Chlorothiazide (Monograph)
Brand name: Diuril
Drug class: Thiazide Diuretics
- Diuretics, Thiazide
Introduction
Thiazide diuretic and antihypertensive agent.
Uses for Chlorothiazide
Hypertension
Used alone or in combination with other antihypertensive agents for all stages of hypertension.b 110 1200
Thiazide diuretics are recommended as one of several preferred agents for the initial management of hypertension according to current evidence-based guidelines; other preferred options include ACE inhibitors, angiotensin II receptor antagonists, and calcium-channel blockers.501 502 503 504 1200 While there may be individual differences with respect to recommendations for initial drug selection and use in specific patient populations, current evidence indicates that these antihypertensive drug classes all generally produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.501 502 504 1200 1213
Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).501 502 503 504 515 1200 1201
A 2017 ACC/AHA multidisciplinary hypertension guideline classifies BP in adults into 4 categories: normal, elevated, stage 1 hypertension, and stage 2 hypertension.1200 (See Table 1.)
Source: Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13-115.
Individuals with SBP and DBP in 2 different categories (e.g., elevated SBP and normal DBP) should be designated as being in the higher BP category (i.e., elevated BP).
Category |
SBP (mm Hg) |
DBP (mm Hg) |
|
---|---|---|---|
Normal |
<120 |
and |
<80 |
Elevated |
120–129 |
and |
<80 |
Hypertension, Stage 1 |
130–139 |
or |
80–89 |
Hypertension, Stage 2 |
≥140 |
or |
≥90 |
The goal of hypertension management and prevention is to achieve and maintain optimal control of BP.1200 However, the BP thresholds used to define hypertension, the optimum BP threshold at which to initiate antihypertensive drug therapy, and the ideal target BP values remain controversial.501 503 504 505 506 507 508 515 523 526 530 1200 1201 1207 1209 1222 1223 1229
The 2017 ACC/AHA hypertension guideline generally recommends a target BP goal (i.e., BPs to achieve with drug therapy and/or nonpharmacologic intervention) of <130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk.1200 In addition, an SBP goal of <130 mm Hg generally is recommended for noninstitutionalized ambulatory patients ≥65 years of age with an average SBP of ≥130 mm Hg.1200 These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.1200 1202 1210
Other hypertension guidelines generally have based target BP goals on age and comorbidities.501 504 536 Guidelines such as those issued by the JNC 8 expert panel generally have targeted a BP goal of <140/90 mm Hg regardless of cardiovascular risk and have used higher BP thresholds and target BPs in elderly patients501 504 536 compared with those recommended by the 2017 ACC/AHA hypertension guideline.1200
Some clinicians continue to support previous target BPs recommended by JNC 8 due to concerns about the lack of generalizability of data from some clinical trials (e.g., SPRINT study) used to support the 2017 ACC/AHA hypertension guideline and potential harms (e.g., adverse drug effects, costs of therapy) versus benefits of BP lowering in patients at lower risk of cardiovascular disease.1222 1223 1224 1229
Consider potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs when deciding a patient's BP treatment goal.1200 1220
For decisions regarding when to initiate drug therapy (BP threshold), the 2017 ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors.1200 1207 ASCVD risk assessment recommended by ACC/AHA for all adults with hypertension.1200
ACC/AHA currently recommend initiation of antihypertensive drug therapy in addition to lifestyle/behavioral modifications at an SBP ≥140 mm Hg or DBP ≥90 mm Hg in adults who have no history of cardiovascular disease (i.e., primary prevention) and a low ASCVD risk (10-year risk <10%).1200
For secondary prevention in adults with known cardiovascular disease or for primary prevention in those at higher risk for ASCVD (10-year risk ≥10%), ACC/AHA recommend initiation of antihypertensive drug therapy at an average SBP ≥130 mm Hg or an average DBP ≥80 mm Hg.1200
Adults with hypertension and diabetes mellitus, chronic kidney disease (CKD), or age ≥65 years are assumed to be at high risk for cardiovascular disease; ACC/AHA state that such patients should have antihypertensive drug therapy initiated at a BP ≥130/80 mm Hg.1200 Individualize drug therapy in patients with hypertension and underlying cardiovascular or other risk factors.502 1200
In stage 1 hypertension, experts state that it is reasonable to initiate drug therapy using the stepped-care approach in which one drug is initiated and titrated and other drugs are added sequentially to achieve the target BP.1200 Initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes recommended in adults with stage 2 hypertension and average BP >20/10 mm Hg above BP goal.1200
Black hypertensive patients generally tend to respond better to monotherapy with thiazide diuretics or calcium-channel blockers than to other antihypertensive drug classes (e.g., ACE inhibitors, angiotensin II receptor antagonists).g 109 501 504 1200 However, the combination of an ACE inhibitor or an angiotensin II receptor antagonist with a calcium channel blocker or thiazide diuretic produces similar BP lowering in black patients as in other racial groups.1200
Thiazides may be preferred in hypertensive patients with osteoporosis.i j Secondary beneficial effect in hypertensive geriatric patients of reducing the risk of osteoporosis due to effect on calcium homeostasis and bone mineralization.i j
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 Scr or BUN concentrations greater than twice normal.b
May be ineffective in patients with GFR <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 Heart Failure
Management of edema associated with heart failure.b c
Most experts state that all patients with symptomatic heart failure who have evidence for, or history of, fluid retention generally should receive diuretic therapy in conjunction with moderate sodium restriction, an agent to inhibit the renin-angiotensin-aldosterone (RAA) system (e.g., ACE inhibitor, angiotensin II receptor antagonist, angiotensin receptor-neprilysin inhibitor [ARNI]), a β-adrenergic blocking agent (β-blocker), and in selected patients, an aldosterone antagonist.524 n
Loop diuretics (e.g., bumetanide, ethacrynic acid, furosemide, torsemide) are diuretics of choice for most patients with heart failure.524
Do not use diuretics as monotherapy in heart failure even if symptoms (e.g., peripheral edema, pulmonary congestion) are well controlled; diuretics alone do not prevent progression of heart failure.e f
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).e
Diuretics should be continued in heart failure and comorbid conditions (e.g., hypertension) where ongoing therapy with the drugs are indicated.524
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
General
Monitoring and BP Treatment Goals
-
Monitor BP regularly (i.e., monthly) during therapy and adjust dosage of the antihypertensive drug until BP controlled.1200
-
If unacceptable adverse effects occur, discontinue drug and initiate another antihypertensive agent from a different pharmacologic class.1200 1216
-
Assess patient's renal function and electrolytes 2–4 weeks after initiation of diuretic therapy.1200 (See Electrolyte Imbalance under Cautions.)
