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Abrupt Withdrawal of Therapy: Abrupt withdrawal of β-adrenergic blocking agents (β-blockers) may exacerbate angina symptoms and/or precipitate myocardial infarction and ventricular arrhythmias in patients with coronary artery disease. Therefore, patients receiving nebivolol (especially those with ischemic heart disease) should be warned not to interrupt or abruptly discontinue therapy without consulting their clinician. When discontinuance of nebivolol therapy is planned, dosage of the drug should be reduced gradually over a period of 1-2 weeks. Patients should be carefully monitored and advised to temporarily limit their physical activity. If exacerbation of angina occurs or acute coronary insufficiency develops after nebivolol therapy is interrupted or discontinued, treatment with the drug should be reinstituted, at least temporarily.
Heart Failure: In patients with heart failure, sympathetic stimulation is vital for support of circulatory function. Nebivolol should be used with caution in patients with inadequate cardiac function, since further depression of myocardial contractility and cardiac failure may be precipitated.
Although β-blockers should be avoided in patients with overt heart failure, nebivolol may be administered cautiously, if necessary, to patients with well-compensated heart failure. If heart failure worsens, discontinuance of nebivolol should be considered.
Ischemic Heart Disease: Safety and efficacy of nebivolol in patients with angina pectoris or recent myocardial infarction have not been established to date.
Anesthesia and Major Surgery: Nebivolol should be used with caution in patients undergoing major surgery involving general anesthesia. Particular caution should be employed if anesthetics that depress the myocardium are used. Severe, protracted hypotension and difficulty in restarting or maintaining a heart beat have occurred during surgery in some patients who have received β-blockers. The β-adrenergic blocking effects of nebivolol can be reversed by administration of β-agonists (e.g., dobutamine, isoproterenol).
Bronchospastic Diseases: Patients with bronchospastic disease generally should not receive β-blockers.
Diabetes Mellitus and Hypoglycemia: β-Blockers may mask signs and symptoms of hypoglycemia (e.g., tachycardia). Nonselective β-blockers may potentiate insulin-induced hypoglycemia and delay recovery of serum glucose concentrations.
Nebivolol should be used with caution in patients subject to spontaneous hypoglycemia and in diabetic patients receiving insulin or oral hypoglycemic agents.
Thyrotoxicosis: β-Blockers may mask signs of hyperthyroidism (e.g., tachycardia). Abrupt withdrawal of β-adrenergic blockade may exacerbate manifestations of hyperthyroidism or precipitate thyroid storm.
Peripheral Vascular Disease: β-Blockers may precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease, nebivolol should be used with caution in these patients.
Nondihydropyridine Calcium-channel Blocking Agents: Because of their negative inotropic and chronotropic effects, nebivolol and nondihydropyridine calcium-channel blocking agents (e.g. verapamil, diltiazem) should be used concomitantly with caution.
Risk of Anaphylactic Reactions: Patients who have a history of anaphylactic reactions to a variety of allergens reportedly may be more reactive to repeated accidental, diagnostic, or therapeutic challenges with such allergens while taking β-blockers and may be unresponsive to usual doses of epinephrine used to treat such reactions.
Pheochromocytoma: In patients with known or suspected pheochromocytoma, treatment with an α-adrenergic blocking agent should be instituted prior to use of a β-blocker (e.g., nebivolol).
