NEBIVOLOL Drug Interactions: What You Need to Know

7. DRUG INTERACTIONS

• CYP2D6 enzyme inhibitors may increase nebivolol levels. ( 7.1 )
• Reserpine or clonidine may produce excessive reduction of sympathetic activity. ( 7.2 )
• Both digitalis glycosides and β-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia. ( 7.3 )
• Verapamil- or diltiazem-type calcium channel blockers may cause excessive reductions in heart rate, blood pressure, and cardiac contractility. ( 7.4 )

7.1 CYP2D6 Inhibitors Use caution when nebivolol tablets are co-administered with CYP2D6 inhibitors (quinidine, propafenone, fluoxetine, paroxetine, etc.) <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.5 )]</span> .

7.2 Hypotensive Agents Do not use nebivolol tablets with other β-blockers. Closely monitor patients receiving catecholamine-depleting drugs, such as reserpine or guanethidine, because the added β-blocking action of nebivolol tablets may produce excessive reduction of sympathetic activity. In patients who are receiving nebivolol tablets and clonidine, discontinue nebivolol tablets for several days before the gradual tapering of clonidine.

7.3 Digitalis Glycosides Both digitalis glycosides and β-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.

7.4 Calcium Channel Blockers Nebivolol tablets can exacerbate the effects of myocardial depressants or inhibitors of AV conduction, such as certain calcium antagonists (particularly of the phenylalkylamine [verapamil] and benzothiazepine [diltiazem] classes), or antiarrhythmic agents, such as disopyramide.

4.

Contraindications

Nebivolol tablets are contraindicated in the following conditions:

• Severe bradycardia
• Heart block greater than first degree
• Patients with cardiogenic shock
• Decompensated cardiac failure
• Sick sinus syndrome (unless a permanent pacemaker is in place)
• Patients with severe hepatic impairment (Child-Pugh >B)
• Patients who are hypersensitive to any component of this product.
• Severe bradycardia ( 4 )
• Heart block greater than first degree ( 4 )
• Patients with cardiogenic shock ( 4 )
• Decompensated cardiac failure ( 4 )
• Sick sinus syndrome (unless a permanent pacemaker is in place) ( 4 )
• Patients with severe hepatic impairment (Child-Pugh >B) ( 4 )
• Hypersensitive to any component of this product ( 4 )

5. WARNINGS AND PRECAUTIONS

• Acute exacerbation of coronary artery disease upon cessation of therapy: Do not abruptly discontinue. ( 5.1 )
• Diabetes: Monitor glucose as β-blockers may mask symptoms of hypoglycemia. ( 5.5 )

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 Diabetes and Hypoglycemia β-blockers may mask some of the manifestations of hypoglycemia, particularly tachycardia. Nonselective β-blockers may potentiate insulin-induced hypoglycemia and delay recovery of serum glucose levels. It is not known whether nebivolol has these effects. Advise patients subject to spontaneous hypoglycemia and diabetic patients receiving insulin or oral hypoglycemic agents about these possibilities.

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 <span class="opacity-50 text-xs">[see Drug Interactions ( 7 )]</span> . 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 <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.4 ) and Dosage and Administration ( 2.1 )]</span> .

5.11 Impaired Hepatic Function Metabolism of nebivolol is decreased in patients with moderate hepatic impairment. Nebivolol tablets have not been studied in patients with severe hepatic impairment <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.4 ) and Dosage and Administration ( 2.1 )]</span> .

5.12 Risk of Anaphylactic Reactions While taking β-blockers, patients with a history of severe anaphylactic reactions to a variety of allergens may be more reactive to repeated accidental, diagnostic, or therapeutic challenge. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reactions.

5.13 Pheochromocytoma In patients with known or suspected pheochromocytoma, initiate an α-blocker prior to the use of any β-blocker.