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Metolazone

Pronunciation

Class: Thiazide-like Diuretics
VA Class: CV701
CAS Number: 17560-51-9
Brands: Zaroxolyn

Introduction

Diuretic and antihypertensive agent; structurally and pharmacologically similar to thiazide diuretics.a e

Uses for Metolazone

Hypertension

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

Used concomitantly with a loop diuretic to manage hypertension and/or induce diuresis in patients who did not respond to either diuretic alone (e.g., in those with advanced renal insufficiency); monotherapy may be effective in some patients who are unresponsive to a loop diuretic.a

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

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).500 501 502 504 515

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

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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

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).108 500 501 504 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 secondary to effect on calcium homeostasis and bone mineralization.

Edema in Heart Failure

Zaroxolyn tablets and bioequivalent formulations used in management of edema and salt retention associated with heart failure.a b e

Mykrox tablets (no longer commercially available in US) not evaluated for management of heart failure; appropriate safe and effective dosage not established.a Do not use when diuresis is desired therapeutic effect.a

Zaroxolyn tablets and bioequivalent formulations 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

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

Loop diuretics (e.g., bumetanide, ethacrynic acid, furosemide, torsemide) are diuretics of choice for most patients with heart failure.

Edema in Renal Diseases

Zaroxolyn tablets and bioequivalent formulations used in management of edema and salt retention associated with renal diseases (e.g., nephrotic syndrome, impaired renal function).a e

Mykrox tablets (no longer commercially available in US) not evaluated for management of fluid retention caused by renal or hepatic disease; appropriate safe and effective dosage not established.a Do not use when diuresis is desired therapeutic effect.a

May be more effective than other thiazide-like diuretics in management of edema in patients with impaired renal function.a b

Use in diabetes insipidus, in renal tubular acidosis, or in prophylaxis of renal calculus formation associated with hypercalciuria not established.a

Edema in Pregnancy

Do not use thiazides as routine therapy in pregnant women with mild edema who are otherwise healthy.b

Use of thiazide-like diuretics may be appropriate in the management of edema of pathologic origin during pregnancy when clearly needed; routine use of diuretics in otherwise healthy pregnant women is irrational and exposes the woman and fetus to unnecessary hazard.e

Dependent edema secondary to restriction of venous return by the expanded uterus should be managed by elevating the lower extremities and/or by wearing support hose; use of diuretics in these pregnant women is inappropriate.e

In rare cases when the hypervolemia associated with normal pregnancy results in edema that produces extreme discomfort, a short course of diuretic therapy may provide relief and may be considered when other methods (e.g., increased recumbency, rest) are ineffective.e

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

Metolazone Dosage and Administration

General

Formulation Considerations

  • Do not interchange Mykrox and bioequivalent formulations with Zaroxolyn and bioequivalent formulations.a e Mykrox tablets (no longer commercially available in US) are more rapidly and extensively absorbed than other metolazone formulations; not therapeutically equivalent to Zaroxolyn or other formulations of drug that share the latter’s slower and incomplete absorption.a e

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 as a single daily dose.a e

Dosage

Dosage depends on specific formulation used and condition being treated.a

Individualize dosage according to individual requirements and response.a e

Adjust dosage to achieve an initial therapeutic response and to determine minimal dose necessary to maintain desired therapeutic response.e

More careful dosage adjustment may be necessary in patients receiving concomitant therapy with other antihypertensive agents or diuretics.e (See Specific Drugs under Interactions.)

Pediatric Patients

Heart Failure, Hypertension, Bronchopulmonary Dysplasia, Nephrotic Syndrome, Nephrogenic Diabetes Insipidus
Oral

0.05–0.1 mg/kg once daily has been given.e (See Pediatric Use under Cautions.)

Prolonged use (beyond a few days) not recommended.e (See Pediatric Use under Cautions.)

