Chlorthalidone is an oral antihypertensive/diuretic.
Diuretics such as chlorthalidone are indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effect of other antihypertensive drugs in the more severe forms of hypertension.
Chlorthalidone is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy.
Chlorthalidone has also been found useful in edema due to various forms of renal dysfunction, such as nephrotic syndrome, acute glomerulonephritis, and chronic renal failure.
Usage in Pregnancy
The routine use of diuretics in an otherwise healthy woman is inappropriate and exposes mother and fetus to unnecessary hazard. Diuretics do not prevent development of toxemia of pregnancy, and there is no satisfactory evidence that they are useful in the treatment of developed toxemia. Edema during pregnancy may arise from pathologic causes or from the physiologic and mechanical consequences of pregnancy. Chlorthalidone is indicated in pregnancy when edema is due to pathologic causes, just as it is in the absence of pregnancy (however, see PRECAUTIONS, below). Dependent edema in pregnancy, resulting from restriction of venous return by the expanded uterus, is properly treated through elevation of the lower extremities and use of support hose; use of diuretics to lower intravascular volume in this case is illogical and unnecessary. There is hypervolemia during normal pregnancy that is harmful to neither the fetus nor the mother (in the absence of cardiovascular disease), but that is associated with edema, including generalized edema, in the majority of pregnant women. If this edema produces discomfort, increased recumbency will often provide relief. In rare instances, this edema may cause extreme discomfort that is not relieved by rest. In these cases, a short course of diuretics may provide relief and be appropriate.
Published Studies Related to Chlorthalidone
Spironolactone and chlorthalidone in uncontrolled elderly hypertensive patients treated with calcium antagonists and angiotensin II receptor-blocker: effects on endothelial function, inflammation, and oxidative stress. [2009.10]
The side effects of thiazide-type diuretics include metabolic abnormality and increased oxidative stress, which might cause endothelial dysfunction despite blood pressure reduction. In hypertensive patients with heart failure, treatment with an aldosterone antagonist resulted in improvements in endothelial function and significant blood pressure reduction...
Antihypertensive efficacy of metoprolol XL/low dose chlorthalidone (6.25 mg) combination: a randomized, comparative study in indian patients with mild-to-moderate essential hypertension. [2009.07.22]
OBJECTIVE: High blood pressure is one of the most important risk factors, directly responsible for increasing the cardiovascular morbidity and mortality. The primary objective was to evaluate the efficacy of metoprolol XL/chlorthalidone against metoprolol XL/hydrochlorothiazide with respect to mean fall in systolic and diastolic blood pressure. The secondary objective was to compare the response rates and to evaluate the tolerability of study medications in patients with mild-to-moderate essential hypertension... CONCLUSION: Chlorthalidone in combination with metoprolol XL is as effective and well tolerated as widely used combination of metoprolol XL/HCTZ, thus providing an alternative therapeutic option.
A randomized, comparative study evaluating the efficacy and tolerability of losartan-low dose chlorthalidone (6.25 mg) combination with losartan-hydrochlorothiazide (12.5 mg) combination in Indian patients with mild-to-moderate essential hypertension. [2009.07]
OBJECTIVE: The relationship of blood pressure (BP) to cardiovascular risk is linear, positive, and continuous. Lowering elevated BP reduces the risk of cardiovascular events. The primary objective of this randomized, multicenter, comparative, 3-month, open-label study was to evaluate the antihypertensive efficacy of losartan/chlorthalidone versus losartan/hydrochlorothiazide in mild-to-moderate essential hypertension... CONCLUSIONS: The losartan/low-dose chlorthalidone (6.25 mg) combination is as effective as the widely used losartan/hydrochlorothiazide combination in lowering BP and is well tolerated, thus providing a useful therapeutic option for treating mild-to-moderate hypertension.
Differential effects of chlorthalidone versus spironolactone on muscle sympathetic nerve activity in hypertensive patients. [2009.04]
CONTEXT: Previous studies in rats indicated that thiazide-type diuretics reduced blood pressure (BP) and triggered baroreflex-mediated increase in sympathetic nerve activity (SNA), whereas spironolactone exerted central sympathoinhibitory action in addition to diuretic effects. OBJECTIVES: The objectives were to determine effects of spironolactone and chlorthalidone on SNA and the role of SNA on diuretic-induced insulin resistance in human hypertension... CONCLUSIONS: Our data suggest that chlorthalidone, the first-line drug therapy for hypertension, causes persistent activation of sympathetic nervous system and insulin resistance in hypertensive patients. These side effects, however, are avoided by spironolactone despite similar reduction in BP.
