NEBIVOLOL

5mg: The dose is 5 mg (two tablets) daily, preferably at the same time of the day. 5mg: The dose is 5 mg (one tablet) daily, preferably at the same time of the day. The blood pressure lowering effect becomes evident after 1-2 weeks of treatment.

Occasionally, the optimal effect is reached only after 4 weeks. Combination with other antihypertensive agents Beta –Blockers can be used alone or concomitantly with other antihypertensive agents. 5-25 mg. 5 mg daily. If needed, the daily dose may be increased to 5 mg.

Patients with hepatic insufficiency Data in patients with hepatic insufficiency or impaired liver function are limited. 5mg or Nebivolol 5mg tablets in these patients is contra-indicated. 5 mg daily. If needed, the daily dose may be increased to 5 mg.

However, in view of the limited experience in patients above 75 years, caution must be exercised and these patients monitored closely. 5mg or Nebivolol 5mg Tablets in children and adolescents aged below 18 years has not been established.

No data are available. Therefore, use in children and adolescents is not recommended. Chronic heart failure (CHF) The treatment of stable chronic heart failure has to be initiated with a gradual uptitration of dosage until the optimal individual maintenance dose is reached.

Patients should have stable chronic heart failure without acute failure during the past six weeks. It is recommended that the treating physician should be experienced in the management of chronic heart failure. 5mg or Nebivolol 5mg Tablets treatment.

5 mg nebivolol once daily, then to 5 mg once daily and then to 10 mg once daily. The maximum recommended dose is 10 mg nebivolol once daily. Initiation of therapy and every dose increase should be done under the supervision of an experienced physician over a period of at least 2 hours to ensure that the clinical status (especially as regards blood pressure, heart rate, conduction disturbances, signs of worsening of heart failure) remains stable.

Occurrence of adverse events may prevent all patients being treated with the maximum recommended dose. If necessary, the dose reached can also be decreased step by step and reintroduced as appropriate. During the titration phase, in case of worsening of the heart failure or intolerance, it is recommended first to reduce the dose of nebivolol, or to stop it immediately if necessary (in case of severe hypotension, worsening of heart failure with acute pulmonary oedema, cardiogenic shock, symptomatic bradycardia or AV block).

Treatment of stable chronic heart failure with nebivolol is generally a long-term treatment. The treatment with nebivolol is not recommended to be stopped abruptly since this might lead to a transitory worsening of heart failure. If discontinuation is necessary, the dose should be gradually decreased divided into halves weekly.

Patients with renal insufficiency No dose adjustment is required in mild to moderate renal insufficiency since uptitration to the maximum tolerated dose is individually adjusted. There is no experience in patients with severe renal insufficiency (serum creatinine ≥250μmol/L).

Therefore, the use of nebivolol in these patients is not recommended. Patients with hepatic insufficiency Data in patients with hepatic insufficiency are limited. 5mg or Nebivolol 5mg Tablets in these patients is contra-indicated. Elderly No dose adjustment is required since up-titration to the maximum tolerated dose is individually adjusted.

5mg or Nebivolol 5mg Tablets in children and adolescents aged below 18 years has not been established. Therefore, use in children and adolescents is not recommended. No data are available. Method of administration Oral use. g one glass of water).

The tablet can be taken with or without food.

8. The following warnings and precautions apply to beta-adrenergic antagonists, such as nebivolol, in general. Anaesthesia Continuation of beta blockade reduces the risk of arrhythmias during induction and intubation. If beta blockade is interrupted in preparation for surgery, the beta- adrenergic antagonist should be discontinued at least 24 hours beforehand.

Caution should be observed with certain anaesthetics that cause myocardial depression. The patient can be protected against vagal reactions by intravenous administration of atropine. Cardiovascular In general, beta-adrenergic antagonists should not be used in patients with untreated congestive heart failure (CHF), unless their condition has been stabilised.

e. over 1-2 weeks. If necessary replacement therapy should be initiated at the same time, to prevent exacerbation of angina pectoris. Beta-adrenergic antagonists may induce bradycardia: if the pulse rate drops below 50- 55 bpm at rest and/or the patient experiences symptoms that are suggestive of bradycardia, the dosage should be reduced.

Beta-adrenergic antagonists should be used with caution: • in patients with peripheral circulatory disorders (Raynaud's disease or syndrome, intermittent claudication), as aggravation of these disorders may occur; • in patients with first degree heart block, because of the negative effect of beta- blockers on conduction time; • in patients with Prinzmetal's angina due to unopposed alphareceptor mediated coronary artery vasoconstriction: beta-adrenergic antagonists may increase the number and duration of anginal attacks.

