Schedule H

Oral, Intravenous (IV)

• Tablets: 100 mg, 200 mg

• Injection: 5 mg/mL (20 mL ampoule — 100 mg total)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Severe Hypertension in Pregnancy / Pre-Eclampsia / Eclampsia — Acute Blood Pressure Control

Intravenous Route — Bolus Method

Step Dose Clinical Notes

Starting dose 20 mg IV over 2 minutes Patient must be supine; begin continuous BP monitoring

Titration Double dose every 10 minutes (20 → 40 → 80 → 80 mg) Continue until target BP achieved

Usual maintenance dose Not applicable for bolus method Switch to oral or infusion after control

Maximum dose 300 mg total cumulative dose per episode Higher doses rarely provide additional benefit

Intravenous Route — Continuous Infusion Method

Step Dose Clinical Notes

Starting dose 20 mg IV bolus, then start infusion at 1 mg/min Use infusion pump

Titration Adjust rate every 10–15 minutes based on BP response Reduce rate once target achieved

Usual maintenance dose 0.5–2 mg/min Target: SBP 140–150 mmHg, DBP 90–100 mmHg

Maximum dose 300 mg total; maximum infusion rate 2 mg/min

Key points:

• First-line agent for acute severe hypertension in pregnancy (AIIMS, MoHFW protocols)

• Patient MUST be supine during IV administration — risk of severe postural hypotension

• Target BP: Reduce by 15–25% in first hour; avoid precipitous drop

• Monitor fetal heart rate during treatment

1. Hypertensive Emergency / Hypertensive Urgency (Non-Pregnant Adults)

Intravenous Route

Step Dose Clinical Notes

Starting dose 20 mg IV over 2 minutes In ICU/CCU with continuous monitoring

Titration Additional 40–80 mg every 10 minutes as needed Assess response before each increment

Usual maintenance dose Continuous infusion 0.5–2 mg/min after initial control

Maximum dose 300 mg total IV per treatment episode

Key points:

• Preferred in hypertensive emergencies with tachycardia (balanced alpha-beta blockade)

• Suitable for aortic dissection (reduces heart rate and BP simultaneously)

• Avoid in acute decompensated heart failure, severe bradycardia

1. Chronic Hypertension/ Preeclampsia with non severe features — Oral Maintenance

Oral Route

Step Dose Clinical Notes

Starting dose 100 mg twice daily May start with 100 mg once daily if sensitive

Titration Increase by 100 mg BD every 2–3 days based on response Assess standing and supine BP

Usual maintenance dose 200–400 mg twice daily Divided dosing essential

Maximum dose 2400 mg/day in divided doses Rarely required; most patients controlled at 400–800 mg/day

Key points:

• Effective for essential hypertension and pregnancy-associated hypertension

• May combine with diuretics or vasodilators if needed

• Do not stop abruptly — taper over 1–2 weeks to avoid rebound hypertension

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

Acute Aortic Dissection IV: Same as hypertensive emergency; target HR 60 bpm and SBP 100–120 mmHg Until surgical intervention or stabilisation OFF-LABEL for this specific indication; Specialist (cardiology/vascular surgery) only; ICU setting; Evidence: International guidelines, Indian ICU protocols

Phaeochromocytoma (pre-operative/intraoperative) IV infusion titrated to BP response Peri-operative period OFF-LABEL; Specialist only; ONLY after adequate alpha-blockade established; Evidence: Endocrine surgery protocols

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

1. Hypertensive Emergency

Intravenous Route — Weight-Based

Step Dose Clinical Notes

Starting dose (Bolus) 0.2–0.5 mg/kg IV over 2 minutes Maximum single bolus 20 mg initially

Titration May repeat every 10 minutes; increase to 1 mg/kg/dose if needed Maximum single bolus 40 mg

Usual maintenance dose Continuous infusion 0.25–1 mg/kg/hour Start after bolus achieves partial control

Maximum dose 3 mg/kg/hour infusion OR 40 mg single bolus

Safety monitoring:

• Continuous cardiac monitoring (HR, rhythm)

• Arterial BP monitoring (invasive preferred in PICU)

• Watch for excessive bradycardia and hypotension

Secondary Indications — Paediatrics (Off-label)

Indication Dose Duration Notes

Chronic Hypertension (Oral) 1–3 mg/kg/day in 2–3 divided doses Long-term OFF-LABEL; Paediatric nephrology/cardiology specialist only; Maximum 10 mg/kg/day or 1200 mg/day; Evidence: Limited paediatric data; used in refractory cases

