Chlorthalidone
Chlorthalidone is a long-acting thiazide-like diuretic widely used for hypertension and oedema. Several major outcome trials suggest it produces greater blood-pressure reduction and cardiovascular benefit than hydrochlorothiazide at equivalent doses, leading some guidelines to prefer it.
- Chemical formula
- C14H11ClN2O4S
- CAS number
- 77-36-1
- ATC code
- C03BA04
- Molecular weight
- 338.77 g/mol
- Drug class
- Thiazide-like diuretic
- Also known as
- Thalitone, Hygroton
What is it?
Chlorthalidone is a thiazide-like diuretic in clinical use since the 1960s, marketed as Thalitone and Hygroton with widely available authorised generics. Unlike the chemically related thiazides, it has a long elimination half-life and was used in landmark cardiovascular outcome trials including SHEP and ALLHAT. According to current US hypertension guidelines, chlorthalidone is the preferred thiazide-class agent for cardiovascular outcomes, although hydrochlorothiazide remains more widely prescribed because of cost and combination availability.
Mechanism of action
Chlorthalidone blocks the sodium-chloride symporter in the distal convoluted tubule of the kidney, reducing sodium reabsorption and producing modest diuresis. The blood-pressure lowering effect develops over 1–2 weeks and is mediated by both diuretic and direct vasodilatory mechanisms. Compared with hydrochlorothiazide at typical clinical doses, chlorthalidone produces greater 24-hour blood-pressure reduction, partly because of its longer half-life.
Pharmacokinetics
Chlorthalidone is well absorbed after oral administration with bioavailability of about 65%. Onset of diuresis is within 2–3 hours, peak effect at 2–6 hours, and duration up to 72 hours — markedly longer than hydrochlorothiazide. The terminal half-life is 40–60 hours, supporting once-daily or alternate-day dosing. The drug is partly metabolised and partly excreted unchanged in urine.
Indications
Chlorthalidone is approved for hypertension and oedema in heart failure, hepatic cirrhosis or nephrotic syndrome. According to current hypertension guidelines (US JNC and ACC/AHA), chlorthalidone is the preferred thiazide-class agent based on outcome data. Doses are 12.5–25mg daily for hypertension, occasionally up to 50mg for oedema. Lower doses are recommended where possible to minimise metabolic side effects.
Safety profile
Common adverse effects include hypokalaemia, hyponatraemia, hyperuricaemia (with gout flares), hyperglycaemia, dyslipidaemia and orthostatic hypotension. The metabolic side effects may be slightly greater than with hydrochlorothiazide because of the longer duration of action, particularly hypokalaemia. Sulfa allergy is a relative contraindication. Serum potassium, sodium, glucose, uric acid and renal function require periodic monitoring.
Products containing this ingredient
Frequently asked questions
Is chlorthalidone better than hydrochlorothiazide? ▾
Chlorthalidone produces greater 24-hour blood-pressure reduction than hydrochlorothiazide at typical clinical doses, and the largest outcome trials (SHEP, ALLHAT) used chlorthalidone. According to current US hypertension guidelines, chlorthalidone is the preferred thiazide-class agent for cardiovascular outcomes, though HCTZ remains widely used because it is cheap and available in many fixed combinations.
What lab tests are needed on chlorthalidone? ▾
Serum potassium, sodium, glucose, uric acid and renal function are checked at baseline and periodically — typically at 1–2 months after starting and annually thereafter. Hypokalaemia is the most common abnormality and may be slightly more pronounced than with hydrochlorothiazide. Combination with an ACE inhibitor or ARB usually manages potassium without supplementation.
Can I take chlorthalidone if I have gout? ▾
Chlorthalidone raises serum uric acid and can precipitate gout flares. In patients with gout history, the prescriber may use lower doses, alternative antihypertensives, or add allopurinol to control uric acid. According to current guidelines, gout is not an absolute contraindication but warrants individual assessment, particularly when starting chlorthalidone for the first time.
The information on this website is provided for reference and educational purposes only. It does not replace consultation with a qualified healthcare professional.