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 (, 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'.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
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.
16 pairs found. Sorted from critical to minor.
Mechanism
Hydrochlorothiazide causes hypokalaemia and hypomagnesaemia; combined with dofetilide leads to torsades de pointes. Tikosyn Section 4.3 strict contraindication.
Symptoms
Torsades de pointes, syncope, cardiac arrest.
Management
Combination contraindicated. Use loop diuretic with potassium monitoring.
Mechanism
Hydrochlorothiazide (thiazide diuretic) increases potassium and magnesium loss. Low levels amplify amiodarone's QT-prolonging effect.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
The combination is common (hypertension plus atrial fibrillation). Check potassium and magnesium every 3 months; if potassium drops below 4.0 mmol/L, add a potassium-sparing diuretic or potassium supplement.
Sources
Mechanism
Both cause renal potassium loss. Dual hypokalaemia with arrhythmia risk.
Symptoms
K+ below 3.0 mmol/L, weakness, arrhythmia.
Management
Daily potassium check, potassium and magnesium replacement.
Mechanism
Hydrochlorothiazide (thiazide diuretic) increases urinary potassium loss. Low potassium amplifies dronedarone's QT effect.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Severe cases: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia and hypomagnesaemia.
Management
The combination is common (hypertension + atrial fibrillation). Check potassium and magnesium every 3 months; if potassium drops below 4.0 mmol/L, add a potassium-sparing diuretic or potassium supplement.
Mechanism
Hydrochlorothiazide increases sodium and lithium reabsorption in the distal tubule. Lithium plasma concentration rises 25–40% (up to 100% in some patients). Lithium toxicity develops within 1–2 weeks.
Symptoms
Tremor, nausea, diarrhea, confusion; in severe cases seizures and coma.
Management
For hypertension in a lithium patient, choose another class: calcium channel blocker (amlodipine) or a potassium-sparing diuretic with caution. If thiazide is required, halve lithium and check level on days 5–7 and at 2 weeks.
Sources
Mechanism
A thiazide diuretic plus an ARB synergistically lower blood pressure: the thiazide reduces circulating volume, losartan vasodilates by suppressing the RAAS. This is a target combination in hypertension and available as a fixed-dose product (losartan + hydrochlorothiazide).
Symptoms
Excessive blood pressure drop during titration: postural dizziness, syncope. Hypokalaemia and hyponatraemia from the thiazide, plus a mild rise in creatinine, can occur in the first weeks.
Management
The combination is a treatment standard. Doses are individualised, usually starting with losartan 50 mg + hydrochlorothiazide 12.5 mg/day. Check potassium, sodium, and creatinine 2–4 weeks after start, then annually.
Sources
Mechanism
Thiazide diuretics raise allopurinol and oxypurinol metabolite levels, increasing hypersensitivity risk, including allopurinol hypersensitivity syndrome (DRESS).
Symptoms
Rash, fever, facial oedema, lymphadenopathy, abnormal liver function. Reactions develop 2–8 weeks after starting allopurinol, more often in older patients and chronic kidney disease.
Management
On the combination, dose allopurinol by creatinine clearance: if below 60 mL/min, start at 100 mg/day with titration of 100 mg every 4 weeks until target uric acid is reached. In Asian patients (especially Han Chinese and Thai), HLA-B*58:01 testing is recommended before starting allopurinol. Alternatives in hyperuricaemia: febuxostat (if no heart failure), or replace the thiazide with losartan (urocosuric effect).
Mechanism
Additive hypotension and fall risk. No direct pharmacokinetic interaction.
Symptoms
Lower blood pressure, postural dizziness, fatigue. Older patients: fall risk.
Management
In older patients, check standing and sitting blood pressure 1–2 weeks after start. Alternative anxiolytic: hydroxyzine or a short lorazepam course.
Mechanism
Additive orthostatic hypotension. Older patients: fall and delirium risk with thiazide-induced hypovolaemia.
Symptoms
Postural dizziness, syncope, fatigue. Older patients: fall and fracture risk.
Management
In older patients, check standing and sitting blood pressure and assess fluid and electrolyte balance. For neuropathic pain, alternative: gabapentin or pregabalin.
Mechanism
Standard combination in hypertension – additive antihypertensive effect. Thiazide diuretic causes hypokalaemia.
Symptoms
Lower blood pressure, postural dizziness, fatigue. Older patients: fall risk. With additional antihypertensives: bradycardia (pulse below 60/min).
