Chlorthalidone, which is structurally and pharmacologically similar to the thiazides, is a diuretic and antihypertensive agent.
Chlorthalidone is administered orally.
Dosage of chlorthalidone should be individualized according to the patient's requirements and response. If chlorthalidone is added to the regimen of a patient stabilized on a potent hypotensive agent, the dosage of the hypotensive agent should initially be reduced to avoid the possibility of severe hypotension.
For the management of edema in adults, the usual initial dosage of chlorthalidone is 50-100 mg daily in a single dose after breakfast. Alternatively, therapy may be initiated at a dosage of 100 mg every other day or 3 times a week. Some patients require dosages of 150-200 mg daily or every other day. Dosages greater than 200 mg daily do not produce a greater response. In edematous patients, reduction of dosage to a lower maintenance level may be possible after several days or when nonedematous weight is attained.
For the management of fluid retention (e.g., edema) associated with heart failure, some experts recommend initiating chlorthalidone at a low dosage (e.g., 12.5-25 mg once daily) and increasing the dosage (maximum of 100 mg daily) until urine output increases and weight decreases, generally by 0.5-1 kg daily.524 Experts state that diuretics should be administered at a dosage sufficient to achieve optimal volume status and relieve congestion without inducing an excessively rapid reduction in intravascular volume, which could result in hypotension, renal dysfunction, or both.524
The usual manufacturer-recommended initial dosage of chlorthalidone for the management of hypertension in adults is 25 mg once daily.600 If blood pressure remains uncontrolled, the dosage may be increased to 50 mg once daily.600 Some experts recommend a chlorthalidone dosage of 12.5-25 mg once daily1200 based on efficacy and tolerance demonstrated in clinical studies.109, 1200 Dosages of chlorthalidone exceeding 100 mg daily usually do not increase efficacy.600
When combination therapy is required in the management of hypertension, dosage can be adjusted first by administering each drug separately. If it is determined that the optimum maintenance dosage corresponds to the ratio in a commercial combination preparation, the fixed combination may be used. The manufacturer states that commercially available preparations containing chlorthalidone in fixed combination with atenolol should not be used for initial antihypertensive therapy;601 however, some experts state that initiation of therapy with a fixed-combination preparation may increase patient compliance.1200
Monitoring and Blood Pressure Treatment Goals
The patient's renal function and electrolytes should be assessed 2-4 weeks after initiation of diuretic therapy.1200 Blood pressure should be monitored regularly (i.e., monthly) during therapy and dosage of the antihypertensive drug adjusted until blood pressure is controlled.600, 601, 1200 If an adequate blood pressure response is not achieved with chlorthalidone monotherapy, another antihypertensive agent with demonstrated benefit and preferably with a complementary mechanism of action (e.g., angiotensin-converting enzyme [ACE] inhibitor, angiotensin II receptor antagonist, calcium-channel blocker) may be added; if goal blood pressure is still not achieved, a third drug may be added.1200 (See Uses: Hypertension in Adults, in the Thiazides General Statement 40:28.20.) In patients who develop unacceptable adverse effects with chlorthalidone, the drug should be discontinued and another antihypertensive agent from a different pharmacologic class should be initiated.1200, 1216
The goal of hypertension management and prevention is to achieve and maintain optimal control of blood pressure.1200 However, the optimum blood pressure threshold for initiating antihypertensive drug therapy and specific treatment goals remain controversial.501, 503, 504, 505, 506, 507, 508, 515, 523, 526, 530, 1201, 1207, 1209, 1222, 1223, 1229 A 2017 multidisciplinary hypertension guideline from the American College of Cardiology (ACC), American Heart Association (AHA), and a number of other professional organizations generally recommends a blood pressure goal of less than 130/80 mm Hg in all adults, regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk.1200 Many patients will require at least 2 drugs from different pharmacologic classes to achieve this blood pressure goal; the potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs also should be considered when deciding a patient's blood pressure treatment goal.1200, 1220
For additional information on target levels of blood pressure and on monitoring therapy in the management of hypertension, see Blood Pressure Monitoring and Treatment Goals under Dosage: Hypertension, in Dosage and Administration in the Thiazides General Statement 40:28.20.
For the management of hypertension in children†, some experts recommend an initial dosage of 0.3 mg/kg once daily.1150 Experts state that the dosage should be increased every 2-4 weeks until blood pressure is controlled, the maximum dosage is reached (2 mg/kg [up to 50 mg] daily), or adverse effects occur.1150 For information on overall principles and expert recommendations for treatment of hypertension in pediatric patients, see Uses: Hypertension in Pediatric Patients, in the Thiazides General Statement 40:28.20.
Chlorthalidone shares the pharmacologic actions, uses, and toxic potentials of the thiazides, and the usual precautions of thiazide administration should be observed. (See Cautions in the Thiazides General Statement 40:28.20.)
Chlorthalidone is absorbed from the GI tract. Little information is available on the extent of absorption of the drug.
About 90% of chlorthalidone is bound in the body, principally to or in red blood cells. The high degree of binding accounts for the long half-life of the drug which is reported to be 54 hours. During long-term oral administration, 30-60% of the daily dose is excreted unchanged in urine.
Chlorthalidone is a phthalimidine derivative of benzenesulfonamide that is structurally and pharmacologically similar to the thiazide diuretics. The drug occurs as a white to yellowish-white, crystalline powder. The drug is practically insoluble in water and slightly soluble in alcohol and has a pKa of 9.4.
Chlorthalidone tablets should be stored in tight, light-resistant containers at 20-25°C.600
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets | 25 mg* | ||
50 mg* | Chlorthalidone Tablets |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets | Atenolol 50 mg and Chlorthalidone 25 mg* | ||
Atenolol 100 mg and Chlorthalidone 25 mg* | Atenolol and Chlorthalidone Tablets | |||
Tenoretic® | AstraZeneca |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Only references cited for selected revisions after 1984 are available electronically.
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