Schedule H

Oral

Form Available Strengths

Tablets 1.25 mg, 2.5 mg, 5 mg, 10 mg

FDC with Amlodipine Bisoprolol 2.5 mg/5 mg + Amlodipine 5 mg

FDC with Hydrochlorothiazide Bisoprolol 2.5 mg/5 mg + HCTZ 6.25 mg

Note: 1.25 mg tablets available from select manufacturers; alternatively, 2.5 mg tablets may be halved for initial HF dosing.

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Essential Hypertension

Parameter Recommendation

Starting dose 2.5–5 mg orally once daily (morning)

Titration Increase by 2.5–5 mg every 2–4 weeks based on BP response

Usual maintenance dose 5–10 mg once daily

Maximum dose 20 mg once daily

Clinical Notes:

• Can be used as first-line or add-on therapy

• Once-daily dosing ensures good compliance

• Effect on BP seen within 1–2 weeks; maximum effect by 4–8 weeks

1. Stable Chronic Heart Failure with Reduced Ejection Fraction (HFrEF) — NYHA Class II–IV

Parameter Recommendation

Starting dose 1.25 mg orally once daily

Titration Double dose every 1–2 weeks as tolerated

Titration steps 1.25 mg → 2.5 mg → 3.75 mg → 5 mg → 7.5 mg → 10 mg

Usual maintenance dose 10 mg once daily (target dose)

Maximum dose 10 mg once daily

Pre-initiation Requirements:

• Patient must be clinically stable (no IV diuretics, no fluid overload)

• On optimised ACE inhibitor/ARB and diuretic therapy

• No recent decompensation (<4 weeks)

Clinical Notes:

• Evidence-based mortality benefit (CIBIS-II trial)

• Initiate only when patient euvolaemic and stable

• Temporary worsening of HF symptoms may occur during up-titration — manage with diuretic adjustment, not beta-blocker discontinuation

• Never withdraw abruptly — risk of acute decompensation

1. Stable Angina Pectoris

Parameter Recommendation

Starting dose 5 mg orally once daily

Titration Increase to 10 mg once daily after 1–2 weeks if symptoms persist

Usual maintenance dose 5–10 mg once daily

Maximum dose 20 mg once daily

Clinical Notes:

• Aim for resting HR 55–60 bpm for optimal anti-anginal effect

• Often combined with long-acting nitrates or dihydropyridine CCBs (amlodipine)

• Avoid combination with rate-limiting CCBs (verapamil, diltiazem) — risk of severe bradycardia

1. Cardiac Arrhythmias — Ventricular Rate Control

Parameter Recommendation

Starting dose 2.5 mg orally once daily

Titration Increase every 1–2 weeks based on HR control

Usual maintenance dose 5–10 mg once daily

Maximum dose 10 mg once daily for rate control

Clinical Notes:

• Useful for rate control in atrial fibrillation/flutter when rapid ventricular response

• Less effective in high catecholamine states compared to non-selective beta-blockers

• Monitor for excessive bradycardia

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

Atrial fibrillation (rate control) 2.5–10 mg once daily Long-term OFF-LABEL; Cardiology specialist; established Indian practice

Premature ventricular complexes (PVCs) 2.5–10 mg once daily Long-term OFF-LABEL; Cardiology specialist; symptomatic patients

Thyrotoxicosis (symptomatic control) 5–10 mg once daily Until euthyroid OFF-LABEL; For palpitations/tremor control; non-selective preferred for severe cases

Migraine prophylaxis 5–10 mg once daily ≥3 months trial OFF-LABEL; Neurology practice; propranolol more commonly used

Performance anxiety 2.5–5 mg single dose PRN As needed OFF-LABEL; Situational use

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

Limited approved paediatric indications in India. Use is OFF-LABEL and requires paediatric cardiology supervision.

Heart Failure / Cardiomyopathy (Paediatric)

Age/Weight Starting Dose Titration Maximum Dose

Children ≥6 years 0.05–0.1 mg/kg/day once daily Double every 1–2 weeks as tolerated 0.2 mg/kg/day (max 10 mg/day)

Adolescents ≥12 years 1.25 mg once daily As per adult HF protocol 10 mg once daily

Secondary Indications — Paediatrics (Off-label)

Indication Age Dose Duration Notes

Congenital long QT syndrome ≥5 years 0.1–0.2 mg/kg/day Long-term OFF-LABEL; Paediatric cardiology only

Hypertrophic cardiomyopathy ≥5 years 0.1–0.2 mg/kg/day Long-term OFF-LABEL; Specialist only

