|Total Cardiac Arrests||4||(1.6%)||16||(6.9%)|
|Nonfatal Cardiac Arrests||4||(1.6%)||12||(5.1%)|
|Development of Ventricular
|Development of Mitral
(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:
| IV Atenolol
(less than 5 mg)*
| Oral Partial
|Heart Block (> first degree)||5||(0.06%)||143||(1.7%)|
10 mg but more than 5 mg.
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.
with other beta-adrenergic blocking agents, and may be considered potential
adverse effects of atenolol.
throat, laryngospasm, and respiratory distress.
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
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
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.
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5
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.
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.
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
blockade, give isoproterenol cautiously. In refractory cases, a transvenous
cardiac pacemaker may be indicated.
has been reported to be useful.
Monitor blood pressure continuously.
or terbutaline and/or aminophylline.
care and facilities for applying cardiac and respiratory support.
DOSAGE AND ADMINISTRATION
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7
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
agents including thiazide-type diuretics, hydralazine, prazosin, and
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.
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.
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
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.)
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).
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
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.
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.
renally-impaired patients and for patients with renal impairment due to other
|15 to 35||16 to 27||50 mg daily|
|less than 15||> 27||25 mg daily|
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.
renally-impaired patients being treated for indications other than hypertension,
data are not available for these patient populations.
this should be done under hospital supervision as marked falls in blood pressure
achieved gradually and patients should be carefully observed and advised to
limit physical activity to a minimum.
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
flat face, beveled edge tablet, debossed with ‘RE 21’ on one side and plain on
the other side. They are supplied as follows:
effects to FDA at
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4
copy of label