Minimum age: Not recommended below 1 year of age except under paediatric intensivist supervision for life-threatening hypertensive emergency

Notes:

• Labetalol is primarily hepatically metabolised

• Use with caution in advanced CKD due to risk of hypotension and reduced renal perfusion

• Not significantly removed by haemodialysis — no supplemental dose needed

Note: Labetalol undergoes extensive hepatic first-pass metabolism; bioavailability increases significantly in hepatic impairment

• Asthma or history of bronchospasm (including reactive airway disease)

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

• Severe sinus bradycardia (<45–50 bpm)

• Cardiogenic shock

• Uncompensated heart failure

• Severe hypotension (SBP <90 mmHg)

• Sick sinus syndrome (without pacemaker)

• Known hypersensitivity to labetalol

• Phaeochromocytoma without prior adequate alpha-blockade

• Diabetes mellitus — beta-blockade may mask hypoglycaemic symptoms (tachycardia, tremor); glucose monitoring advised

• Compensated heart failure — may worsen; use with caution if at all

• Peripheral vascular disease — may exacerbate symptoms

• First-degree heart block — monitor for progression

• COPD (non-reversible) — use with caution; labetalol has some beta-1 selectivity but not entirely cardioselective

• Prinzmetal's angina — beta-blockade may worsen coronary vasospasm

• Concurrent general anaesthesia — additive myocardial depression

• Elderly patients — increased sensitivity to hypotensive effects

• Rapid IV administration — risk of severe postural hypotension

• Abrupt discontinuation — may cause rebound hypertension and tachycardia

Parameter Recommendation

Safety category Generally considered SAFE; extensive experience in pregnancy; preferred antihypertensive for severe hypertension in pregnancy

Preferred alternatives Methyldopa (for chronic hypertension, especially first trimester); nifedipine (alternative for acute control); hydralazine (alternative IV agent)

When it may be used Acute severe hypertension in pre-eclampsia/eclampsia (first-line IV); chronic hypertension in pregnancy (oral maintenance)

Monitoring Maternal: BP (supine and standing), heart rate, signs of heart failure; Fetal: Continuous fetal heart rate monitoring during IV administration; growth surveillance with chronic use

Notes:

• Preferred over atenolol (which causes IUGR)

• May cause neonatal bradycardia and hypoglycaemia if used close to delivery — observe neonate for 24–48 hours

• Standard of care as per AIIMS and MoHFW obstetric protocols

Parameter Recommendation

Compatibility Compatible with breastfeeding

Drug levels in milk Low (0.004–0.07% of maternal dose reaches infant)

Preferred alternatives Not required — labetalol is considered safe

Infant monitoring Observe for bradycardia, hypotension, hypoglycaemia (especially in premature or low-birth-weight infants); routine monitoring usually sufficient

• Recommended starting dose: 50–100 mg once or twice daily (oral); reduced IV boluses (10–20 mg initially)

• Titration: Slower titration intervals (every 5–7 days for oral); more cautious IV titration

• Additional risks:

• Increased susceptibility to orthostatic hypotension — fall risk

• Higher risk of excessive bradycardia

• Age-related reduction in hepatic metabolism — prolonged drug action

• Masked hypoglycaemia in diabetics

• May precipitate or worsen heart failure

• Monitoring: Standing and supine BP at each visit; heart rate; renal function; symptoms of heart failure

Drug Interaction Management

Verapamil / Diltiazem (non-DHP CCBs) Additive negative inotropic and chronotropic effects → severe bradycardia, heart block, hypotension AVOID combination; if essential, use with extreme caution and continuous ECG monitoring

Insulin and oral hypoglycaemics Beta-blockade masks hypoglycaemic symptoms (tachycardia, tremor); may prolong hypoglycaemia Educate patient on hypoglycaemia recognition; more frequent glucose monitoring

MAO inhibitors Potential for exaggerated hypertensive response (paradoxical) or severe hypotension AVOID combination; ensure adequate washout period

Clonidine Rebound hypertension if clonidine withdrawn while on beta-blocker; also additive bradycardia Discontinue beta-blocker several days BEFORE withdrawing clonidine

Class I antiarrhythmics (flecainide, propafenone) Additive negative inotropic effect Use with caution; monitor cardiac function

Sotalol / Amiodarone Additive bradycardia; QT prolongation with sotalol Avoid sotalol combination; amiodarone with caution and monitoring

