Dosage of hydrochlorothiazide should be individualized according to the patient's requirements and response. The lowest dosage necessary to produce the desired clinical effect should be used. If hydrochlorothiazide is added to the regimen of a patient stabilized on a potent hypotensive agent, dosage of the hypotensive agent should initially be reduced to avoid the possibility of severe hypotension.
For the management of edema, the usual adult dosage of hydrochlorothiazide is 25-100 mg daily in 1-3 divided doses. Many patients also may respond to intermittent therapy (e.g., on alternate days or on 3-5 days weekly). Excessive diuretic response and the resulting undesirable electrolyte imbalance are less likely to occur with such intermittent administration of the drug.
For the management of fluid retention (e.g., edema) associated with heart failure, some experts recommend initiating hydrochlorothiazide at a low dosage (e.g., 25 mg once or twice daily) and increasing the dosage (maximum of 200 mg daily) until urine output increases and weight decreases, generally by 0.5-1 kg daily. When hydrochlorothiazide is used for sequential nephron blockade in the management of fluid retention in heart failure, some experts recommend an initial dosage of 25-100 mg once or twice daily in combination with a loop diuretic. 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.
The panel members appointed to the Eighth Joint National Committee on the Prevention, Detection, 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. Initial hydrochlorothiazide dosages of 12.5-25 mg daily and target dosages of 25-100 mg daily (in 1 or 2 divided doses) were used in randomized controlled studies; however, the JNC 8 expert panel recommends a lower target dosage of 25-50 mg daily for management of hypertension in adults for optimal balance between efficacy and safety. Other experts and the manufacturers also recommend an initial adult hydrochlorothiazide dosage of 12.5-25 mg daily and a usual maximum dosage of 50 mg daily. Dosages exceeding 50 mg daily usually are associated with marked hypokalemia. Target dosages 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 hydrochlorothiazide 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 hydrochlorothiazide, 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 combination therapy is required in the management of hypertension, dosage can first be adjusted by administering each drug separately. If it is determined that the optimum maintenance dosage corresponds to the ratio in the commercial combination preparation, the fixed combination may be used. Alternatively, therapy can be initiated with a fixed combination of 2 antihypertensive agents. Use of fixed-combination preparations may increase patient compliance.
For information on commercially available preparations containing hydrochlorothiazide in fixed combination with a potassium-sparing diuretic, see the individual monographs in 40:28.10.
Blood Pressure Monitoring and Treatment Goals
Careful monitoring of blood pressure during initial titration or subsequent upward adjustment in dosage of hydrochlorothiazide 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 hydrochlorothiazide dosage in the management of hypertension, .
In children 6 months to 12 years of age, the usual dosage of hydrochlorothiazide for the management of hypertension or for diuresis is 1-2 mg/kg daily given as a single dose or in 2 divided doses. Infants younger than 6 months of age may require up to 3 mg/kg daily in 2 divided doses. The total daily dosage should not exceed 37.5 mg for children up to 2 years of age or 100 mg for children 2-12 years of age. Alternatively, if hydrochlorothiazide is used for the management of hypertension in children, some experts recommend an initial dosage of 1 mg/kg once daily. These experts state that dosage may be increased as necessary to a maximum of 3 mg/kg (up to 50 mg) once daily.
Because an increased incidence of adverse effects to hydrochlorothiazide and excessive reduction in blood pressure may occur in geriatric patients (older than 65years of age), hydrochlorothiazide should be initiated at the lowest dosage (12.5 mg daily); dosage may be adjusted in increments of 12.5 mg if needed.
Hydrochlorothiazide shares the pharmacologic actions, uses, and toxic potentials of the thiazides, and the usual precautions of thiazide administration should be observed.
Some commercially available formulations of hydrochlorothiazide contain sulfites that may cause allergic-type reactions, including anaphylaxis and life-threatening or less severe asthmatic episodes, in certain susceptible individuals. The overall prevalence of sulfite sensitivity in the general population is unknown but probably low; such sensitivity appears to occur more frequently in asthmatic than in nonasthmatic individuals.
Hydrochlorothiazide is well absorbed from the GI tract, with an oral bioavailability of approximately 65-75%. Although the rate and extent of absorption have been reported to vary depending on the formulation administered, no studies have been performed to determine the clinical importance (if any) of variations in absorption in patients receiving chronic hydrochlorothiazide therapy. Following oral administration of hydrochlorothiazide at doses of 12.5-100 mg, peak plasma concentrations of 70-490 ng/mL are observed within 1-5 hours of dosing. Food decreases the rate and extent of absorption of hydrochlorothiazide capsules (Microzide). Bioavailability and peak plasma concentrations of the drug were decreased by about 10 and 20%, respectively, when hydrochlorothiazide capsules (Microzide) were administered with food. Times to peak plasma concentration for such capsules were delayed by 1.3 hours (from 1.6 to 2.9 hours). Absorption of hydrochlorothiazide is reduced in patients with heart failure.
Approximately 40-68% of the drug is bound to plasma proteins.
Hydrochlorothiazide exhibits linear pharmacokinetics. Based on determination of plasma drug concentrations over a period of at least 24 hours, the plasma half-life of hydrochlorothiazide reportedly ranges from 5.6-15 hours. Hydrochlorothiazide apparently is not metabolized and is excreted unchanged in urine. At least 61% of the drug is reportedly eliminated from the body within 24 hours. Increased hydrochlorothiazide plasma concentrations and a prolonged elimination half-life have been reported in patients with renal impairment. The effect of hemodialysis on the elimination of the drug has not been determined.