Adults

Hypertension
Oral (Zaroxolyn or another bioequivalent formulation)

Initial dosage of 1.25–2.5 mg once daily has been suggested.a

Usual dosage range is 2.5–5 mg once daily.109 500 e

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

Edema in Heart Failure
Monotherapy
Oral (Zaroxolyn or another bioequivalent formulation)

Manufacturer recommends a usual initial dosage range of 5–20 mg once daily.109 e

Some experts recommend an initial dosage of 2.5 mg once daily up to a maximum total daily dosage of 20 mg.f

Has been administered every other day after response of patient was stabilized.28

Daily dosage depends on severity of patient’s condition, sodium intake, and responsiveness.e Adjust daily dosage based on results of thorough clinical and laboratory evaluations.e

Reduction of dosage to a lower maintenance level may be possible if desired therapeutic response attained.e

High doses may prolong diuresis and saluresis; single daily dose is recommended.e (See Absorption under Pharmacokinetics.)

Combination Therapy
Oral (Zaroxolyn or another bioequivalent formulation)

For sequential nephron blockade in the management of edema in heart failure, some experts recommend an initial dosage of 2.5–10 mg once daily in combination with a loop diuretic.f

For sequential nephron blockade in the management of severe heart failure, some experts recommend an initial dosage of 2.5–5 mg once or twice daily in combination with a loop diuretic.f

Edema in Renal Diseases
Oral (Zaroxolyn or another bioequivalent formulation)

Usual initial dosage range is 5–20 mg once daily.109 e

Daily dosage depends on severity of patient’s condition, sodium intake, and responsiveness.e Adjust daily dosage based on results of thorough clinical and laboratory evaluations.e

Reduction of dosage to a lower maintenance level may be possible if desired therapeutic response attained.e

High doses may prolong diuresis and saluresis; single daily dose is recommended.e (See Absorption under Pharmacokinetics.)

Prescribing Limits

Adults

Hypertension
Oral

Usual maximum is 5 mg daily.a

Edema in Heart Failure
Monotherapy
Oral (Zaroxolyn or another bioequivalent formulation)

Maximum total daily dose: 20 mg.f

Special Populations

Hepatic Impairment

No specific dosage recommendations.e (See Hepatic Impairment under Cautions.)

Renal Impairment

No specific dosage recommendations.e (See Renal Impairment under Cautions.)

Geriatric Patients

Select dosage with caution, usually initiating therapy at the low end of the dosing range, because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.e (See Geriatric Use under Cautions.)

Paroxysmal Nocturnal Dyspnea Patients

May be advisable to administer an increased dosage in the management of edematous conditions to ensure prolongation of diuresis and saluresis for a full 24-hour period.e

Cautions for Metolazone

Contraindications

  • Anuria.e

  • Hepatic coma or pre-coma.a e

  • Known hypersensitivity to metolazone or any ingredient in the formulation.a e (See Hypersensitivity under Cautions.)

Warnings/Precautions

Warnings

Rapid-onset Hyponatremia and/or Hypokalemia

Rapid onset of severe hyponatremia and/or hypokalemia reported rarely following initial doses of thiazide and nonthiazide diuretics.e

Immediately discontinue drug and initiate supportive measures when symptoms consistent with severe electrolyte imbalance appear rapidly; parenteral electrolytes may be required.e Carefully reevaluate adequacy of therapy.e

Hypokalemia

Dose-related hypokalemia may occur with consequent weakness, cramps, and cardiac dysrhythmias.e

Increased risk of hypokalemia with large doses, rapid diuresis, severe hepatic disease, concomitant corticosteroids, inadequate oral intake, or excessive extrarenal potassium loss (e.g., vomiting, diarrhea).e

Determine serum potassium concentrations at regular and appropriate intervals; initiate dosage reduction, potassium supplementation, or addition of a potassium-sparing diuretic as needed.e

Particular concern in patients who are digitalized or those with ventricular arrhythmias or a history of ventricular arrhythmias; may result in dangerous or fatal arrhythmias.e

Concomitant Therapy

Concomitant use with certain drugs requires particular caution (e.g., furosemide, other antihypertensive drugs).a e (See Specific Drugs under Interactions.)

Generally, do not use with lithium salts.e (See Specific Drugs under Interactions.)

Sensitivity Reactions

Hypersensitivity

Cross-sensitivity may occur when used in patients known to be allergic to sulfonamide-derived drugs, thiazides, or quinethazone.e

Although some thiazide manufacturers state that 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.