-
If adequate BP response not achieved with a single antihypertensive agent, either increase dosage of single drug or add a second drug with demonstrated benefit and preferably a complementary mechanism of action (e.g., ACE inhibitor, angiotensin II receptor antagonist, calcium-channel blocker).1200 1216 Many patients will require ≥2 drugs from different pharmacologic classes to achieve BP goal; if goal BP still not achieved, add a third drug.1200 1216 1220
Administration
Administer orally or IV.a 110 111 Manufacturer states that 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; use IV route only when patients unable to take drug orally or in emergency situations.a 111
Must avoid extravasation of the alkaline solution.a 111
Reconstitution
Reconstitute only with sterile water for injection.a
Add 18 mL of sterile water for injection to 500-mg vial; provides a solution containing about 28 (27.8) mg/mL.a 111 Use no less than 18 mL of diluent for initial reconstitution.a 111
Dilution
May administer injection undiluted or may further dilute 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 identical.a 111
Individualize dosage according to requirements and response.a
If added to potent hypotensive agent regimen, initially reduce dosage of hypotensive agent to avoid 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
Hypertension
Oral
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 1150
Experts recommend initiation of drug at low end of dosage range; may increase dosage every 2–4 weeks until BP controlled, maximum dosage reached, or adverse effects occur.1150
Diuresis
Oral
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
IV
Experience in infants and children is limited, and IV use in this age group generally is not recommended.a 111
Adults
Hypertension
Oral
Initially, 0.5–1 g daily 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
If adequate response is not achieved with monotherapy, add another antihypertensive agent.1200
Edema
Oral
Usually, 0.5–1 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
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 dosing schedule, excessive response and the resulting undesirable electrolyte imbalance are less likely to occur.a
IV
Usually, 0.5–1 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 0.5–1 g once daily in combination with a loop diuretic.524
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
Rarely, up to 2 g daily in divided doses may be required.600 601
Edema
Oral
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
IV
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
Cautions for Chlorothiazide
Contraindications
-
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.k l m
Warnings/Precautions
Warnings
Hypotensive Agents
May potentiate effects of other hypotensive agents.110 111 Although additive or potentiated antihypertensive effect usually is used to therapeutic advantage, 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 1200
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 1200
Perform periodic serum electrolyte determinations (particularly of potassium, sodium, chloride, and bicarbonate); institute measures to maintain normal serum electrolyte concentrations if necessary.1200 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, rarely, precipitation of gout may occur; generally avoid or use with caution in patients with history of gout unless patient is receiving uric acid lowering therapy.110 111 502 1200
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 occurs rarely.b
Specific Populations
Pregnancy
Diuretics are considered second-line agents for control of chronic hypertension in pregnant women;142 if initiation of antihypertensive therapy is necessary in a pregnant woman, other antihypertensives (i.e., methyldopa, nifedipine, labetalol) are preferred.142 540
Edema associated with pregnancy generally responds well to thiazides except when caused by renal disease; however, routine use not recommended in pregnant women with mild edema who are otherwise healthy.b 110 111
Diuretics are not recommended for prevention or management of gestational hypertension or preeclampsia.141 539 540
Lactation
Distributed into milk.h 110 111 141 Manufacturer states to discontinue nursing or the drug;110 111 however, considered to be compatible with breast-feeding.141
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 Cautions.)
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
Renal Impairment
Use with caution in severe renal impairment; thiazides decrease GFR and may precipitate azotemia.b 110 111 Effects may be cumulative in impaired renal function.b 110 111
Consider interruption or discontinuance if progressive renal impairment (rising nonprotein nitrogen, BUN, or Scr) 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
Drug Interactions
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 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 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 141
Distributed into breast milk.a h 141
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, light-resistant containers at 20–25°C.601
Suspension
Tight containers at 15–30°C; avoid freezing.600
Parenteral
Powder for Injection
20–25°C.602
Compatibility
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
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.1200
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.1200
-
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.)
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.
Preparations
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.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Oral |
Suspension |
250 mg/5 mL |
Diuril |
Salix |
Tablets |
250 mg* |
Chlorothiazide Tablets |
||
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)* |
Sodium Diuril |
Oak |
AHFS DI Essentials™. © Copyright 2025, Selected Revisions June 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
References
Only references cited for selected revisions after 1984 are available electronically.
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b. AHFS drug information 2017. McEvoy GK, ed. Thiazides general statement. Bethesda, MD: American Society of Health-System Pharmacists; 2017: .
c. AHFS drug information 2007. McEvoy GK, ed. Cardiac glycosides general statement. Bethesda, MD: American Society of Health-System Pharmacists; 2007: 1584-91.
d. AHFS drug information 2007. McEvoy GK, ed. Captopril. Bethesda, MD: American Society of Health-System Pharmacists; 2007: 1835-45.
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