Schedule H

Oral, Intravenous (IV)

• Tablets (Immediate-release — Metoprolol Tartrate): 25 mg, 50 mg, 100 mg

• Tablets (Extended-release — Metoprolol Succinate): 12.5 mg, 25 mg, 50 mg, 100 mg, 200 mg

• Injection: 1 mg/mL (5 mL ampoule)

Fixed-Dose Combinations (FDCs) Available:

• Metoprolol + Amlodipine

• Metoprolol + Hydrochlorothiazide

• Metoprolol + Telmisartan

• Metoprolol + Ramipril

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Hypertension

Metoprolol Tartrate (Immediate-Release):

Parameter Dose

Starting dose 25–50 mg orally twice daily

Titration Increase every 1–2 weeks based on BP response

Usual maintenance dose 100–200 mg/day in 2 divided doses

Maximum dose 400 mg/day (in divided doses)

Metoprolol Succinate (Extended-Release):

Parameter Dose

Starting dose 25–50 mg orally once daily

Titration Increase every 1–2 weeks based on BP response

Usual maintenance dose 50–100 mg once daily

Maximum dose 200 mg once daily

Clinical Notes:

• Not first-line for uncomplicated hypertension per current ICMR/Indian guidelines (CCBs, ACE inhibitors, ARBs, thiazides preferred)

• Preferred when compelling indications exist: post-MI, heart failure, tachyarrhythmias, angina

• Extended-release formulation preferred for once-daily dosing and better compliance

• Avoid abrupt discontinuation — taper over 1–2 weeks

1. Chronic Stable Angina Pectoris

Metoprolol Tartrate (Immediate-Release):

Parameter Dose

Starting dose 25–50 mg orally twice daily

Titration Increase every 7–14 days based on anginal frequency and heart rate

Usual maintenance dose 100–200 mg/day in 2–3 divided doses

Maximum dose 400 mg/day

Metoprolol Succinate (Extended-Release):

Parameter Dose

Starting dose 50 mg orally once daily

Titration Increase every 1–2 weeks based on response

Usual maintenance dose 100–200 mg once daily

Maximum dose 200 mg once daily

Clinical Notes:

• Titrate to resting heart rate of 55–60 bpm for optimal antianginal effect

• May be combined with long-acting nitrates and/or dihydropyridine CCBs

• Avoid combining with non-dihydropyridine CCBs (verapamil, diltiazem) — risk of severe bradycardia

• Do not discontinue abruptly — risk of rebound angina and MI

1. Heart Failure with Reduced Ejection Fraction (HFrEF)

⚠️ Only Metoprolol Succinate (Extended-Release) is indicated for heart failure. Metoprolol Tartrate is NOT recommended for HFrEF.

Parameter Dose

Starting dose 12.5–25 mg orally once daily

Titration Double dose every 2 weeks as tolerated (guided by symptoms, BP, HR)

Usual maintenance dose 100–200 mg once daily

Maximum dose 200 mg once daily

Clinical Notes:

• Initiate only when patient is euvolaemic (volume-stable) and on optimal doses of ACE inhibitor/ARB and diuretics

• Evidence-based therapy (MERIT-HF trial): reduces mortality and hospitalisations

• Hold or reduce dose if: HR <50 bpm, SBP <90 mmHg, worsening HF symptoms, or significant fatigue

• Avoid initiation during acute decompensated heart failure

• Do not switch between tartrate and succinate formulations interchangeably in HF

1. Acute Myocardial Infarction (Secondary Prevention — Post-MI)

Acute Phase (if haemodynamically stable):

Route Dose

IV (early) 5 mg IV bolus over 1–2 minutes; may repeat every 5 minutes x 2 doses (total 15 mg); followed by oral therapy

Oral (following IV) 25–50 mg orally every 6 hours for 48 hours, then maintenance

Long-term Secondary Prevention:

Parameter Dose

Starting dose 25–50 mg orally twice daily (tartrate) OR 25–50 mg once daily (succinate)

Titration Increase every 1–2 weeks as tolerated

Usual maintenance dose 100–200 mg/day (tartrate in divided doses; succinate once daily)

Maximum dose 200 mg/day

PAEDIATRIC DOSING (Specialist Only)

⚠️ Not recommended in neonates and infants below 1 year of age except under paediatric cardiology supervision in ICU settings.

