Atenolol precautions

List of precautions
General Impaired Renal Function Drug Interactions Carcinogenesis, Mutagenesis, Impairment of Fertility Animal Toxicology Pregnancy Teratogenic Effects Nursing Mothers Pediatric Use Geriatric Use Hypertension and Angina Pectoris Due to Coronary Atherosclerosis Acute Myocardial Infarction

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.

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Impaired Renal Function
The drug should be used with caution in patients with impaired renal function.

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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.

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 If the two drugs are coadministered, the beta blocker should be withdrawn several days before the gradual withdrawal of clonidine.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.

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Carcinogenesis, Mutagenesis, Impairment of Fertility
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 dose, 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 dose*) 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 dose*) was unaffected by Atenolol administration.

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Animal Toxicology
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 dose) 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 dose (Based on the maximum dose of 100 mg/day in a 50 kg patient), respectively].

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Teratogenic Effects
Pregnancy category D

Nursing Mothers
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 breast fed 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 breast-feeding may be at risk for hypoglycemia and bradycardia. Caution should be exercised when Atenolol is administered during pregnancy or to a woman who is breast-feeding

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Pediatric Use
Safety and effectiveness in pediatric patients has not been established.

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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.

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Acute Myocardial Infarction
Of the 8,037 patients with suspected acute myocardial infarction randomized to Atenolol in the ISIS-1 trial, 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 <120 mmHg seemed less likely to benefit.

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.

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