Chlorothiazide Sodium

Thiazide diuretic and antihypertensive agent.

General

BP Monitoring and Treatment Goals

• Carefully monitor BP during initial titration or subsequent upward adjustment in dosage.500 501

• When available, use evidence-based dosing information (i.e., dosages shown in randomized controlled trials to reduce complications of hypertension) to determine target dosages; target dosages usually can be achieved within 2–4 weeks but may take up to several months.501

• If adequate BP response not achieved with a single antihypertensive agent, add a second drug with demonstrated benefit; if goal BP still not achieved with optimal dosages of 2 antihypertensive agents, add a third drug.501 May maximize dosage of the first drug before adding a second drug, or add a second drug before maximizing dosage of the initial drug.501

• Consider initiating antihypertensive therapy with a combination of drugs if patient's BP exceeds goal BP by >20/10 mm Hg.500 501 503 504

• Goal is to achieve and maintain optimal control of BP; individualize specific target BP based on consideration of multiple factors, including patient age and comorbidities, and currently available evidence from clinical studies.500 501 (See Hypertension under Uses.)

Administration

Administer orally or IV.a 110 111 IV preparations not indicated for hypertension management.602

The injection must not be administered subcutaneously or IM, and extravasation of the alkaline solution must be avoided.a 111

Oral Administration

Administer chlorothiazide tablets and suspension orally.a 110

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer chlorothiazide sodium by slow IV injection or by IV infusion; however, the IV route should be used only when patients are unable to take the drug orally or in emergency situations.a 111

Extravasation of the alkaline solution must be avoided.a 111

Reconstitute only with sterile water for injection.a

Addition of 18 mL of sterile water for injection to 500-mg vial provides a solution containing about 28 (27.8) mg/mL.a 111 No less than 18 mL of diluent should be used for initial reconstitution.a 111

The injection may be administered undiluted or may be further diluted with sodium chloride, dextrose, or other compatible infusion fluids before administration.a 111

Slowly by direct IV injection or by IV infusion.a 111

Dosage

Dosage of chlorothiazide sodium is expressed in terms of chlorothiazide.a 111

IV and oral dosage are the same.a 111

Individualize according to requirements and response.a

If added to potent hypotensive agent regimen, initially reduce hypotensive dosage to avoid the possibility of severe hypotension.a

For the management of fluid retention associated with heart failure, experts state that diuretics should be administered at a dosage sufficient to achieve optimal volume status and relieve congestion without inducing excessively rapid reduction in intravascular volume, which could result in hypotension, renal dysfunction, or both.524

Pediatric Patients

Infants <6 months of age: May require up to 30 mg/kg daily given in 2 divided doses.110 601

Children 6 months to 12 years of age: Usually 10–20 mg/kg daily in 1 or 2 divided doses.110 601

Infants <6 months of age: May require up to 30 mg/kg daily given in 2 divided doses.110 601

Children 6 months to 12 years of age: Usually 10–20 mg/kg daily in 1 or 2 divided doses.110 601

Experience in infants and children is limited, and IV use in this age group generally is not recommended.a 111

Adults

Initially, 125–250 mg daily.101 102

Usual dosage: 125–500 mg daily in 1 or 2 doses.101 102 500

If adequate response is not achieved with monotherapy, add another antihypertensive agent.501

If intolerable adverse effects occur, consider dosage reduction; if adverse effects worsen or fail to resolve, may need to discontinue and switch to another antihypertensive drug class.501

Usually, 500 mg to 1 g daily in 1 or 2 doses.110 Occasionally, up to 2 g daily in 1 or 2 doses.a

After several days or when nonedematous weight is attained, dosage reduction to a lower maintenance level may be possible.a

For management of fluid retention associated with heart failure, some experts recommend initiating chlorothiazide at a low dosage (e.g., 250–500 mg once or twice daily) and increasing dosage until urine output increases and weight decreases, generally by 0.5–1 kg daily.524

With an intermittent schedule, excessive response and the resulting undesirable electrolyte imbalance are less likely to occur.a

