Pharmacology · Thiazide and thiazide-like diuretics
Metolazone !
A thiazide-like diuretic often added to a loop diuretic when oedema resists treatment. The pair can cause very large fluid and salt losses.
Updated 2026-11-01
Mechanism of action
Metolazone, a quinazoline sulfonamide, acts mainly at the cortical diluting site of the distal tubule like the thiazides, blocking sodium and chloride reabsorption. Given with a loop diuretic it blocks the distal sodium reabsorption that rises when the loop is blocked (sequential nephron blockade), producing a much larger diuresis.
- Metolazone blocks sodium reabsorption in the distal tubule
- Alone: moderate thiazide-like diuresis
- With a loop diuretic: two nephron sites blocked in sequence
- Large diuresis in resistant oedema; large K⁺ and Na⁺ losses
Pharmacokinetics
- Absorption
- Absorbed by mouth; peak levels about eight hours after a dose
- Metabolism
- A small fraction is metabolised
- Elimination
- Mostly unchanged in the urine
Indications
- Oedema from heart failure, including resistant oedema with a loop diuretic Heart failure →
- Oedema from kidney disease Chronic kidney disease →
- High blood pressure Arterial hypertension →
Adverse effects
Common
- Hypokalaemia and hyponatraemia
- Dizziness and low blood pressure
- High uric acid and glucose
- Muscle cramps
Contraindications
- Anuria
- Hepatic coma or precoma
- Hypersensitivity to metolazone
Key interactions
- Furosemide and other loop diuretics
- Unusually large or prolonged losses of fluid and electrolytes
- Digoxin
- Hypokalaemia increases sensitivity to digoxin; serious arrhythmias
- Neuromuscular blockers
- Hypokalaemia can enhance the block
- Lithium
- Less lithium clearance and risk of toxicity
What is monitored
- Sodium and potassium, closely when combined with a loop diuretic
- Kidney function
- Weight and fluid balance
- Blood pressure
Administration and safety
- Formulations of metolazone are not therapeutically equivalent: one product is not swapped for another without the prescriber's review.
- When added to a loop diuretic, the combination is started with close electrolyte and weight monitoring, often in hospital.
Nursing care
- Before giving: sodium, potassium, kidney function and blood pressure.
- Daily weight; report a large fall in weight or reduced urine output.
- Watch for confusion, weakness, cramps or palpitations.
- Teach: report dizziness, fainting or muscle weakness at once.
Pregnancy and breastfeeding
Used only for oedema from pathological causes; it crosses the placenta.
Test yourself
Think of the answer, then tap the question to see it.
Why is metolazone added to a loop diuretic in resistant oedema?
Blocking the loop increases sodium reabsorption downstream; metolazone blocks that distal site too, giving a much larger diuresis (sequential nephron blockade).
What is the main risk of metolazone with furosemide?
Unusually large or prolonged losses of fluid and electrolytes, with severe hyponatraemia or hypokalaemia.
Why can different metolazone products not be swapped freely?
Its formulations are not therapeutically equivalent, so a change of product can change the effect.
Related drugs
Related conditions
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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - METOLAZONE tablet (DailyMed (U.S. National Library of Medicine), 2026); Metolazone: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2017); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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