Chlorthalidone tablets are available in 25 and 50 mg form.1 Contrary to practice guideline recommendations,2-6 the FDA approval for chlorthalidone therapy initiation is 25 mg in the treatment of hypertension.1 The initial dose can be increased to 50 and then 100 mg if necessary for blood pressure (BP) control. Increasing the dose beyond 100 mg does not increase efficacy of the drug.
For edema treatment, chlorthalidone therapy can be initiated at 50 or 100 mg daily.1 The dose can be increased to 150 or 200 mg a day. Rather than daily administration, alternating days can be used for edema treatment.
Studies investigating the different dose responses of chlorthalidone found that doses greater than 25 mg do not translate to greater blood pressure lowering effects.7,8 For example, in a randomized, placebo-controlled dose study of 171 patients with isolated systolic hypertension (sitting systolic BP ≥160 mm Hg and diastolic ≤90 mm Hg), the average reduction in systolic hypertension was comparable in the 25 and 50 mg groups.8 After 12 weeks of treatment, the average reduction in the 25 mg group was 28.9 mm Hg compared to an average reduction of 30.9 mm Hg in the 50 mg group. However, the percentage of patients reporting an adverse reaction was 13% greater in the 50 mg group (66%) than in the 25 mg group (53%). These findings suggest that lower doses of chlorthalidone may produce the same antihypertensive effects as higher doses, with less adverse effects.
Multiple society practice guidelines have made recommendations regarding chlorthalidone dosing.2-6 According to the 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults, the usual administration of chlorthalidone is 12.5 – 50 mg taken once daily.2 The 2017 guideline does not provide a recommended dose for initiating chlorthalidone treatment. Based on reviews of randomized controlled trials, the Eighth Joint National Committee (JNC 8) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends an initial chlorthalidone dose of 12.5 mg.3
The American Heart Association (AHA), the American College of Cardiology (ACC), and the Center for Disease Control and Prevention (CDC) developed evidence based hypertension treatment algorithms.4 According to their algorithms, the AHA, ACC, and CDC recommend starting chlorthalidone treatment with 12.5 mg, titrating up to 25 mg if needed.
Clinical practice guidelines developed by the American Society of Hypertension and the International Society of Hypertension advise using chlorthalidone doses of 12.5 or 25 mg.5 These doses help reduce metabolic side effects that commonly occur with thiazide and thiazide-like diuretics. When blood pressure control is not achieved with chlorthalidone 25 mg, the clinical practice guidelines do not recommend increasing the dose, and instead recommends adding an additional antihypertensive agent. The National Institute for Care Excellence (NICE) provide the same recommendation: thiazide-like diuretics should be limited to 12.5 or 25 mg doses, adding a different antihypertensive agent if needed.6
References
- Chlorthalidone [package insert]. Morgantown, WV: Mylan Pharmaceuticals Inc.; 2017.
- Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2017.
- James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507-520.
- Go AS, Bauman MA, Coleman King SM, et al. An effective approach to high blood pressure control from the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention. Hypertension. 2014;63(4):878-885.
- Weber MA, Schiffrin EL, White WB, et al. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hypertens. Jan 2014;16(1):14-26.
- McCormack T, Krause T, O'Flynn N. Management of hypertension in adults in primary care: NICE guideline. Br J Gen Pract. 2012;62(596):163-164.
- Materson BJ, Oster JR, Michael UF, et al. Dose response to chlorthalidone in patients with mild hypertension; efficacy of a lower dose. Clin Pharmacol Ther. 1978;24(2):192-198.
- Morledge JH, Ettinger B, Aranda J, et al. Isolated systolic hypertension in the elderly. A placebo-controlled, dose-response evaluation of chlorthalidone. J Am Geriatr Soc. 1986;34(3):199-206.
