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Hydrochlorothiazide and spironolactone: Pediatric drug information

Hydrochlorothiazide and spironolactone: Pediatric drug information
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For additional information see "Hydrochlorothiazide and spironolactone: Drug information" and "Hydrochlorothiazide and spironolactone: Patient drug information"

For abbreviations, symbols, and age group definitions show table
Brand Names: US
  • Aldactazide [DSC]
Brand Names: Canada
  • TEVA-Spironolactone/HCTZ
Therapeutic Category
  • Antihypertensive Agent, Combination;
  • Diuretic, Combination
Dosing: Neonatal

Dosage guidance:

Dosage form information: Product is a fixed combination of equal mg proportions of components; the following dosing represents mg of each component (hydrochlorothiazide and spironolactone), not the total.

Bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD): Limited data available; efficacy results variable. Note: Although the benefits of diuretic therapy in the management of BPD are variable (eg, optimal duration of therapy, impact on pulmonary end points), diuretics continue to be used in clinical practice (Ref).

Preterm neonates: Oral: 1.5 mg/kg/dose every 12 hours (Ref); used most often in preterm neonates at a PNA >28 days (Ref).

Edema, hypertension

Edema (diuresis), hypertension: Limited data available: Neonates: Oral: 2 to 3 mg/kg/day in divided doses every 12 hours (Ref); if inadequate clinical response (ie, higher dose of hydrochlorothiazide necessary), therapy should be converted to single-entity dosage forms to allow specific titration.

Dosing adjustment in kidney impairment: Neonates: There are no neonatal-specific recommendations; per manufacturer labeling (adult), use of the combination product is contraindicated in patients with anuria, acute kidney impairment, significant impairment of renal excretory function, hypercalcemia, and hyperkalemia.

Hydrochlorothiazide is excreted by the kidney; use with caution; consider dosage adjustments (eg, 50% to 100% of normal dose) for moderate kidney impairment; avoid use in severe kidney impairment (Ref).

Spironolactone is substantially excreted by the kidney; use with caution; monitor serum potassium closely; consider extended dosing intervals (eg, every 24 to 48 hours) for moderate kidney impairment; avoid use in severe kidney impairment (Ref).

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

Dosing: Pediatric

Dosage guidance:

Dosage form information: Product is a fixed combination of equal mg proportions of components; the following dosing represents mg of each component (hydrochlorothiazide and spironolactone), not the total.

Bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD): Limited data available; efficacy results variable. Note: Although the benefits of diuretic therapy in the management of BPD are variable (eg, optimal duration of therapy, impact on pulmonary end points), diuretics continue to be used in clinical practice (Ref).

Infants: Oral: 1.5 mg/kg/dose every 12 hours (Ref).

Edema

Edema (diuresis): Limited data available: Infants, Children, and Adolescents: Oral: Initial: 1 mg/kg/day in divided doses once or twice daily; may titrate up to maximum daily dose: 3 mg/kg/day not to exceed 37.5 mg/day of hydrochlorothiazide in infants and children <2 years and 100 mg/day of hydrochlorothiazide in children ≥2 years and adolescents (Ref). Note: If inadequate clinical response (ie, higher dose of hydrochlorothiazide or spironolactone necessary), therapy should be converted to single-entity dosage forms to allow specific titration.

Hypertension

Hypertension: Limited data available: Infants, Children, and Adolescents: Oral: Initial: 1 mg/kg/day in divided doses once or twice daily; may titrate up to maximum daily dose: 3 mg/kg/day not to exceed 37.5 mg/day of hydrochlorothiazide in infants and children <2 years and 100 mg/day of hydrochlorothiazide in children ≥2 years and adolescents (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: Pediatric

Infants, Children, and Adolescents: There are no pediatric-specific recommendations; per manufacturer labeling (adult), use of combination product is contraindicated in patients with anuria, acute kidney impairment, significant impairment of renal excretory function, hypercalcemia, and hyperkalemia.

Hydrochlorothiazide is excreted by the kidney; use with caution. The following recommendations have been suggested: In pediatric patients with moderate kidney failure, consider dosage adjustments (eg, 50% to 100% of the normal dose); avoid use in severe kidney impairment (Ref).

Spironolactone is substantially excreted by the kidney; use with caution; monitor serum potassium closely. The following recommendations have been suggested: In pediatric patients with mild to moderate kidney failure, consider extended dosing intervals (eg, every 12 to 24 hours); avoid use in severe kidney impairment (Ref).

Dosing: Liver Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling. Based on experience in adult patients, use is contraindicated in acute or severe hepatic failure.

Dosing: Adult

(For additional information see "Hydrochlorothiazide and spironolactone: Drug information")

Edema

Edema: Oral: Hydrochlorothiazide 25 to 200 mg daily and spironolactone 25 to 200 mg daily in single or divided doses.

Hypertension

Hypertension: Oral:

Usual dosage range: Hydrochlorothiazide 50 to 100 mg daily and spironolactone 50 to 100 mg daily.