Sensitivity reactions (e.g., angioedema, bronchospasm) reported with or without a history of allergy or bronchial asthma; may occur with first dose.e

General Precautions

Fluid and Electrolyte Imbalance

Hyponatremia may occur at any time during long-term therapy; life-threatening rarely.e

Increased urinary excretion of magnesium reported with thiazide-like diuretics; may result in hypomagnesemia.e

Possible low-salt syndrome in patients with severe edema accompanying cardiac failure or renal disease, especially with hot weather and a low-salt diet.e

Observe for signs of fluid or electrolyte imbalance (particularly hyponatremia, hypochloremic alkalosis, and hypokalemia) such as dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains, cramps, fatigue, hypotension, oliguria, tachycardia, GI disturbances (e.g., nausea, vomiting).e e (See Hypokalemia under Cautions.)

Measure serum electrolytes at appropriate intervals.e

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

Glucose Tolerance

May increase blood glucose concentrations and possibly cause hyperglycemia and glycosuria in patients with diabetes or latent diabetes.e

Hyperuricemia

Regularly increases serum uric acid concentrations and occasionally precipitates gouty attacks, including in patients without a prior history; generally avoid or use with caution in patients with history of gout or elevated uric acid concentrations.500 502 e

Azotemia

Azotemia, presumably prerenal azotemia, may occur.e

Discontinue drug if azotemia and oliguria worsen during treatment in patients with severe renal disease.e

Orthostatic Hypotension

Orthostatic hypotension reported; may be potentiated by alcohol, barbiturates, narcotics, or concomitant therapy with other antihypertensive drugs.e (See Specific Drugs under Interactions.)

Hypercalcemia

Hypercalcemia may occur infrequently, particularly in patients receiving high doses of vitamin D or with high bone turnover states; may indicate undetected hyperparathyroidism.e

Discontinue drug before performing parathyroid function tests.e

Lupus Erythematosus

Consider possible exacerbation or activation of systemic lupus erythematosus.e

Fetal/Neonatal Morbidity

Crosses placental barrier and appears in cord blood.a e Use with caution; possible fetal or neonatal jaundice, thrombocytopenia, and other adverse effects reported in adults.e

Specific Populations

Pregnancy

Category B.e

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

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

Lactation

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

Pediatric Use

Safety and efficacy not established in controlled clinical studies.a e

Limited experience with use in pediatric patients with heart failure, hypertension, bronchopulmonary dysplasia, nephrotic syndrome, and nephrogenic diabetes insipidus; dosages used generally ranged from 0.05–0.1 mg/kg once daily, and resulted in a 1- to 2.8-kg weight loss and 150- to 300-mL increase in urine output.e Response was observed in first few days of therapy; not all pediatric patients responded and some gained weight.e Prolonged use (beyond a few days) not recommended; generally associated with no further beneficial effect or a return to baseline status.e

Limited experience with concomitant metolazone and furosemide therapy in pediatric patients with furosemide-resistant edema; exaggerated response with hypovolemia, tachycardia, orthostatic hypotension requiring fluid replacement, severe hypokalemia, hyperbilirubinemia, and persistent diuresis for up to 24 hours after discontinuance reported.e

Perform careful clinical and laboratory monitoring in all pediatric patients receiving diuretic therapy.e

Geriatric Use

Insufficient experience in clinical studies in patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients.e Other reported clinical experience has not identified differences in response between geriatric patients and younger adults.e

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.e (See Geriatric Patients under Dosage and Administration.)

Substantially eliminated by kidneys; risk of toxic reactions may be greater in patients with impaired renal function.e Monitor renal function and adjust dosage accordingly since geriatric patients are more likely to have decreased renal function.e

Hepatic Impairment

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

Discontinue immediately if signs of impending hepatic coma appear.b

May produce a greater incidence of electrolyte disturbances and encephalopathy, but a lower incidence of azotemia, than thiazides in patients with ascites caused by liver disease.a

Renal Impairment

Use with caution in patients with severe renal impairment.e (See Elimination under Pharmacokinetics)

Common Adverse Effects

Potassium depletion,b e hypochloremic alkalosis in patients at risk (e.g., patients with hypokalemia and loss of chloride),b dilutional hyponatremia,b e hyperuricemia (usually asymptomatic; rarely leading to gout),b e hyperglycemia and glycosuria in diabetic patients.b e Abdominal bloating,a e palpitation,a e chest pain,a e and chills and also reported.a e

Interactions for Metolazone

Specific Drugs

Drug

Interaction

Comments

Alcohol

Hypotensive effect of alcohol may be potentiated by volume contraction associated with metolazonee

