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Chlorothiazide

Class: Thiazide Diuretics
VA Class: CV701
CAS Number: 58-94-6
Brands: Diuril

Introduction

Chlorothiazide is a thiazide diuretic and antihypertensive agent.

Uses for Chlorothiazide

Hypertension

Used alone or in combination with other antihypertensive agents for all stages of hypertension.b f 110

Thiazides have well-established benefits, can be useful in achieving goal blood pressure alone or combined with other antihypertensive drugs, enhance the antihypertensive efficacy of multidrug regimens, and are more affordable than other agents.b f

JNC 7 recommends that thiazides be used as initial therapy for the treatment of uncomplicated hypertension in most patients, either alone or combined with other classes of antihypertensive drugs with demonstrated benefit (e.g., ACE inhibitors, angiotensin II receptor antagonists, β-blockers, calcium-channel blockers).f

Most hypertension outcome studies have involved thiazides, which generally have been unsurpassed in preventing cardiovascular complications of hypertension and are relatively inexpensive and well tolerated.f

The principal goal of preventing and treating hypertension is to reduce the risk of cardiovascular and renal morbidity and mortality, including target organ damage.f The higher the baseline blood pressure, the more likely the development of myocardial infarction, heart failure, stroke, and renal disease.f

Effective antihypertensive therapy reduces the risk of stroke by about 34–40%, MI by about 20–25%, and heart failure by more than 50%.f

Antihypertensive drug therapy is recommended for all patients with systolic/diastolic blood pressure ≥140/90 mm Hg who fail to respond to lifestyle/behavioral modifications.f

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Initial antihypertensive therapy with drugs generally is recommended for anyone with diabetes mellitus, chronic renal impairment, or heart failure having systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥80 mm Hg.f

Black hypertensive patients generally tend to respond better to monotherapy with diuretics or calcium-channel blockers than to monotherapy with ACE inhibitors, angiotensin II receptor antagonists, or β-blockers.f

Diuretics largely eliminate the diminished response in blacks to ACE inhibitors, angiotensin II receptor antagonists, or β-blockers.f

Thiazides preferred in hypertensive patients with osteoporosis. Secondary beneficial effect in hypertensive geriatric patients of reducing the risk of osteoporosis due to effect on calcium homeostasis and bone mineralization.

Preeclampsia and Eclampsia

Although hypertension during pregnancy responds well to thiazides, and the drugs had been used widely in the past for preeclampsia and eclampsia,b g such use no longer is recommended and other antihypertensives (e.g., methyldopa, hydralazine, labetalol) currently are preferred.f

Although rarely induces acute gout, generally avoid or use with caution in hypertensive patients with a history of gout or elevated uric acid concentrations.f

Edema (General)

Management of edema resulting from various causes; diagnose etiology before use.b 110 111

Edema caused by renal disease or by corticosteroids or estrogens may be relatively resistant to treatment.b

Ineffective in patients with serum creatinine or BUN concentrations > twice normal.b

May be ineffective in patients with a GFR of <15–25 mL/minute; even when GFR is 25–50 mL/minute, more potent (e.g., loop) diuretics may be indicated.b

No substantial difference in clinical effects or toxicity of comparable thiazide or thiazide-like diuretics except metolazone may be more effective in edema with renal impairment.b

Edema in CHF

Management of edema associated with CHF.b c

Used in conjunction with moderate sodium restriction (3 g or less of sodium daily), an ACE inhibitor, and usually a β-adrenergic blocking agent, with or without a cardiac glycoside.c d

Beneficial effects are additive with those of cardiac glycosides and/or ACE inhibitors.c

Unless contraindicated or not tolerated, all patients with mild to severe CHF secondary to left ventricular systolic dysfunction (ejection fraction less than 35–40%) generally should receive therapy with a diuretic in conjunction with an ACE inhibitor with or without a cardiac glycoside or a β-adrenergic blocking agent.d

Diuretic therapy and sodium restriction are not routinely necessary in patients with left ventricular systolic dysfunction and no or minimal overt signs or symptoms of heart failure (NYHA functional class I heart failure);d diuretics should be added to ACE inhibitor therapy if volume overload develops or if symptoms of heart failure continue.