Primary Indications: Hypertension, Supraventricular Tachyarrhythmias

Oral Dosing (Children ≥1 year):

Parameter Dose

Starting dose 0.5–1 mg/kg/day orally in 2–3 divided doses

Titration Increase every 1–2 weeks based on BP and HR response

Usual maintenance dose 1–2 mg/kg/day in 2–3 divided doses

Maximum dose 6 mg/kg/day OR 200 mg/day (whichever is lower)

IV Dosing (Acute Arrhythmia — Hospital/PICU Setting):

Parameter Dose

Starting dose 0.1 mg/kg IV slowly over 5 minutes (maximum single dose: 5 mg)

Titration May repeat every 5–10 minutes if inadequate response

Maximum dose 0.5 mg/kg total OR 15 mg (whichever is lower)

Safety Monitoring:

• Continuous ECG monitoring during IV administration

• Heart rate and blood pressure (before each dose and frequently after)

• Signs of hypoperfusion (cold extremities, prolonged capillary refill)

• Blood glucose (especially in diabetic children or prolonged fasting)

• Signs of bronchospasm in asthmatic children

Clinical Notes:

• Extended-release formulations not routinely studied in children; use immediate-release for dose flexibility

• Always have atropine, glucagon, and pacing capability available during IV use

• Paediatric cardiology supervision mandatory

Secondary Indications – Paediatrics (Off-label)

Indication Age Dose Duration Supervision Evidence Basis

Migraine Prophylaxis (OFF-LABEL) ≥6 years 0.5–1 mg/kg/day in 2 divided doses; Maximum: 100 mg/day 2–3 months trial Specialist recommended (Paediatric Neurology) Limited paediatric RCT data; IAP guidance; propranolol more commonly used

Thyrotoxicosis — Rate Control (OFF-LABEL) ≥1 year 0.5–1 mg/kg/day in 2–3 divided doses Until euthyroid Specialist only (Paediatric Endocrinology) Indian paediatric endocrine practice

Long QT Syndrome (adjunct) (OFF-LABEL) Any age Individualised dosing Long-term Specialist only (Paediatric Cardiology/Electrophysiology) Used when propranolol not tolerated; limited evidence

Age Restrictions:

• Not recommended below 1 year of age except under specialist supervision in ICU/PICU settings

• Use in neonates only in exceptional circumstances (e.g., SVT refractory to other agents)

Note: Metoprolol is primarily hepatically metabolised (<10% excreted unchanged in urine). Use with caution if uraemia-associated bradycardia or hypotension is present.

Note: Metoprolol undergoes extensive first-pass hepatic metabolism via CYP2D6. Hepatic impairment significantly increases systemic exposure and prolongs half-life.

• Known hypersensitivity to metoprolol or other beta-blockers

• Sinus bradycardia (HR <50 bpm unless paced)

• Sick sinus syndrome (without pacemaker)

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

• Cardiogenic shock

• Decompensated heart failure requiring IV inotropic support

• Severe peripheral arterial disease with limb-threatening ischaemia

• Severe hypotension (SBP <90 mmHg)

• Untreated phaeochromocytoma (use only with alpha-blocker)

• Metabolic acidosis

• Concurrent IV administration of calcium channel blockers (verapamil, diltiazem)

• Asthma or severe COPD — may precipitate bronchospasm even with cardioselective agents; use with extreme caution or avoid

• Diabetes mellitus — masks hypoglycaemia symptoms (tachycardia, tremor); does not mask sweating

• Hyperthyroidism/Thyrotoxicosis — may mask tachycardia; withdraw gradually to avoid thyroid storm

• Prinzmetal's (vasospastic) angina — may worsen coronary vasospasm; use with caution

• First-degree AV block (PR interval >0.2 sec) — monitor closely

• Peripheral vascular disease (non-critical) — may worsen claudication

• Depression or history of depression — may exacerbate

• Myasthenia gravis — may worsen weakness

• Concurrent use with other AV nodal blocking agents (digoxin, verapamil, diltiazem, amiodarone)

• Elderly patients — increased sensitivity to bradycardia and hypotension

• Abrupt discontinuation — risk of rebound tachycardia, hypertension, angina, or MI; always taper over 1–2 weeks

Parameter Information

Overall Safety Use only if benefit clearly outweighs risk; some evidence of safety but concerns remain

Risk Intrauterine growth restriction (IUGR), fetal bradycardia, neonatal hypoglycaemia, neonatal respiratory depression

Preferred Alternatives Labetalol (first-line beta-blocker in pregnancy for hypertension); Nifedipine ER (for hypertension); Methyldopa

When Use May Be Justified Maternal arrhythmias not controlled by other agents; pre-existing cardiovascular disease; specialist (Cardiology + Obstetrics) supervision required

