Drug reference

Metolazone

Thiazide Diuretic · Diuretic, Antihypertensive

Thiazide DiureticDiuretic, Antihypertensive

CDSCO approved

EXCRETION

—

not curated

INTERACTIONS

12 major

incl. contraindicated

PREGNANCY

Should not be used to treat gestational hypertension. May cause neonatal thrombocytopenia, bone marrow suppression, jaundice, electrolyte disturbances, and hypoglycaemia; placental perfusion may also be reduced. Stimulation of labour, uterine inertia, and meconium staining have also been reported.

FDA category + note

Top interactionssee all 12 →

QuinidineContraindicatedTextbookG&G 14e · p567
LithiumSevereTextbookG&G 14e · p378
Aminolevulinic AcidSevereDatabaseDDInter
AmiodaroneSevereDatabaseDDInter

Mechanism

Metolazone acts as an inhibitor of the Na+-Cl− symport in the distal convoluted tubule, leading to increased excretion of sodium and chloride. It is notable for its ability to increase bicarbonate and phosphate excretion, unlike some other symport inhibitors.

Indications

HypertensionDiuretic-resistant oedemaedema associated with diseases of the heart (CHF)edema associated with diseases of the liver (hepatic cirrhosis)edema associated with diseases of the kidney (nephrotic syndrome, chronic renal failure, acute glomerulonephritis)Ca2+ nephrolithiasisosteoporosisnephrogenic diabetes insipidusBr− intoxicationedema associated with congestive heart failureliver cirrhosischronic kidney diseasenephrotic syndromekidney stones caused by Ca2+ crystalsEdema associated with heart failureEdema associated with liver cirrhosisEdema associated with chronic kidney diseaseEdema associated with nephrotic syndromeovercome resistance to high ceiling diuretics in advanced CHFEdema (mild-to-moderate, maintenance in cardiac edema, effective in renal failure)Diabetes insipidus (nephrogenic and pituitary origin)Hypercalciuria with recurrent calcium stones

Dosing

Adult: Edema (5–10 mg/day, rarely 20 mg), Hypertension (2.5–5 mg/day)
Renal adjustment: Effective if eGFR is less than 30 mL/minute/1.73 m2, but associated with a risk of excessive diuresis; monitor electrolytes
Hepatic adjustment: Caution in mild to moderate impairment; avoid in severe impairment

Pharmacokinetics

Onset

within 1 hour

Duration

12–24 hours

Half-life

8–14

Bioavailability

~65%

Metabolism

~10% B, ~10% M

Excretion

~80% renal excretion of intact drug

Contraindications

Current significant hypokalaemia (serum potassium less than 3 mmol/L)
Hyponatraemia (serum sodium less than 130 mmol/L)
Hypercalcaemia (corrected serum calcium greater than 2.65 mmol/L)
History of gout
hypersensitive to sulfonamides
Toxaemia of pregnancy

Side effects

Common

Alkalosis hypochloraemicConstipationDiarrhoeaDizzinessDry mouthElectrolyte imbalanceErectile dysfunctionFatigueHeadacheHyperglycaemiaHyperuricaemiaNauseaPostural hypotensionSkin reactionsvertigophotosensitivityskin rasheshypokalemiahyperuricemiadecreased glucose toleranceincreased plasma LDL cholesterolincreased plasma total cholesterolincreased plasma total triglyceridesIncreased K+ excretionIncreased HCO3¯ excretionIncreased PO43¯ excretionReduced g.f.r.Decreased renal Ca2+ excretionIncreased Mg2+ excretionGreater reduction in urate excretion than furosemideSlowly developing fall in BP (in hypertensives)Elevation of blood sugar (due to decreased insulin release/hypokalaemia)HypokalaemiaWeaknessMuscle crampsVomitingGiddinessParesthesiasImpotenceAlkalosis (with hypokalaemia)Magnesium depletion

Serious

Agranulocytosis
Aplastic anaemia
Leucopenia
Pancreatitis
Photosensitivity reaction
Thrombocytopenia
Vomiting
Paraesthesia
systemic lupus erythematosus
sulfa allergic reactions
extracellular volume depletion
hypotension
hyponatremia (severe, potentially fatal)
hypochloremia
metabolic alkalosis
hypomagnesemia
hypercalcemia
unmask latent diabetes mellitus
Cardiac arrhythmias (due to hypokalaemia)
Acute saline depletion (dehydration, marked fall in BP, haemoconcentration, peripheral venous thrombosis)
Dilutional hyponatraemia
Rashes
Photosensitivity
Blood dyscrasias
Aggravated renal insufficiency
Mental disturbances and hepatic coma (in cirrhotics)