Nebivolol

Nebivolol is a beta-adrenergic blocking agent indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions.( 1.1 ) 1.1 Hypertension Nebivolol tablets are indicated for the treatment of hypertension, to lower blood pressure [ see Clinical Studies ( 14.1 ) ]. Nebivolol may be used alone or in combination with other antihypertensive agents [ see Drug Interactions ( 7 )]. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. …

• Can be taken with and without food
• Individualize to the needs of the patient and monitor during up-titration
• Hypertension: Most patients start at 5 mg once daily
• Dose can be increased at 2-week intervals up to 40 mg
• 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
• Renal Impairment In patients with severe renal impairment (ClCr less than 30 mL/min) the recommended initial dose is 2.5 mg once daily; titrate up slowly if needed
• Nebivolol tablets have not been studied in patients receiving dialysis [ see Clinical Pharmacology ]
• Hepatic Impairment In patients with moderate hepatic impairment, the recommended initial dose is 2.5 mg once daily; titrate up slowly if needed
• Nebivolol tablets have not been studied in patients with severe hepatic impairment and Therefore it is not recommended in that population [ see Clinical Pharmacology ]
• Subpopulations Geriatric Patients It is not necessary to adjust the dose in the elderly [ see use in Specific Populations ]
• CYP2D6 Polymorphism No dose adjustments are necessary for patients who are CYP2D6 poor metabolizers. …

Nebivolol is available as tablets for oral administration containing nebivolol hydrochloride equivalent to 2.5, 5, 10, and 20 mg of nebivolol. Nebivolol tablets are white to off white, round, biconvex, unscored tablet debossed with "C50" (for 2.5 mg), "C51"(for 5 mg), "C52"(for 10 mg), "C53"(for 20 mg) on one side and plain on the other side. Tablets: 2.5, 5, 10, 20 mg ( 3 )

• Safety and effectiveness
• In pediatric patients have not been established
• Pediatric studies in ages newborn to 18 years old have not been conducted because of incomplete characterization of developmental toxicity and possible adverse effects on long-term fertility [ see Nonclinical Toxicology ]
• Juvenile Animal Toxicity Data Daily oral doses of nebivolol to juvenile rats from post-natal day 14 to post-natal day 27 showed sudden unexplained death at exposures equal to those in human poor metabolizers given a single dose of 10 mg
• No mortality was seen at half the adult human exposure. …

Of the 2,800 patients in the U.S. sponsored placebo-controlled clinical hypertension studies, 478 patients were 65 years of age or older. No overall differences in efficacy or in the incidence of adverse events were observed between older and younger patients.

• See FDA-approved patient labeling (Patient Information). • Patient Advice Advise patients to take nebivolol tablets regularly and continuously, as directed
• Nebivolol tablets can be taken with or without food
• If a dose is missed, take the next scheduled dose only (without doubling it)
• Do not interrupt or discontinue nebivolol tablets without consulting the physician
• Patients should know how they react to this medicine before they operate automobiles, use machinery, or engage in other tasks requiring alertness. …

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. …

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 is co-administered with CYP2D6 inhibitors (quinidine, propafenone, fluoxetine, paroxetine, etc.) [ see Clinical Pharmacology ( 12.5 ) ]. …

Acute exacerbation of coronary artery disease upon cessation of therapy: Do not abruptly discontinue. ( 5.1 ) Diabetes: May mask symptoms of hypoglycemia and alter glucose levels; monitor (5.5) 5.1 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. …

Most common adverse reactions ( 6.1 ): Headache, fatigue To report SUSPECTED ADVERSE REACTIONS, contact Modavar Pharmaceuticals LLC at 1-800-688-4697, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 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. …

8.1 Pregnancy Risk Summary Available data regarding use of nebivolol tablets in pregnant women are insufficient to determine whether there are drug-associated risks of adverse developmental outcomes. There are risks to the mother and fetus associated with poorly controlled hypertension in pregnancy.The use of beta blockers during the third trimester of pregnancy may increase the risk of hypotension, bradycardia, hypoglycemia, and respiratory depr …

In clinical trials and worldwide post marketing experience there were reports of nebivolol overdose. The most common signs and symptoms associated with nebivolol tablets over dosage are bradycardia and hypotension. Other important adverse reactions reported with nebivolol tablets overdose include cardiac failure, dizziness, hypoglycemia, fatigue and vomiting. Other adverse reactions associated with β-blocker overdose include bronchospasm and heart block. …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.