Monitoring Maternal heart rate and blood pressure; fetal heart rate; fetal growth by serial ultrasound; neonatal blood glucose and heart rate after delivery

Parameter Information

Compatibility Generally compatible with breastfeeding; monitor infant

Expected Drug Level in Milk Low to moderate (milk:plasma ratio ~3:1, but absolute amounts small due to high protein binding)

Preferred Alternatives Labetalol, Propranolol (lower milk penetration; more breastfeeding data)

Infant Monitoring Heart rate (for bradycardia), feeding pattern, weight gain, lethargy

Recommendation Acceptable if metoprolol is the optimal maternal therapy; monitor infant

Parameter Recommendation

Starting dose Lower end of dosing range (12.5–25 mg once daily for succinate; 25 mg twice daily for tartrate)

Titration Increase slowly every 2–4 weeks; monitor HR and BP closely

Maximum recommended Same as adults but often lower doses sufficient

Increased Risks Symptomatic bradycardia, orthostatic hypotension, falls, fatigue, depression, cold extremities, exacerbation of peripheral vascular disease

Additional Precautions Assess for occult conduction disease (ECG); check renal function (even though drug is not renally cleared — affects volume status); monitor for cognitive effects with chronic use

Interacting Drug Mechanism Effect Management

Verapamil, Diltiazem (Non-DHP CCBs) Additive negative chronotropic and inotropic effects Severe bradycardia, AV block, heart failure, asystole Avoid combination, especially IV; if oral combination essential, use with extreme caution and close monitoring

Clonidine Both cause sympathetic suppression Rebound hypertensive crisis if clonidine withdrawn; severe bradycardia If discontinuing both, taper metoprolol first, then clonidine over several days

Digoxin Additive AV nodal suppression Severe bradycardia, AV block Monitor heart rate closely; reduce doses if HR <55 bpm

MAO Inhibitors Enhanced hypotensive effect Severe hypotension Avoid combination; wait 14 days after stopping MAOI

Class I Antiarrhythmics (flecainide, propafenone) Additive negative inotropic effect; propafenone inhibits CYP2D6 Bradycardia, AV block, heart failure; increased metoprolol levels with propafenone Monitor closely; reduce metoprolol dose if necessary

Amiodarone Additive negative chronotropic effect Severe bradycardia, AV block Monitor HR closely; consider dose reduction; ECG monitoring

Strong CYP2D6 Inhibitors (fluoxetine, paroxetine, bupropion, quinidine, terbinafine) Inhibit metoprolol metabolism Significantly increased metoprolol levels (2–5 fold); bradycardia, hypotension Monitor closely; reduce metoprolol dose; consider alternative antidepressant or use beta-blocker not metabolised by CYP2D6

Interacting Drug Effect Management

NSAIDs (ibuprofen, diclofenac, naproxen) Reduced antihypertensive efficacy (prostaglandin inhibition); fluid retention Monitor BP; use lowest NSAID dose for shortest duration

Rifampicin CYP enzyme induction; reduced metoprolol levels and efficacy Monitor BP and HR; may need higher metoprolol dose

Dihydropyridine CCBs (amlodipine, nifedipine) Additive hypotensive effect; generally beneficial combination Monitor for excessive hypotension; commonly used together intentionally

Insulin and Oral Antidiabetics Masks hypoglycaemia symptoms (tachycardia, tremor); may prolong hypoglycaemia Monitor blood glucose more frequently; educate patient on alternative hypoglycaemia symptoms

Alcohol Enhanced hypotensive effect Counsel patient; moderate intake

Alpha-blockers (prazosin, tamsulosin) Additive hypotension; first-dose phenomenon Start alpha-blocker at low dose; monitor BP

Ergot Alkaloids Additive vasoconstriction Monitor for peripheral ischaemia

Lidocaine Reduced lidocaine clearance Monitor for lidocaine toxicity if concurrent use

Theophylline Mutual antagonism Reduced efficacy of both; may need dose adjustment

• Fatigue, tiredness (very common)

• Bradycardia

• Dizziness, lightheadedness

• Cold extremities

• Hypotension, orthostatic hypotension

• Gastrointestinal disturbances (nausea, diarrhoea, constipation)

• Sleep disturbances, vivid dreams, nightmares

• Headache

• Shortness of breath (mild)

• Erectile dysfunction (with chronic use)

• Weight gain

Adverse Effect Clinical Action

Severe Bradycardia (HR <40 bpm) or AV Block Withhold dose; atropine 0.5–1 mg IV if symptomatic; glucagon 1–10 mg IV if refractory; temporary pacing if necessary

