A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Tenormin Side Effects, and Drug Interactions - Atenolol
Tenormin Side Effects, and Drug Interactions - Atenolol
SIDE EFFECTS
Most adverse effects have been mild and transient.
The frequency estimates in TABLE 1 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.
| TABLE 1 Adverse Effects |
| |
Volunteered |
Total - Volunteered and Elicited |
| |
(US Studies) |
(Foreign + US Studies) |
| |
Atenolol |
Placebo |
Atenolol |
Placebo |
| |
(n = 164) |
(n = 206) |
(n = 399) |
(n = 407) |
| |
% |
% |
% |
% |
| Cardiovascular |
|
|
3 |
|
3 |
|
|
|
|
0.5 |
12 |
5 |
|
|
2 |
1 |
4 |
5 |
|
|
|
0.5 |
3 |
1 |
| Central Nervous System/Neuromuscular |
|
|
4 |
1 |
13 |
6 |
|
|
2 |
0.5 |
2 |
0.2 |
|
|
1 |
|
3 |
0.7 |
|
|
0.6 |
0.5 |
26 |
13 |
|
|
3 |
1 |
6 |
5 |
|
|
1 |
|
3 |
0.7 |
|
|
0.6 |
|
2 |
0.5 |
|
|
0.6 |
0.5 |
12 |
9 |
|
|
|
|
3 |
1 |
| Gastrointestinal |
|
|
2 |
|
3 |
2 |
|
|
4 |
1 |
3 |
1 |
| Respiratory (see WARNINGS) |
|
|
|
|
3 |
3 |
|
|
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 TABLE 2.
In a study of 477 patients, the following adverse events were reported
during either intravenous
and/or oral atenolol
administration (see
TABLE 2).
| TABLE 2 Adverse Effects |
| |
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 8037 were randomized to receive atenolol
treatment, the dosage of intravenous
and subsequent oral atenolol
was either discontinued or reduced for the following reasons (see TABLE
3).
|
TABLE 3 Reasons For Reduced Dosage
|
| |
I.V. Atenolol Reduced Dose (< 5 mg)* |
Oral Partial Dose |
| Hypotension/Bradycardia |
105 |
(1.3%) |
1168 |
(14.5%) |
| Cardiogenic Shock |
4 |
(.04%) |
35 |
(.44%) |
| Reinfarction |
|
(0%) |
5 |
(.06%) |
| Cardiac Arrest |
5 |
(.06%) |
28 |
(.34%) |
| Heart Block (> first degree) |
5 |
(.06%) |
143 |
(1.7%) |
| Cardiac Failure |
1 |
(.01%) |
233 |
(2.9%) |
| Arrhythmias |
3 |
(.04%) |
22 |
(.27%) |
| Bronchospasm |
1 |
(.01%) |
50 |
(.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 and visual
disturbances. Atenolol, like other beta-blockers, has been associated
with the development of
antinuclear antibodies
(ANA), and lupus syndrome.
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, Raynaud's Phenomenon.
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 DOSAGE AND
ADMINISTRATION).
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.
DRUG INTERACTIONS
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).
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 withdraw 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.
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.
Additional Information for the I.V. Injection: Caution
should be exercised with atenolol
I.V. when given in close proximity with drugs that may also have depressant
effect on myocardial
contractility. On rare occasions, concomitant
use of I.V. beta-blockers and I.V. verapamil has resulted in serious adverse
reactions, especially in patients with severe cardiomyopathy, congestive
heart failure, or recent myocardial
infarction.
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