What is the recommended dosage and management of chlorthalidone (diuretic) for treating hypertension and edema?

Chlorthalidone Dosage and Management for Hypertension and Edema

For treating hypertension, chlorthalidone should be initiated at 25 mg once daily in the morning with food, with a maximum dose of 50 mg daily for most patients, while edema treatment typically requires 50-100 mg daily initially. 1

Dosing Recommendations for Hypertension

• Initial therapy should start with 25 mg once daily in the morning with food 1
• If blood pressure response is insufficient after an adequate trial period, dosage may be increased to 50 mg once daily 1
• Doses above 50 mg daily rarely provide additional antihypertensive benefit but significantly increase side effects 1, 2
• Lower maintenance doses (12.5-25 mg) may be effective for long-term management and should be adjusted according to individual response 1, 2
• Chlorthalidone 25 mg has been shown to be at least as effective as 50 mg and 75 mg doses with less potassium disturbance 2

Dosing Recommendations for Edema

• Initial therapy for edema should start with 50-100 mg daily or 100 mg on alternate days 1
• Some patients may require 150-200 mg at these intervals or up to 200 mg daily 1
• Maintenance doses are often lower than initial doses and should be individualized 1

Pharmacological Considerations

• Chlorthalidone has an extremely long half-life (40-60 hours) and large volume of distribution compared to hydrochlorothiazide 3
• At equivalent doses, chlorthalidone is more potent than hydrochlorothiazide, particularly for overnight blood pressure reduction 3, 4
• Chlorthalidone 12.5 mg has been shown to be more effective than hydrochlorothiazide 25 mg in some studies 4

Monitoring and Management

• All patients treated with diuretics should have electrolytes monitored shortly after initiating therapy and periodically thereafter 5
• Monitor specifically for hypokalemia, hyponatremia, hyperuricemia, and changes in calcium levels 5, 3
• Chlorthalidone may precipitate azotemia in patients with renal diseases and should be used with caution in those with severe renal impairment 5
• Dose-related increases in serum uric acid and decreases in serum potassium occur over the 25-100 mg/day range 1

Clinical Applications

• Chlorthalidone is useful as add-on therapy in patients being treated with drugs from other classes 5
• In heart failure with preserved ejection fraction (HFpEF) with volume overload, diuretics including chlorthalidone should be prescribed to control hypertension 5
• The ALLHAT study showed that treatment with chlorthalidone reduced the risk of heart failure compared with amlodipine, doxazosin, and lisinopril 5
• For patients with resistant hypertension, addition of a thiazide (e.g., metolazone) to treatment with a loop diuretic should be reserved for those who do not respond to moderate or high-dose loop diuretics 5

Potential Adverse Effects

• Chlorthalidone is associated with higher risk of hypokalemia, hyponatremia, acute renal failure, chronic kidney disease, and type 2 diabetes compared to hydrochlorothiazide 6
• Thiazide-induced hypokalemia is associated with increased blood glucose, and treatment of hypokalemia may reverse glucose intolerance 3
• Thiazide-induced hyperuricemia occurs due to volume contraction and competition with uric acid for renal tubular secretion 3
• Consider step-down treatment after blood pressure has been well-controlled for 6 months to minimize side effects 7

Special Populations

• In patients with chronic kidney disease, chlorthalidone may be effective for BP management even with advanced CKD (eGFR <30 mL/min/1.73 m²) 5
• In pediatric patients, the initial dose is 0.3 mg/kg/day with a maximum of 2 mg/kg/day up to 50 mg/day 5