NEBIVOLOL- nebivolol tablet

Land: USA

Språk: engelsk

Kilde: NLM (National Library of Medicine)

Aktiv ingrediens:

NEBIVOLOL HYDROCHLORIDE (UNII: JGS34J7L9I) (NEBIVOLOL - UNII:030Y90569U)

Tilgjengelig fra:

Camber Pharmaceuticals, Inc.

Administreringsrute:

ORAL

Resept typen:

PRESCRIPTION DRUG

Indikasjoner:

Nebivolol tablets are indicated for the treatment of hypertension, to lower blood pressure [see Clinical Studies ( 14.1)] . Nebivolol tablets 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. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes, including the class to which this drug principally belongs. There are no controlled trials demonstrating risk reduction with nebivolol tablets. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. 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. Risk Summary Available data regarding use of nebivolol 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 depression in the neonate [see Clinical Considerations] . Oral administration of nebivolol to pregnant rats during organogenesis resulted in embryofetal and perinatal lethality at doses approximately equivalent to the maximum recommended human dose (MRHD). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. Pregnant women with hypertension should be carefully monitored and managed accordingly. Fetal/Neonatal adverse reactions Neonates of women with hypertension, who are treated with beta-blockers during the third trimester of pregnancy, may be at increased risk for hypotension, bradycardia, hypoglycemia, and respiratory depression. Observe newborns for symptoms of hypotension, bradycardia, hypoglycemia and respiratory depression and manage accordingly. Data Animal Data Nebivolol was shown to increase embryo-fetal and perinatal lethality in rats at approximately 1.2 times the MRHD or 40 mg/day on a mg/m 2 basis. Decreased pup body weights occurred at 1.25 and 2.5 mg/kg in rats, when exposed during the perinatal period (late gestation, parturition and lactation). At 5 mg/kg and higher doses (1.2 times the MRHD), prolonged gestation, dystocia and reduced maternal care were produced with corresponding increases in late fetal deaths and stillbirths and decreased birth weight, live litter size and pup survival. These events occurred only when nebivolol was given during the perinatal period (late gestation, parturition and lactation). Insufficient numbers of pups survived at 5 mg/kg to evaluate the offspring for reproductive performance. In studies in which pregnant rats were given nebivolol during organogenesis, reduced fetal body weights were observed at maternally toxic doses of 20 and 40 mg/kg/day (5 and 10 times the MRHD), and small reversible delays in sternal and thoracic ossification associated with the reduced fetal body weights and a small increase in resorption occurred at 40 mg/kg/day (10 times the MRHD). No adverse effects on embryo-fetal viability, sex, weight or morphology were observed in studies in which nebivolol was given to pregnant rabbits at doses as high as 20 mg/kg/day (10 times the MRHD). Risk Summary There is no information regarding the presence of nebivolol in human milk, the effects on the breastfed infant, or the effects on milk production. Nebivolol is present in rat milk [see Data] . Because of the potential for β-blockers to produce serious adverse reactions in nursing infants, especially bradycardia, nebivolol is not recommended during nursing. Data In lactating rats, maximum milk levels of unchanged nebivolol were observed at 4 hours after single and repeat doses of 2.5 mg/kg/day. The daily dose (mg/kg body weight) ingested by a rat pup is 0.3% of the dam dose for unchanged nebivolol. 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 ( 13.1)] . 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. In surviving rats, cardiomyopathy was seen at exposures greater than or equal to the human exposure. Male rat pups exposed to twice the human exposure showed decreases in total sperm count as well as decreases in the total and percentage of motile sperm. 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. In a placebo-controlled trial of 2,128 patients (1,067 nebivolol tablets, 1,061 placebo) over 70 years of age with chronic heart failure receiving a maximum dose of 10 mg per day for a median of 20 months, no worsening of heart failure was reported with nebivolol compared to placebo. However, if heart failure worsens consider discontinuation of nebivolol.

