Hydrochlorothiazide (Monograph)
Brand name: Microzide
Drug class: Thiazide Diuretics
CAS number: 58-93-5
hydroCHLOROthiazide (Systemic) is also contained as an ingredient in the following combinations:
Amiloride Hydrochloride and hydroCHLOROthiazide
Methyldopa and hydroCHLOROthiazide
Propranolol Hydrochloride and hydroCHLOROthiazide
Spironolactone and hydroCHLOROthiazide
Triamterene and hydroCHLOROthiazide
Introduction
Thiazide diuretic and antihypertensive agent.a
Uses for Hydrochlorothiazide
Hypertension
Used alone or in combination with other antihypertensive agents for all stages of hypertension.b 501 600 601 1200
Thiazide diuretics are recommended as one of several preferred agents for the initial management of hypertension according to current evidence-based hypertension 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) <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 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
Previous 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 patients compared with501 504 536 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 current 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 1229
For decisions regarding when to initiate drug therapy (BP threshold), the current 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 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 108 501 504 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 secondary to effect on calcium homeostasis and bone mineralization.i j
Thiazide diuretics (unlike potassium-sparing diuretics) may be used in patients who are at an increased risk for developing hyperkalemia (e.g., those receiving an ACE inhibitor).112
Edema (General)
Management of edema resulting from various causes; diagnose etiology before use.b
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 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 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 a history of, fluid retention generally should receive diuretic therapy in conjunction with moderate sodium restriction, an agent to inhibit the renin-angiotensin-aldosterone 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
Once fluid retention has resolved in heart failure, diuretic therapy should be maintained to prevent recurrence of fluid retention.e 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.e
Diuretics should be continued in heart failure and comorbid conditions (e.g., hypertension) where ongoing therapy with the drugs is 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 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
Diabetes Insipidus
Has been used widely in the treatment of diabetes insipidus† [off-label].b
Effective in both the neurohypophyseal and nephrogenic forms of the disease, decreasing urine volume by up to 50%.b
Particularly useful in nephrogenic diabetes insipidus, since this form of the disease is unresponsive to vasopressin or lypressin and chlorpropamide.b
Useful in patients who are allergic or refractory to vasopressin or lypressin and has been used in combination with one of these hormones and a low-salt diet in patients who excrete an exceptionally large volume of urine.b
Renal Tubular Acidosis
Has been used with success in the treatment of electrolyte disturbances associated with renal tubular acidosis† [off-label].b
Renal Calculus Formation
Has been used with success in the prophylaxis of renal calculus formation associated with hypercalciuria† [off-label].b
Hydrochlorothiazide 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 at least 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.a
Dosage
Individualize according to requirements and response.a Use lowest dosage necessary to produce desired clinical effect.109
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
Hypertension and Diuresis
Oral
Infants <6 months of age: Up to 3 mg/kg daily in 2 divided doses; up to 37.5 mg daily.600
Infants 6 months to 2 years of age: Usually 1–2 mg/kg daily in a single dose or 2 divided doses, up to 37.5 mg daily.600 1150
Children 2–12 years of age: 1–2 mg/kg daily in a single dose or 2 divided doses,600 1150 up to 100 mg daily.600
Hypertension: 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
Adults
Edema
Oral
Usually, 25–100 mg daily in 1–3 divided doses.109
For management of fluid retention associated with heart failure, some experts recommend initiating hydrochlorothiazide at a low dosage (e.g., 25 mg once or twice daily) and increasing dosage (up to 200 mg daily) until urine output increases and weight decreases, generally by 0.5–1 kg daily.524
For sequential nephron blockade in the management of fluid retention (e.g., edema) in heart failure, some experts recommend an initial dosage of 25–100 mg once or twice daily in combination with a loop diuretic.524
Many patients also may respond to intermittent therapy (e.g., alternate days or 3–5 days weekly); decreases risk of excessive diuretic response and resulting electrolyte imbalance.109
Hypertension
Usual Dosage
OralManufacturers recommend initial dosage of 12.5–25 mg daily; may increase to 50 mg daily given in 1 or 2 divided doses.600 601
Dosages of 25–100 mg daily (in 1 or 2 divided doses) used in randomized, controlled studies; experts recommend a dosage of 25–50 mg daily for optimal balance between efficacy and safety in the management of hypertension.501 1200
Fixed-combination Therapy
OralInitially, administer each drug separately to adjust dosage;a may use fixed combination if optimum maintenance dosage corresponds to drug ratio in combination preparation.a Alternatively, may initiate therapy with a fixed-combination preparation; may increase patient compliance.502 1200
Prescribing Limits
Pediatric Patients
Hypertension and Diuresis
Oral
Infants <2 years of age: Maximum 37.5 mg daily.600
Children 2–12 years of age: Maximum 100 daily.600
Adults
Edema
Oral
Management of fluid retention in heart failure: 200 mg maximum daily dosage recommended by ACCF/AHA.524
Hypertension
Oral
Dosages >50 mg daily associated with marked hypokalemia;600 some manufacturers state that such dosages not recommended.601
Special Populations
Hepatic Impairment
No specific dosage recommendations for hepatic impairment; caution because of risk of precipitating hepatic coma.a 109
Renal Impairment
No specific dosage recommendations for renal impairment; caution because of risk of precipitating azotemia.a 109
Geriatric Patients
Initiate therapy at the lowest dosage (12.5 mg daily); may adjust dosage in increments of 12.5 mg if needed.112
Cautions for Hydrochlorothiazide
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,109 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.109 Although additive or potentiated antihypertensive effects usually are used to therapeutic advantage,1200 hypotension could occur.109 b (See Interactions.)
