Nebivolol Hydrochloride
Therapeutic Class: Beta-Blocker (Beta-adrenoceptor blocking drugs, Beta-blockers)
Indications:
Nebivolol is indicated in-
Nebivolo 2.5 : Each tablet contains Nebivolol hydrochloride INN equivalent to Nebivolol 2.5 mg.
Nebivolo 5 : Each tablet contains Nebivolol hydrochloride INN equivalent to Nebivolol 5 mg.
Description:
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 the beta-blocking activity.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.
Nebivolo 2.5 : Each tablet contains Nebivolol hydrochloride INN equivalent to Nebivolol 2.5 mg.
Nebivolo 5 : Each tablet contains Nebivolol hydrochloride INN equivalent to Nebivolol 5 mg.
Description:
Mode of Action of Nebivolol involved include:
- decreased heart rate
- decreased myocardial contractility
- diminution of tonic sympathetic outflow to the periphery from cerebral vasomotor centers
- suppression of renin activity and
- vasodilation and decreased peripheral vascular resistance
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.
Dosage & Administration:
Hypertension
Adults: 5mg daily, preferably at the same time of the day.
Elderly (In patients over 65 years): The recommended starting dose is 2.5 mg daily. The dose may be increased to 5mg daily if needed.
Patient with renal insufficiency: The recommended starting dose is 2.5 mg daily. The daily dose may be increased to 5mg if needed.
Patients with hepatic insufficiency: Data in patients with hepatic insufficiency or impaired liver function are limited. Therefore the use of Nebivolol in these patients is contraindicated.
Chronic Heart Failure
The initial up-titration in case of chronic heart failure patients should be done according to the following steps at 1-2 weekly intervals based on the patient’s tolerability.
1.25mg daily, to be increased to 2.5mg once daily, then to 5mg once daily, and then to 10mg once daily. The maximum recommended dose is 10mg daily.
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.
Dosage & Administration:
Hypertension
Adults: 5mg daily, preferably at the same time of the day.
Elderly (In patients over 65 years): The recommended starting dose is 2.5 mg daily. The dose may be increased to 5mg daily if needed.
Patient with renal insufficiency: The recommended starting dose is 2.5 mg daily. The daily dose may be increased to 5mg if needed.
Patients with hepatic insufficiency: Data in patients with hepatic insufficiency or impaired liver function are limited. Therefore the use of Nebivolol in these patients is contraindicated.
Chronic Heart Failure
The initial up-titration in case of chronic heart failure patients should be done according to the following steps at 1-2 weekly intervals based on the patient’s tolerability.
1.25mg daily, to be increased to 2.5mg once daily, then to 5mg once daily, and then to 10mg once daily. The maximum recommended dose is 10mg daily.
with or without food, as monotherapy, or in combination with other agents.
Side Effects:
The most common side effects are headache, nausea, and bradycardia.
Precautions:
Patients with coronary artery disease treated with Nebivolol should be advised against abrupt discontinuation of therapy. Caution should be exercised in patients with circulatory disorders, first-degree heart block, anesthesia, diabetes, hyperthyroidism, chronic obstructive pulmonary disorders, and allergen sensitivity.
Use in Pregnancy & Lactation:
Nebivolol is contra-indicated in pregnancy and lactation.
Interaction:
As Nebivolol metabolism involves the CYP2D6 isoenzyme, co-administration with substances inhibiting this enzyme, especially paroxetine, fluoxetine, thioridazine, and quinidine may lead to increased plasma levels of nebivolol associated with an increased risk of excessive bradycardia and adverse events.
Overdose:
The symptoms of overdose are bradycardia, hypotension, bronchospasm, and acute cardiac insufficiency.
Side Effects:
The most common side effects are headache, nausea, and bradycardia.
Precautions:
Patients with coronary artery disease treated with Nebivolol should be advised against abrupt discontinuation of therapy. Caution should be exercised in patients with circulatory disorders, first-degree heart block, anesthesia, diabetes, hyperthyroidism, chronic obstructive pulmonary disorders, and allergen sensitivity.
Use in Pregnancy & Lactation:
Nebivolol is contra-indicated in pregnancy and lactation.
Interaction:
As Nebivolol metabolism involves the CYP2D6 isoenzyme, co-administration with substances inhibiting this enzyme, especially paroxetine, fluoxetine, thioridazine, and quinidine may lead to increased plasma levels of nebivolol associated with an increased risk of excessive bradycardia and adverse events.
Overdose:
The symptoms of overdose are bradycardia, hypotension, bronchospasm, and acute cardiac insufficiency.
Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.