Concomitant diuretic therapy usually is indicated in patients with symptomatic heart failure (NYHA class II or greater) because of the likelihood of sodium and fluid retention.d

Do not use diuretics as monotherapy in CHF even if symptoms (e.g., peripheral edema, pulmonary congestion) are well controlled; diuretics alone do not prevent progression of heart failure.

Diuretics produce rapid symptomatic benefits, relieving pulmonary and peripheral edema more rapidly (within hours or days) than cardiac glycosides, ACE inhibitors, or β-blockers (in weeks or months).

Once fluid retention has resolved in CHF, diuretic therapy should be maintained to prevent recurrence of fluid retention. Ideally, diuretic therapy should be adjusted according to changes in body weight (as an indicator of fluid retention) rather than maintained at a fixed dosage.

Diuretics should be continued in CHF and comorbid conditions (e.g., hypertension) where ongoing therapy with the drugs are indicated.

Edema Secondary to Nephrotic Syndrome

May be useful if the patient fails to respond to corticosteroid therapy.b

More likely to become refractory to thiazides than edema associated with congestive heart failure, and more potent diuretics may be required.b

Edema in Pregnancy

Generally responds well to thiazides except when caused by renal disease.b

Thiazides should not be used for routine therapy in pregnant women with mild edema who are otherwise healthy.b

Chlorothiazide Dosage and Administration

Administration

Administer orally or IV.a 110 111

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

Reconstitution

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

Dilution

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

Rate of Administration

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

Pediatric Patients

Usual Dosage
Oral

Infants <6 Months of Age: Up to 30 mg/kg daily given in 2 divided doses.110

Children 6 Months to 12 Years of Age: 10–20 mg/kg daily in 1 or 2 divided doses.110

IV

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

Adults

Hypertension
Blood Pressure Monitoring and Treatment Goals

Carefully monitor blood pressure during initial titration or subsequent upward adjustment in dosage.d

Avoid large or abrupt reductions in blood pressure.d

Adjusted dosage at approximately monthly intervals (more aggressively in high-risk patients [stage 2 hypertension, comorbid conditions]) if blood pressure control is inadequate at a given dosage; it may take months to control hypertension adequately while avoiding adverse effects of therapy.d

Systolic blood pressure is the principal clinical end point, especially in middle-aged and geriatric patients.d Once the goal systolic blood pressure is attained, the goal diastolic blood pressure usually is achieved.

The goal is to achieve and maintain a lifelong systolic blood pressure <140 mm Hg and a diastolic blood pressure<90 mm Hg if tolerated.d

The goal in hypertensive patients with diabetes mellitus or renal impairment is to achieve and maintain a systolic blood pressure <130 mm Hg and a diastolic blood pressure <80 mm Hg.d

Monotherapy
Oral

Initially, 125–250 mg daily.101 102

Gradually increase until the desired therapeutic response is achieved or adverse effects become intolerable, up to 500 mg daily.a

If adequate response is not achieved at maximum dosage, add or substitute another hypotensive agent.101 102 103 110

Maintenance

Usually, 125–500 mg daily in 1 or 2 divided doses.102 109 110

IV

Not indicated for hypertension.111

Edema
Oral

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

IV

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

Prescribing Limits

Pediatric Patients

Oral

Infants <2 Years of Age: Maximum of 375 mg daily.a 110

Children ≥2 Years of Age: 1 g daily.a 110

Adults

Hypertension
Oral

Maximum before switching/adding alternative drug is 500 mg daily.a 101 102 103

Higher dosages had been used (up to 2 g daily in divided doses)e but no longer are recommended.101 Instead, switch to or add alternative drug.f

Edema
Oral

Maximum of 2 daily in divided doses.a 110

IV

Maximum of 2 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

Cautions for Chlorothiazide

Contraindications

  • Anuria.b 110 111

  • Known hypersensitivity to hydrochlorothiazide, other thiazides, or any ingredient in the formulation.b

  • Although manufacturers state allergy to other sulfonamide derivatives is a contraindication,110 111 evidence to support cross-sensitivity is limited, and history of sensitivity to sulfonamide anti-infectives (“sulfa sensitivity”) should not be considered an absolute contraindication.