Lupus Erythematosus
Possible exacerbation or activation of systemic lupus erythematosus.109
Lithium
Generally, do not use with lithium salts.109 (See Interactions.)
Sensitivity Reactions
Hypersensitivity
May occur with or without history of allergy or bronchial asthma.109
Sulfonamide cross-sensitivity unlikely. (See Contraindications under Cautions.)
General Precautions
Electrolyte Imbalance
Monitor for fluid or electrolyte imbalance (hyponatremia, hypochloremic alkalosis, hypokalemia).b 109
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).109
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 recommended 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.109
May cause cardiac arrhythmias, exaggerate cardiac response to cardiac glycoside toxicity (increase ventricular irritability).109
Use potassium-sparing diuretics and/or potassium supplementation to avoid or treat hypokalemia.109
Hypochloremia
Generally mild, usually does not require specific treatment except in renal or hepatic impairment.109
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.109
In actual salt depletion, appropriate replacement is treatment of choice.109
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.109 502 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.109
Sympathectomy
Antihypertensive effect may be enhanced after sympathectomy.109
Hypomagnesemia
May increase magnesium urinary excretion, resulting in hypomagnesemia.109
Hypercalcemia
May decrease calcium urinary excretion, cause slight intermittent serum calcium increase in absence of known calcium metabolism disorder; marked hypercalcemia may indicate hyperparathyroidism.109
Discontinue prior to performing parathyroid tests.109
Hyperlipidemia
May increase cholesterol and triglyceride concentrations.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
Use in Fixed Combinations
When hydrochlorothiazide is used in fixed combination with other drugs (e.g., other antihypertensive agents), consider cautions, precautions, contraindications, and interactions associated with the concomitant agent(s).
Specific Populations
Pregnancy
Category B.109
Diuretics are considered second-line agents for control of chronic hypertension in pregnant women;142 if initiation of antihypertensive therapy is necessary during pregnancy, other antihypertensives (i.e., methyldopa, nifedipine, labetalol) are preferred.142 540
Diuretics are not recommended for prevention or management of gestational hypertension or preeclampsia.141 539 540
Edema associated with pregnancy generally responds well to thiazides except when caused by renal disease; however, do not use as routine therapy in pregnant women with mild edema who are otherwise healthy.b
Lactation
Distributed into milk.h 109 141 Manufacturer states to discontinue nursing or the drug;109 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.109
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.)
Increased incidence of adverse effects and excessive reduction in BP in those >65 years of age.112 (See Geriatric Patients under Dosage and Administration.)
