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Metolazone: Drug information

Metolazone: Drug information
2024© UpToDate, Inc. and its affiliates and/or licensors. All Rights Reserved.
For additional information see "Metolazone: Patient drug information" and "Metolazone: Pediatric drug information"

For abbreviations, symbols, and age group definitions show table
Brand Names: Canada
  • Zaroxolyn
Pharmacologic Category
  • Diuretic, Thiazide-Related
Dosing: Adult
Edema or general volume overload

Edema or general volume overload (adjunctive to loop diuretic):

Note: Optimize loop diuretic therapy before adding metolazone; combination diuretic therapy is typically for short-term use to restore euvolemia in patients already taking high-dose loop diuretic therapy who are resistant (eg, furosemide total daily dose of 160 to 320 mg/day IV or the oral equivalent). Combination diuretic therapy can cause severe electrolyte depletion (eg, potassium, magnesium, sodium); prior to and during therapy, electrolytes should be monitored and appropriately repleted or managed (Ref).

Oral: Initial: 2.5 to 5 mg once daily; may increase dose as needed up to a maximum of 20 mg/day in 1 to 2 divided doses depending on patient response; may administer every other day or on specific days of the week; may be administered in combination with or shortly before the scheduled loop diuretic. Assess volume status frequently (eg, daily or at least every 2 to 3 days) to determine effectiveness and to avoid over diuresis. Continue until euvolemia is restored, although some patients may require scheduled treatment for maintenance (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Altered kidney function:

Metolazone undergoes minimal hepatic metabolism; the primary route of clearance is excretion of unchanged drug in the urine. Plasma concentrations are expected to be increased with kidney impairment (Ref).

eGFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary.

eGFR <30 mL/minute/1.73 m2: No dosage adjustment necessary (Ref). When used in combination with loop diuretics to augment diuresis, due to prolonged half-life, dosing frequency may be adjusted based on patient-specific diuretic needs (eg, administration every other day or 2 times per week). Additionally, if diuresis is too rapid, temporarily holding the dose until the diuresis has diminished (as opposed to continuing therapy with a decreased dose) may be necessary (Ref). Close monitoring of electrolytes and volume status is necessary (Ref).

Hemodialysis, intermittent (thrice weekly): Not significantly dialyzed (90% to 95% protein bound) (Ref). In general, use is not recommended due to lack of efficacy. Consider loop diuretic in patients with residual kidney function (Ref).

Peritoneal dialysis: Unlikely to be significantly dialyzed (Ref). In general, use not recommended due to lack of efficacy. Consider loop diuretic in patients with residual kidney function (Ref).

CRRT: In general, use is not recommended; fluid management can be more effectively managed using CRRT ultrafiltration (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration): In general, use is not recommended; fluid management can be more effectively managed using PIRRT ultrafiltration (Ref).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; contraindicated in hepatic coma or precoma.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Metolazone: Pediatric drug information")

Edema, refractory

Edema, refractory: Limited data available: Infants, Children, and Adolescents: Oral: Usual range: 0.2 to 0.4 mg/kg/day divided every 12 to 24 hours in combination with furosemide; adjust dose to minimal effective dose for maintenance (Ref); maximum adult daily dose: 20 mg/day. Note: Published efficacy of metolazone in infants and children are limited; underlying disease state, renal function, and concomitant therapies all may affect response (Ref). According to the manufacturer, a lower dose of 0.05 to 0.1 mg/kg once daily has also been reported to result in weight loss and increase urine output in some pediatric patients.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; use caution in patients with severe kidney impairment, as most of the drug is excreted by the kidney and accumulation may occur.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling; contraindicated in hepatic coma or precoma.

Adverse Reactions (Significant): Considerations
Electrolyte disturbances

Reversible hypokalemia and hypomagnesemia may occur with metolazone and may increase the risk of arrhythmias. Contraction alkalosis, hypercalcemia, and hyponatremia can also occur; hyponatremia, in severe cases, can lead to seizures or coma (Ref). Electrolyte disturbances may be more significant with longer-acting agents (eg, metolazone, chlorthalidone) as compared to shorter-acting thiazide diuretics (eg, hydrochlorothiazide) (Ref). Development of electrolyte disturbances may be minimized when used in combination with other electrolyte-sparing antihypertensives (eg, angiotensin-converting enzyme, angiotensin receptor blockers, or aldosterone inhibitors) (Ref).

