hydrochlorothiazide

Thiazide diuretic· Brands: Esidrex, HydroDIURIL, MicrozidePO

Mechanism of action

Hydrochlorothiazide inhibits the Na+-Cl- symporter in the distal convoluted tubule, reducing sodium and chloride reabsorption. This increases urinary excretion of water, sodium, chloride, and to a lesser extent potassium and magnesium. It also reduces urinary calcium excretion.

Pharmacokinetics

Well absorbed after oral administration. Diuresis begins within 1 to 2 hours, peaks at about 4 hours, and lasts 6 to 12 hours. Not metabolized; excreted unchanged by the kidneys. Half-life is approximately 6 to 15 hours but is prolonged by accumulation in red blood cells. Crosses the placenta and is present in breast milk.

Indications & dosing

Hypertension

May be used alone or with other antihypertensives. Monitor electrolytes, renal function and blood glucose.

adult · PO: 12.5–25 mg once daily · May be used alone or with other antihypertensives. Monitor electrolytes, renal function and blood glucose.

Oedema (e.g. heart failure, hepatic cirrhosis, renal disease)

Can be given on alternate days. Monitor electrolytes, fluid balance and renal function.

adult · PO: 25–100 mg once daily · Can be given on alternate days. Monitor electrolytes, fluid balance and renal function.

Idiopathic hypercalciuria (prevention of calcium kidney stones)off-label

Specialist use. Monitor serum and urine calcium, and electrolytes.

adult · PO: 25–50 mg once daily · Specialist use. Monitor serum and urine calcium, and electrolytes.

Contraindications & precautions

Anuria · Thiazides are ineffective in the absence of urine output and may accumulate.
Hypersensitivity to thiazides or sulfonamides · Cross-sensitivity between thiazides and sulfonamides is well recognised.
Severe renal impairment (eGFR <30 mL/min/1.73 m²) · Thiazides are unlikely to be effective and risk of adverse effects is increased.
Symptomatic hyperuricaemia or gout · Thiazides raise serum uric acid and may precipitate gout flares.
Pregnancy · Use only if essential; thiazides have been associated with fetal harm. Consider alternative antihypertensives in pregnancy.
Monitor serum electrolytes (particularly potassium and sodium) and renal function at baseline and regularly during therapy.
Use with caution in patients with diabetes mellitus, gout, or hyperlipidaemia, as thiazides may worsen these conditions.
May potentiate the hypotensive effect of other antihypertensive agents; dose adjustment may be required.
Avoid in pregnancy unless essential; consider alternative agents where possible.
Reduce dose or use with caution in the elderly, as they are more susceptible to electrolyte disturbances and hypotension.
Advise patients to report symptoms of electrolyte imbalance, such as weakness, palpitations, or confusion.

Adverse effects

Hypokalaemiaserious
Hyponatraemiaserious
Hyperuricaemia
Hyperglycaemia
Hypercalcaemia
Pancreatitisserious
Blood dyscrasias (e.g. agranulocytosis, thrombocytopenia)serious

Interactions

digoxinmajorMonitor serum potassium and renal function at baseline, within 1-2 weeks after starting or changing doses, and periodically thereafter. Consider potassium supplementation or use of potassium-sparing diuretics if hypokalemia develops. Adjust digoxin dose if renal function deteriorates. In patients with concurrent hypokalemia, correct the potassium deficit and reassess digoxin levels. Consider digoxin level monitoring in patients with symptoms of toxicity or if potassium is persistently low.
lithiummajorAvoid the combination if possible. If unavoidable, reduce the lithium dose and monitor serum lithium levels closely, especially after starting or stopping the thiazide. Consider using an alternative diuretic that has less effect on lithium clearance.

Renal & hepatic adjustment

eGFR 0–29: Avoid; thiazides are ineffective in severe renal impairment. Consider a loop diuretic. (avoid)
eGFR 30–59: Use with caution; monitor renal function and electrolytes regularly.
eGFR 60+: No dose adjustment required.
Hepatic impairment (mild): No dose adjustment required; monitor electrolytes and liver function.
Hepatic impairment (moderate): Use with caution; monitor electrolytes and watch for signs of hepatic encephalopathy.
Hepatic impairment (severe): Avoid in severe hepatic impairment, particularly if there is risk of encephalopathy. (avoid)

Monitoring, pregnancy & toxicity

Blood pressure · Baseline, then as needed to achieve target
Serum potassium · Baseline, then within 1 to 2 weeks after starting or dose increase, then periodically
Serum sodium · Baseline, then periodically
Renal function (eGFR/creatinine) · Baseline, then periodically
Blood glucose (in patients with diabetes) · Baseline, then periodically
Serum uric acid (in patients with gout) · Baseline, then periodically
Pregnancy: Avoid in pregnancy unless clearly necessary. Consider alternative antihypertensives such as labetalol, nifedipine, or methyldopa. If used, monitor maternal electrolytes and fetal growth.
Toxicity: Electrolyte disturbances: hypokalaemia, hyponatraemia, hypomagnesaemia · Replace electrolytes and monitor serum levels closely. Oral or intravenous supplementation as required.
Toxicity: Dehydration and hypotension · Administer intravenous fluids to restore volume. Monitor blood pressure and urinary output.
Toxicity: Hyperglycaemia and metabolic alkalosis · Monitor blood glucose and acid-base status. Treat symptomatically.

Clinical notes

Used to treat hypertension and oedema due to heart failure, hepatic cirrhosis, or renal disease, and to prevent calcium kidney stones. Can cause electrolyte disturbances, hyperglycaemia, hyperuricaemia, hypercalcaemia, and lipid changes. Monitor blood pressure, electrolytes, renal function, and glucose. Caution in gout, diabetes, and renal impairment. Possibly cross-reactive in sulphonamide allergy.

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BNF; local formulary