Schedule H

Oral

• Tablet: 2.5 mg

• Tablet: 5 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Hypertension (Adjunctive Therapy)

Parameter Recommendation

Starting dose 2.5 mg orally once daily

Titration May increase after 1–2 weeks based on BP response

Usual maintenance dose 2.5–5 mg once daily

Maximum dose 10 mg once daily

Key Clinical Notes:

• Typically used in combination with other antihypertensives

• Particularly useful in resistant hypertension

• Monitor for volume depletion and electrolyte disturbances

• Administer in the morning to avoid nocturia

1. Oedema (Heart Failure, Chronic Kidney Disease, Hepatic Cirrhosis)

Parameter Recommendation

Starting dose 2.5–5 mg orally once daily

Titration Increase by 2.5–5 mg every 5–7 days based on diuretic response

Usual maintenance dose 2.5–10 mg once daily

Maximum dose 20 mg/day

Key Clinical Notes:

• Use lowest effective dose to minimise electrolyte disturbances

• Retains efficacy in advanced CKD (eGFR <30 mL/min/1.73 m²) unlike conventional thiazides

• Often used synergistically with loop diuretics (e.g., furosemide) in refractory oedema

• Administer 30–60 minutes before loop diuretic for sequential nephron blockade

• Onset of action: 2–4 hours; duration: 12–24 hours

Secondary Indications — Adults Only (Off-label)

Indication Refractory Oedema in Nephrotic Syndrome

Dose 2.5–5 mg orally once daily

Duration As per clinical response; often short-term synergistic use with loop diuretics

Status OFF-LABEL; Specialist only (Nephrologist)

Evidence Indian nephrology practice; enhanced diuresis when combined with loop diuretics

Indication Hypercalciuria / Nephrolithiasis Prevention

Dose 2.5 mg orally once daily

Duration Long-term; requires periodic electrolyte monitoring

Status OFF-LABEL; Specialist only (Nephrologist/Urologist)

Evidence Extrapolated from thiazide class effect; Indian specialist practice in calcium stone prevention

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

1. Oedema (Nephrotic Syndrome, Heart Failure)

1–12 years 0.1–0.2 mg/kg/day orally once daily 0.4 mg/kg/day or 10 mg/day (whichever is lower)

12 years 2.5 mg once daily 10 mg/day

Key Clinical Notes:

• Often used as adjunct to loop diuretics in refractory oedema

• Administer 30–60 minutes before loop diuretic for synergistic effect

• Closely monitor electrolytes and fluid balance

Safety Monitoring:

• Serum electrolytes (Na⁺, K⁺, Mg²⁺)

• Renal function

• Daily weight and fluid balance

• Blood pressure

Secondary Indications — Paediatric Doses (Off-label)

Indication Hypercalciuria-related Nephrolithiasis

Dose 0.1 mg/kg/day orally once daily

Duration Long-term as per specialist guidance

Status OFF-LABEL; Specialist only (Paediatric Nephrologist)

Evidence Extrapolated from adult thiazide data and Indian paediatric nephrology practice

⚠️ Not recommended below 1 year of age except under supervision of paediatric nephrologist or cardiologist

Advanced CKD (eGFR <30) Remains effective — major advantage over conventional thiazides; use with close monitoring

Dialysis-dependent May have limited efficacy; avoid in anuric patients

Note: Unlike conventional thiazides, metolazone retains diuretic efficacy in advanced CKD. This makes it valuable for sequential nephron blockade with loop diuretics in refractory oedema. Monitor closely for profound electrolyte disturbances (hypokalaemia, hyponatraemia).

• Known hypersensitivity to metolazone or sulfonamide-derived drugs

• Anuria

• Hepatic coma or pre-coma

• Refractory hypokalaemia

• Refractory hyponatraemia

• Severe untreated electrolyte depletion

• Gout or hyperuricaemia — may elevate serum uric acid and precipitate acute gout

• Diabetes mellitus — may impair glucose tolerance; monitor glycaemic control

• Elderly patients — increased risk of dehydration and orthostatic hypotension

• Concurrent digitalis (digoxin) therapy — hypokalaemia increases digoxin toxicity risk

• Concomitant loop diuretic therapy — synergistic but potentially profound diuresis; close monitoring essential

• Hyperlipidaemia — may cause mild lipid elevations

• Cirrhotic ascites — avoid rapid fluid removal; risk of precipitating hepatorenal syndrome or encephalopathy

• Systemic lupus erythematosus — may exacerbate or activate

Parameter Information

Risk category Use only if benefit clearly outweighs risk; generally avoided

Preferred alternatives Labetalol, nifedipine, methyldopa for hypertensive disorders of pregnancy

When to use May be considered for severe refractory oedema with specialist supervision

Monitoring Maternal BP, electrolytes, volume status; fetal growth assessment

Parameter Information

Compatibility Limited data; likely compatible with caution

Preferred alternatives Hydrochlorothiazide (more data available); furosemide if loop diuretic needed

