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, 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 (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
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(< 5 mg)*	Oral Partial Dose
Full dosage was 10 mg and some patients received less than 10 mg but more than 5 mg.
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 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.