Paediatric hypertension ≥6 years 0.05–0.2 mg/kg/day Long-term OFF-LABEL; Limited data

Paediatric Safety Notes

Parameter Recommendation

Minimum age Not recommended <5 years except under paediatric cardiologist supervision

Monitoring HR, BP, ECG at baseline and during titration

Formulation Use tablets (no liquid formulation available in India); may need extemporaneous preparation

Contraindications Same as adults — asthma, severe bradycardia, AV block

60 No adjustment required

30–60 No adjustment; monitor for accumulation

10–30 Start 1.25–2.5 mg once daily; titrate cautiously

<10 or Dialysis Start 1.25 mg once daily; maximum 5 mg/day; not significantly dialysed

Note: Bisoprolol has balanced hepatic (50%) and renal (50%) elimination — dose reduction needed mainly in severe combined impairment.

• Severe sinus bradycardia (HR <50 bpm at rest)

• Sick sinus syndrome (without pacemaker)

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

• Cardiogenic shock

• Decompensated heart failure requiring IV inotropes

• Severe bronchial asthma or severe COPD with bronchospasm

• Symptomatic hypotension (SBP <90 mmHg)

• Untreated phaeochromocytoma

• Severe peripheral arterial disease with rest pain/gangrene

• Metabolic acidosis

• Known hypersensitivity to bisoprolol or other beta-blockers

• Controlled asthma / mild-moderate COPD — use with caution; β1-selectivity reduces but does not eliminate bronchospasm risk

• Diabetes mellitus — may mask tachycardia and tremor of hypoglycaemia; sweating preserved

• Peripheral vascular disease — may worsen claudication

• Prinzmetal's (variant) angina — unopposed alpha-mediated vasoconstriction may worsen

• First-degree AV block — monitor for progression

• Psoriasis — may exacerbate

• History of anaphylaxis — may reduce efficacy of adrenaline

• Concurrent use with rate-limiting CCBs (verapamil, diltiazem) — risk of severe bradycardia/AV block

• Myasthenia gravis — may worsen symptoms

• Depression — caution advised

• Abrupt withdrawal — may precipitate rebound angina, MI, or arrhythmias; always taper over 1–2 weeks

Parameter Recommendation

Overall safety Use only if potential benefit outweighs risk

Known risks Fetal bradycardia, hypoglycaemia, intrauterine growth restriction

Trimester considerations Relatively more data in 3rd trimester; limited 1st trimester data

Preferred alternatives Labetalol (first choice in pregnancy), Methyldopa

When to use Maternal cardiac conditions (HF, arrhythmias) where beta-blockade essential

Monitoring Serial fetal growth scans, fetal HR monitoring, neonatal observation for 48–72 hours post-delivery

Parameter Recommendation

Compatibility Generally compatible with breastfeeding

Drug levels in milk Low (milk:plasma ratio ~0.1–0.3)

Preferred alternatives Metoprolol, Propranolol (more lactation data available)

Infant monitoring Heart rate, feeding patterns, weight gain, signs of beta-blockade (lethargy, poor feeding)

Parameter Recommendation

Starting dose 1.25–2.5 mg once daily

Titration Slower than standard — increase every 2–4 weeks

Maximum dose As per indication; often lower doses sufficient

Extra risks Bradycardia, orthostatic hypotension, falls, fatigue, cognitive effects, reduced cardiac reserve

Monitoring Orthostatic BP measurement; HR; renal function

Interacting Drug Effect Recommendation

Verapamil, Diltiazem Additive negative chronotropic and inotropic effects → severe bradycardia, AV block, hypotension Avoid combination or use only with continuous ECG monitoring; specialist supervision

Class I antiarrhythmics (Disopyramide, Flecainide, Propafenone) Additive cardiac depression Avoid or use with extreme caution; ECG monitoring

Clonidine Rebound hypertension if clonidine stopped first Withdraw bisoprolol first, then taper clonidine

MAO inhibitors (non-selective) Exaggerated hypotension Avoid concurrent use

Adrenaline (Epinephrine) Unopposed alpha-stimulation → severe hypertension Avoid in patients on beta-blockers; use with caution in anaphylaxis

Fingolimod Additive bradycardia at initiation Avoid combination; specialist supervision if essential

Interacting Drug Effect Recommendation

Insulin / Sulfonylureas Masking of hypoglycaemia symptoms (except sweating) Counsel diabetic patients; monitor glucose closely

Digoxin Additive bradycardia; AV conduction delay Monitor HR and ECG; digoxin levels if toxicity suspected

NSAIDs (Ibuprofen, Diclofenac) Blunted antihypertensive effect Monitor BP; consider paracetamol for analgesia

