Chlorthalidone Dosing for Hypertension
For hypertension treatment, initiate chlorthalidone at 12.5-25 mg once daily in the morning, with 12.5-25 mg being the optimal dose range for cardiovascular protection based on major clinical trials. 1
Initial Dosing Strategy
- Start with 12.5 mg once daily for most patients to minimize metabolic adverse effects while maintaining proven cardiovascular benefit 1, 2
- Alternative starting dose of 25 mg once daily is appropriate and equally effective, particularly supported by landmark trials like ALLHAT 1, 3
- Both 12.5 mg and 25 mg doses provide equivalent blood pressure reduction with the lower dose causing less hypokalemia 4, 5
Dose Titration
- If blood pressure remains uncontrolled after 4 weeks, increase to 25 mg once daily (if started at 12.5 mg) 1, 2
- Maximum recommended dose is 25 mg daily for optimal cardiovascular endpoint protection 1
- Doses of 50 mg may be used if 25 mg is insufficient, though increases above 25 mg provide minimal additional blood pressure reduction with significantly more metabolic side effects 3, 4
- Do not exceed 100 mg daily, as higher doses increase adverse effects without meaningful additional efficacy 3, 6
Critical Monitoring Requirements
- Check electrolytes (potassium, sodium), creatinine, and eGFR within 2-4 weeks of initiation or any dose escalation 2, 7
- Monitor uric acid and calcium levels, as chlorthalidone can precipitate gout and cause hypercalcemia 2, 7
- Chlorthalidone carries a 3-fold higher risk of hypokalemia compared to hydrochlorothiazide, even at 12.5 mg 2, 8
- Hypokalemia can contribute to ventricular ectopy and sudden death, making potassium monitoring essential 2
Administration Details
- Take once daily in the morning with food 3
- Divided daily doses are unnecessary due to chlorthalidone's long half-life (24-72 hours) 7, 9
- Provides superior 24-hour blood pressure control compared to hydrochlorothiazide 9, 10
Special Populations and Considerations
- Black patients with hypertension: Chlorthalidone is particularly effective as initial therapy at 12.5-25 mg daily 1
- Diabetic patients: Despite slightly higher diabetes incidence with chlorthalidone, this does not translate to worse cardiovascular outcomes 1, 2
- Advanced CKD (eGFR <30 mL/min/1.73 m²): Chlorthalidone remains effective and superior to hydrochlorothiazide, though use with caution and monitor closely 2
- History of gout: Use caution unless patient is on uric acid-lowering therapy 2, 7
Combination Therapy
- For Stage 2 hypertension (≥140/90 mmHg), initiate combination therapy with chlorthalidone 12.5 mg plus another antihypertensive class (ACE inhibitor, ARB, or CCB) 1, 8
- Two or more medications are typically required for adequate blood pressure control, especially in black patients 1
Why Chlorthalidone Over Hydrochlorothiazide
- Chlorthalidone is the preferred thiazide-type diuretic based on prolonged half-life and proven cardiovascular disease reduction in clinical trials 1, 2
- Network meta-analyses demonstrate superior clinical outcomes with chlorthalidone versus hydrochlorothiazide 2
- Chlorthalidone 12.5-25 mg is equivalent to hydrochlorothiazide 25-50 mg, but with better 24-hour blood pressure control 1, 2, 9