Hepatic Impairment
Use with caution in hepatic impairment or progressive liver disease (particularly with associated potassium deficiency); electrolyte imbalance may precipitate hepatic coma.b 109
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 109 Effects may be cumulative in impaired renal function.b 109
Consider interruption or discontinuance if progressive renal impairment (rising nonprotein nitrogen, BUN, or Scr) occurs.109
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 hypotension with thiazidesb |
|
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 loss b |
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 resin |
May bind thiazides, reduce their GI absorption, with cholestyramine reportedly producing greater binding in vitrob |
Administer thiazides at least 2 hours before cholestyramine or colestipol when used concomitantlyb |
Corticosteroids |
Additive/potentiated potassium loss b |
Severe potassium depletion may occur when used concomitantlyb |
Corticotropin |
Additive/potentiated potassium loss b |
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 carefully.b Generally, avoid concomitant use because of increased lithium toxicity risk.b |
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 |
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 |
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 diuretics b |
Monitor closely for possible adverse effects and/or attenuation of diuretic-induced therapeutic effects during concomitant useb |
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) |
Hydrochlorothiazide causes falsely decreased values by interfering with formation of the Kober chromogen, and with the assay of estriol by degrading estriol at the acid hydrolytic stage of the assay; 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 |
Hydrochlorothiazide Pharmacokinetics
Absorption
Bioavailability
Variable absorption from GI tract.b
Onset
Diuretic effect: Within 2 hours; peak effect in 3–6 hours.b 109
Hypotensive effect: Generally 3–4 days.b
Duration
Diuretic effect: 6–12 hours.b 109
Food
Food decreases rate and extent of absorption of Microzide capsules.112
Distribution
Extent
Distributed in the extracellular space.a b
Does not cross blood-brain barrier.a
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 ≥61% eliminated in 24 hours.a
Half-life
5.6–15 hours.a
Special Populations
In patients with uncompensated heart failure or impaired renal function, excretion may be delayed.b Effect of hemodialysis on elimination of the drug has not been determined.112
Stability
Storage
Oral
Capsules
Tight containers at <40°C, preferably at 15–30°C; protect from light, moisture, and freezing.112
Oral Solution
Tight containers at <40°C, preferably at 15–30°C.a Avoid freezing.a
Tablets
Tight containers at <40°C, preferably at 15–30°C; protect from light, moisture, and freezing.109 a
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, 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 |
Capsules |
12.5 mg* |
Hydrochlorothiazide Capsules |
|
Microzide |
Watson |
|||
Tablets |
12.5 mg* |
Hydrochlorothiazide Tablets |
||
25 mg* |
Hydrochlorothiazide Tablets |
|||
50 mg* |
Hydrochlorothiazide Tablets |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Oral |
Tablets |
5 mg of Anhydrous Amiloride Hydrochloride and Hydrochlorothiazide 50 mg* |
Amiloride Hydrochloride and Hydrochlorothiazide Tablets |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Oral |
Tablets |
25 mg Captopril and Hydrochlorothiazide 15 mg* |
Captopril and Hydrochlorothiazide Tablets |
|
25 mg Captopril and Hydrochlorothiazide 25 mg* |
Captopril and Hydrochlorothiazide Tablets |
|||
50 mg Captopril and Hydrochlorothiazide 15 mg* |
Captopril and Hydrochlorothiazide Tablets |
|||
50 mg Captopril and Hydrochlorothiazide 25 mg* |
Captopril and Hydrochlorothiazide Tablets |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Oral |
Tablets |
5 mg Enalapril Maleate and Hydrochlorothiazide 12.5 mg* |
Enalapril Maleate and Hydrochlorothiazide Tablets |
|
10 mg Enalapril Maleate and Hydrochlorothiazide 25 mg* |
