Schedule H

Oral

• Tablets: 2.5 mg, 5 mg, 10 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Hypertension

Parameter Recommendation

Starting dose 5 mg once daily orally

Titration Increase by 2.5–5 mg every 1–2 weeks based on BP response

Usual maintenance dose 5–10 mg once daily

Maximum dose 40 mg/day (doses above 10 mg rarely used in Indian practice)

Clinical Notes:

• Administer preferably in the morning

• Not suitable for acute hypertensive emergencies

• Vasodilatory action provides additional BP lowering effect

• Metabolically neutral compared to older beta-blockers

1. Chronic Heart Failure (NYHA Class II–III) — Specialist Only

Parameter Recommendation

Starting dose 1.25 mg once daily orally

Titration Double the dose every 1–2 weeks as tolerated

Usual maintenance dose 5–10 mg once daily

Maximum dose 10 mg/day

Clinical Notes:

• Initiate only in stable, compensated heart failure

• Contraindicated in acute decompensated heart failure

• Must be used alongside standard HF therapy (ACE inhibitors/ARBs, diuretics)

• Avoid initiation during hospital admission for acute HF exacerbation

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

Stable Angina Pectoris (OFF-LABEL) Starting: 5 mg once daily; Maintenance: 5–10 mg once daily; Maximum: 10 mg/day Long-term Specialist only; evidence from international trials; occasional use in Indian cardiology practice

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

Not applicable — Nebivolol is not routinely indicated in paediatric population. Safety and efficacy not established in children through robust clinical trials.

Secondary Indications — Paediatrics (Off-label)

Indication Dose Age Notes

Hypertension (OFF-LABEL) Starting: 0.15 mg/kg once daily; Titration: Gradual increase based on response; Maximum: 0.3 mg/kg/day or 5 mg/day (whichever is lower) ≥6 years Specialist only; limited paediatric pharmacokinetic data

Monitoring Required:

• Heart rate and BP monitoring at each visit

• Watch for bradycardia, hypotension, fatigue

Age Restriction: Not recommended in children below 6 years of age except under strict paediatric cardiologist supervision.

Dialysis: Nebivolol is not significantly removed by haemodialysis or peritoneal dialysis; no supplemental dosing required post-dialysis.

• Severe sinus bradycardia (<50 bpm)

• Second-degree or third-degree AV block (without functioning pacemaker)

• Sick sinus syndrome

• Cardiogenic shock

• Acute decompensated heart failure requiring inotropic support

• Severe hepatic impairment (Child-Pugh C)

• Severe bronchial asthma or history of bronchospasm

• Phaeochromocytoma (unless adequately alpha-blocked)

• Hypersensitivity to nebivolol or any excipient

• Concurrent use with MAO inhibitors (except MAO-B inhibitors)

• Diabetes mellitus — may mask tachycardia and tremor associated with hypoglycaemia; sweating is preserved

• COPD — beta-1 selectivity offers relative safety but use cautiously; avoid in severe obstructive disease

• Peripheral vascular disease — may aggravate symptoms of arterial insufficiency

• First-degree AV block — monitor for progression to higher-grade block

• Thyrotoxicosis — may mask clinical signs of hyperthyroidism (tachycardia)

• Psoriasis — beta-blockers may exacerbate or trigger new lesions

• Depression history — use with caution

• Prinzmetal angina — may worsen vasospastic episodes

• Abrupt withdrawal — taper gradually over 1–2 weeks to avoid rebound angina, hypertension, or arrhythmias

Aspect Details

Safety Category Not recommended; associated with fetal risks (based on beta-blocker class data)

Known Risks Intrauterine growth restriction (IUGR), fetal bradycardia, neonatal hypoglycaemia

Preferred Alternatives Labetalol (first-line), methyldopa, nifedipine for gestational hypertension in India

When to Use Only if no safer alternative available and benefits clearly outweigh risks; specialist input essential

Monitoring Serial fetal growth scans, fetal heart rate monitoring, maternal BP

Aspect Details

Compatibility Likely compatible with breastfeeding; limited human data

Drug Levels in Milk Expected to be low due to high protein binding (~98%)

Preferred Alternatives Labetalol or propranolol (more safety data available)

Infant Monitoring Observe for bradycardia, hypotension, lethargy, poor feeding

Aspect Recommendation

Starting dose 2.5 mg once daily

Titration Slower than younger adults; increase at 2–4 week intervals

Special Risks Orthostatic hypotension, bradycardia, falls, variable hepatic/renal function