Mechanism: Dose-related; related to the pharmacologic action. Thiazide and thiazide-related diuretics block the NaCl cotransporter in the distal convoluted tubule, leading to decreased reabsorption of sodium and chloride and increased delivery of sodium to the collecting duct, which leads to increased potassium wasting. Diluting capacity of the kidney is also impaired, leading to decreased magnesium and increased calcium concentrations (Ref).

Onset: Varied; hypokalemia generally occurs within 2 weeks of initiation (Ref). Hyponatremia onset may range from 2 weeks to 10 years after treatment initiation (Ref).

Risk factors:

• High doses or concurrent loop diuretic therapy (Ref)

• Hypokalemia: GI losses (eg, vomiting, diarrhea) (Ref)

• Hypomagnesemia: Heart failure, poor magnesium intake, high alcohol intake (Ref)

• Hyponatremia: Increased water intake (Ref); older patients (Ref); females (Ref)

• Hypercalcemia: Older patients, females (Ref)

Hypersensitivity reactions (immediate and delayed)

Hypersensitivity reactions, both immediate (eg, urticaria, angioedema) and delayed, have been reported. Delayed hypersensitivity reactions range from skin rash to rare severe cutaneous adverse reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (Ref).

Mechanism: Immediate hypersensitivity reactions: Non–dose-related; immunologic (ie, IgE-mediated, with specific antibodies formed against a drug allergen following initial exposure) (Ref). Delayed hypersensitivity reactions: Non–dose-related; immunologic (ie, involving a T-cell mediated drug-specific immune response) (Ref).

Onset: Immediate hypersensitivity reactions: Rapid; generally occur within 1 hour of administration but may occur up to 6 hours after exposure (Ref). Delayed hypersensitivity reactions: Varied; typically occur days to 6 weeks after drug exposure, but may occur more rapidly (usually within 1 to 4 days) upon reexposure (Ref).

Risk factors:

• Cross-reactivity: Limited published information regarding possible cross-reactivity between thiazide diuretics and other sulfonamides (Ref). Cross-reactivity due to antibody production (anaphylaxis) is unlikely to occur with nonantibiotic sulfonamides and antibiotic sulfonamides (Ref). Cross-reactivity among thiazide diuretics is unknown.

Orthostatic hypotension

Hypotension, including orthostatic hypotension, may occur (Ref). The occurrence of hypotension may be dose-limiting or result in treatment discontinuation (Ref).

Mechanism: Dose-related; related to the pharmacologic action (ie, volume depletion) (Ref).

Onset: Varied; hypotension may occur following a single dose, especially when combined with loop diuretic therapy (Ref).

Risk factors:

• Concomitant use of barbiturates, narcotics, or other hypotensive agents

• Concurrent loop diuretic therapy (Ref)

• Older patients (Ref).

Adverse Reactions

The following adverse drug reactions are derived from product labeling unless otherwise specified.

Frequency not defined:

Cardiovascular: Chest discomfort, chest pain, necrotizing angiitis, palpitations, syncope, venous thrombosis

Dermatologic: Pruritus, purpuric rash, skin necrosis, skin photosensitivity, skin rash, urticaria

Endocrine & metabolic: Acute gout attack, hyperglycemia, hyperuricemia, hypochloremic alkalosis, hypomagnesemia, hypophosphatemia, hypovolemia

Gastrointestinal: Abdominal pain, anorexia, bloating, constipation, diarrhea, epigastric distress, nausea, vomiting, xerostomia

Genitourinary: Erectile dysfunction, glycosuria

Hematologic & oncologic: Agranulocytosis, aplastic anemia, hemoconcentration, hypoplastic anemia, leukopenia, petechia, thrombocytopenia

Hepatic: Cholestatic jaundice, hepatitis

Nervous system: Asthenia, chills, depression with psychosis, dizziness, drowsiness, fatigue, headache, neuropathy, paresthesia, restlessness, vertigo

Neuromuscular & skeletal: Arthralgia, muscle cramps, muscle spasm

Ophthalmic: Transient blurred vision

Renal: Increased blood urea nitrogen

Postmarketing:

Cardiovascular: Hypotension (Steuber 2020), orthostatic hypotension (Bennett 1973)

Dermatologic: Stevens-Johnson syndrome (Kumar 2016), toxic epidermal necrolysis (Kumar 2016)

Endocrine & metabolic: Hypercalcemia (Anderson 1992), hypochloremia (Steuber 2020), hypokalemia (Steuber 2020), hyponatremia (Steuber 2020)

Gastrointestinal: Pancreatitis (Anderson 1991)

Hematologic & oncologic: Neutropenia (Donovan 1989)

Renal: Increased serum creatinine (Steuber 2020)

Contraindications

Hypersensitivity to metolazone or any component of the formulation; anuria; hepatic coma or precoma.