5. Metabolic/Endocrinological Nebivolol does not affect glucose levels in diabetic patients. Care should be taken in diabetic patients however, as nebivolol may mask certain symptoms of hypoglycaemia (tachycardia, palpitations). Beta-blockers could further increase the risk of severe hypoglycaemia when used concurrently with sulfonylureas.

Diabetic patients should be advised to carefully monitor blood glucose levels. 5). Beta-adrenergic blocking agents may mask tachycardic symptoms in hyperthyroidism. Abrupt withdrawal may intensify symptoms. Respiratory In patients with chronic obstructive pulmonary disorders, beta-adrenergic antagonists should be used with caution as airway constriction may be aggravated.

Other Patients with a history of psoriasis should take beta-adrenergic antagonists only after careful consideration. Beta-adrenergic antagonists may increase the sensitivity to allergens and the severity of anaphylactic reactions. Beta-blockers may rarely cause decreased lacrimation.

The initiation of Chronic Heart Failure treatment with nebivolol necessitates regular monitoring. 2. Treatment discontinuation should not be done abruptly unless clearly indicated. 2. This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

4). Calcium channel antagonists of verapamil/diltiazem type: negative influence on contractility and atrio-ventricular conduction. 4). 4). Abrupt withdrawal, particularly if prior to beta-blocker discontinuation, may increase risk of “rebound hypertension”.

Combinations to be used with caution:

Class III antiarrhythmic drugs (Amiodarone): effect on atrio-ventricular conduction time may be potentiated. 4). As a general rule, avoid sudden withdrawal of beta-blocker treatment. 5mg or Nebivolol 5mg Tablets Insulin and oral antidiabetic drugs: although nebivolol does not affect glucose level, concomitant use may mask certain symptoms of hypoglycaemia (palpitations, tachycardia).

The concomitant use of beta-blockers with sulfonylureas could increase the risk of severe hypoglycaemia. 4). Baclofen (antispastic agent), amifostine (antineoplastic adjunct): concomitant use with antihypertensives is likely to increase the fall in blood pressure, therefore the dosage of the antihypertensive medication should be adjusted accordingly.

Mefloquine (antimalarian drug):

Theoretically co-administration with β-adrenergic blocking agents might contribute to a prolongation of the QTc interval.

Combinations to be considered:

Digitalis glycosides: concomitant use may increase atrio-ventricular conduction time. Clinical trials with nebivolol have not shown any clinical evidence of an […]

8. The following warnings and precautions apply to beta-adrenergic antagonists, such as nebivolol, in general. Anaesthesia Continuation of beta blockade reduces the risk of arrhythmias during induction and intubation. If beta blockade is interrupted in preparation for surgery, the beta- adrenergic antagonist should be discontinued at least 24 hours beforehand.

Caution should be observed with certain anaesthetics that cause myocardial depression. The patient can be protected against vagal reactions by intravenous administration of atropine. Cardiovascular In general, beta-adrenergic antagonists should not be used in patients with untreated congestive heart failure (CHF), unless their condition has been stabilised.

e. over 1-2 weeks. If necessary replacement therapy should be initiated at the same time, to prevent exacerbation of angina pectoris. Beta-adrenergic antagonists may induce bradycardia: if the pulse rate drops below 50- 55 bpm at rest and/or the patient experiences symptoms that are suggestive of bradycardia, the dosage should be reduced.

Beta-adrenergic antagonists should be used with caution: • in patients with peripheral circulatory disorders (Raynaud's disease or syndrome, intermittent claudication), as aggravation of these disorders may occur; • in patients with first degree heart block, because of the negative effect of beta- blockers on conduction time; • in patients with Prinzmetal's angina due to unopposed alphareceptor mediated coronary artery vasoconstriction: beta-adrenergic antagonists may increase the number and duration of anginal attacks.

Combination of nebivolol with calcium channel antagonists of the verapamil and diltiazem type, with Class I antiarrhythmic drugs, and with centrally acting antihypertensive drugs is generally not recommended, for details please refer to section

1. - Liver insufficiency or liver function impairment. v. inotropic therapy. In addition, as with other beta-blocking agents, Nebivolol is contra-indicated in: - sick sinus syndrome, including sino-atrial block. - second and third degree heart-block (without a pacemaker).

- history of bronchospasm and bronchial asthma. - untreated phaeochromocytoma. - metabolic acidosis. - bradycardia (heart rate < 60 bpm prior to start therapy). - hypotension (systolic blood pressure < 90 mmHg). - severe peripheral circulatory disturbances.