ADVERSE REACTIONS
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, eg, by checklist (foreign studies). The reported frequency of elicited adverse effects was higher for both TENORMIN and placebo-treated patients than when these reactions were volunteered. Where frequency of adverse effects of TENORMIN and placebo is similar, causal relationship to TENORMIN is uncertain.
|
Volunteered
(US Studies)
|
Total Volunteered
and Elicited
(Foreign + US 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
|
|
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
|
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 TENORMIN treatment, the dosage of intravenous and subsequent oral TENORMIN was either discontinued or reduced for the following reasons:
|
Reasons for Reduced Dosage
|
|
IV Atenolol Reduced
Dose (<5mg)Full dosage was 10 mg and some patients received less than 10 mg but more than 5 mg.
|
Oral Partial
Dose
|
|
Hypotension/Bradycardia
|
105
|
(1.3%)
|
1168
|
(14.5%)
|
|
Cardiogenic Shock
|
4
|
(.04%)
|
35
|
(.44%)
|
|
Reinfarction
|
0
|
(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%)
|
During postmarketing experience with TENORMIN, 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 disturbances, sick sinus syndrome, and dry mouth. TENORMIN, 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 TENORMIN.
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 DOSAGE AND ADMINISTRATION.)
The oculomucocutaneous syndrome associated with the beta blocker practolol has not been reported with TENORMIN. Furthermore, a number of patients who had previously demonstrated established practolol reactions were transferred to TENORMIN therapy with subsequent resolution or quiescence of the reaction.
|