Warnings/Precautions

Concerns related to adverse effects:

• Sulfonamide ("sulfa") allergy: The FDA-approved product labeling for many medications containing a sulfonamide chemical group includes a broad contraindication in patients with a prior allergic reaction to sulfonamides. There is a potential for cross-reactivity between members of a specific class (eg, two antibiotic sulfonamides). However, concerns for cross-reactivity have previously extended to all compounds containing the sulfonamide structure (SO2NH2). An expanded understanding of allergic mechanisms indicates cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur or at the very least this potential is extremely low (Brackett 2004; Johnson 2005; Slatore 2004; Tornero 2004). In particular, mechanisms of cross-reaction due to antibody production (anaphylaxis) are unlikely to occur with nonantibiotic sulfonamides. T-cell-mediated (type IV) reactions (eg, maculopapular rash) are less well understood and it is not possible to completely exclude this potential based on current insights. In cases where prior reactions were severe (Stevens-Johnson syndrome/TEN), some clinicians choose to avoid exposure to these classes.

Disease-related concerns:

• Adrenal insufficiency: Avoid use of diuretics for treatment of elevated blood pressure in patients with primary adrenal insufficiency (Addison disease). Adjustment of glucocorticoid/mineralocorticoid therapy and/or use of other antihypertensive agents is preferred to treat hypertension (Bornstein 2016; Inder 2015).

• Bariatric surgery: Dehydration: Avoid diuretics in the immediate postoperative period after bariatric surgery; electrolyte disturbances and dehydration may occur. Diuretics may be resumed, if indicated, once oral fluid intake goals are met (Ziegler 2009).

• Diabetes: Use with caution in patients with prediabetes or diabetes mellitus; may see a change in glucose control.

• Gout: Hyperuricemia can occur and gout can be precipitated.

• Hepatic impairment: Use with caution in patients with severe hepatic dysfunction.

• Renal impairment: Use caution in severe renal disease. If azotemia and oliguria worsen during treatment in these patients, discontinue therapy.

• Systemic lupus erythematosus (SLE): Can cause SLE exacerbation or activation.

Special populations:

• Surgical patients: If given the morning of surgery, metolazone may render the patient volume depleted and blood pressure may be labile during general anesthesia.

Other warnings/precautions:

• Interchangeability: Do not interchange Zaroxolyn with other formulations of metolazone that are not therapeutically equivalent at the same doses (eg, Mykrox, no longer available in the US).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Generic: 2.5 mg, 5 mg, 10 mg

Generic Equivalent Available: US

Yes

Pricing: US

Tablets (metOLazone Oral)

2.5 mg (per each): $0.19 - $3.75

5 mg (per each): $0.27 - $4.26

10 mg (per each): $0.36 - $3.51

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Zaroxolyn: 2.5 mg

Administration: Adult

Oral: Administer as a single daily dose with or without food. Therapy should be taken early in the day to avoid nocturia.

Administration: Pediatric

Oral: Administer early in day to avoid nocturia.

Use: Labeled Indications

Edema or general volume overload: Treatment of edema due to heart failure or renal diseases, including the nephrotic syndrome and states of diminished renal function.

Medication Safety Issues
Sound-alike/look-alike issues:

MetOLazone may be confused with metaxalone, methadone, methazolAMIDE, methIMAzole, methotrexate, metoclopramide, metoprolol, minoxidil

Zaroxolyn may be confused with Zarontin

Older Adult: High-Risk Medication:

Beers Criteria: Diuretics are identified in the Beers Criteria as potentially inappropriate medications to be used with caution in patients 65 years and older due to the potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium concentration closely when initiating or adjusting the dose in older adults (Beers Criteria [AGS 2023]).

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Agents with Clinically Relevant Anticholinergic Effects: May increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Ajmaline: Sulfonamides may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Risk C: Monitor therapy

Alcohol (Ethyl): May enhance the orthostatic hypotensive effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Allopurinol: Thiazide and Thiazide-Like Diuretics may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Risk C: Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification

Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination

Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Angiotensin-Converting Enzyme Inhibitors: Thiazide and Thiazide-Like Diuretics may enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Thiazide and Thiazide-Like Diuretics may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Antidiabetic Agents: Thiazide and Thiazide-Like Diuretics may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy

Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Arsenic Trioxide: Thiazide and Thiazide-Like Diuretics may enhance the hypotensive effect of Arsenic Trioxide. Thiazide and Thiazide-Like Diuretics may enhance the QTc-prolonging effect of Arsenic Trioxide. Management: When possible, avoid concurrent use of arsenic trioxide with drugs that can cause electrolyte abnormalities, such as the thiazide and thiazide-like diuretics. Risk D: Consider therapy modification

