Cardoneb Tablet 5 mg

Nebivolol is indicated in-

• Hypertension
• Treatment of essential hypertension
• Chronic heart failure (CHF)
• Treatment of stable mild and moderate chronic heart failure in addition to standard therapies in elderly patients.

Nebivolol is a β adrenergic receptor blocking agent. Nebivolol inhibits both β1 and β1 adrenergic receptors. Nebivolol lacks intrinsic sympathomimetic and membrane stabilizing activity at therapeutically relevant concentrations. At clinically relevant doses, Nebivolol does not demonstrate β1-adrenergic receptor blockade activity. Various metabolites, including glucuronides, contribute to beta-blocking activity.

Mode of Action of Nebivolol involved include:

• decreased heart rate
• decreased myocardia contractility
• diminution of tonic sympathetic outflow to the periphery from cerebral vasomotor centers
• suppression of renin activity and
• vasodilation and decreased peripheral vascular resistance

Pharmacokinetics: Nebivolol is metabolized by a number of routes, including glucuronidation and hydroxylation by CYP2D6. The active isomer (d-nebivolol) has an effective half-life of about 12 hours in CYP2D6 extensive metabolizers (most people), and 19 hours in poor metabolizers and exposure to d-nebivolol is substantially increased in poor metabolizers. This has less importance than usual, however, because the metabolites, including the hydroxyl metabolite and glucuronides (the predominant circulating metabolites), contribute to b blocking activity.

Absorption and Distribution: Absorption of Nebivolol is similar to an oral solution. Mean peak plasma nebivolol concentrations occur approximately 1.5 to 4 hours post-dosing in EMs and PMs. Food does not alter the pharmacokinetics of nebivolol. Nebivolol may be administered without regard to meals. The in vitro human plasma protein binding of nebivolol is approximately 98%, mostly to albumin, and is independent of nebivolol concentrations.

Metabolism and Excretion: Nebivolol is predominantly metabolized via direct glucuronidation of parent and to a lesser extent via N-dealkylation and oxidation via cytochrome P450 2D6. After a single oral administration of 14C-nebivolol, 38% of the dose was recovered in urine and 44% in feces for EMs and 67% in urine and 13% in feces for PMs.

Digoxin: Concomitant administration of Nebivolol (10 mg once daily) and digoxin (0.25 mg once daily) for 10 days in 14 healthy adult individuals resulted in no significant changes in the pharmacokinetics of digoxin or nebivolol.

Warfarin: Administration of Nebivolol (10 mg once daily for 10 days) led to no significant changes in the pharmacokinetics of nebivolol or R- or S-warfarin following a single 10 mg dose of warfarin. Similarly, nebivolol has no significant effects on the anticoagulant activity of warfarin, as assessed by Prothrombin time and INR profiles from 0 to 144 hours after a single 10 mg warfarin dose in 12 healthy adult volunteers. The starting dose should be reduced in patients with moderate hepatic impairment. No formal studies have been performed in patients with severe hepatic impairment and nebivolol should be contraindicated for these patients.

The dose of Nebivolol should 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.

Nebivolol should be used with care when myocardial depressants or inhibitors of AV conduction, such as certain calcium antagonists (particularly of the phenylalkylamine [verapamil] and benzothiazepine [diltiazem] classes), or antiarrhythmic agents, such as disopyramide, are used concurrently. Both digitalis glycosides and β-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.

Nebivolol should not be combined with other β-blockers. Patients receiving catecholamine-depleting drugs, such as reserpine or guanethidine, should be closely monitored, because the added β-blocking action of Nebivolol may produce excessive reduction of sympathetic activity. In patients who are receiving Nebivolol and clonidine, Nebivolol should be discontinued for several days before the gradual tapering of clonidine.

CYP2D6 Inhibitors: Use caution when Nebivolol is co-administered with CYP2D6 inhibitors (quinidine, propafenone, fluoxetine, paroxetine, etc.)

Nebivolol is contraindicated in patients with severe bradycardia, heart block greater than first degree, cardiogenic shock, decompensated cardiac failure, sick sinus syndrome (unless a permanent pacemaker is in place), or severe hepatic impairment (Child-Pugh >B), and in patients who are hypersensitive to any component of this product.

Headache, nausea and bradycardia.