Warnings/Precautions

Warnings

Severe Renal Impairment

Use with caution; thiazides decrease GFR and may precipitate azotemia.b 110 111

Effects may be cumulative in impaired renal function.b 110 111

Hepatic Impairment

Use with caution in patients with hepatic impairment or progressive liver disease (particularly with associated potassium deficiency); electrolyte imbalance may precipitate hepatic coma.b 110 111

Discontinue immediately if signs of impending hepatic coma appear.b

Hypotensive Agents

May potentiate effects of other hypotensive agents.110 111 Although additive or potentiated antihypertensive effect usually is used to therapeutic advantage,f hypotension could occur.110 111 b (See Interactions.)

Lupus Erythematosus

Possible exacerbation or activation of systemic lupus erythematosus.110 111

Lithium

Generally, do not use with lithium salts.110 111 (See Interactions.)

Sensitivity Reactions

Hypersensitivity

May occur with or without history of allergy or bronchial asthma.110 111

Sulfonamide cross-sensitivity unlikely. (See Contraindications under Cautions.)

General Precautions

Electrolyte Imbalance

Monitor for fluid or electrolyte imbalance (hyponatremia, hypochloremic alkalosis, hypokalemia).b 110 111

Observe for signs of electrolyte imbalance (e.g., dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, confusion, seizures, oliguria, muscle pains, cramps, muscular fatigue, hypotension, tachycardia, nausea, vomiting).110 111

Perform periodic serum electrolyte determinations (particularly of potassium, sodium, chloride, and bicarbonate); institute measures to maintain normal serum concentrations if necessary.b

Serum and urinary electrolyte measurements are especially important with diabetes mellitus, vomiting, diarrhea, parenteral fluid therapy, or expectations of excessive diuresis.b

Weekly (or more frequent) electrolyte measurement early in treatment; possible to extend interval between measurements to ≥3 months when electrolyte response has stabilized.b

Hypokalemia

May occur after brisk diuresis, when cirrhosis is present, or with prolonged therapy; inadequate oral electrolyte intake may contribute.110 111

May cause cardiac arrhythmias, exaggerate cardiac response to cardiac glycoside toxicity (increase ventricular irritability).110 111

Use potassium-sparing diuretics and/or potassium supplementation to avoid or treat hypokalemia.110 111

Hypochloremia

Generally mild, usually does not require specific treatment except in renal or hepatic impairment.110 111

Chloride replacement may be required for metabolic acidosis.109

Hyponatremia

Dilutional hyponatremia may occur in edematous patients in hot weather; appropriate treatment usually is water restriction rather than salt administration except when hyponatremia is life-threatening.110 111

In actual salt depletion, appropriate replacement is treatment of choice.110 111

Gout

Hyperuricemia or precipitation of gout may occur.110 111

Hyperglycemia

In diabetic patients, dosage adjustment of insulin or oral hypoglycemics may be required; hyperglycemia may occur and latent diabetes mellitus may become evident.110 111

Sympathectomy

Antihypertensive effect may be enhanced after sympathectomy.110 111

Hypomagnesemia

May increase magnesium urinary excretion, resulting in hypomagnesemia.110 111

Hypercalcemia

May decrease calcium urinary excretion, cause slight intermittent serum calcium increase in absence of known calcium metabolism disorder; marked hypercalcemia may indicate hyperparathyroidism.110 111

Discontinue parathyroid tests.110 111

Hyperlipidemia

May increase cholesterol and triglyceride concentrations.110 111 109

Clinical importance of these changes is unknown.b Diet low in saturated fat and cholesterol usually compensates.b

Hypotensive Effects

Orthostatic hypotension rarely occurs.b

Specific Populations

Pregnancy

Category C.110 111

Although hypertension during pregnancy responds well to thiazides, and the drugs had been used widely in the past for preeclampsia and eclampsia,b g such use no longer is recommended and other antihypertensives (e.g., methyldopa, hydralazine, labetalol) currently are preferred.f

Diuretics are not recommended for pregnancy-induced hypertension because of the maternal hypovolemia associated with this form of hypertension; decreased placental perfusion is possible.g

Diuretics are considered second-line agents for control of chronic hypertension in pregnant women.f

