Chlorthalidone

Class: Thiazide-like Diuretics
VA Class: CV701
CAS Number: 77-36-1
Brands: Clorpres, Tenoretic, Thalitone

Introduction

Diuretic and antihypertensive agent, structurally and pharmacologically similar to thiazides.

Uses for Chlorthalidone

Hypertension

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

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

JNC 7 recommends that thiazides be used as initial therapy for the treatment of uncomplicated hypertension in most patients, either alone or combined with other classes of antihypertensive drugs with demonstrated benefit (e.g., ACE inhibitors, angiotensin II receptor antagonists, β-blockers, calcium-channel blockers).^{f 110}

Most hypertension outcome studies have involved thiazides, which generally have been unsurpassed in preventing cardiovascular complications of hypertension and are relatively inexpensive and well tolerated.^{f 110}

The principal goal of preventing and treating hypertension is to reduce the risk of cardiovascular and renal morbidity and mortality, including target organ damage.^{f 110 112} The higher the baseline BP, the more likely the development of MI, heart failure, stroke, and renal disease.^{f 110 112}

Effective antihypertensive therapy reduces the risk of stroke by about 34–40%, MI by about 20–25%, and heart failure by more than 50%.^{f 110}

Antihypertensive drug therapy is recommended for all patients with SBP/DBP ≥140/90 mm Hg who fail to respond to lifestyle/behavioral modifications.^{f 110}

Initial antihypertensive therapy with drugs generally is recommended for anyone with diabetes mellitus, chronic renal impairment, or heart failure having SBP ≥130 mm Hg or DBP ≥80 mm Hg.^{f 110}

Black hypertensive patients generally tend to respond better to monotherapy with diuretics or calcium-channel blockers than to monotherapy with ACE inhibitors, angiotensin II receptor antagonists, or β-blockers.^{f 100 110 112}

Diuretics largely eliminate the diminished response in blacks to ACE inhibitors, angiotensin II receptor antagonists, or β-blockers.^{f 110}

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

Preeclampsia and Eclampsia

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

Although rarely induces acute gout, generally avoid or use with caution in hypertensive patients with a history of gout or elevated uric acid concentrations.^{f 110 112}

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 S_cr 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 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

Edema in CHF

Management of edema associated with CHF.^{b c}

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

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

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

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

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

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

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

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

Diuretics should be continued in CHF and comorbid conditions (e.g., hypertension) where ongoing therapy with the drugs is indicated.¹¹⁰

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 CHF, and more potent diuretics may be required.^b

Diabetes Insipidus

Has been used widely in the treatment of diabetes insipidus†.^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 and chlorpropamide.^b

Useful in patients who are allergic or refractory to vasopressin and have 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†.^b

Renal Calculus Formation

Has been used with success in the prophylaxis of renal calculus formation associated with hypercalciuria†.^b

Chlorthalidone Dosage and Administration

Administration

Administer orally.^a

Dosage

Individualize according to requirements and response.^a

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

Thalitone tablets are formulated with povidone to enhance oral bioavailability of chlorthalidone; because of the enhanced bioavailability of this formulation, Thalitone tablets are not bioequivalent with other formulations of the drug, and the tablets cannot be substituted for other preparations or vice versa on a mg-for-mg basis.¹⁰³

Pediatric Patients

Usual Dosage

Oral (conventional tablets)

Children†: Usually, 2 mg/kg or 60 mg/m² 3 times weekly.^a

Oral (enhanced bioavailability tablets [Thalitone])

Dosage not established.¹⁰³

Hypertension†

Oral (conventional tablets)

Initially, 0.3 mg/kg once daily.¹¹³ Increase dosage as necessary up to a maximum of 2 mg/kg (up to 50 mg) once daily.¹¹³

Adults

Hypertension

BP Monitoring and Treatment Goals

Carefully monitor BP during initial titration or subsequent upward adjustment in dosage.^d

Avoid large or abrupt reductions in BP.^d

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

SBP is the principal clinical end point, especially in middle-aged and geriatric patients.^d Once the goal SBP is attained, the goal DBP usually is achieved.