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Beta2-Agonists: May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Bile Acid Sequestrants: May decrease the absorption of Thiazide and Thiazide-Like Diuretics. The diuretic response is likewise decreased. Management: Consider separating administraton of bile acid sequestrants and thiazide diuretics by at least 4 hours. Monitor for decreased therapeutic effects of thiazide diuretics if coadministered with a bile acid sequestrant. Risk D: Consider therapy modification

Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination

Calcium Salts: Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Calcium Salts. Risk C: Monitor therapy

Cardiac Glycosides: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Cardiac Glycosides. Specifically, cardiac glycoside toxicity may be enhanced by the hypokalemic and hypomagnesemic effect of thiazide diuretics. Risk C: Monitor therapy

Corticosteroids (Systemic): May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

CycloPHOSphamide: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of CycloPHOSphamide. Specifically, granulocytopenia may be enhanced. Risk C: Monitor therapy

Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy

Dexketoprofen: May enhance the adverse/toxic effect of Sulfonamides. Risk C: Monitor therapy

Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy

Diacerein: May enhance the therapeutic effect of Diuretics. Specifically, the risk for dehydration or hypokalemia may be increased. Risk C: Monitor therapy

Diazoxide: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Diazoxide. Risk C: Monitor therapy

Dichlorphenamide: Thiazide and Thiazide-Like Diuretics may enhance the hypokalemic effect of Dichlorphenamide. Risk C: Monitor therapy

Dofetilide: Thiazide and Thiazide-Like Diuretics may enhance the QTc-prolonging effect of Dofetilide. Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Dofetilide. Management: Although hydrochlorothiazide is specifically cited as a contraindication, the risk likely extends to all thiazide and thiazide-like diuretics and may be even greater with chlorthalidone or bendroflumethiazide. Consider alternatives when possible. Risk D: Consider therapy modification

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy

Flunarizine: May enhance the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy

Herbal Products with Blood Pressure Increasing Effects: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Iloperidone: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Indoramin: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Ipragliflozin: May enhance the adverse/toxic effect of Thiazide and Thiazide-Like Diuretics. Specifically, the risk for intravascular volume depletion may be increased. Risk C: Monitor therapy

Isocarboxazid: May enhance the hypotensive effect of Diuretics. Risk X: Avoid combination

Ivabradine: Thiazide and Thiazide-Like Diuretics may enhance the arrhythmogenic effect of Ivabradine. Risk C: Monitor therapy

Levodopa-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. Risk C: Monitor therapy

Levosulpiride: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Levosulpiride. Risk X: Avoid combination

Licorice: May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Lithium: Thiazide and Thiazide-Like Diuretics may decrease the excretion of Lithium. Management: Reduce the lithium dose if coadministered with thiazide or thiazide-like diuretics. Monitor serum lithium levels during coadministration with thiazide and thiazide-like diuretics. Risk D: Consider therapy modification

Loop Diuretics: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Mecamylamine: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Mecamylamine. Management: Consider avoiding the use of mecamylamine and thiazide diuretics. If combined, mecamylamine prescribing information suggests reducing the mecamylamine dose by 50% in order to avoid excessive hypotension. Risk D: Consider therapy modification

Methenamine: Thiazide and Thiazide-Like Diuretics may diminish the therapeutic effect of Methenamine. Risk C: Monitor therapy

Methoxsalen (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Methoxsalen (Systemic). Risk C: Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Multivitamins/Fluoride (with ADE): May enhance the hypercalcemic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): Thiazide and Thiazide-Like Diuretics may enhance the hypercalcemic effect of Multivitamins/Minerals (with ADEK, Folate, Iron). Risk C: Monitor therapy

Multivitamins/Minerals (with AE, No Iron): Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Multivitamins/Minerals (with AE, No Iron). Specifically, thiazide diuretics may decrease the excretion of calcium, and continued concomitant use can also result in metabolic alkalosis. Risk C: Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Neuromuscular-Blocking Agents (Nondepolarizing): Thiazide and Thiazide-Like Diuretics may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: Thiazide and Thiazide-Like Diuretics may enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (Topical): May diminish the therapeutic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification

Opioid Agonists: May enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics. Risk C: Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Polyethylene Glycol-Electrolyte Solution: Diuretics may enhance the nephrotoxic effect of Polyethylene Glycol-Electrolyte Solution. Risk C: Monitor therapy