Enalapril Maleate and Hydrochlorothiazide Tablets |
|||
Vaseretic |
Valeant |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Oral |
Tablets, film-coated |
250 mg Methyldopa and Hydrochlorothiazide 15 mg* |
Methyldopa and Hydrochlorothiazide Tablets |
|
250 mg Methyldopa and Hydrochlorothiazide 25 mg* |
Methyldopa and Hydrochlorothiazide Tablets |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Oral |
Tablets |
50 mg Metoprolol Tartrate and Hydrochlorothiazide 25 mg* |
Lopressor HCT (scored) |
Validus |
Metoprolol Tartrate and Hydrochlorothiazide Tablets |
||||
100 mg Metoprolol Tartrate and Hydrochlorothiazide 25 mg* |
Lopressor HCT (scored) |
Validus |
||
Metoprolol Tartrate and Hydrochlorothiazide Tablets |
||||
100 mg Metoprolol Tartrate and Hydrochlorothiazide 50 mg* |
Lopressor HCT (scored) |
Validus |
||
Metoprolol Tartrate and Hydrochlorothiazide Tablets |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Oral |
Tablets |
40 mg Propranolol Hydrochloride and Hydrochlorothiazide 25 mg* |
Propranolol Hydrochloride and Hydrochlorothiazide Tablets |
|
80 mg Propranolol Hydrochloride and Hydrochlorothiazide 25 mg* |
Propranolol Hydrochloride and Hydrochlorothiazide Tablets |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Oral |
Tablets, film-coated |
25 mg Spironolactone and Hydrochlorothiazide 25 mg* |
Aldactazide |
Pfizer |
Spironolactone and Hydrochlorothiazide Tablets |
||||
50 mg Spironolactone and Hydrochlorothiazide 50 mg |
Aldactazide (scored) |
Pfizer |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Oral |
Capsules |
37.5 mg Triamterene and Hydrochlorothiazide 25 mg* |
Dyazide |
GlaxoSmithKline |
Triameterene and Hydrochlorothiazide Capsules |
||||
Tablets |
37.5 mg Triamterene and Hydrochlorothiazide 25 mg* |
Maxzide (scored) |
Mylan |
|
Triameterene and Hydrochlorothiazide Tablets |
||||
75 mg Triamterene and Hydrochlorothiazide 50 mg* |
Maxzide (scored) |
Mylan |
||
Triameterene and Hydrochlorothiazide Tablets |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Oral |
Tablets |
12.5 mg with Candesartan 16 mg |
Atacand HCT |
AstraZeneca |
12.5 mg with Candesartan 32 mg |
Atacand HCT |
AstraZeneca |
||
12.5 mg with Fosinopril Sodium 10 mg* |
Fosinopril Sodium and hydroCHLOROthiazide Tablets |
|||
12.5 mg with Fosinopril Sodium 20 mg* |
Fosinopril Sodium and hydroCHLOROthiazide Tablets |
|||
12.5 mg with Irbesartan 150 mg |
Avalide |
Bristol-Myers Squibb |
||
12.5 mg with Irbesartan 300 mg |
Avalide |
Bristol-Myers Squibb |
||
12.5 mg with Lisinopril 10 mg* |
Lisinopril and Hydrochlorothiazide Tablets |
|||
Prinzide |
Merck |
|||
Zestoretic |
AstraZeneca |
|||
12.5 mg with Lisinopril 20 mg* |
Lisinopril and Hydrochlorothiazide Tablets |
|||
Prinzide |
Merck |
|||
Zestoretic |
AstraZeneca |
|||
12.5 mg with Telmisartan 40 mg* |
Micardis HCT |
Boehringer Ingelheim |
||
Telmisartan and Hydrochlorothiazide Tablets |
||||
12.5 mg with Telmisartan 80 mg* |
Micardis HCT |
Boehringer Ingelheim |
||
Telmisartan and Hydrochlorothiazide Tablets |
||||
25 mg with Irbesartan 300 mg |
Avalide |
Bristol-Myers Squibb |
||
25 mg with Lisinopril 20 mg* |
Lisinopril and Hydrochlorothiazide Tablets |
|||
Prinzide |
Merck |
|||
Zestoretic |
AstraZeneca |
|||
25 mg with Telmisartan 80 mg* |
Micardis HCT |
Boehringer Ingelheim |
||
Telmisartan and Hydrochlorothiazide Tablets |
||||
Tablets, film-coated |
6.25 mg with Benazepril Hydrochloride 5 mg* |
Benazepril Hydrochloride and Hydrochlorothiazide Tablets |
||
Lotensin HCT (scored) |
Novartis |
|||
6.25 mg with Bisoprolol Fumarate 2.5 mg* |
Bisoprolol Fumarate and Hydrochlorothiazide Tablets |
|||
Ziac |
Duramed |
|||
6.25 mg with Bisoprolol Fumarate 5 mg* |
Bisoprolol Fumarate and Hydrochlorothiazide Tablets |
|||
Ziac |
Duramed |
|||
6.25 mg with Bisoprolol Fumarate 10 mg* |
Bisoprolol Fumarate and Hydrochlorothiazide Tablets |
|||
Ziac |
Duramed |
|||
12.5 mg with Aliskiren Hemifumarate 150 mg (of aliskiren) |
Tekturna HCT |
Noden |
||
12.5 mg with Aliskiren Hemifumarate 300 mg (of aliskiren) |
Tekturna HCT |
Noden |
||
12.5 mg with Amlodipine Besylate 5 mg (of amlodipine) and Olmesartan Medoxomil 20 mg |
