Nebivolol - Warnings and Precautions

WARNINGS AND PRECAUTIONS • Acute exacerbation of coronary artery disease upon cessation of therapy: Do not abruptly discontinue. • Diabetes: May mask symptoms of hypoglycemia and alter glucose levels; monitor 5.1 Abrupt Cessation of Therapy Do not abruptly discontinue nebivolol tablets therapy in patients with coronary artery disease.

Severe exacerbation of angina, myocardial infarction and ventricular arrhythmias have been reported in patients with coronary artery disease following the abrupt discontinuation of therapy with β-blockers.

Myocardial infarction and ventricular arrhythmias may occur with or without preceding exacerbation of the angina pectoris.

Caution patients without overt coronary artery disease against interruption or abrupt discontinuation of therapy.

As with other β-blockers, when discontinuation of nebivolol tablets is planned, carefully observe and advise patients to minimize physical activity.

Taper nebivolol tablets over 1 to 2 weeks when possible.

If the angina worsens or acute coronary insufficiency develops, re-start nebivolol tablets promptly, at least temporarily.

5.2 Angina and Acute Myocardial Infarction Nebivolol tablets were not studied in patients with angina pectoris or who had a recent MI.

5.3 Bronchospastic Diseases In general, patients with bronchospastic diseases should not receive β-blockers.

5.4 Anesthesia and Major Surgery Because beta-blocker withdrawal has been associated with an increased risk of MI and chest pain, patients already on beta-blockers should generally continue treatment throughout the perioperative period.

If nebivolol tablets are to be continued perioperatively, monitor patients closely when anesthetic agents which depress myocardial function, such as ether, cyclopropane, and trichloroethylene, are used.

If β-blocking therapy is withdrawn prior to major surgery, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures.

The β-blocking effects of nebivolol tablets can be reversed by β-agonists, e.g., dobutamine or isoproterenol.

However, such patients may be subject to protracted severe hypotension.

Additionally, difficulty in restarting and maintaining the heartbeat has been reported with β-blockers.

5.5 Hypoglycemia Beta-blockers may prevent early warning signs of hypoglycemia, such as tachycardia, and increase the risk for severe or prolonged hypoglycemia at anytime during treatment, especially in patients with diabetes mellitus or children and patients who are fasting (i.e., surgery, not eating regularly, or are vomiting).

If severe hypoglycemia occurs, patients should be instructed to seek emergency treatment.

5.6 Thyrotoxicosis β-blockers may mask clinical signs of hyperthyroidism, such as tachycardia.

Abrupt withdrawal of β-blockers may be followed by an exacerbation of the symptoms of hyperthyroidism or may precipitate a thyroid storm.

5.7 Peripheral Vascular Disease β-blockers can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease.

5.8 Non-dihydropyridine Calcium Channel Blockers Because of significant negative inotropic and chronotropic effects in patients treated with β-blockers and calcium channel blockers of the verapamil and diltiazem type, monitor the ECG and blood pressure in patients treated concomitantly with these agents.

5.9 Use with CYP2D6 Inhibitors Nebivolol exposure increases with inhibition of CYP2D6 [see Drug Interactions ] .

The dose of nebivolol tablets may need to be reduced.

5.10 Impaired Renal Function Renal clearance of nebivolol is decreased in patients with severe renal impairment.

Nebivolol tablets have not been studied in patients receiving dialysis [see Clinical Pharmacology and Dosage and Administration ] .