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy

Prazosin: Antihypertensive Agents may enhance the hypotensive effect of Prazosin. Risk C: Monitor therapy

Promazine: Thiazide and Thiazide-Like Diuretics may enhance the QTc-prolonging effect of Promazine. Risk X: Avoid combination

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Reboxetine: May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hyponatremic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Sodium Phosphates: Diuretics may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Risk C: Monitor therapy

Terazosin: Antihypertensive Agents may enhance the hypotensive effect of Terazosin. Risk C: Monitor therapy

Topiramate: Thiazide and Thiazide-Like Diuretics may enhance the hypokalemic effect of Topiramate. Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Topiramate. Risk C: Monitor therapy

Toremifene: Thiazide and Thiazide-Like Diuretics may enhance the hypercalcemic effect of Toremifene. Risk C: Monitor therapy

Urapidil: Antihypertensive Agents may enhance the hypotensive effect of Urapidil. Risk C: Monitor therapy

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: Monitor therapy

Vitamin D Analogs: Thiazide and Thiazide-Like Diuretics may enhance the hypercalcemic effect of Vitamin D Analogs. Risk C: Monitor therapy

Pregnancy Considerations

Metolazone crosses the placenta and appears in cord blood.

Hypoglycemia, hypokalemia, hyponatremia, jaundice, and thrombocytopenia are reported as complications to the fetus or newborn following maternal use of thiazide diuretics.

Use to treat edema during normal pregnancies is not appropriate; use may be considered when edema is due to pathologic causes (as in the nonpregnant patient); monitor.

Breastfeeding Considerations

Metolazone is present in breast milk.

Due to the potential for serious adverse reactions in the breastfeeding infant, the manufacturer recommends a decision be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of treatment to the mother.

Dietary Considerations

May require potassium supplementation

Monitoring Parameters

Serum electrolytes, uric acid, fluid balance, renal function, blood pressure (standing, sitting/supine).

Mechanism of Action

Inhibits sodium reabsorption in the distal tubules causing increased excretion of sodium and water, as well as, potassium and hydrogen ions

Pharmacokinetics (Adult Data Unless Noted)

Onset of action: Diuresis: ~60 minutes.

Duration: ≥24 hours.

Distribution: Vd: 113 L (Ernst 2009).

Protein binding: 95% (Ernst 2009).

Bioavailability: 65% (Ernst 2009).

Half-life elimination: 8 to 14 hours (Ernst 2009).

Excretion: Urine (80%) (Ernst 2009).

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: Accumulation may occur in severe renal impairment.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (BD) Bangladesh: Merozolyn | Metolaz;
  • (BE) Belgium: Zaroxolyn;
  • (CH) Switzerland: Metolazon | Zaroxolyn;
  • (CL) Chile: Pavedal;
  • (DE) Germany: Zaroxolyn;
  • (EE) Estonia: Zaroxolyn;
  • (EG) Egypt: Demafight | Efectinix | Metolanix;
  • (FI) Finland: Barolyn | Metolazon abcur;
  • (GB) United Kingdom: Metenix | Xaqua | Xuret | Zaroxolyn;
  • (GR) Greece: Metenix | Zaroxolyn;
  • (HK) Hong Kong: Diulo | Zaroxolyn;
  • (IE) Ireland: Zaroxolyn;
  • (IL) Israel: Zaroxolyn;
  • (IN) India: Diurem | Lazon | Mela | Metadure | Metolaz | Metoz | Metozide | Zalat | Zytanix;
  • (IT) Italy: Zaroxolyn;
  • (JP) Japan: Normelan;
  • (KE) Kenya: Metoz;
  • (KR) Korea, Republic of: Metonic | Zaroxolyn;
  • (LV) Latvia: Zaroxolyn;
  • (MY) Malaysia: Zaroxolyn;
  • (NO) Norway: Metolazon abcur | Zaroxolyn;
  • (NZ) New Zealand: Zaroxolyn;
  • (PH) Philippines: Metoz;
  • (PK) Pakistan: Metxone;
  • (PL) Poland: Zaroxolyn;
  • (PR) Puerto Rico: Mykrox | Zaroxolyn;
  • (PT) Portugal: Diulo | Metolazona;
  • (QA) Qatar: Zaroxolyn;
  • (SE) Sweden: Metolazon abcur | Zaroxolyn;
  • (TH) Thailand: Zaroxolyn;
  • (TW) Taiwan: Diulo | Mycros | Mykrox | Mykyo | Rixia | Zaroxolyn;
  • (UG) Uganda: Metoz;
  • (ZA) South Africa: Zaroxolyn
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