May potentiate orthostatic hypotensione

Anticoagulants

Metolazone may affect hypoprothrombinemic response to anticoagulantse

Dosage adjustment may be necessarye

Antidiabetic agents (sulfonylurea)

Metolazone may increase blood glucose concentrations possibly resulting in hyperglycemia and glycosuria in patients with diabetes or latent diabetese

Antihypertensive agents

May potentiate orthostatic hypotensione

Use with caution, particularly during initial therapye

Dosage adjustment of other antihypertensive agent may be necessarye

Barbiturates

Hypotensive effect of barbiturates may be potentiated by volume contraction associated with metolazonee

May potentiate orthostatic hypotensione

Cardiac glycosides

Diuretic-induced hypokalemia may increase myocardium sensitivity to digitalis; possibility of serious arrhythmiase

Corticosteroids

Increased risk of hypokalemia and salt and water retentione

Corticotropin (adrenocorticotropic hormone, ACTH)

Increased risk of hypokalemia and salt and water retentione

Diuretics, loop (e.g., furosemide)

Concomitant therapy with furosemide may cause excessive or prolonged fluid and electrolyte depletiona e

Concomitant therapy with furosemide produced marked diuresis in some patients in whom edema or ascites was refractory to maximum recommended dosages of these or other diuretics alone; mechanism not knowne

Use with cautiona

Insulin

Metolazone may increase blood glucose concentrations possibly resulting in hyperglycemia and glycosuria in patients with diabetes or latent diabetese

Lithium

Reduced renal clearance of lithium, and increased serum lithium concentrations and risk of lithium toxicitye

Generally, do not use with lithium saltse

Methenamine

Urinary alkalizing effect of metolazone may decrease efficacy of methenaminee

Neuromuscular blocking agents (e.g., tubocurarine)

Diuretic-induced hypokalemia may enhance neuromuscular blocking effects of curariform drugs (e.g., tubocurarine); possibility of respiratory depression leading to apneae

Advisable to discontinue metolazone 3 days prior to elective surgerye

NSAIAs

NSAIAs and salicylates may decrease antihypertensive effects of metolazonee

Opiates

Hypotensive effect of opiates may be potentiated by volume contraction associated with metolazonee

May potentiate orthostatic hypotensione

Vasopressors (norepinephrine)

Possible decreased arterial responsiveness to norepinephrinee

Decrease in pressor response not sufficient to preclude efficacy of pressor agent for therapeutic usee

Vitamin D

Concomitant therapy may increase risk of hypercalcemiae

Metolazone Pharmacokinetics

Absorption

Bioavailability

Rate and extent of absorption of commercially available tablets vary depending on the preparation.a

Mykrox 0.5-mg tablets are more rapidly and extensively absorbed than Zaroxolyn tablets and other formulations of metolazone with dissolution and absorption characteristics similar to the latter.a e (See Administration under Dosage and Administration.)

Zaroxolyn and other similar metolazone formulations: Slowly and incompletely absorbed from GI tract; peak blood concentrations occur about 8 hours after administration and absorption continues for an additional 12 hours.a e Average of 65 or 40% of a dose of such a metolazone formulation reported to be absorbed following oral administration in healthy individuals or in patients with cardiac disease, respectively.a

Mykrox and other similar metolazone formulations: Rate and extent of absorption reportedly equivalent to those of an oral solution of the drug; peak blood concentrations attained within 2–4 hours following oral administration.a Blood concentrations of drug are proportional to dose at Mykrox doses of 0.5–2 mg; steady-state blood concentrations usually attained within 4–5 days.a

Onset

Zaroxolyn and other similar metolazone formulations: Onset of antihypertensive effect varies from 3–4 days to 3–6 weeks following initial dose.e

Zaroxolyn and other similar metolazone formulations: Diuresis and saluresis usually occur within 1 hour following initial dose.e

Duration

Zaroxolyn and other similar metolazone formulations: Diuresis and saluresis usually persist for ≥24 hours following initial dose; duration of effect may be varied by adjusting daily dosage.e (See Dosage and Administration.)