Tribenzor |
Daiichi Sankyo |
||
12.5 mg with Amlodipine Besylate 5 mg (of amlodipine) and Olmesartan Medoxomil 40 mg |
Tribenzor |
Daiichi Sankyo |
||
12.5 mg with Amlodipine Besylate 5 mg (of amlodipine) and Valsartan 160 mg* |
Amlodipine Besylate, Valsartan, and Hydrochlorothiazide Tablets |
|||
Exforge HCT |
Novartis |
|||
12.5 mg with Amlodipine Besylate 10 mg (of amlodipine) and Olmesartan Medoxomil 40 mg |
Tribenzor |
Daiichi Sankyo |
||
12.5 mg with Amlodipine Besylate 10 mg (of amlodipine) and Valsartan 160 mg* |
Amlodipine Besylate, Valsartan, and Hydrochlorothiazide Tablets |
|||
Exforge HCT |
Novartis |
|||
12.5 mg with Benazepril Hydrochloride 10 mg* |
Benazepril Hydrochloride and Hydrochlorothiazide Tablets |
|||
Lotensin HCT (scored) |
Novartis |
|||
12.5 mg with Benazepril Hydrochloride 20 mg |
Benazepril Hydrochloride and Hydrochlorothiazide Tablets |
|||
Lotensin HCT (scored) |
Novartis |
|||
12.5 mg with Eprosartan Mesylate 600 mg (of eprosartan) |
Teveten HCT |
Abbott |
||
12.5 mg with Losartan Potassium 50 mg |
Hyzaar |
Merck |
||
12.5 mg with Losartan Potassium 100 mg |
Hyzaar |
Merck |
||
12.5 mg with Moexipril Hydrochloride 7.5 mg* |
Moexipril Hydrochloride and Hydrochlorothiazide Tablets |
|||
Uniretic (scored) |
UCB |
|||
12.5 mg with Moexipril 15 mg* |
Moexipril Hydrochloride and Hydrochlorothiazide Tablets |
|||
Uniretic (scored) |
UCB |
|||
12.5 mg with Olmesartan Medoxomil 20 mg |
Benicar HCT |
Daiichi-Sankyo |
||
12.5 mg with Olmesartan Medoxomil 40 mg |
Benicar HCT |
Daiichi-Sankyo |
||
12.5 mg with Quinapril Hydrochloride 10 mg (of quinapril)* |
Accuretic (scored) |
Pfizer |
||
Quinapril Hydrochloride and Hydrochlorothiazide Tablets |
||||
12.5 mg with Quinapril Hydrochloride 20 mg (of quinapril)* |
Accuretic (scored) |
Pfizer |
||
Quinapril Hydrochloride and Hydrochlorothiazide Tablets |
||||
12.5 mg with Valsartan 80 mg* |
Diovan HCT |
Novartis |
||
Valsartan and Hydrochlorothiazide Tablets |
||||
12.5 mg with Valsartan 160 mg* |
Diovan HCT |
Novartis |
||
Valsartan and Hydrochlorothiazide Tablets |
||||
12.5 mg with Valsartan 320 mg* |
Diovan HCT |
Novartis |
||
Valsartan and Hydrochlorothiazide Tablets |
||||
25 mg with Aliskiren Hemifumarate 150 mg (of aliskiren) |
Tekturna HCT |
Noden |
||
25 mg with Aliskiren Hemifumarate 300 mg (of aliskiren) |
Tekturna HCT |
Noden |
||
25 mg with Amlodipine Besylate 5 mg (of amlodipine) and Olmesartan Medoxomil 40 mg |
Tribenzor |
Daiichi Sankyo |
||
25 mg with Amlodipine Besylate 5 mg (of amlodipine) and Valsartan 160 mg* |
Amlodipine Besylate, Valsartan, and Hydrochlorothiazide Tablets |
|||
Exforge HCT |
Novartis |
|||
25 mg with Amlodipine Besylate 10 mg (of amlodipine) and Olmesartan Medoxomil 40 mg |
Tribenzor |
Daiichi Sankyo |
||
25 mg with Amlodipine Besylate 10 mg (of amlodipine) and Valsartan 160 mg* |
Amlodipine Besylate, Valsartan, and Hydrochlorothiazide Tablets |
|||
Exforge HCT |
Novartis |
|||
25 mg with Amlodipine Besylate 10 mg (of amlodipine) and Valsartan 320 mg* |
Amlodipine Besylate, Valsartan, and Hydrochlorothiazide Tablets |
|||
Exforge HCT |
Novartis |
|||
25 mg with Benazepril Hydrochloride 20 mg* |
Benazepril Hydrochloride and Hydrochlorothiazide Tablets |
|||
Lotensin HCT (scored) |
Novartis |
|||
25 mg with Eprosartan Mesylate 600 mg (of eprosartan) |
Teveten HCT |
Abbott |
||
25 mg with Losartan Potassium 100 mg |
Hyzaar |
Merck |
||
25 mg with Moexipril Hydrochloride 15 mg* |
Moexipril Hydrochloride and Hydrochlorothiazide Tablets |
|||
Uniretic (scored) |
UCB |
|||
25 mg with Olmesartan Medoxomil 40 mg |
Benicar HCT |
Daiichi-Sankyo |
||
25 mg with Quinapril Hydrochloride 20 mg (of quinapril)* |
Accuretic (scored) |
Pfizer |
||
Quinapril Hydrochloride and Hydrochlorothiazide Tablets |
||||
25 mg with Valsartan 160 mg* |
Diovan HCT |
Novartis |
||
Valsartan and Hydrochlorothiazide Tablets |
||||
25 mg with Valsartan 320 mg* |
Diovan HCT |
Novartis |
||
Valsartan and Hydrochlorothiazide Tablets |
AHFS DI Essentials™. © Copyright 2024, Selected Revisions April 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.