Drug Interaction Management

Dihydropyridine CCBs (amlodipine, nifedipine) Additive hypotensive effect Common combination; monitor BP; adjust doses as needed

Diuretics Additive hypotension Common combination; monitor for excessive hypotension

Digoxin Additive bradycardia; possible increased digoxin levels Monitor heart rate; consider digoxin level monitoring

NSAIDs (ibuprofen, diclofenac) May reduce antihypertensive efficacy Monitor BP; avoid prolonged NSAID use if possible

Anaesthetic agents Enhanced hypotensive effect Inform anaesthetist; may need dose adjustment of anaesthetic

Cimetidine Increases labetalol bioavailability via hepatic enzyme inhibition Monitor for excessive beta-blockade; use alternative H2 blocker

Tricyclic antidepressants Increased tremor; possible enhanced hypotension Monitor; clinical significance usually minor

• Dizziness and lightheadedness

• Fatigue and tiredness

• Nausea

• Orthostatic hypotension

• Headache

• Nasal congestion

• Scalp tingling (especially during IV administration)

• Bradycardia (dose-related)

• Erectile dysfunction (with chronic use)

Reaction Action Required

Severe bradycardia (<40 bpm) Stop labetalol; IV atropine 0.5–1 mg; if refractory, consider temporary pacing or isoprenaline

Bronchospasm Stop labetalol; bronchodilators (salbutamol nebulisation); consider IV aminophylline if severe

Severe hypotension Stop infusion; supine position with legs elevated; IV fluids; vasopressors if needed (noradrenaline preferred)

Heart block (second/third-degree) Stop labetalol; IV atropine; temporary pacing if needed

Acute heart failure / Pulmonary oedema Stop labetalol; standard heart failure management; diuretics; oxygen

Hepatotoxicity (rare — cholestatic jaundice) Discontinue permanently; monitor LFTs; hepatology referral if severe

During IV administration Continuous BP monitoring (every 5 minutes initially); heart rate; ECG if available; fetal heart rate (in pregnancy)

After IV boluses BP and HR after each bolus before administering next dose

Oral therapy initiation BP and HR at 1–2 weeks; assess for postural hypotension

Long-term (oral) BP, HR, symptoms of heart failure at each visit; LFTs if prolonged use (>6–8 weeks); blood glucose in diabetics; reassess periodically for need to continue

Single-ingredient products:

• Lobet (Sun Pharma)

• Labetalol IP (generic — various manufacturers)

• Normadate (Abbott — verify current availability)

• Trandate (Imported — limited availability)

• Labeta (Intas)

Note: Both oral tablets and IV injection formulations are widely available; injection increasingly available through government supply for obstetric emergencies

NLEM status: Labetalol injection 5 mg/mL is included in NLEM 2022 — ceiling price applicable under NPPA

Government supply: Increasingly available through NHM maternal health programmes for management of severe hypertension in pregnancy

• Supine position mandatory for IV: Always administer IV labetalol with patient supine — severe postural hypotension can occur within minutes if patient is upright

• Preferred in pregnancy: First-line for acute severe hypertension in pre-eclampsia/eclampsia; preferred over hydralazine due to more predictable effect and fewer side effects

• Avoid in asthma: Unlike cardioselective beta-blockers, labetalol has significant beta-2 blocking activity — absolutely contraindicated in asthma

• No rebound tachycardia: Combined alpha-beta blockade prevents reflex tachycardia seen with pure vasodilators — advantage in aortic dissection

• Taper don't stop: With chronic use, taper over 1–2 weeks to avoid rebound hypertension and tachycardia

• Monitor neonate: If used near delivery, observe neonate for bradycardia, hypotension, and hypoglycaemia for 24–48 hours

labetalol; antihypertensive; alpha-beta blocker; hypertensive emergency; pre-eclampsia; pregnancy-safe; IV antihypertensive; obstetric emergency; aortic dissection; NLEM India

RxIndia v1.1 — 14 Jun 2025

• CDSCO Approved Product Information

• Indian Pharmacopoeia 2022

• National Formulary of India 2021

• NLEM 2022 (National List of Essential Medicines)

• MoHFW Guidelines on Hypertensive Disorders in Pregnancy

• FOGSI Good Clinical Practice Recommendations

• AIIMS Obstetrics Protocols — Management of Severe Pre-eclampsia and Eclampsia

• API Textbook of Medicine (11th Edition)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics (13th Edition)

• Harrison's Principles of Internal Medicine (21st Edition)