The goal is to achieve and maintain a lifelong SBP <140 mm Hg and a DBP <90 mm Hg if tolerated.^d

The goal in hypertensive patients with diabetes mellitus or renal impairment is to achieve and maintain a SBP <130 mm Hg and a DBP <80 mm Hg.^d

Monotherapy

Oral (conventional tablets)

Initially, 12.5–25 mg daily.^{101 102 109 110}

May gradually increase dosage until the desired therapeutic response is achieved, adverse effects become intolerable, or a usual maximum adult dosage of 25 mg daily is attained.^{101 102 110}

If an adequate response is not achieved with this maximum dosage, another hypotensive agent may be added or substituted.^{101 102 109}

Dosages >100 mg daily usually do not increase efficacy.^a

Oral (enhanced bioavailability tablets [Thalitone])

Initially, 15 mg once daily.¹⁰³

May increase dosage to 30 mg once daily and, if necessary, to 45–50 mg daily if response is inadequate after a sufficient trial.¹⁰³

If BP control still is inadequate at the upper dosage, a second antihypertensive drug should be added rather than increasing the dosage of Thalitone further.¹⁰³

Combination Therapy

Oral (conventional tablets)

Initially, administer each drug separately to adjust dosage.^a

May use fixed combination if optimum maintenance dosage corresponds to drug ratio in combination preparation.^a Combination preparations do not contain chlorthalidone in enhanced bioavailability formulations; therefore, combination dosing does not apply to dosages attained with Thalitone.

Administer each drug separately whenever dosage adjustment is necessary.^a

Alternatively, may initially use certain (low-dose chlorthalidone/other antihypertensive) fixed combinations for potentiation of antihypertensive effect and minimization of potential dose-related adverse effects of each drug.¹⁰²

Edema

Oral (conventional tablets)

Usually, 50–100 mg daily in a single dose after breakfast.^a

Alternatively, initiate 100 mg every other day or 3 times a week; some patients require dosages of 150–200 mg daily or every other day.^a

Dosages >200 mg daily do not produce a greater response.^a

Maintenance: Reduction of dosage to a lower level may be possible after several days or when nonedematous weight is attained.^a

Oral (enhanced bioavailability tablets [Thalitone])

Usual initial dosage: 30–60 mg daily or 60 mg on alternate days.¹⁰³

Adjust dosage as necessary to 90–120 mg on alternate days or daily.¹⁰³

Dosages >120 mg daily usually do not produce a greater response.¹⁰³

Maintenance: May be lower than initial dosages and therefore should be adjusted according to individual response.¹⁰³

Prescribing Limits

Pediatric Patients

Hypertension†

Oral (conventional tablets)

Maximum 2 mg/kg (up to 50 mg) once daily.¹¹³

Adults

Hypertension

Oral (conventional tablets)

Maximum before switching/adding alternative drug is 25 mg daily.^{101 102 110}

Higher dosages had been used (up to 100 mg daily)^a but no longer are recommended.¹⁰¹ Instead, switch to or add alternative drug.^f

Oral (enhanced bioavailability tabets [Thalitone])

Maximum before switching/adding alternative drug is 50 mg daily.¹⁰³

Edema

Oral (conventional tablets)

Dosages >200 mg daily do not produce a greater response.^a

Oral (enhanced bioavailability tabets [Thalitone])

Dosages >120 mg daily usually do not produce a greater response.¹⁰³

Special Populations

Hepatic Impairment

No specific dosage recommendations for hepatic impairment; caution because of risk of precipitating hepatic coma.^{a y}

Renal Impairment

No specific dosage recommendations for renal impairment; caution because of risk of precipitating azotemia.^{a y}

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.¹⁰³

Cautions for Chlorthalidone

Contraindications

• 
  

  Anuria.^{103 b}

  
  


• 
  

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

  
  


• 
  

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

  
  