Usually, 500 mg to 1 g daily in 1 or 2 doses.110 Occasionally, up to 2 g daily in 1 or 2 doses.a

After several days or when nonedematous weight is attained, dosage reduction to a lower maintenance level may be possible.a

With an intermittent schedule, excessive response and the resulting undesirable electrolyte imbalance are less likely to occur.a 111

For sequential nephron blockade in the management of fluid retention in heart failure, some experts recommend an initial dosage of 500 mg to 1 g once daily in combination with a loop diuretic.524

Prescribing Limits

Pediatric Patients

Infants <2 years of age: Maximum of 375 mg daily.a 110

Children ≥2 years of age: 1 g daily.a 110

Adults

Usual maximum is 500 mg daily.a 101 102 103 Higher dosages (up to 2 g daily in divided doses)110 e previously used but no longer recommended.101

Maximum recommended by manufacturer: 2 g daily in divided doses.a 110

Management of fluid retention in heart failure: 1 g maximum daily dosage recommended by ACCF/AHA.524

Maximum of 2 g daily in divided doses.a 111

Special Populations

Hepatic Impairment

No specific dosage recommendations for hepatic impairment; caution because of risk of precipitating hepatic coma.a 110 111

Renal Impairment

No specific dosage recommendations for renal impairment; caution because of risk of precipitating azotemia.a 110 111

Geriatric Patients

No specific geriatric dosage recommendations.a 110 111

Storage

Oral

Tight, light-resistant containers at 20–25°C.601

Tight containers at 15–30°C; avoid freezing.600

Parenteral

20–25°C.602

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

• Exact mechanism of diuretic action is unclear; may act by altering metabolism of the tubular cells.b

• Enhances excretion of sodium, chloride, and water by interfering with the transport of sodium ions across the renal tubular epithelium.b

• Primary site of diuretic action appears to be the cortical diluting segment of the nephron.b

• GFR decreases, but unclear whether secondary to a direct effect on renal vasculature or to the decrease in intravascular fluid volume or an increase in tubular pressure caused by the inhibition of sodium and water reabsorption.b The fall in GFR is not important in the mechanism of action.b

• Enhances urinary excretion of potassium secondary to increased amount of sodium at distal tubular site of sodium-potassium exchange.b

• Increases urinary bicarbonate excretion (although to a lesser extent than chloride excretion) but change in urinary pH is usually minimal; diuretic efficacy is not affected by the acid-base balance of the patient.b

• Hypocalciuric effect is thought to result from a decrease in extracellular fluid (ECF) volume, although calcium reabsorption in the nephron may be increased; also, slight or intermittent elevations in serum calcium concentration.b

• Rate of uric acid excretion is decreased, probably because of competitive inhibition of uric acid secretion or a decrease in ECF volume and a secondary increase in uric acid reabsorption.b

• Hypotensive activity in hypertensive patients; also augments the action of other hypotensive agents.b Precise mechanism of hypotensive action has not been determined, but postulated that part of this effect is caused by direct arteriolar dilation.b

• Advise patient of signs of electrolyte imbalance (e.g., dryness of the mouth, thirst, weakness, lethargy, drowsiness, restlessness, confusion, seizures, oliguria, or muscle pains or cramps, muscular fatigue, hypotension, tachycardia, GI disturbances such as nausea and vomiting).b

• Advise patients of importance of compliance with scheduled determinations of serum electrolyte concentrations (particularly potassium, sodium, chloride, and bicarbonate).b

• Advise hypertensive patients of importance of continuing lifestyle/behavioral modifications that include weight reduction (for those who are overweight or obese), dietary changes to include foods that are rich in potassium and calcium and moderately restricted in sodium (adoption of the Dietary Approaches to Stop Hypertension [DASH] eating plan), increased physical activity, smoking cessation, and moderation of alcohol intake.500

  Advise that lifestyle/behavioral modifications reduce BP, enhance antihypertensive drug efficacy, and decrease cardiovascular risk and remain an indispensable part of the management of hypertension.500

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)