Dosage and Administration
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.
Thalitone tablets are formulated with povidone to enhance oral bioavailability of chlorthalidone; because of the enhanced bioavailability of this formulation, Thalitone tablets are not bioequivalent with other formulations of the drug, and the manufacturer states that the tablets cannot be substituted for other preparations or vice versa on a mg-for-mg basis.
The usual initial adult dosage of chlorthalidone for the management of edema 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. 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.
When tablets with enhanced oral bioavailability of chlorthalidone are used (i.e., Thalitone), the usual initial dosage for the management of edema in adults is 30-60 mg daily or 60 mg on alternate days. Dosage then can be adjusted as necessary to 90-120 mg on alternate days or daily. Dosages exceeding 120 mg daily usually do not produce a greater response. Maintenance dosages often may be lower than initial dosages of the drug and therefore should be adjusted according to individual response.
The panel members appointed to the Eighth Joint National Committee on the Detection, Prevention, and Treatment of High Blood Pressure (JNC 8 expert panel) state that evidence-based dosing information (i.e., dosages shown in randomized controlled trials to reduce complications of hypertension) should be used when available to determine target dosages of antihypertensive agents. Based on such information, an initial adult chlorthalidone dosage of 12.5 mg once daily and a target dosage of 12.5-25 mg once daily are recommended. Other experts have recommended an initial adult chlorthalidone dosage of 12.5-25 mg daily and a usual maximum dosage of 25 mg daily. Dosages of chlorthalidone exceeding 100 mg daily usually do not increase efficacy. Target dosages of antihypertensive agents generally can be achieved within 2-4 weeks, but it may take up to several months. Antihypertensive therapy should be titrated until goal blood pressure is achieved.
If an adequate blood pressure response is not achieved with chlorthalidone monotherapy, another antihypertensive agent with demonstrated benefit may be added; if goal blood pressure is still not achieved with the use of 2 antihypertensive agents at optimal dosages, a third drug may be added.
In patients who experience intolerable adverse effects with chlorthalidone, dosage reduction should be considered; if adverse effects worsen or fail to resolve, it may be necessary to discontinue the diuretic and switch to another class of antihypertensive agent.
When tablets with enhanced oral bioavailability of chlorthalidone are used (i.e., Thalitone), the usual initial dosage for the management of hypertension in adults is 15 mg once daily. If response is inadequate after a sufficient trial, dosage can be increased to 30 mg once daily and, if necessary, to 45-50 mg daily. If blood pressure control still is inadequate at the upper dosage, the manufacturer recommends that a second antihypertensive drug be added rather than increasing the dosage of Thalitone further.
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 manufacturers state that commercially available preparations containing chlorthalidone in fixed combination with atenolol or clonidine should not be used for initial antihypertensive therapy.
Blood Pressure Monitoring and Treatment Goals
Careful monitoring of blood pressure during initial titration or subsequent upward adjustment in dosage of chlorthalidone is recommended.
The goal of hypertension management and prevention is to achieve and maintain optimal control of blood pressure; specific target levels of blood pressure should be individualized based on consideration of multiple factors, including patient age and comorbidities, and the currently available evidence from clinical studies.
For additional information on initiating and adjusting chlorthalidone dosage in the management of hypertension, .
For the management of hypertension in children, some experts recommend a usual initial dosage of 0.3 mg/kg once daily. Dosage may be increased as necessary to a maximum dosage of 2 mg/kg (up to 50 mg) once daily. For information on overall principles and expert recommendations for treatment of hypertension in pediatric patients, .
Clinical studies of chlorthalidone did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger adults. While clinical experience generally has not revealed age-related differences in response to the drug, care should be taken in dosage selection of chlorthalidone. Because of the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy in geriatric patients, the manufacturers suggest that patients in this age group receive initial dosages of the drug in the lower end of the usual range. Because chlorthalidone is known to be substantially excreted by the kidney, and because patients with renal impairment are at increased risk of chlorthalidone-induced toxicity, renal function should be monitored closely and dosages adjusted accordingly.