Warnings/Precautions

Warnings

Severe Renal Impairment

Use with caution; thiazides decrease GFR and may precipitate azotemia.ref-^{103 b}

Effects may be cumulative in impaired renal function.^{103 b}

Hepatic Impairment

Use with caution in hepatic impairment or progressive liver disease (particularly with associated potassium deficiency); electrolyte imbalance may precipitate hepatic coma.^{103 b}

Discontinue immediately if signs of impending hepatic coma appear.^b

Hypotensive Agents

May potentiate effects of other hypotensive agents.¹⁰³ Although additive or potentiated antihypertensive effects usually are used to therapeutic advantage,^f hypotension could occur.^{103 b} (See Interactions.)

Lupus Erythematosus

Possible exacerbation or activation of systemic lupus erythematosus.¹⁰³

Sensitivity Reactions

Hypersensitivity

May occur with or without history of allergy or bronchial asthma.^{103 b}

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

General Precautions

Electrolyte Imbalance

Monitor for fluid or electrolyte imbalance (hyponatremia, hypochloremic alkalosis, hypokalemia) prior to initiation of treatment and periodically thereafter.^{103 b}

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).¹⁰³

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

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

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

Hypokalemia

May occur after brisk diuresis, when cirrhosis is present, or with prolonged therapy; inadequate oral electrolyte intake may contribute.^{103 z}

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

Use potassium-sparing diuretics and/or potassium supplementation to avoid or treat hypokalemia.^b

Hypochloremia

Generally mild, usually does not require specific treatment except in renal or hepatic impairment.¹⁰³

Chloride replacement may be required for metabolic acidosis.^{103 z}

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.¹⁰³

In actual salt depletion, appropriate replacement is treatment of choice.¹⁰³

Gout

Hyperuricemia or preciptitaion of gout may occur.¹⁰³

Hyperglycemia

In diabetic patients, dosage adjustment of insulin or oral hypoglycemics may be required; hyperglycemia may occur and latent diabetes mellitus may become evident.¹⁰³

Sympathectomy

Antihypertensive effect may be enhanced after sympathectomy.^b

Hypomagnesemia

May increase magnesium urinary excretion, resulting in hypomagnesemia.¹⁰³

Hypercalcemia

May decrease calcium urinary excretion, cause slight intermittent serum calcium increase in absence of known calcium metabolism disorder; marked hypercalcemia may indicate hyperparathyroidism.^{103 a z}

Discontinue prior to performing parathyroid tests.^b

Hyperlipidemia

May increase cholesterol and triglyceride concentrations.^b

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

Hypotensive Effects

Orthostatic hypotension rarely occurs.^b

Specific Populations

Pregnancy

Category B.¹⁰³

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

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

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

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

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

Lactation

Distributed into milk.^{103 g h} Discontinue nursing or the drug.¹⁰³

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

Pediatric Use

Safety and efficacy not established.^{103 113}

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; select dosage with caution.¹⁰³ Substantially eliminated by kidneys; assess renal function periodically since geriatric patients are more likely to have decreased renal function.¹⁰³

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

Hepatic Impairment

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

Renal Impairment

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

Common Adverse Effects

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

Interactions for Chlorthalidone

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 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 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 insulin.b
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 intoxication b	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 diureticsb	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 on urinary corticosteroids is unclearb
Test, Histamine for pheochromocytoma	False-negative resultsb
Test, Parathyroid function tests	May elevate serum calcium in the absence of known disorders of calcium metabolismb	Discontinue thiazides prior to performing parathyroid function testsb
Test, Phenolsulfonphthalein (PSP)	Thiazides compete with phenolsulfonphthalein (PSP) for secretion by the proximal renal tubulesb	Importance unknownb
Test, Phentolamine	False-negative resultsb
Test, Protein-bound iodine (PBI)	Values may be decreased, although usually not to subnormalb
Test, Triiodothyronine resin uptake	Decreased slightly, but 24-hour I 131 uptake is not affectedb
Test, Tyramine	False-negative resultsb
Vasopressors (e.g., norepinephrine)	Possible decreased arterial responsiveness to vasopressor amines b	Clinical importance not established;b decrease in pressor response not sufficient to preclude vasopressor use109

Chlorthalidone Pharmacokinetics

Absorption

Bioavailability

Absorbed from the GI tract.