Cost-effectiveness of chlorthalidone, amlodipine, and lisinopril as first-step treatment for patients with hypertension: an analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). [2008.05]
OBJECTIVE: To evaluate the cost-effectiveness of first-line treatments for hypertension. BACKGROUND: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) found that first-line treatment with lisinopril or amlodipine was not significantly superior to chlorthalidone in terms of the primary endpoint, so differences in costs may be critical for optimizing decision-making... CONCLUSIONS: Initial treatment with chlorthalidone is less expensive than lisinopril or amlodipine, but amlodipine provided a nonsignificantly greater survival benefit and may be a cost-effective alternative. A randomized trial with power to exclude "clinically important" differences in survival will often have inadequate power to determine the most cost-effective treatment.
Clinical Trials Related to Chlorthalidone
Study to Evaluate the Efficacy and Safety of the Combination of Valturna and Amlodipine or Valturna and Chlorthalidone Versus Valturna Alone in Patients With Stage 2 Hypertension and Diabetes [Recruiting]
This is a study to assess the safety and efficacy of Valturna and amlodipine or Valturna and
chlorthalidone when compared to Valturna alone in patients with stage 2 hypertension and
diabetes mellitus 2.
Safety and Tolerability of Azilsartan Medoxomil Plus Chlorthalidone Compared to Olmesartan Medoxomil Plus Hydrochlorothiazide in Subjects With Essential Hypertension [Recruiting]
The purpose of this study is to compare the safety and tolerability of azilsartan medoxomil
plus chlorthalidone, once daily (QD), versus olmesartan medoxomil-hydrochlorothiazide in
subjects with essential hypertension.
A Study to Evaluate the Effectiveness and Safety of TAK-491(Azilsartan Medoxomil) and Chlorthalidone Combined in One Tablet (40/12.5 and 40/25 mg) in Patients With High Blood Pressure Who do Not Achieve Target Blood Pressure on Treatment With TAK-491 40 mg Alone [Not yet recruiting]
The purpose of this study is to evaluate the efficacy and safety of the fixed dose
combinations of azilsartan medoxomil plus chlorthalidone, once daily (QD), in participants
with grades 2 or 3 essential hypertension who do not reach target blood pressure following
treatment with 40 mg azilsartan medoxomil monotherapy after 4 weeks.
Safety and Efficacy of Chlorthalidone + Amiloride to Elderly Patients Treatment With Arterial Hypertension [Recruiting]
The purpose of this study is to assess the efficacy and safety of Chlorthalidone 25 mg +
amiloride hydrochloride 5 mg association in the treatment of elderly patients with arterial
EBMtrialcentral- Comparing Initial Diuretic Therapies Using a Collaborative Network [Not yet recruiting]
- Clinical equipoise exists with respect to the important question, "What is the best
initial diuretic for the treatment of Hypertension"? A pragmatic comparative
effectiveness research (CER) study comparing Chlorthalidone to Hydrochlorthiazide could
help inform decision making for this common problem.
- The investigators aim to harness both the power of bioinformatics (using web-based
data-capture and electronic health records) and of online media (through collaboration)
in order to facilitate such a CER in "usual-care" settings. This process may also
provide a foundation for testing a wealth of important clinical questions which
commonly arise in the delivery of contemporary healthcare and would otherwise be left
- To this end the investigators are developing a website, EBMtrialcentral, where eligible
physicians can go online and join their collaborative network. Physicians can then
enroll eligible patients in this study. These will include under-served urban patients.
Clinical information will be entered online (using a secure database housed at Johns
Hopkins), patient consent will be obtained electronically and treatment recommendations
will be randomly allocated to either 25mg daily of oral HCTZ or 12. 5mg daily of oral
Chlorthalidone. The investigators aim to increase to 50mg HCTZ and 25mg Chlorthalidone
over 8 weeks and compare their effects on BP measured with a 24 hour monitor.
- The investigators' primary hypothesis is that non-blinded, random, parallel allocation
of 12. 5mg daily Chlorthalidone (titrated to 25mg at 4 weeks) will demonstrate a
clinically meaningful ≥5mmHg improvement in BP control (as measured by change in BP
from baseline using 24hr ABPM) compared to 25mg daily HCTZ (titrated to 50mg at 4
weeks) in newly hypertensive patients followed in a usual-care clinic setting over 8
weeks. They will also analyze differences in side-effects or safety (serum
electrolytes) between these two medications.
Reports of Suspected Chlorthalidone Side Effects
Blood Creatinine Increased (4),
Blood Pressure Increased (4),
Muscular Weakness (3),
Confusional State (2),
Drug Interaction (2), more >>
Page last updated: 2010-10-05