Nebivolol

2 DOSAGE AND ADMINISTRATION Can be taken with and without food. Individualize to the needs of the patient and monitor during up-titration. ( 2 ) Hypertension: Most patients start at 5 mg once daily. Dose can be increased at 2-week intervals up to 40 mg.

1 Hypertension The dose of nebivolol tablets must be individualized to the needs of the patient. For most patients, the recommended starting dose is 5 mg once daily, with or without food, as monotherapy or in combination with other agents.

For patients requiring further reduction in blood pressure, the dose can be increased at 2-week intervals up to 40 mg. A more frequent dosing regimen is unlikely to be beneficial. 5 mg once daily; titrate up slowly if needed. 4 ) ]. 5 mg once daily; titrate up slowly if needed.

4 ) ]. 5 ) ]. CYP2D6 Polymorphism No dose adjustments are necessary for patients who are CYP2D6 poor metabolizers. 3 ) ].

gov/medwatch . 1 Clinical Studies Experience Nebivolol tablets have been evaluated for safety in patients with hypertension and in patients with heart failure. The observed adverse reaction profile was consistent with the pharmacology of the drug and the health status of the patients in the clinical trials.

Adverse reactions reported for each of these patient populations are provided below. Excluded are adverse reactions considered too general to be informative and those not reasonably associated with the use of the drug because they were associated with the condition being treated or are very common in the treated population.

The data described below reflect worldwide clinical trial exposure to nebivolol tablets in 6,545 patients, including 5,038 patients treated for hypertension and the remaining 1,507 subjects treated for other cardiovascular diseases.

5 mg to 40 mg. Patients received nebivolol tablets for up to 24 months, with over 1,900 patients treated for at least 6 months, and approximately 1,300 patients for more than one year. 2% of patients given placebo. 2%). Table 1 lists treatment-emergent adverse reactions that were reported in three 12-week, placebo- controlled monotherapy trials involving 1,597 hypertensive patients treated with either 5 mg, 10 mg, or 20 to 40 mg of nebivolol and 205 patients given placebo and for which the rate of occurrence was at least 1% of patients treated with nebivolol and greater than the rate for those treated with placebo in at least one dose group.

Table 1. Treatment-Emergent Adverse Reactions with an Incidence (over 6 weeks) ≥ 1% in Nebivolol Tablets-Treated Patients and at a Higher Frequency than Placebo-Treated Patients System Organ Class – Placebo Nebivolol Nebivolol Nebivolol Preferred Term 5 mg 10 mg 20 to 40 mg (n = 205) (n = 459) (n = 461) (n = 677) (%) (%) (%) (%) Cardiac Disorders Bradycardia 0 0 0 1 Gastrointestinal Disorders Diarrhea 2 2 2 3 Nausea 0 1 3 2 General Disorders Fatigue 1 2 2 5 Chest pain 0 0 1 1 Peripheral edema 0 1 1 1 Nervous System Disorders Headache 6 9 6 7 Dizziness 2 2 3 4 Psychiatric Disorders Insomnia 0 1 1 1 Respiratory Disorders Dyspnea 0 0 1 1 Skin and subcutaneous Tissue Disorders Rash 0 0 1 1 Listed below are other reported adverse reactions with an incidence of at least 1% in the more than 4,300 patients treated with nebivolol tablets in controlled or open-label trials except for those already appearing in Table 1 , terms too general to be informative, minor symptoms, or adverse reactions unlikely to be attributable to drug because they are common in the population.

5 WARNINGS AND PRECAUTIONS Acute exacerbation of coronary artery disease upon cessation of therapy: Do not abruptly discontinue. 1 Abrupt Cessation of Therapy Do not abruptly discontinue nebivolol 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. Taper nebivolol over 1 to 2 weeks when possible. If the angina worsens or acute coronary insufficiency develops, re-start nebivolol promptly, at least temporarily.

2 Angina and Acute Myocardial Infarction Nebivolol was not studied in patients with angina pectoris or who had a recent MI. 3 Bronchospastic Diseases In general, patients with bronchospastic diseases should not receive β-blockers. 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 is 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.

, 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. , surgery, not eating regularly, or are vomiting).

4 CONTRAINDICATIONS Nebivolol Tablets is 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 )