Expected levels in milk Likely low

Infant monitoring Hydration status, weight gain, adequate feeding

Parameter Recommendation

Starting dose 2.5 mg once daily (lower end of range)

Titration Slower titration; reassess every 1–2 weeks

Extra risks Orthostatic hypotension, falls, volume depletion, acute kidney injury, electrolyte disturbances (especially hyponatraemia), confusion

Monitoring Electrolytes and renal function within 3–5 days of initiation; standing BP assessment

Interacting Drug/Class Mechanism Clinical Effect Recommendation

Lithium Reduced renal lithium clearance Lithium toxicity Avoid combination; if essential, monitor lithium levels closely

Digoxin Metolazone-induced hypokalaemia Digoxin toxicity (arrhythmias) Monitor potassium; supplement or add potassium-sparing agent

Loop diuretics (furosemide, bumetanide) Synergistic diuresis via sequential nephron blockade Profound diuresis, severe hypokalaemia, hyponatraemia, hypovolaemia Use intentionally but with close monitoring; check electrolytes 24–48 hours after initiation

NSAIDs (chronic use) Inhibit prostaglandin-mediated renal blood flow Reduced diuretic efficacy; increased AKI risk Avoid long-term co-administration

Interacting Drug/Class Effect Recommendation

ACE inhibitors / ARBs Additive hypotension; risk of AKI in volume-depleted state Start at low doses; monitor BP and renal function

Antidiabetic agents (insulin, sulfonylureas) Hyperglycaemic effect of metolazone Monitor blood glucose; adjust antidiabetic doses

Corticosteroids Enhanced hypokalaemia Monitor potassium; supplement if needed

QT-prolonging drugs (quinolones, macrolides, antipsychotics) Hypokalaemia potentiates QT prolongation Monitor electrolytes; correct hypokalaemia promptly

Carbamazepine Additive hyponatraemia Monitor sodium levels

Cholestyramine, colestipol Reduced metolazone absorption Administer metolazone 1 hour before or 4–6 hours after resin

• Hypokalaemia

• Hyponatraemia

• Hypomagnesaemia

• Dizziness

• Orthostatic hypotension

• Hyperuricaemia

• Hyperglycaemia (mild)

• Fatigue

• Muscle cramps

• Polyuria

Adverse Effect Action Required

Severe electrolyte disturbances (symptomatic hyponatraemia, hypokalaemia) May require hospitalisation; IV electrolyte replacement; discontinue or reduce dose

Acute pancreatitis (rare) Discontinue immediately; supportive care

Aplastic anaemia / agranulocytosis (rare) Discontinue; haematology consultation

Stevens-Johnson Syndrome / TEN (rare) Discontinue immediately; hospitalisation; dermatology consultation

Severe photosensitivity reaction Discontinue; avoid sun exposure

Phase Parameters

Baseline Serum electrolytes (Na⁺, K⁺, Mg²⁺), renal function (creatinine, eGFR), uric acid, fasting glucose, BP, weight

After initiation/dose change Electrolytes and renal function at 3–5 days; earlier (24–48 hours) if combining with loop diuretics

Long-term Electrolytes every 2–4 weeks during high-dose or combination therapy; glucose and uric acid periodically

• Zaroxolyn

• Metoz

• Metowin

• Metzol

• Xone-M

• Multiple generic formulations available

Note: Not listed in NLEM India; not under NPPA price control

1. Key advantage over thiazides in CKD — Metolazone remains effective even when eGFR falls below 30 mL/min/1.73 m², unlike conventional thiazides; makes it invaluable for refractory oedema in advanced CKD

1. Sequential nephron blockade strategy — Administer metolazone 30–60 minutes before loop diuretic (e.g., furosemide) to achieve synergistic diuresis in diuretic-resistant heart failure or nephrotic syndrome

1. Potent electrolyte effects — Hypokalaemia and hyponatraemia are common, especially when combined with loop diuretics; always check electrolytes within 24–48 hours of starting combination therapy

1. Delayed onset of action — Peak diuresis occurs 2–4 hours after oral administration; duration extends 12–24 hours (longer than most loop diuretics)

1. Avoid rapid fluid removal in cirrhosis — May precipitate hepatorenal syndrome or hepatic encephalopathy; use cautiously with close specialist supervision

1. Potassium supplementation or potassium-sparing agent — Strongly consider adding when using metolazone, particularly in combination with loop diuretics or in patients on digoxin

Metolazone; thiazide-like diuretic; refractory oedema; CKD; heart failure; sequential nephron blockade; loop diuretic adjunct; resistant hypertension; electrolyte monitoring; hypokalaemia

RxIndia v1.0 — 04 Apr 2025

• CDSCO Drug Safety Updates

• Indian Pharmacopoeia

• National Formulary of India (NFI)

• API Textbook of Medicine

• AIIMS Drug Formulary and Institutional Protocols

• Harrison's Principles of Internal Medicine

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Indian Society of Nephrology practice recommendations

• Cardiological Society of India heart failure management protocols

• NLEM India — Not listed