Adult: As monotherapy or in combination with other antihypertensive agents: Initially, 5 mg once daily; may increase as necessary at 2-week intervals up to Max of 40 mg once daily. Adjust dose according to individual requirements. Elderly: Initially, 2.5 mg daily; may increase to 5 mg daily if necessary.
Oral Chronic heart failure
Elderly: ≥70 years In stable mild and moderate cases, as an adjunct to standard therapies: Initially, 1.25 mg once daily; if tolerated, may gradually double the dose every 1-2 weeks. Max: 10 mg once daily. Adjust dose according to patient's clinical response and tolerability. Treatment recommendations may vary among individual products and between countries (refer to specific product guidelines).
Renal Impairment
Hypertension:
Initially, 2.5 mg daily; may increase to 5 mg daily if necessary.
Chronic heart failure:
Severe: Not recommended.
Hepatic Impairment
Contraindicated.
Administration
May be taken with or without food.
Contraindications
Acute heart failure, cardiogenic shock or episodes of heart failure decompensation requiring IV inotropic therapy; sick sinus syndrome (including sinoatrial block), 2nd- or 3rd-degree heart block (without a pacemaker); history of bronchospasm and bronchial asthma; untreated phaeochromocytoma; severe bradycardia, hypotension (systolic blood pressure of <90 mmHg), severe peripheral circulatory disturbances; metabolic acidosis. Hepatic impairment.
Special Precautions
Patient with peripheral circulatory disorders (e.g. Raynaud's disease, intermittent claudication), 1st-degree heart block, Prinzmetal's angina, diabetes mellitus, thyroid disease, history of psoriasis, COPD, history of severe anaphylaxis to a variety of allergens; myasthenia gravis. Patients undergoing surgery. Avoid abrupt withdrawal; chronic therapy must not be routinely withdrawn before major surgery. May mask the signs and symptoms of hypoglycaemia and hyperthyroidism (particularly tachycardia). Renal impairment; not recommended in severe renal impairment when used for chronic heart failure. Elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Bradycardia. Cardiac disorders: Heart failure, slowed atrioventricular conduction, atrioventricular block. Eye disorders: Impaired vision. Gastrointestinal disorders: Nausea, diarrhoea, constipation, dyspepsia, flatulence, vomiting, abdominal discomfort. General disorders and administration site conditions: Fatigue, peripheral oedema. Nervous system disorders: Headache, dizziness, paraesthesia. Psychiatric disorders: Insomnia, nightmares, depression. Reproductive system and breast disorders: Impotence. Respiratory, thoracic and mediastinal disorders: Dyspnoea, bronchospasm. Skin and subcutaneous tissue disorders: Rash erythematous, pruritus. Very rarely, aggravated psoriasis. Vascular disorders: Hypotension, claudication.
Monitor blood pressure and heart rate (before and during therapy and following any dose changes); serum glucose (in diabetic patients); renal and liver function. Obtain ECG.
Overdosage
Symptoms: Bradycardia, hypotension, bronchospasm, acute cardiac insufficiency, dizziness, hypoglycaemia, vomiting, and fatigue. Management: Symptomatic and supportive treatment. Administer IV atropine for bradycardia; if insufficient response, give isoprenaline or another agent with positive chronotropic properties cautiously. Administer IV fluids and vasopressors for hypotension; IV glucagon may also be useful. For 2nd- or 3rd-degree heart block, monitor the patient and administer isoprenaline infusion. Give digitalis glycoside and diuretics for CHF; may consider inotropic and vasodilating agents in some cases. Administer bronchodilator therapy (e.g. short-acting inhaled β2-agonist and/or aminophylline) for bronchospasm. Administer IV glucose for hypoglycaemia.
Drug Interactions
Effect on atrioventricular conduction time may be potentiated and the negative inotropic effect increased with class I (e.g. quinidine, flecainide, lidocaine, disopyramide, mexiletine, propafenone, hydroquinidine, cibenzoline) and class III (e.g amiodarone) antiarrhythmics. May cause profound hypotension and atrioventricular block with IV verapamil . Concomitant use with Ca channel antagonists of verapamil or diltiazem type may have a negative influence on contractility and atrioventricular conduction. May worsen heart failure with centrally acting antihypertensives (e.g. clonidine, methyldopa, guanfacine, moxonidine, rilmenidine). May attenuate reflex tachycardia and increase the risk of hypotension with anaesthetics. May enhance the hypoglycaemic effects of antidiabetic agents. May increase atrioventricular conduction time with digitalis glycosides. Increase risks of hypotension with dihydropyridine Ca antagonists (e.g. amlodipine, nifedipine), amifostine, baclofen, TCAs, barbiturates, and phenothiazines. Increased plasma concentration associated with an increased risk of excessive bradycardia and adverse events with CYP2D6 inhibitors (e.g. fluoxetine, paroxetine, thioridazine, quinidine). Increased plasma concentration with cimetidine. May produce an excessive reduction of sympathetic activity with catecholamine-depleting drugs (e.g. reserpine, guanethidine).
Lab Interference
May cause false-positive aldosterone/renin ratio.
Action
Description: Mechanism of Action: Nebivolol exhibits high selectivity for β1-adrenergic receptors. The possible factors that may be involved in its mechanism of action are decreased heart rate, myocardial contractility, or sympathetic outflow from the CNS, inhibition of renin activity, and decreased peripheral vascular resistance. Additionally, it produces an endothelium-derived nitric oxide-dependent vasodilation which leads to the reduction of systemic vascular resistance. Pharmacokinetics: Absorption: Rapidly absorbed. Bioavailability: Approx 12% (extensive metabolisers); 96% (poor metabolisers). Time to peak plasma concentration: 1.5-4 hours. Distribution: Volume of distribution: 8-12 L/kg. Plasma protein binding: Approx 98%, mainly to albumin. Metabolism: Extensively metabolised in the liver via direct glucuronidation of the parent drug, and to a lesser extent via N-dealkylation, and oxidation by CYP2D6 isoenzyme. Undergoes extensive first-pass metabolism. Excretion: Via urine (extensive metabolisers: 38%; poor metabolisers: 67%; <0.5% as unchanged drug); faeces (extensive metabolisers: 44%; poor metabolisers: 13%; <0.5% as unchanged drug). Elimination half-life: 12 hours (extensive metabolisers); 19 hours (poor metabolisers).
Chemical Structure
Nebivolol Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 71301, Nebivolol. https://pubchem.ncbi.nlm.nih.gov/compound/71301. Accessed July 27, 2022.
C07AB12 - nebivolol ; Belongs to the class of selective beta-blocking agents. Used in the treatment of cardiovascular diseases.
References
Anon. Nebivolol Hydrochloride. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 04/07/2022.Anon. Nebivolol. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 04/07/2022.Buckingham R (ed). Nebivolol. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/07/2022.Joint Formulary Committee. Nebivolol. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/07/2022.Nebilet 5 mg (A. Menarini Singapore Pte. Ltd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 04/07/2022.Nebivolol 5 mg Tablets (Milpharm Limited). MHRA. https://products.mhra.gov.uk. Accessed 04/07/2022.Nebivolol Tablet (American Health Packaging). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 04/07/2022.
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