Produkt oppsummering:

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 supplied in the following strengths and package configurations: Nebivolol tablets, 2.5 mg are white to off-white, triangular biconvex tablets debossed with ‘J’ on one side and ‘8’ on other side. Bottle of 30 tablets                                                                          NDC 31722-585-30 Bottle of 100 tablets                                                                        NDC 31722-585-01 Blister card of 10 Unit dose tablets (PVC/PVdC)                          NDC 31722-585-31 Blister pack of 120 (12 x 10) Unit dose tablets (PVC/PVdC)        NDC 31722-585-32 Blister card of 10 Unit dose tablets (Alu-Alu)                               NDC 31722-585-33 Blister pack of 150 (15 x 10) Unit dose tablets (Alu-Alu)             NDC 31722-585-34 Nebivolol tablets, 5 mg are light orange, triangular biconvex tablets debossed with ‘J’ on one side and ‘9’ on other side. Bottle of 30 tablets                                                                          NDC 31722-586-30 Bottle of 90 tablets                                                                          NDC 31722-586-90 Bottle of 100 tablets                                                                        NDC 31722-586-01 Blister card of 10 Unit dose tablets (PVC/PVdC)                          NDC 31722-586-31 Blister pack of 100 (10 x 10) Unit dose tablets (PVC/PVdC)        NDC 31722-586-32 Blister card of 7 Unit dose tablets (Alu-Alu)                                  NDC 31722-586-33  Blister pack of 126 (18 x 7) Unit dose tablets (Alu-Alu)               NDC 31722-586-34 Nebivolol tablets, 10 mg are light peach color, triangular shaped biconvex tablets debossed with ‘J’ on one side and ‘10’ on other side. Bottle of 30 tablets                                                                          NDC 31722-587-30 Bottle of 90 tablets                                                                          NDC 31722-587-90 Bottle of 100 tablets                                                                        NDC 31722-587-01 Blister card of 10 Unit dose tablets (PVC/PVdC)                          NDC 31722-587-31 Blister pack of 100 (10 x 10) Unit dose tablets (PVC/PVdC)        NDC 31722-587-32 Blister card of 7 Unit dose tablets (Alu-Alu)                                  NDC 31722-587-33 Blister pack of 126 (18 x 7) Unit dose tablets (Alu-Alu)               NDC 31722-587-34 Nebivolol tablets, 20 mg are white to off-white, triangular biconvex tablets debossed with ‘J’ on one side and ‘11’ on other side. Bottle of 30 tablets                                                                          NDC 31722-588-30 Bottle of 90 tablets                                                                          NDC 31722-588-90 Bottle of 100 tablets                                                                        NDC 31722-588-01 Blister card of 10 Unit dose tablets (PVC/PVdC)                          NDC 31722-588-31 Blister pack of 100 (10 x 10) Unit dose tablets (PVC/PVdC)        NDC 31722-588-32 Blister card of 7 Unit dose tablets (Alu-Alu)                                 NDC 31722-588-33 Blister pack of 126 (18 x 7) Unit dose tablets (Alu-Alu)               NDC 31722-588-34 Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

Autorisasjon status:

Abbreviated New Drug Application

Preparatomtale

NEBIVOLOL - NEBIVOLOL TABLET
CAMBER PHARMACEUTICALS, INC.
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
NEBIVOLOL TABLETS
SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR NEBIVOLOL
TABLETS.
NEBIVOLOL TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 2007
RECENT MAJOR CHANGES
Warnings and Precautions, Hypoglycemia (5.5) 6/2023
INDICATIONS AND USAGE
Nebivolol tablet 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_)
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. ( _2.1_)
DOSAGE FORMS AND STRENGTHS
Tablets: 2.5, 5, 10, 20 mg ( _3_)
CONTRAINDICATIONS
• 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_)
WARNINGS AND PRECAUTIONS
• 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_)
ADVERSE REACTIONS
MOST COMMON ADVERSE REACTIONS ( _6.1_):
• Headache, fatigue
TO REPORT SUSPECTED ADVERSE REACTIONS, CONTACT HETERO LABS LIMITED AT
1-866-495-1995
OR FDA AT 1-800-FDA-1088 OR WWW.FDA.GOV/MEDWATCH.
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 glyc