Thiazides should not be used as routine therapy in pregnant women with mild edema who are otherwise healthy.b 110 111

Edema associated with pregnancy generally responds well to thiazides except when caused by renal disease.b

Lactation

Distributed into milk.g h 110 111 Discontinue nursing or the drug.110 111

Although hydrochlorothiazide use generally is considered compatible with breast-feeding,g h thiazides can reduce milk volume and thus suppress lactation.f g

Pediatric Use

No controlled studies in children; use is supported by experience and published literature about hypertension treatment in children.110

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

Geriatric Use

Elderly may be at increased risk of dilutional hyponatremia, especially underweight females with poor oral fluid and electrolyte intake or excessive low-sodium nutritional supplement intake.b (See Hyponatremia under Warnings/Precautions.)

Hepatic Impairment

Use caution.b (See Hepatic Impairment under Warnings.)

Renal Impairment

Use caution.b (See Severe Renal Impairment under Warnings.)

Consider interruption or discontinuance if progressive renal impairment (rising nonprotein nitrogen, BUN, or serum creatinine) occurs.110 111

Common Adverse Effects

Potassium depletion, hyperuricemia (usually asymptomatic; rarely leading to gout).b Hypochloremic alkalosis in patients at risk (e.g., hypokalemic patients).b Hyperglycemia and glycosuria in diabetics.b

Interactions for Chlorothiazide

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Alcohol

Increased risk of postural hypotensionb

Amphetamine

Thiazides may cause slightly more alkaline urinary pH; may decrease urinary excretion of some amines (e.g., amphetamine) with concurrent useb

Urine pH change is not great during thiazide use and, toxic blood concentrations of amines usually do not occurb

Monitor for signs of toxicity after initiation of thiazides in patients receiving amphetamineb

Amphotericin B

Additive/potentiated potassium lossb

Severe potassium depletion may occur when used concomitantlyb

Anticoagulants, oral

Postulated that may antagonize oral anticoagulant effectsb

Confirmatory evidence is lackingb

Antidiabetic agents (sulfonylureas)

Thiazide hyperglycemic effect may exacerbate diabetes mellitus, increase antidiabetic agent requirements, and/or cause temporary loss of diabetic control or secondary failure to antidiabetic agentb

Barbiturates

Increased risk of postural hypotension with thiazidesb

Cholestyramine or colestipol

May bind thiazides, reduce their GI absorption, with cholestyramine reportedly producing greater binding in vitrob

Administer thiazides ≥2 hours before cholestyramine or colestipol when used concomitantlyb

Corticosteroids

Additive/potentiated potassium lossb

Severe potassium depletion may occur when used concomitantlyb

Corticotropin

Additive/potentiated potassium lossb

Severe potassium depletion may occur when used concomitantlyb

Diazoxide

May potentiate diazoxide hyperglycemic, hypotensive, and hyperuricemic effectsb

Use concomitantly with cautionb

Digitalis glycosides

Thiazide-induced electrolyte disturbances (principally hypokalemia, but also hypomagnesemia and hypercalcemia) may increase digitalis toxicity riskb

Perform periodic electrolyte determinations with concomitant use; correct hypokalemia if warrantedb

Hypotensive agents

Increased hypotensive effects of most other hypotensive agents b

Addition of thiazide to stabilized regimen with potent hypotensive agent (e.g., guanethidine sulfate, methyldopa, ganglionic blocking agent) may cause severe postural hypotensionb

Usually used to therapeutic advantageb

Insulin

May exacerbate diabetes mellitus, increase insulin requirements, cause temporary loss of diabetic control, or secondary failure to insulinb

Lithium

Thiazides (sometimes used with lithium to reduce lithium-induced polyuria), Reduced renal lithium clearance within several daysb

Can increase serum lithium concentrations and the risk of lithium intoxicationb

Occasionally, used to therapeutic advantage to reduce lithium-induced polyuria, but reduce lithium dosage by about 50% and monitor serum lithium carefullyb

Generally, avoid concomitant use because of increased lithium toxicity riskb

Methenamine

Urinary alkalinization may decrease the effectiveness of methenamine compounds which require a urinary pH of ≤5.5 for optimal activityb