References
Only references cited for selected revisions after 1984 are available electronically.
103. Izzo JL, Levy D, Black HR. Importance of systolic blood pressure in older Americans. Hypertension. 2000; 35:1021-4. http://www.ncbi.nlm.nih.gov/pubmed/10818056?dopt=AbstractPlus
104. Frohlich ED. Recognition of systolic hypertension for hypertension. Hypertension. 2000; 35:1019-20. http://www.ncbi.nlm.nih.gov/pubmed/10818055?dopt=AbstractPlus
105. 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. http://www.ncbi.nlm.nih.gov/pubmed/10977801?dopt=AbstractPlus
106. Associated Press (American Diabetes Association). Diabetics urged: drop blood pressure. Chicago, IL; 2000 Aug 29. Press Release from web site. http://www.diabetes.org/newsroom/
107. Appel LJ. The verdict from ALLHAT—thiazide diuretics are the preferred initial therapy for hypertension. JAMA. 2002; 288:3039-42. http://www.ncbi.nlm.nih.gov/pubmed/12479770?dopt=AbstractPlus
108. 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. http://www.ncbi.nlm.nih.gov/pubmed/12479763?dopt=AbstractPlus
109. Merck & Co., Inc. HydroDiuril (hydrochlorothiazide) tablets prescribing information. West Point, PA; 1998 Jun.
112. Microzide capsules (hydrocholorothiazide 12.5 mg) prescribing information. Watson Pharmaceuticals, Inc. Corona, CA; 2003 Apr.
141. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation: a reference guide to fetal and neonatal risk. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2011:255-8.
142. ACOG task force on hypertension in pregnancy: hypertension in pregnancy. Washington, DC: American College of Obstetricians and Gynecologists; 2013.
218. National Kidney Foundation Guideline. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Kidney Disease Outcome Quality Initiative. Am J Kidney Dis. 2002; 39(Suppl 2):S1-246.
501. James PA, Oparil S, Carter BL et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014; 311:507-20. http://www.ncbi.nlm.nih.gov/pubmed/24352797?dopt=AbstractPlus
502. Mancia G, Fagard R, Narkiewicz K et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013; 31:1281-357. http://www.ncbi.nlm.nih.gov/pubmed/23817082?dopt=AbstractPlus
503. Go AS, Bauman MA, Coleman King SM et al. An effective approach to high blood pressure control: a science advisory from the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention. Hypertension. 2014; 63:878-85. http://www.ncbi.nlm.nih.gov/pubmed/24243703?dopt=AbstractPlus
504. Weber MA, Schiffrin EL, White WB et al. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hypertens (Greenwich). 2014; 16:14-26. http://www.ncbi.nlm.nih.gov/pubmed/24341872?dopt=AbstractPlus
505. Wright JT, Fine LJ, Lackland DT et al. Evidence supporting a systolic blood pressure goal of less than 150 mm Hg in patients aged 60 years or older: the minority view. Ann Intern Med. 2014; 160:499-503. http://www.ncbi.nlm.nih.gov/pubmed/24424788?dopt=AbstractPlus
506. Mitka M. Groups spar over new hypertension guidelines. JAMA. 2014; 311:663-4. http://www.ncbi.nlm.nih.gov/pubmed/24549531?dopt=AbstractPlus
507. Peterson ED, Gaziano JM, Greenland P. Recommendations for treating hypertension: what are the right goals and purposes?. JAMA. 2014; 311:474-6. http://www.ncbi.nlm.nih.gov/pubmed/24352710?dopt=AbstractPlus
508. Bauchner H, Fontanarosa PB, Golub RM. Updated guidelines for management of high blood pressure: recommendations, review, and responsibility. JAMA. 2014; 311:477-8. http://www.ncbi.nlm.nih.gov/pubmed/24352759?dopt=AbstractPlus
511. JATOS Study Group. Principal results of the Japanese trial to assess optimal systolic blood pressure in elderly hypertensive patients (JATOS). Hypertens Res. 2008; 31:2115-27. http://www.ncbi.nlm.nih.gov/pubmed/19139601?dopt=AbstractPlus
515. Thomas G, Shishehbor M, Brill D et al. New hypertension guidelines: one size fits most?. Cleve Clin J Med. 2014; 81:178-88. http://www.ncbi.nlm.nih.gov/pubmed/24591473?dopt=AbstractPlus
523. Fihn SD, Gardin JM, Abrams J et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2012; 126:e354-471.
524. WRITING COMMITTEE MEMBERS, Yancy CW, Jessup M et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013; 128:e240-327.