Additional Notes Lower doses often sufficient due to reduced clearance; monitor closely

Interacting Drug Effect/Risk Management

Verapamil / Diltiazem Severe bradycardia, AV block, hypotension Avoid combination or use with extreme caution; ECG monitoring essential

Class I antiarrhythmics (disopyramide, flecainide) Additive negative inotropic and chronotropic effects Avoid concurrent use

Clonidine Rebound hypertensive crisis if clonidine withdrawn abruptly Discontinue nebivolol several days before tapering clonidine

MAO inhibitors (except MAO-B) Risk of severe hypertensive reaction Contraindicated

Strong CYP2D6 inhibitors (fluoxetine, paroxetine, quinidine) Significantly increased nebivolol plasma levels Reduce nebivolol dose; monitor closely for bradycardia

Interacting Drug Effect/Risk Management

NSAIDs Blunted antihypertensive effect Monitor BP; adjust dose if needed

Insulin / Oral hypoglycaemics Masking of hypoglycaemia symptoms Counsel patients; more frequent glucose monitoring

Digoxin Additive bradycardia and AV nodal depression Monitor heart rate and ECG

Rifampicin Reduced nebivolol efficacy via CYP2D6 induction Monitor BP response; may need dose increase

Amiodarone Additive AV nodal suppression ECG monitoring; watch for bradycardia

General anaesthetics Enhanced hypotensive effect Inform anaesthetist; may need dose adjustment perioperatively

• Headache

• Fatigue / tiredness

• Dizziness

• Bradycardia (usually asymptomatic)

• Gastrointestinal disturbances (nausea, diarrhoea, constipation)

• Paraesthesia

• Sleep disturbances

• Cold extremities (less common than with non-vasodilating beta-blockers)

Adverse Effect Action Required

Severe symptomatic bradycardia Discontinue; consider atropine or temporary pacing if required

High-grade AV block Immediate discontinuation; cardiology consultation

Acute decompensated heart failure Stop drug; initiate appropriate HF management

Bronchospasm Discontinue; administer bronchodilator

Severe hypotension Supportive care; IV fluids; consider glucagon in severe cases

Hypersensitivity reactions (rash, angioedema) Discontinue permanently

Long-term Periodic assessment of heart rate, BP, fatigue, exercise tolerance, mood; annual renal and hepatic function

Heart Failure Patients Weight monitoring, signs of fluid retention, functional status assessment

• Nebicard (Torrent)

• Nebistar (Lupin)

• Nebicip (Cipla)

• Nebzox (Glenmark)

• Nebilong (Micro Labs)

• Nebula (Sun Pharma)

Common FDCs:

2.5 mg tablet ₹2.5–4 per tablet

5 mg tablet ₹3.5–6 per tablet

10 mg tablet ₹6–10 per tablet

Note: Included in NLEM 2022; prices regulated by NPPA. Available through government supply at subsidised rates.

1. Metabolic advantage: Unlike older beta-blockers (atenolol, metoprolol), nebivolol has neutral effects on glucose and lipid metabolism — preferred choice in hypertensives with metabolic syndrome or diabetes.

1. Vasodilatory benefit: Nitric oxide-mediated vasodilation reduces peripheral vascular resistance — better tolerated in elderly and patients with borderline cold extremities.

1. Heart failure dosing: Always start at 1.25 mg in CHF and uptitrate slowly; never initiate during acute decompensation.

1. CYP2D6 metabolism: Poor metabolizers (approximately 10% of Indian population) may have higher plasma levels — start low in patients on CYP2D6 inhibitors (SSRIs, quinidine).

1. Withdrawal caution: Taper over 1–2 weeks before discontinuation in patients with ischaemic heart disease to prevent rebound phenomena.

1. BNP interpretation: Transient BNP elevation may occur after initiation in heart failure — not necessarily indicative of clinical worsening.

Nebivolol; hypertension; beta-blocker; heart failure; vasodilating-beta-blocker; cardioselective; metabolically-neutral; elderly-friendly; NLEM India; cardiology

RxIndia v1.0 — 04 Apr 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia (IP)

• National List of Essential Medicines (NLEM) 2022

• API Textbook of Medicine

• AIIMS Hospital Drug Formulary

• AIIMS Hypertension Management Protocol

• ICMR Guidelines on Hypertension Management

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• International RCTs (SENIORS trial — for heart failure indication, marked as supportive evidence)