Monitor urine pH during concurrent therapyb

NSAIAs

Increased risk of NSAIA-induced renal failure secondary to prostaglandin inhibition and decreased renal blood flowb

NSAIAs may interfere with the natriuretic, diuretic, and antihypertensive response to diureticsb

Monitor closely for possible adverse effects and/or attenuation of diuretic-induced therapeutic effects during concomitant useb

Neuromuscular blocking agents (e.g., tubocurarine chloride or gallamine triethiodide [both no longer commercially available in the US])

May cause prolonged neuromuscular blockadeb

Confirmatory evidence lackingb

Opiates

Increased risk of postural hypotension with thiazidesb

Probenecid

Blocks thiazide-induced uric acid retentionb

Also blocks renal tubular secretion of thiazide, but effect on thiazide duration of action apparently not studiedb

Apparently enhances excretion of calcium, magnesium, and citrate during thiazide therapy, but urinary calcium concentrations remain below normalb

Sodium, potassium, ammonia, chloride, bicarbonate, phosphate, and titratable acid excretion apparently not affected by concomitant probenecid and thiazide therapyb

Used to therapeutic advantageb

Quinidine

Thiazides may cause slightly more alkaline urinary pH; may decrease urinary excretion of some amines (e.g., quinidine) with concurrent useb

Urine pH change is not great during thiazide use and toxic blood concentrations of amines usually do not occurb

Monitor for signs of toxicity after initiation of thiazideb

Test, Amylase (serum)

Values may be increased substantially in both asymptomatic patients and in patients developing acute pancreatitis who are receiving thiazidesb

Test, Corticosteroids (urinary)(Glenn-Nelson technique)

Decreased values by interfering in vitro with the absorbance in the modified Glenn-Nelson technique for urinary 17-hydroxycorticosteroids; may also decrease urinary cortisol excretionb

Importance of effect on urinary corticosteroids is unclearb

Test, Estrogens (spectrophotometric assay of total urinary estrogen; assay of estradiol)

Although hydrochlorothiazide causes falsely decreased values, similar interference does not occur with chlorothiazideb

Test, Histamine for pheochromocytoma

False-negative resultsb

Test, Parathyroid function tests

May elevate serum calcium in the absence of known disorders of calcium metabolismb

Discontinue thiazides prior to performing parathyroid function testsb

Test, Phenolsulfonphthalein (PSP)

Thiazides compete with phenolsulfonphthalein (PSP) for secretion by the proximal renal tubulesb

Importance unknownb

Test, Phentolamine

False-negative resultsb

Test, Protein-bound iodine (PBI)

Values may be decreased, although usually not to subnormalb

Test, Triiodothyronine resin uptake

Decreased slightly, but 24-hour I 131 uptake is not affectedb

Test, Tyramine

False-negative resultsb

Vasopressors (e.g., norepinephrine)

Possible decreased arterial responsiveness to vasopressor amines b

Clinical importance not established;b decrease in pressor response not sufficient to preclude vasopressor use109

Chlorothiazide Pharmacokinetics

Absorption

Bioavailability

Incompletely and variably absorbed from the GI tract.a

Absorption from the GI tract appears to be site specific and saturable.a Several studies indicate that about 50 mg 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.a

Onset

Diuretic effect (oral): within 2 hours; peak effect in 3–6 hours.b 109

Diuretic effect (IV): within 15 minutes; peak effect in 30 minutes.b

Hypotensive effect (oral): generally 3–4 days.b

Duration

Diuretic effect: 6–12 hours.b

Food

Concomitant administration with food appears to increase the extent of absorption.a

Distribution

Extent

Distributed in the extracellular space.a b

Readily crosses the placenta.a b g

Distributed into breast milk.a g h

Elimination

Metabolism

Not metabolized.a

Elimination Route

Excreted unchanged in urine;a about 95% of an IV dose is eliminated in 5 hours and about 20 or 10% of a 250- or 500-mg oral dose, respectively, is eliminated in 48–72 hours.a