526. Kernan WN, Ovbiagele B, Black HR et al. Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2014; :. http://www.ncbi.nlm.nih.gov/pubmed/24788967?dopt=AbstractPlus
530. Myers MG, Tobe SW. A Canadian perspective on the Eighth Joint National Committee (JNC 8) hypertension guidelines. J Clin Hypertens (Greenwich). 2014; 16:246-8. http://www.ncbi.nlm.nih.gov/pubmed/24641124?dopt=AbstractPlus
535. Taler SJ, Agarwal R, Bakris GL et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for management of blood pressure in CKD. Am J Kidney Dis. 2013; 62:201-13. http://www.ncbi.nlm.nih.gov/pubmed/23684145?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3929429&blobtype=pdf
536. Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int Suppl. 2012: 2: 337-414.
539. Churchill D, Beevers GD, Meher S et al. Diuretics for preventing pre-eclampsia. Cochrane Database Syst Rev. 2007; :CD004451.
540. Magee LA, Pels A, Helewa M et al., for the Canadian Hypertensive Disorders of Pregnancy (HDP) Working Group. Diagnosis, evaluation, and management of the hypertensive disorders of pregnancy. Pregnancy Hypertens. 2014; 4:105-45. http://www.ncbi.nlm.nih.gov/pubmed/26104418?dopt=AbstractPlus
541. Perk J, De Backer G, Gohlke H et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J. 2012; 33:1635-701. http://www.ncbi.nlm.nih.gov/pubmed/22555213?dopt=AbstractPlus
600. Teva Pharmaceuticals. Hydrochlorothiazide tablets prescribing information. North Wales, PA; 2016 May.
601. Watson. Microzide (hydrochlorothiazide 12.5 mg) capsules prescribing information. Parsippany, NJ; 2011 Oct.
1150. Flynn JT, Kaelber DC, Baker-Smith CM et al. Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics. 2017; 140 http://www.ncbi.nlm.nih.gov/pubmed/28827377?dopt=AbstractPlus
1200. 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:el13-e115. http://www.ncbi.nlm.nih.gov/pubmed/29133356?dopt=AbstractPlus
1201. Bakris G, Sorrentino M. Redefining hypertension - assessing the new blood-pressure guidelines. N Engl J Med. 2018; 378:497-499. http://www.ncbi.nlm.nih.gov/pubmed/29341841?dopt=AbstractPlus
1202. Carey RM, Whelton PK, 2017 ACC/AHA Hypertension Guideline Writing Committee. Prevention, detection, evaluation, and management of high blood pressure in adults: synopsis of the 2017 American College of Cardiology/American Heart Association hypertension guideline. Ann Intern Med. 2018; 168:351-358. http://www.ncbi.nlm.nih.gov/pubmed/29357392?dopt=AbstractPlus
1207. Burnier M, Oparil S, Narkiewicz K et al. New 2017 American Heart Association and American College of Cardiology guideline for hypertension in the adults: major paradigm shifts, but will they help to fight against the hypertension disease burden?. Blood Press. 2018; 27:62-65. http://www.ncbi.nlm.nih.gov/pubmed/29447001?dopt=AbstractPlus
1209. Qaseem A, Wilt TJ, Rich R et al. Pharmacologic treatment of hypertension in adults aged 60 years or older to higher versus lower blood pressure targets: a clinical practice guideline From the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2017; 166:430-437. http://www.ncbi.nlm.nih.gov/pubmed/28135725?dopt=AbstractPlus
1210. SPRINT Research Group, Wright JT, Williamson JD et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015; 373:2103-16. http://www.ncbi.nlm.nih.gov/pubmed/26551272?dopt=AbstractPlus
1213. Reboussin DM, Allen NB, Griswold ME et al. Systematic review for the 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. J Am Coll Cardiol. 2017; http://www.ncbi.nlm.nih.gov/pubmed/29146534?dopt=AbstractPlus
1216. Taler SJ. Initial Treatment of Hypertension. N Engl J Med. 2018; 378:636-644. http://www.ncbi.nlm.nih.gov/pubmed/29443671?dopt=AbstractPlus
1220. Cifu AS, Davis AM. Prevention, detection, evaluation, and management of high blood pressure in adults. JAMA. 2017; 318:2132-2134. http://www.ncbi.nlm.nih.gov/pubmed/29159416?dopt=AbstractPlus
1222. Bell KJL, Doust J, Glasziou P. Incremental benefits and harms of the 2017 American College of Cardiology/American Heart Association high blood pressure guideline. JAMA Intern Med. 2018; 178:755-7. http://www.ncbi.nlm.nih.gov/pubmed/29710197?dopt=AbstractPlus
1223. LeFevre M. ACC/AHA hypertension guideline: What is new? What do we do?. Am Fam Physician. 2018; 97(6):372-3. http://www.ncbi.nlm.nih.gov/pubmed/29671534?dopt=AbstractPlus
1224. Brett AS. New hypertension guideline is released. From NEJM Journal Watch website. Accessed 2018 Jun 18. https://www.jwatch.org/na45778/2017/12/28/nejm-journal-watch-general-medicine-year-review-2017
1229. Ioannidis JPA. Diagnosis and treatment of hypertension in the 2017 ACC/AHA guidelines and in the real world. JAMA. 2018; 319(2):115-6. http://www.ncbi.nlm.nih.gov/pubmed/29242891?dopt=AbstractPlus
a. AHFS drug information 2017. McEvoy GK, ed. Hydrochlorothiazide. Bethesda, MD: American Society of Health-System Pharmacists; 2017: .
