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Thalitone

Generic Name: Chlorthalidone
Class: Thiazide-like Diuretics
VA Class: CV701
CAS Number: 77-36-1

Introduction

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

Uses for Thalitone

Hypertension

Used alone or in combination with other antihypertensive agents for all stages of hypertension.b 500 501 600

JNC 7 classifies chlorthalidone as a thiazide-like drug with regard to management of hypertension.500

Thiazide-type diuretics are recommended as one of several preferred agents for the initial management of hypertension; other options include ACE inhibitors, angiotensin II receptor antagonists, and calcium-channel blockers.501 502 503 504 While there may be individual differences with respect to specific outcomes, these antihypertensive drug classes all produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.500 501 502 504 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).500 501 502 503 504 515

The optimum BP threshold for initiating antihypertensive drug therapy is controversial.501 504 505 506 507 508 515 523 530 Further study needed to determine optimum BP thresholds/goals; individualize treatment decisions.501 503 507 515 526 530

JNC 7 recommends initiation of drug therapy in all patients with uncomplicated hypertension and BP ≥140/90 mm Hg;500 JNC 8 panel recommends SBP threshold of 150 mm Hg for patients ≥60 years of age.501 Although many experts agree that SBP goal of <150 mm Hg may be appropriate for patients ≥80 years of age,502 504 505 530 application of this goal to those ≥60 years of age is controversial, especially for those at higher cardiovascular risk.501 502 505 506 508 511 515

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In the past, initial antihypertensive drug therapy was recommended for patients with diabetes mellitus or chronic kidney disease who had BP ≥130/80 mm Hg;500 503 current hypertension management guidelines generally recommend a BP threshold of 140/90 mm Hg for these individuals (same as for the general population of patients without these conditions), although a goal of <130/80 mm Hg may still be considered.501 502 503 504 520 530 535 536 541

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).109 500 501 504 However, diminished response to these other drug classes is largely eliminated when administered concomitantly with a thiazide diuretic or calcium-channel blocker.500 504

Thiazide-like diuretics may be 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.

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 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 Heart Failure

Management of edema associated with heart failure.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.500 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 heart failure 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 heart failure 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 heart failure, 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 heart failure and comorbid conditions (e.g., hypertension) where ongoing therapy with the drugs is indicated.500

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

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

Thalitone Dosage and Administration

General

BP Monitoring and Treatment Goals

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

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

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

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

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

Administration

Administer orally.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

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
Usual Dosage
Oral (conventional tablets)

JNC 8 expert panel recommends initial dosage of 12.5 mg once daily and target dosage of 12.5–25 mg once daily based on dosages used in randomized controlled studies.501 Other experts have recommended initial dosage of 12.5–25 mg daily and usual maximum dosage of 25 mg daily.101 102 109

Dosages >100 mg daily usually do not increase efficacy.600

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

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

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

Fixed-combination Therapy
Oral (conventional tablets)

Initially, administer each drug separately to adjust dosage; may use fixed combination if optimum maintenance dosage corresponds to drug ratio in combination preparation.a

Manufacturers state that fixed-combination preparations containing chlorthalidone and atenolol or clonidine should not be used for initial antihypertensive therapy.601 602

Combination preparations do not contain chlorthalidone in enhanced bioavailability formulations; therefore, combination dosing does not apply to dosages attained with Thalitone.

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)

Usual maximum is 25 mg daily.101 102 500 Higher dosages (up to 100 mg daily)a previously used but no longer recommended.101

Oral (enhanced bioavailability tablets [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 tablets [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 Thalitone

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

Hypotensive Agents

May potentiate effects of other hypotensive agents.103 Although additive or potentiated antihypertensive effects usually are used to therapeutic advantage,500 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, rarely, precipitation of gout may occur; generally avoid or use with caution in patients with history of gout or elevated uric acid concentrations.103 500 502

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

Diuretics are considered second-line agents for control of chronic hypertension in pregnant women;142 500 if initiation of antihypertensive therapy is necessary during pregnancy, other antihypertensives (i.e., methyldopa, nifedipine, labetalol) are preferred.142 540

Edema associated with pregnancy generally responds well to thiazides except when caused by renal disease; however, do not use as routine therapy in pregnant women with mild edema who are otherwise healthy.b

Diuretics are not recommended for prevention or management of gestational hypertension or preeclampsia.141 539 540

Lactation

Distributed into milk.103 h 141 Manufacturer states to discontinue nursing or the drug;600 however, considered to be compatible with breast-feeding.141

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 Cautions.)

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

Renal Impairment

Use with caution in severe renal impairment; thiazides decrease GFR and may precipitate azotemia.103 b Effects may be cumulative in impaired renal function.103 b

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 Thalitone

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, 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 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

Thalitone 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, light-resistant containers at 20–25°C.600

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.500

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

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

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

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

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

Monarch

25 mg*

Chlorthalidone Tablets

50 mg*

Chlorthalidone Tablets

* 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

Tenoretic

AstraZeneca

Atenolol 100 mg and Chlorthalidone 25 mg*

Atenolol and Chlorthalidone Tablets

Tenoretic

AstraZeneca

Clonidine Hydrochloride and Chlorthalidone

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

0.1 mg Clonidine Hydrochloride and Chlorthalidone 15 mg

Clorpres (scored)

Mylan

0.2 mg Clonidine Hydrochloride and Chlorthalidone 15 mg

Clorpres (scored)

Mylan

0.3 mg Clonidine Hydrochloride and Chlorthalidone 15 mg

Clorpres (scored)

Mylan

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2015. 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/$45.99 or 180/$85.97

Chlorthalidone 50MG Tablets (MYLAN): 30/$26.99 or 60/$44.97

Clorpres 0.1-15MG Tablets (MYLAN): 60/$127.99 or 180/$358.57

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/$56.99 or 90/$158.96

AHFS DI Essentials. © Copyright, 2004-2015, Selected Revisions January 26, 2015. 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.

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 pressure. Chicago, IL; 2000 Aug 29. Press Release from web site.

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

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

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

113. National high blood pressure education program working group on hypertension control in children and adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004; 114(Suppl 2):555-76. [PubMed 15286277]

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.

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