Thalitone tablets are formulated with povidone to enhance oral bioavailability of chlorthalidone; bioavailability from this formulation is 104–116% that from an oral solution of the drug.¹⁰³

Because of the enhanced bioavailability of this formulation, Thalitone tablets are not bioequivalent with other formulations of the drug, and the tablets cannot be substituted for other preparations or vice versa on a mg-for-mg basis.¹⁰³

Onset

Diuretic action begins around 2.5 hours after dosing.¹⁰³

Duration

Up to 72 hours.¹⁰³

Distribution

Plasma Protein Binding

About 75% is bound in the body, principally to or in erythrocytes.¹⁰³

Elimination

Elimination Route

30–60% excreted unchanged in urine.^a

Half-life

40–60 hours.^{103 a}

Stability

Storage

Oral

Tablets

Tight containers at 15–30°C.^a

ActionsActions

• 
  

  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.¹¹⁰

  
  

  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.^{110 112}

  
  


• 
  

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

  
  


• 
  

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

  
  


• 
  

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

  
  

Preparations

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

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

Chlorthalidone

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	15 mg	Thalitone (with povidone)	Monarch
		25 mg*	Chlorthalidone Tablets	Mylan, Pliva, UDL
		50 mg*	Chlorthalidone Tablets	Mylan, Pliva, UDL
		100 mg*	Chlorthalidone Tablets	Pliva

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

Atenolol and Chlorthalidone

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	Atenolol 50 mg and Chlorthalidone 25 mg*	Atenolol and Chlorthalidone Tablets	Mutual, Mylan, United Research, Watson
			Tenoretic (with povidone)	AstraZeneca
		Atenolol 100 mg and Chlorthalidone 25 mg*	Atenolol and Chlorthalidone Tablets	Mutual, Mylan, United Research, Watson
			Tenoretic (with povidone)	AstraZeneca

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

Clonidine Hydrochloride and Chlorthalidone

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	0.1 mg Clonidine Hydrochloride and Chlorthalidone 15 mg*	Clorpres (scored)	Bertek
		0.2 mg Clonidine Hydrochloride and Chlorthalidone 15 mg*	Clorpres (scored)	Bertek
		0.3 mg Clonidine Hydrochloride and Chlorthalidone 15 mg*	Clorpres (scored)	Bertek

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Atenolol-Chlorthalidone 100-25MG Tablets (MYLAN): 90/$30.99 or 180/$59.97

Atenolol-Chlorthalidone 50-25MG Tablets (MYLAN): 30/$13.99 or 90/$32.97

Chlorthalidone 100MG Tablets (TEVA PHARMACEUTICALS USA): 30/$33.99 or 90/$59.97

Chlorthalidone 25MG Tablets (MYLAN): 90/$29.99 or 180/$59.98

Chlorthalidone 50MG Tablets (MYLAN): 30/$19.99 or 60/$29.98

Clorpres 0.1-15MG Tablets (MYLAN BERTEK): 60/$78.64 or 180/$217.77

Clorpres 0.2-15MG Tablets (MYLAN BERTEK): 60/$115.99 or 180/$315.96

Tenoretic 100 100-25MG Tablets (ASTRAZENECA): 30/$86.99 or 90/$240.98

Tenoretic 50 50-25MG Tablets (ASTRAZENECA): 30/$61.99 or 90/$170.96

Thalitone 15MG Tablets (MONARCH PHARMACEUTICALS): 30/$49.99 or 90/$139.98

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions July 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† 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.

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

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

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

103. Monarch Pharmaceuticals. Thalitone (chlorthalidone) tablets prescribing information. Bristol, TN; 2004 Jan.

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

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

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

107. Associated Press (American Diabetes Association). Diabetics urged: drop blood p