Half-life

45–120 minutes.a

Stability

Storage

Oral

Tablets

Tight containers at 15–30°C; avoid freezing.100

Suspension

Tight containers at 15–30°C; avoid freezing.100

Parenteral

Powder for Injection

2–25°C.111

Compatibility

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

Parenteral

Solution CompatibilityHID

Compatible

Dextrose–Ringer’s injection combinations

Dextrose–Ringer’s injection, lactated, combinations

Dextrose–saline combinations

Dextrose 5% in sodium chloride 0.9%

Dextrose 2.5, 5, or 10% in water

Ionosol MB with dextrose 5%

Ionosol T with dextrose 5%

Ringer’s injection

Ringer’s injection, lactated

Sodium chloride 0.45 or 0.9%

Sodium lactate (1/6) M

Incompatible

Ionosol B with dextrose 5%

Normosol M in dextrose 5%

Normosol R in dextrose 5%

Drug CompatibilityHID
Admixture Compatibility

Compatible

Lidocaine HCl

Nafcillin sodium

Ranitidine HCl

Incompatible

Amikacin sulfate

Chlorpromazine HCl

Hydralazine HCl

Polymyxin B sulfate

Prochlorperazine mesylate

Promethazine HCl

Actions

  • 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

Advice to Patients

  • 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.

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

  • 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.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Chlorothiazide

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Suspension

250 mg/5 mL

Diuril

Merck

Tablets

250 mg*

Chlorothiazide Tablets

500 mg*

Chlorothiazide Tablets

Chlorothiazide Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV use only

500 mg (of chlorothiazide)

Diuril Sodium Intravenous

Ovation

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Chlorothiazide 250MG Tablets (MYLAN): 30/$14.99 or 90/$25.97

Chlorothiazide 500MG Tablets (MYLAN): 30/$14.99 or 60/$20.97

Diuril 250MG/5ML Suspension (SALIX PHARMACEUTICALS): 237/$29.99 or 711/$75.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions June 19, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

Only references cited for selected revisions after 1984 are available electronically.

100. Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The 1984 report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1984; 144:1045-57. [IDIS 184763] [PubMed 6143542]

101. 1988 Joint National Committee. The 1988 report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1988; 148:1023-38. [IDIS 242588] [PubMed 3365073]

102. Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The fifth report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V). Arch Intern Med. 1993; 153:154-83. [IDIS 309043] [PubMed 8422206]

103. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). Bethesda, MD: National Institutes of Health. (NIH publication No. 98-4080.)

104. Izzo JL, Levy D, Black HR. Importance of systolic blood pressure in older Americans. Hypertension. 2000; 35:1021-4. [PubMed 10818056]

105. Frohlich ED. Recognition of systolic hypertension for hypertension. Hypertension. 2000; 35:1019-20. [PubMed 10818055]

106. Bakris GL, Williams M, Dworkin L et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. Am J Kidney Dis. 2000; 36:646-61. [IDIS 452007] [PubMed 10977801]

107. Associated Press (American Diabetes Association). Diabetics urged: drop blood pressure. Chicago, IL; 2000 Aug 29. Press Release from web site.

108. Appel LJ. The verdict from ALLHAT—thiazide diuretics are the preferred initial therapy for hypertension. JAMA. 2002; 288:3039-42. [IDIS 490723] [PubMed 12479770]

109. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002; 288:2981-97. [IDIS 490721] [PubMed 12479763]

110. Merck and Co., Inc. Diuril (chlorothiazide) tablets and oral suspension prescribing information. West Point, PA; 1998 Jun.

111. Merck and Co., Inc. Sodium Diuril (chlorothiazide sodium) IV powder for injection prescribing information. West Point, PA; 1999 Sep.

112. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII) Express. Bethesda, MD: May 14 2003. From NIH website. (Also published in JAMA. 2003; 289.

113. American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care. 2003; 26(Suppl 1):S80-2.

114. Guidelines Committee. 2003 European Society of Hypertension–European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertension. 2003; 21:1011-53.

a. AHFS drug information 2004. McEvoy GK, ed. Chlorothiazide. Bethesda, MD: American Society of Health-System Pharmacists; 2004: 2542-3.

b. AHFS drug information 2004. McEvoy GK, ed. Thiazides general statement. Bethesda, MD: American Society of Health-System Pharmacists; 2004: 2534-42.

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HID. Trissel LA. Handbook on injectable drugs. 17th ed; Bethesda, MD: American Society of Health-System Pharmacists; 2013:258-9.

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