Thiazide diuretics
ATC code: C03AA03 (Hydrochlorothiazide)
Brand names
Microzide, Hydrodiuril
Inhibits the Na+/Cl– symporter in the early distal convoluted tubule – produces modest natriuresis and BP reduction. Used as part of antihypertensive therapy, usually at low doses (12.5–25 mg). Decreases calcium excretion (beneficial in osteoporosis), increases potassium and magnesium excretion. May cause hyponatremia, hypokalemia, hyperuricemia, hyperglycemia, and dyslipidemia – particularly in older adults.
First line
Hydrochlorothiazide is a first-line antihypertensive alongside ACE inhibitors, ARBs, and calcium channel blockers. Recommended by 2024, 2017, and JNC 8. Stroke and cardiovascular event reduction is confirmed in classic trials ALLHAT, SHEP, and MRFIT. Current European and UK guidelines often prefer thiazide-like diuretics (indapamide, chlorthalidone) when choosing a thiazide due to a smoother 24-hour effect.
Standard hypertension dose is 12.5-25 mg in the morning. Doses above 25 mg daily do not enhance the antihypertensive effect but increase metabolic adverse effects. Fixed combinations with ACEi, ARB, and calcium channel blockers are common for better adherence.
Second line
For mild-to-moderate edema in HF, thiazides can complement loop diuretics. In severe HF and eGFR < 30 mL/min/1.73 m², thiazides lose efficacy – loop diuretics (furosemide, torsemide) are preferred. For diuretic-resistant edema, a thiazide is combined with a loop diuretic for 'sequential nephron blockade'.
Not recommended
Thiazide diuretics are not used for weight loss. The effect on body mass is a short-term fluid loss followed by rebound retention. No real fat loss occurs. International obesity guidelines do not list thiazides. Combined with other diuretics, laxatives, or caffeine-containing sports supplements, hypokalaemia and dehydration risk is high.
8 pairs found. Sorted from critical to minor.
Mechanism
Thiazides cause hypokalemia and hypomagnesemia. Falling potassium and magnesium boost digoxin's arrhythmogenicity – QT prolongation and digitalis-induced rhythm disturbances.
Management
When combining, monitor electrolytes every 1–3 months. Keep potassium above 4.0 mmol/L. Alternatives include switching to a potassium-sparing diuretic or using a thiazide at low dose (12.5 mg).
Sources
Mechanism
Synergistic BP reduction (a target combination in hypertension – even an enalapril/hydrochlorothiazide fixed-dose product exists). Hypovolemia can cause an abrupt BP drop and acute kidney injury at the first ACE-inhibitor dose. Hydrochlorothiazide shifts the RAAS toward activation, amplifying the first-dose ACE-inhibitor effect.
Management
Start both at low doses. Confirm normovolemia before initiating the ACE inhibitor – hold the thiazide for 24–48 hours if needed. Check BP (including orthostatic measurement), creatinine, and potassium at 3–7 days.
Sources
Mechanism
Synergistic BP reduction, a target combination in hypertension (losartan/hydrochlorothiazide fixed-dose product). In older patients with hypovolemia and RAAS activation, the first sartan dose can cause orthostatic hypotension and acute kidney injury.
Management
Start losartan at 25–50 mg (25 mg in older patients) and hydrochlorothiazide at 12.5 mg. Check BP with an orthostatic measurement, creatinine, potassium, and sodium at 7–14 days.
Sources
Mechanism
Thiazides cause dose-dependent hyperglycemia and insulin resistance (especially at doses ≥ 25 mg/day) via hypokalemia and reduced insulin secretion. Metformin's effect is blunted and glycemic control worsens.
Management
Use the lowest hydrochlorothiazide dose of 12.5 mg/day – the diabetogenic effect is minimal at this dose. Check glucose and at 4–8 weeks after initiation. Keep potassium above 4.0 mmol/L – correcting hypokalemia improves glycemic control.
Sources
Mechanism
Same as the amiodarone/furosemide pair: thiazide-induced hypokalemia and hypomagnesemia raise amiodarone's arrhythmogenic potential. Additionally, both thiazides and amiodarone can cause hyponatremia.
Management
Check potassium, magnesium, and sodium every 1–3 months. Keep potassium > 4.0 mmol/L. Obtain an ECG with QT measurement at baseline and every 6 months.
Sources
Mechanism
Sequential nephron blockade: furosemide acts in the loop of Henle, the thiazide in the distal tubule. Additive diuresis in furosemide-resistant HF. Risk of severe dehydration, hypokalemia, hyponatremia, hypomagnesemia, and prerenal azotemia.
Management
Use short term (3–7 days) in patients with resistant HF. Monitor electrolytes, creatinine, and body weight daily in inpatients. Supplement with potassium and/or add spironolactone.
Sources
Mechanism
Thiazides are one of the commonest drug causes of hyponatremia in older adults (via an SIADH-like mechanism plus natriuresis). SSRIs add their own SIADH effect. Additive risk of severe hyponatremia (Na+ < 125 mmol/L) with confusion, seizures, and falls.
Management
Check sodium at baseline, at 1, 2, and 4 weeks after sertraline initiation, then every 3 months. In patients over 75 with sodium < 135 mmol/L, optimize the thiazide or switch the antidepressant.
Sources
Mechanism
Opposing effects on potassium: thiazide depletes, spironolactone retains. The combination is used in resistant hypertension and ascites. In CKD or diabetes, spironolactone dominates – with hyperkalemia risk.
Management
Check potassium, sodium, and creatinine at 7–14 days after initiation, then every 1–3 months. Target potassium is 4.0–5.0 mmol/L. For hyponatremia (Na+ < 130 mmol/L), reassess therapy.
Sources
Contraindicated in the first trimester. Not first-line in the second or third trimester – alternatives (methyldopa, labetalol, nifedipine) are preferred.
Passes into breast milk and may suppress lactation at high doses. Low doses are usually compatible.
hydrochlorothiazide is evaluated for the following indications with varying evidence strength: Hypertension (evidence tier A), Edema in heart failure (evidence tier B), Weight loss in non-diabetics (evidence tier F). See the full indication matrix with dosing and citations above on this page.
Common side effects of hydrochlorothiazide (≥ 1 in 100): Hypokalaemia, Hyperuricaemia, gout flare, Orthostatic hypotension, Elevated glucose and triglycerides, Photosensitivity. See the Safety section for uncommon and serious reactions.
Contraindicated in the first trimester. Not first-line in the second or third trimester – alternatives (methyldopa, labetalol, nifedipine) are preferred.
Passes into breast milk and may suppress lactation at high doses. Low doses are usually compatible.
hydrochlorothiazide is contraindicated in: Hypersensitivity to thiazides or sulfonamides; Severe renal failure (anuria, eGFR < 30); Severe liver disease; Severe hypokalaemia, hyponatraemia, hypercalcaemia; Refractory gout. Full list in the Safety section.