Management
Standard combination (fixed-dose product available). Check potassium 2–4 weeks after start and then annually. If potassium drops below 4.0 mmol/L, add a potassium-sparing component.
Mechanism
Thiazide diuretic causes hypokalaemia and hypomagnesaemia, increasing myocardial sensitivity to digoxin. Arrhythmia risk rises, especially ventricular arrhythmias.
Symptoms
Nausea, vomiting, loss of appetite, confusion, yellow-green halos around lights, arrhythmia (bigeminy, AV block). Symptoms appear earlier in older patients and chronic kidney disease.
Management
On the combination, check potassium and magnesium every 2–4 weeks in the first 3 months, then every 3–6 months. If potassium falls below 4 mmol/L, add potassium supplements or a low-dose potassium-sparing diuretic (spironolactone). Thiazide alternatives in hypokalaemia: indapamide with potassium supplementation or a thiazide/potassium-sparing combination.
Sources
Mechanism
Additive antihypertensive effect. In the first weeks hydrochlorothiazide increases renin-angiotensin system activity, raising sensitivity to the ACE inhibitor. A standard fixed combination for arterial hypertension.
Symptoms
Symptomatic hypotension on starting: dizziness, weakness, especially on standing. In older patients: fall risk. Potassium monitoring matters — thiazide depletes, ACE inhibitor retains.
Management
On starting the combination, begin enalapril at the lowest dose (2.5 mg) at bedtime. Check creatinine and potassium at 1–2 weeks, then every 6 months. In older patients, take the first dose seated.
Sources
Mechanism
Sequential nephron blockade: furosemide acts at the loop of Henle, the thiazide at the distal tubule. Additive diuresis in fluid retention resistant to a single diuretic.
Symptoms
Weakness, dizziness, thirst, reduced urine output, rising creatinine. In older patients, fall risk from orthostatic hypotension. Weakness, muscle cramps, fatigue, palpitations, arrhythmia (particularly dangerous with digoxin). Symptoms appear at potassium below 3.5 mmol/L.
Management
Use only as short courses (3–7 days) with daily weight and creatinine every 1–2 days. Potassium, sodium, magnesium every 2–3 days. When weight loss reaches 1–1.5 kg/day, reduce diuresis pace — return to a single diuretic. For sustained need, consider an SGLT-2 inhibitor or tolvaptan.
Sources
Mechanism
Thiazide diuretics reduce glycaemic control via hypokalaemia-driven suppression of insulin secretion. may rise by 0.3–0.5%, especially in the first 6 months.
Symptoms
Return of thirst and polyuria, rising fasting glucose, signs of worsening control. Symptoms are typically mild.
Management
Check fasting glucose and 3 months after starting hydrochlorothiazide. If HbA1c rises, increase metformin or add another glucose-lowering agent. Potassium every 6 months. In overt diabetes decompensation, alternatives: indapamide (less metabolic effect) or an SGLT-2 inhibitor.
Mechanism
Thiazides are one of the most common drug causes of hyponatraemia in older patients via SIADH-like mechanism and natriuresis. SSRIs (sertraline) add a SIADH-like effect. Additive risk.
Symptoms
Headache, nausea, confusion, drowsiness; severe cases: seizures. Develops slowly over 1–2 weeks and is often missed in older patients.
Management
On the combination, check sodium at 2 and 4 weeks after starting sertraline or the thiazide, then every 6 months. If sodium falls below 130 mmol/L, consider switching sertraline to mirtazapine or agomelatine, or replacing the thiazide with indapamide (lower hyponatraemia risk).
Mechanism
Opposing effects on potassium: thiazide depletes it, spironolactone retains it. Combination in resistant hypertension and ascites. In CKD, hyperkalaemia risk rises.
Symptoms
With a balanced combination, no specific symptoms. Weakness, fatigue, paraesthesias, arrhythmia. Symptoms develop at potassium above 5.5 mmol/L; life-threatening above 6.5 mmol/L.
Management
Check potassium and creatinine at 2 and 4 weeks after starting, then every 3 months. With creatinine clearance below 30 mL/min, do not prescribe spironolactone. In older patients, watch for dehydration, especially in heat or acute illness.
Sources
Opens the checker prefilled with this drug. Pick the second one from your regimen.
Direct links to regulator labels. Open in a new tab.
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.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Hydrochlorothiazide is evaluated for the following indications with varying evidence strength: Hypertension (evidence tier A), Edema in heart failure (evidence tier B), Weight loss (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.
FDA category B. 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.