b. AHFS drug information 2017. McEvoy GK, ed. Thiazides general statement. Bethesda, MD: American Society of Health-System Pharmacists; 2017: .
c. AHFS drug information 2017. McEvoy GK, ed. Cardiac glycosides general statement. Bethesda, MD: American Society of Health-System Pharmacists; 2017: .
d. AHFS drug information 2017. McEvoy GK, ed. Captopril. Bethesda, MD: American Society of Health-System Pharmacists; 2017: .
e. Anon. Consensus recommendations for the management of chronic heart failure. On behalf of the membership of the advisory council to improve outcomes nationwide in heart failure. Part II. Management of heart failure: approaches to the prevention of heart failure. Am J Cardiol. 1999; 83:9-38A.
f. The Captopril-Digoxin Multicenter Research Group. Comparative effects of therapy with captopril and digoxin in patients with mild to moderate heart failure. JAMA. 1988; 259:539-44. http://www.ncbi.nlm.nih.gov/pubmed/2447297?dopt=AbstractPlus
g. Douglas JG, Bakris GL, Epstein M et al. Management of high blood pressure in African Americans: Consensus statement of the Hypertension in African Americans Working Group of the International Society on Hypertension in Blacks. Arch Intern Med. 2003; 163:525-41. http://www.ncbi.nlm.nih.gov/pubmed/12622600?dopt=AbstractPlus
h. American Academy of Pediatrics. The Transfer of Drugs and Other Chemical into Human Milk. Pediatrics. 2001; 108:776-789. http://www.ncbi.nlm.nih.gov/pubmed/11533352?dopt=AbstractPlus
i. Rejnmark L, Vestergaard P, Pedersen AR et al. Dose-effect relations of loop- and thiazide-diuretics on calcium homeostasis: a randomized, double-blinded Latin-square multiple cross-over study in postmenopausal osteopenic women. Eur J Clin Invest. 2003; 33:41-50. http://www.ncbi.nlm.nih.gov/pubmed/12492451?dopt=AbstractPlus
j. Schoofs MW, van der Klift M, Hofman A et al. Thiazide diuretics and the risk for hip fracture. Ann Intern Med. 2003; 139:476-82. http://www.ncbi.nlm.nih.gov/pubmed/13679324?dopt=AbstractPlus
k. Strom BL, Schinnar R, Apter AJ et al. Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics. N Engl J Med. 2003; 349:1628-35. http://www.ncbi.nlm.nih.gov/pubmed/14573734?dopt=AbstractPlus
l. Ditto AM. Drug allergy. A. Introduction, epidemiology, classification of adverse reactions, immunochemical basis, risk factors, evaluation of patients with suspected drug allergy, patient management considerations. In: Grammer LC, Greenberger PA, eds. Patterson’s allergic diseases. 6th ed. Philadelphia: Lippincott Williams & Wilkins. 2002:295-334.
m. Knowles S, Shapiro L, Shear NH. Should celecoxib be contraindicated in patients who are allergic to sulfonamides? Druf Saf. 2001; 24:239-47.
n. Gupta D, Georgiopoulou VV, Kalogeropoulos AP et al. Dietary sodium intake in heart failure. Circulation. 2012; 126:479-85. http://www.ncbi.nlm.nih.gov/pubmed/22825409?dopt=AbstractPlus
Frequently asked questions
- What is the best time of day to take blood pressure medication?
- How long does hydrochlorothiazide stay in your system?
- Should you use a diuretic with diazoxide?
More about hydrochlorothiazide
- Check interactions
- Compare alternatives
- Pricing & coupons
- Reviews (183)
- Drug images
- Side effects
- Dosage information
- Patient tips
- During pregnancy
- Support group
- Drug class: thiazide diuretics
- Breastfeeding
- En español
Patient resources
Professional resources
- Hydrochlorothiazide prescribing information
- Hydrochlorothiazide Capsules (FDA)
- Hydrochlorothiazide Tablets (FDA)