Rifampicin Reduced bisoprolol levels (CYP3A4 induction) May need higher bisoprolol dose; monitor BP and HR

Dihydropyridine CCBs (Amlodipine, Nifedipine) Additive hypotension Generally safe combination; monitor BP

Mefloquine Additive bradycardia Monitor HR

Amiodarone Additive bradycardia, AV block Monitor ECG; often used together in AF but requires monitoring

Anaesthetic agents Enhanced hypotension and bradycardia Inform anaesthetist; usually continued perioperatively

Ergot alkaloids Increased peripheral vasoconstriction Avoid combination

Lidocaine Increased lidocaine levels Monitor for toxicity if IV lidocaine used

• Fatigue, tiredness (most common)

• Bradycardia

• Dizziness, lightheadedness

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

• Headache

• Gastrointestinal disturbances (nausea, diarrhoea, constipation)

• Sleep disturbances (insomnia, vivid dreams — less common than lipophilic beta-blockers)

• Erectile dysfunction

Adverse Effect Clinical Notes

Severe bradycardia / Sinus arrest Discontinue or reduce dose; atropine if symptomatic

High-grade AV block May require temporary/permanent pacing

Acute heart failure decompensation Usually during up-titration; manage with diuretics, do not abruptly stop beta-blocker

Bronchospasm Rare with bisoprolol; more likely in asthmatics; discontinue immediately

Severe hypotension Reduce dose; IV fluids if needed

Masked hypoglycaemia Diabetic patients may not recognise symptoms

Raynaud's phenomenon / Worsening PVD Consider dose reduction or alternative

Psoriasis exacerbation Consider alternative agent

Depression Rare; monitor mood

During HF titration Weekly assessment of symptoms (dyspnoea, weight gain, oedema)

Long-term HR and BP every 3–6 months; annual renal function; ECG if concerns about conduction

Special populations More frequent monitoring in elderly, CKD, diabetes

Target HR: 55–65 bpm in stable angina/HF for optimal benefit

Concor Merck/Abbott 1.25 mg, 2.5 mg, 5 mg, 10 mg

Corbis Torrent 2.5 mg, 5 mg

Biselect Intas 2.5 mg, 5 mg, 10 mg

Zabesta Zydus 2.5 mg, 5 mg

Bisoprol Cipla 2.5 mg, 5 mg, 10 mg

Cardibeta Cadila 5 mg

Lodoz Merck FDC with HCTZ

Fixed-Dose Combinations:

Brand Composition

1.25 mg tablet ₹4–8

2.5 mg tablet ₹2–5

5 mg tablet ₹3–7

10 mg tablet ₹5–10

FDC (Bisoprolol + Amlodipine) ₹8–15

NLEM 2022 Status: Bisoprolol included (2.5 mg, 5 mg tablets) — NPPA price ceiling applicable

Jan Aushadhi Availability: Available at subsidised rates

1. Most β1-selective: Bisoprolol has highest β1-selectivity among commonly used beta-blockers (selectivity ratio ~75:1) — preferred choice in patients with mild controlled asthma/COPD where beta-blockade is essential.

1. Heart failure gold standard: One of only three beta-blockers with proven mortality benefit in HFrEF (along with carvedilol, metoprolol succinate). Target dose is 10 mg — aim to reach it, but any tolerated dose is better than none.

1. Start low, go slow in HF: Never start at full dose in HF. Transient worsening is expected during up-titration — manage with diuretic adjustment, not beta-blocker cessation.

1. Never stop abruptly: Sudden withdrawal in IHD patients can precipitate acute coronary syndrome. Taper over 1–2 weeks if discontinuation needed.

1. Once-daily advantage: Long half-life (~10–12 hours) allows reliable once-daily dosing with consistent 24-hour effect, improving compliance.

1. Diabetes counselling essential: Warn diabetic patients that hypoglycaemia symptoms (palpitations, tremor) may be masked; sweating is preserved as warning sign.

beta-blocker; cardioselective; bisoprolol; hypertension; heart-failure; HFrEF; stable-angina; rate-control; NLEM-India; pregnancy-caution; COPD-safer

RxIndia v1.1 — 30 May 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia (IP)

• National List of Essential Medicines (NLEM) 2022

• API Textbook of Medicine

• ICMR Guidelines for Management of Hypertension

• Cardiological Society of India — Heart Failure Guidelines

• AIIMS Drug Formulary

• CIBIS-II Trial (Lancet 1999) — HF mortality evidence

• Indian Heart Journal — Guidelines and reviews

• Goodman & Gilman's The Pharmacological Basis of Therapeutics