Distribution

Extent

Crosses placental barrier and appears in cord blood.a e

Distributed into milk.a e

Plasma Protein Binding

Approximately ≤33%.a

Approximately 50–70% bound to erythrocytes and 2–5% circulates unbound.a

Elimination

Metabolism

Not metabolized to a substantial extent.a e

Elimination Route

Excreted principally in urine (70–95%) via glomerular filtration and active tubular secretion as unchanged drug;a e remainder of drug eliminated by nonrenal routes, principally in bile, and reportedly undergoes enterohepatic recycling.a (See Renal Impairment under Cautions and see Special Populations under Pharmacokinetics.)

Half-life

Biphasic; approximately 14 hours.a

Special Populations

Accumulation of drug may occur in patients with severe renal impairment.e (See Renal Impairment under Cautions and see Elimination Route under Pharmacokinetics.)

Stability

Storage

Oral

Tablets

Tight, light-resistant containers at 25°C (may be exposed to 15–30°C).a e

Actions

  • Structurally and pharmacologically similar to thiazide diuretics; quinazoline-derivative diuretic.a e

  • Enhances excretion of sodium, chloride, and water by interfering with transport of sodium ions across renal tubular epithelium.b e

  • Exact mechanism of diuretic action is unclear; principal site of action appears to be the cortical diluting segment of the distal convoluted tubules of the nephron, and to a lesser extent the proximal convoluted tubule.b e

  • Sodium and chloride ions excreted in approximately equivalent amounts.e

  • Enhances urinary excretion of potassium secondary to increased amount of sodium at distal tubular site of sodium-potassium exchange.b e

  • Increases excretion of phosphate and magnesium and markedly increases the fractional excretion of sodium in patients with severely compromised glomerular filtration (as proximal actions).e

  • Diuretic potency at maximum therapeutic dosages approximately equal to that of thiazide diuretics;e however, may produce diuresis in patients with GFR <20 mL/minute, unlike thiazides.a e

  • Unlike thiazides, does not substantially decrease GFR or renal plasma flow.a

  • Does not inhibit carbonic anhydrase.e

  • May alter renal vascular resistance at time of maximal diuresis; exact mechanism unclear.a

  • May increase urinary bicarbonate excretion (although to a lesser extent than chloride excretion) but change in urinary pH is usually minimal; diuretic efficacy not affected by acid-base balance of patient.b

  • Hypocalciuric effect thought to result from a decrease in extracellular fluid (ECF) volume, although calcium reabsorption in the nephron may be increased; also, may cause slight or intermittent elevations in serum calcium concentration.b

  • May decrease rate of uric acid excretion, 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 action of other hypotensive agents.b Precise mechanism of hypotensive action not determined, but postulated that part of effect is caused by direct arteriolar dilation.b

Advice to Patients

  • Importance of informing patients of signs of electrolyte imbalance (e.g., dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, confusion, seizures, oliguria, muscle pain or cramps, muscular fatigue, hypotension, tachycardia, GI disturbances (e.g., nausea and vomiting).b

  • Importance of compliance with scheduled determinations of serum electrolyte concentrations (particularly potassium, sodium, chloride, and bicarbonate).b

  • Advise hypertensive patients to continue lifestyle/behavioral modifications including 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

  • Importance of informing hypertensive patients 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 patients taking medication as prescribed.e

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

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

  • Importance of informing patients of other important precautionary information.e (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

Metolazone

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

2.5 mg*

Metolazone Tablets

Zaroxolyn

UCB

5 mg*

Metolazone Tablets

Zaroxolyn

UCB

10 mg*

Metolazone Tablets

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.

Metolazone 2.5MG Tablets (MYLAN): 30/$42.99 or 90/$109.97

Metolazone 5MG Tablets (SANDOZ): 30/$42.99 or 90/$121.97

Zaroxolyn 10MG Tablets (UCB PHARMA): 30/$79.99 or 90/$229.97

Zaroxolyn 2.5MG Tablets (UCB PHARMA): 30/$94.99 or 90/$280.96

Zaroxolyn 5MG Tablets (UCB PHARMA): 30/$88.99 or 90/$259.97

AHFS DI Essentials. © Copyright, 2004-2015, Selected Revisions February 15, 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.

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500. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7). Bethesda, MD: National Institutes of Health; 2004 Aug. (NIH publication No. 04-5230.)

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. [PubMed 24352797]

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. [PubMed 23817082]

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