Chlorothiazide is a thiazide diuretic and antihypertensive agent.
Reconstitution and Administration
Chlorothiazide is administered orally. Chlorothiazide sodium is administered by slow IV injection or by infusion; however, the IV route should be used only when patients are unable to take the drug orally or in emergency situations. The injection must not be administered subcutaneously or IM, and extravasation of the alkaline solution must be avoided . IV preparations of the drug are not indicated for use in the management of hypertension.602
Chlorothiazide sodium for injection should be reconstituted only with sterile water for injection. Addition of 18 mL of sterile water for injection to the vial labeled as containing 500 mg of chlorothiazide provides a solution containing 28 mg/mL. No less than 18 mL of diluent should be used for initial reconstitution. The injection may be further diluted with sodium chloride, dextrose, or other compatible infusion fluids before administration.
Dosage of chlorothiazide sodium is expressed in terms of chlorothiazide. IV dosage of chlorothiazide as the sodium salt is the same as the oral dosage of chlorothiazide.
Dosage of chlorothiazide should be individualized according to the patient's requirements and response. If chlorothiazide 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 dosage of chlorothiazide is 0.5-2 g daily, administered orally or IV in 1 or 2 doses. After several days or when nonedematous weight is attained, reduction of dosage to a lower maintenance level may be possible. Many patients also may respond to intermittent therapy (e.g., on alternate days or on 3-5 days weekly). With an intermittent schedule, excessive response and the resulting undesirable electrolyte imbalance are less likely to occur.111
For the management of fluid retention (e.g., edema) associated with heart failure in adults, some experts recommend initiating chlorothiazide at a low dosage (e.g., 250-500 mg once or twice daily) and increasing the dosage (maximum of 1 g daily) until urine output increases and weight decreases, generally by 0.5-1 kg daily.524 When chlorothiazide is used for sequential nephron blockade in the management of fluid retention in heart failure, some experts recommend an initial IV dosage of 0.5-1 g once daily in combination with a loop diuretic.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 initial oral chlorothiazide dosage recommended by the manufacturers for the management of hypertension in adults is 0.5-1 g daily given as a single dose or in 2 divided doses.600, 601 Adults rarely may require up to 2 g daily in divided doses.600, 601
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.1200 If an adequate blood pressure response is not achieved with chlorothiazide 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, 1216 (See Uses: Hypertension in Adults, in the Thiazides General Statement 40:28.20.) In patients who develop unacceptable adverse effects, 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, 1200, 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 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.
In children 6 months to 12 years of age, the usual dosage of chlorothiazide for management of hypertension or for diuresis is 10-20 mg/kg given daily in 1 or 2 divided doses.110, 601, 1150 Infants younger than 6 months of age may require up to 30 mg/kg daily given in 2 divided doses.110 The total daily dosage should not exceed 375 mg for infants up to 2 years of age or 1 g for children older than 2 up to 12 years of age.110 Experts state that the drug should be initiated at the low end of the dosage range and the dosage increased every 2-4 weeks until blood pressure is controlled, the maximum dosage is reached, or adverse effects occur.1150 Experience with IV administration in infants and children has been limited, and this route generally is not recommended in this age group.111
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.
Chlorothiazide 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.)
Chlorothiazide is incompletely and variably absorbed from the GI tract. Absorption of chlorothiazide from the GI tract appears to be site specific and saturable. Several studies indicate that about 50 mg of drug is absorbed following oral administration of a single 250-mg tablet, a single 500-mg tablet, or two 250-mg tablets to fasting healthy individuals. Concomitant administration with food appears to increase the extent of absorption of the drug.
Chlorothiazide is apparently not metabolized and is excreted unchanged in urine. The plasma half-life of chlorothiazide is 45-120 minutes. About 95% of an IV dose is excreted in urine within 5 hours. About 20% of a 250-mg dose and 10% of a 500-mg dose is excreted in urine within 48-72 hours following oral administration of the drug in tablet form to fasting individuals with normal renal function; most urinary excretion occurs within the first 24 hours.
Chlorothiazide is a thiazide diuretic. Chlorothiazide occurs as a white or practically white, odorless, crystalline powder and has a slightly bitter taste. Chlorothiazide is very slightly soluble in water, slightly soluble in alcohol, and soluble in solutions of alkali hydroxides and has pKas of 6.7 and 9.5. The commercially available chlorothiazide oral suspension occurs as a yellow, creamy suspension and has a pH of 3.2-4.
Chlorothiazide sodium for injection is a sterile, lyophilized mixture of the drug and mannitol. The drug is prepared by neutralizing chlorothiazide with the aid of sodium hydroxide. Chlorothiazide sodium occurs as a white powder, which is usually present in the form of a plug in the commercial preparation, and is very soluble in water and in alcohol. Chlorothiazide sodium powder for injection contains sodium hydroxide to adjust pH; when reconstituted as directed, solutions of the drug are isotonic and have a pH of 9.2-10. A 500-mg vial of chlorothiazide as the sodium salt contains approximately 2.5 mEq of sodium.
Commercially available chlorothiazide tablets have an expiration date of 3 or 5 years following the date of manufacture depending on the packaging. The commercially available chlorothiazide oral suspension should be protected from freezing and has an expiration date of 5 years following the date of manufacture. The powder for injection has an expiration date of 5 years following the date of manufacture.
Commercially available chlorothiazide injection is intended for single use only. Following reconstitution with 18 mL of sterile water for injection, the unused portion should be discarded. Precipitation of chlorothiazide occurs in less than 24 hours if the pH of the reconstituted solution is less than 7.4. It forms a precipitate within 6 hours at a concentration of 2 mg/mL in the following injections: Normosol®-R in 5% dextrose, Ionosol® B with 5% dextrose, or Normosol®-M in 5% dextrose.
Chlorothiazide sodium is reported to be incompatible with injectable preparations of the following drugs: amikacin sulfate, chlorpromazine hydrochloride, hydralazine hydrochloride, insulin, norepinephrine bitartrate, levorphanol tartrate, methadone hydrochloride, morphine sulfate, polymyxin B sulfate, prochlorperazine mesylate, promethazine hydrochloride, streptomycin sulfate, tetracycline hydrochloride, and vancomycin hydrochloride. Specialized references should be consulted for specific compatibility information. Chlorothiazide sodium injection should not be administered simultaneously with whole blood or its derivatives.
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 | Suspension | 250 mg/5 mL | ||
Tablets | 250 mg* | |||
500 mg* | Chlorothiazide Tablets |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | For injection, for IV use only | 500 mg (of chlorothiazide)* |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions June 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
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