Acute Decompensated Heart Failure Reduce or discontinue metoprolol; initiate diuretics and vasodilators; may require inotropic support

Cardiogenic Shock Discontinue immediately; supportive care with IV fluids, inotropes, vasopressors; glucagon for beta-blocker overdose

Severe Bronchospasm (in asthma/COPD patients) Discontinue immediately; nebulised beta-2 agonist; IV aminophylline if severe; consider IV glucagon

Severe Hypotension Supine position; IV fluids; reduce or withhold dose; vasopressors if needed

Depression / Suicidal Ideation (rare) Consider discontinuation if significant; psychiatric evaluation

Worsening Peripheral Arterial Disease Reduce dose or discontinue; vascular surgery input

Rebound Phenomenon (on abrupt withdrawal: tachycardia, hypertensive crisis, angina, MI) Always taper over 1–2 weeks; if severe rebound, reinstate beta-blocker and taper slowly

Long-term (every 3–6 months) Heart rate, blood pressure; weight (for HF patients); symptoms of depression, fatigue, sexual dysfunction; ECG periodically if on high doses or with conduction concerns

Heart Failure Patients Daily weight monitoring; symptoms of congestion; functional class assessment; periodic LVEF

Metoprolol Tartrate (Immediate-Release):

• Betaloc™ (AstraZeneca) — 25 mg, 50 mg, 100 mg

• Metolar™ (Cipla) — 25 mg, 50 mg, 100 mg

• Lopresor™ (Novartis) — 50 mg, 100 mg

• Met™ (Various) — 25 mg, 50 mg

Metoprolol Succinate (Extended-Release):

• Met XL™ (Intas) — 12.5 mg, 25 mg, 50 mg, 100 mg

• Seloken XL™ (AstraZeneca) — 25 mg, 50 mg, 100 mg

• Betaloc ZOK™ (AstraZeneca) — 25 mg, 50 mg, 100 mg

• Metpure XL™ (Mankind) — 25 mg, 50 mg

Injection:

• Betaloc™ Injection (AstraZeneca) — 1 mg/mL, 5 mL ampoule

Fixed-Dose Combinations (Examples):

• Met-AM™ (Metoprolol + Amlodipine)

• Metolar-H™ (Metoprolol + HCTZ)

• Met XL-TH™ (Metoprolol Succinate + Telmisartan)

Regulatory: Listed under NLEM 2022 (Metoprolol Tartrate 25 mg, 50 mg tablets); NPPA price controlled for scheduled strengths; available in government supply

1. Tartrate vs Succinate for Heart Failure — Only Metoprolol Succinate (extended-release) has mortality benefit in HFrEF (MERIT-HF trial); do not use Tartrate for HF; the two formulations are NOT interchangeable

1. Never stop abruptly — Abrupt withdrawal after chronic use can precipitate rebound tachycardia, hypertensive crisis, unstable angina, or MI; always taper over 1–2 weeks

1. HR-guided titration — Target resting HR of 55–65 bpm for most indications (angina, post-MI, HF); hold dose if HR <50–55 bpm or symptomatic bradycardia

1. Cardioselectivity is relative — Beta-1 selectivity is lost at higher doses; exercise caution in asthma/COPD even with metoprolol; avoid if poorly controlled airway disease

1. CYP2D6 variability — Metoprolol is extensively metabolised by CYP2D6; poor metabolisers have 3–5 fold higher drug levels; strong CYP2D6 inhibitors (fluoxetine, paroxetine) significantly increase levels

1. Masks hypoglycaemia — Warn diabetic patients that tachycardia and tremor may be blunted; sweating is preserved; advise frequent glucose monitoring especially during dose changes

beta-blocker; cardioselective; hypertension; angina; heart-failure; HFrEF; post-MI; arrhythmia; rate-control; NLEM-India; renal-safe; pregnancy-caution; CYP2D6; Schedule-H

RxIndia v1.0 — 03 May 2025

• CDSCO Product Information

• Indian Pharmacopoeia (IP)

• National List of Essential Medicines (NLEM) 2022

• API Textbook of Medicine

• ICMR Guidelines for Management of Hypertension 2020

• Indian Society of Hypertension Recommendations

• AIIMS Drug Formulary and Treatment Protocols

• Harrison's Principles of Internal Medicine

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• MERIT-HF Trial (heart failure evidence)

• ISIS-1 Trial (post-MI evidence)

• IAP Guidelines (paediatric dosing support)