PRZ-NEBIVOLOL

2 Recommended Dose and Dosage Adjustment • For most patients, the recommended starting dose is 5 mg once daily, with or without food. Forpatients requiring further reduction in blood pressure, the dose can be increased at two-week intervals up to 20 mg once daily.

4 Drug-Drug Interactions. 5 mg once daily; titrate up slowly if needed. Nebivolol has not been studied in patients receiving dialysis and is therefore not recommended for use in this patient population. 3 Pharmacokinetics . 5 mg oncedaily; titrate up slowly if needed.

Nebivolol has not been studied in patients with severehepatic impairment and therefore is contraindicated in that population. 3 Pharmacokinetics. • Geriatric Patients: No dose adjustments are usually necessary for elderly patients. • CYP2D6 Polymorphism: No dose adjustments are necessary for patients who are CYP2D6 poor metabolizers.

The clinicaleffect and safety profile observed in poor metabolizers were similar to those of extensive metabolizers. 3 Pharmacokinetics. 4 Administration Once-daily dosing has shown to sustain efficacy over 24 hours. A more frequent dosing regimen is unlikely to be beneficial.

Nebivolol tablets can be taken with or without food. 5 Missed Dose If patients miss a dose, they should wait until their next scheduled dose. Patients should notdouble their dose. PRZ-NEBIVOLOL should be taken once approximately every 24 hours.

1 Adverse Reaction Overview Nebivolol tablets has been evaluated for safety in more than 7,100 patients withhypertension with a clinical trial exposure to nebivolol in approximately 5,400 patients. Patients received nebivolol for up to 36 months, with over 1,000 patients treated for at least6 months, and approximately 500 patients for more than one year.

1%). Nebivolol was well tolerated and adverse events have generally been mild to moderate in intensity. 0% of patients givenplacebo (4/205). 1%) for patients who received nebivolol. 2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions.

The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use.

25 mg to 40 mg, and 205 patients were given placebo. The median exposure to treatmentin these three trials was 85-days. 3 Less Common Clinical Trial Adverse Reactions Adverse events reported in the placebo-controlled studies with incidence rates of less than <1% and at a higher frequency than placebo-treated patients are listed below: Blood and Lymphatic System Disorders: anemia; leukopenia; lymphadenopathy Cardiac Disorders: myocardial infarction; myocardial ischemia; angina pectoris; atrioventricular block first degree; cardiac failure congestive; extrasystoles; tachycardia; withdrawal arrhythmia Ear And Labyrinth Disorders: deafness; ear pain; hearing impaired; vertigo Eye Disorders: conjunctival haemorrhage; conjunctivitis; eye pain; glaucoma; vision disturbances Gastrointestinal Disorders: abdominal pain; flatulence; gastro-oesophageal reflux disease; oralmucosal lesions; toothache; vomiting General Disorders and Administration Site Conditions: influenza-like illness; pyrexia; weakness Immune System Disorders: hypersensitivity Infections and Infestations: fungal infection; gastroenteritis; hepatitis; localized infection; lowerrespiratory tract infection Investigations: alanine aminotransferase increased; aspartate aminotransferase increased; bloodalkaline phosphatase increased; blood glucose increased; blood uric acid increased; cardiac murmur; haematocrit/hemoglobin decreased; high density lipoprotein decreased; weight increased Metabolism and […]

3 Pharmacokinetics . 5 mg oncedaily; titrate up slowly if needed. Nebivolol has not been studied in patients with severehepatic impairment and therefore is contraindicated in that population. 3 Pharmacokinetics. • Geriatric Patients: No dose adjustments are usually necessary for elderly patients.

• CYP2D6 Polymorphism: No dose adjustments are necessary for patients who are CYP2D6 poor metabolizers. The clinicaleffect and safety profile observed in poor metabolizers were similar to those of extensive metabolizers. 3 Pharmacokinetics.

4 Administration Once-daily dosing has shown to sustain efficacy over 24 hours. A more frequent dosing regimen is unlikely to be beneficial. Nebivolol tablets can be taken with or without food. 5 Missed Dose If patients miss a dose, they should wait until their next scheduled dose.

Patients should notdouble their dose. PRZ-NEBIVOLOL should be taken once approximately every 24 hours. 5 OVERDOSAGE Symptoms: In clinical trials and worldwide post-marketing experience there were reports of nebivolol overdose. The most common signs and symptoms associated with nebivolol overdosage are bradycardia and hypotension.

Other important adverse reactions reported with nebivolol overdose include heart failure, dizziness, hypoglycemia, fatigue andvomiting. Other adverse reactions associated with β-blocker overdose include bronchospasm andheart block. PRZ-NEBIVOLOL Product Monograph Page 6 of 39 The largest known ingestion of nebivolol worldwide involved a patient who ingested up to 500 mg of nebivolol along with several 100 mg tablets of acetylsalicylic acid in a suicide attempt.

The patient experienced hyperhydrosis, pallor, depressed level of consciousness, hypokinesia, hypotension, sinus bradycardia, hypoglycemia, hypokalemia, respiratory failure andvomiting. The patient recovered.

Treatment:

PRZ-NEBIVOLOL is contraindicated in patients with: • Hypersensitivities to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see the 6 DOSAGE FORMS, STRENGHTS, COMPOSITION AND PACKAGING section of the Product Monograph.

• Severe bradycardia (generally <50 bpm prior to start of therapy) • Cardiogenic shock • Decompensated cardiac failure • Second or third degree atrioventricular (AV) block • Sick sinus syndrome or sinoatrial block • Severe hepatic impairment (Child-Pugh Score >B) • Severe peripheral arterial circulatory disorders • The rare hereditary conditions of Galactose intolerance, Lapp lactase deficiencyor glucose galactose malabsorption