Alternate recommendations: Target dose range of hydrochlorothiazide is 25 to 100 mg in 1 to 2 divided doses (Ref). Usual dosage range: Hydrochlorothiazide 12.5 to 50 mg daily and spironolactone 25 to 50 mg daily (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

There are no dosage adjustments provided in manufacturer’s labeling. Efficacy of hydrochlorothiazide is limited in patients with CrCl <30 mL/minute; use is contraindicated in patients with anuria, acute renal insufficiency, or significant impairment of renal excretory function. For additional considerations, also see individual agents.

Dosing: Liver Impairment: Adult

There are no dosage adjustments provided in manufacturer’s labeling. Use is contraindicated in acute or severe hepatic failure.

Adverse Reactions

See individual agents.

Contraindications

Hypersensitivity to thiazides or sulfonamide-derived drugs; acute renal insufficiency; anuria; significant impairment of renal excretory function; hypercalcemia; hyperkalemia; Addison’s disease; acute or severe hepatic impairment

Note: Although the FDA-approved product labeling states this medication is contraindicated in patients with hypersensitivity to sulfonamide-containing drugs, the scientific basis of this cross-sensitivity has been challenged.

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to spironolactone or any component of the formulation; concomitant use with eplerenone, heparin, or low molecular weight heparin; pregnancy; breastfeeding.

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

Warnings/Precautions

Concerns related to adverse effects:

• CNS effects: Somnolence and dizziness have been reported with use; advise patients to use caution when driving or operating machinery until response to initial treatment has been determined.

• Electrolyte disturbances: Hyperkalemia may occur with spironolactone; risk factors include renal dysfunction, diabetes mellitus, and concomitant use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salts. Use cautiously, if at all, with these agents and monitor potassium closely. Thiazide diuretics may cause hypokalemia, hypochloremic alkalosis, hypomagnesemia, and hyponatremia.

• Gout: In certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure, gout can be precipitated by hydrochlorothiazide. This risk may be increased with doses ≥25 mg (Gurwitz 1997).

• Gynecomastia: Related to dose and duration of spironolactone therapy; typically is reversible following discontinuation of therapy but may persist (rare).

• Hyperkalemia: Monitor closely for hyperkalemia; increases in serum potassium are dose related and rates of hyperkalemia also increase with declining renal function. The concurrent use of larger doses of ACE inhibitors (eg, ≥ lisinopril 10 mg daily in adults) also increases the risk of hyperkalemia (AAHA/ACC/HFSA [Heidenreich 2022]). Dose reduction or interruption of therapy may be necessary with development of hyperkalemia. Use is contraindicated in patients with hyperkalemia; use caution in conditions known to cause hyperkalemia.

• Hypersensitivity reactions: Hypersensitivity reactions may occur with hydrochlorothiazide. Risk is increased in patients with a history of allergy or bronchial asthma.

• Ocular effects: Hydrochlorothiazide may cause acute transient myopia and acute angle-closure glaucoma, typically occurring within hours to weeks following initiation; discontinue therapy immediately in patients with acute decreases in visual acuity or ocular pain. Additional treatments may be needed if uncontrolled intraocular pressure persists. Risk factors may include a history of sulfonamide or penicillin allergy.

• Photosensitivity: Photosensitization may occur.

• Skin cancer, nonmelanoma: Prolonged use (≥3 years) may increase the risk for squamous cell carcinoma up to 4 times and increase the risk for basal cell carcinoma up to 1.25 times compared to patients not treated with hydrochlorothiazide (Pedersen 2018; Pottegård 2017).

• 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.

• Tumorigenic: Spironolactone shown to be a tumorigen in chronic toxicity animal studies. Avoid unnecessary use.

Disease-related concerns:

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

• Hepatic impairment: Use caution in patients with mild or moderate hepatic impairment; use is contraindicated in acute or severe hepatic impairment. In progressive or severe liver disease, electrolyte and acid/base imbalances might lead to hepatic encephalopathy/coma.

• Hypercalcemia: Thiazide diuretics may decrease renal calcium excretion; use is contraindicated in patients with hypercalcemia.

• Hypercholesterolemia: Use with caution in patients with moderate or high cholesterol concentrations; increased cholesterol and triglyceride levels have been reported with thiazides.

• Parathyroid disease: Thiazide diuretics reduce calcium excretion; pathologic changes in the parathyroid glands with hypercalcemia and hypophosphatemia have been observed with prolonged use; should be discontinued prior to testing for parathyroid function.

• Renal impairment: Cumulative effects of hydrochlorothiazide may develop, including azotemia, in patients with impaired renal function. Avoid hydrochlorothiazide in severe renal disease (ineffective). Spironolactone may cause hyperkalemia in patients with renal impairment; risk of hyperkalemia is increased with declining renal function and with the concurrent use of larger doses of ACE inhibitors (eg, ≥ lisinopril 10 mg daily in adults) (AHA/ACC/HFSA [Heidenreich 2022]). Use with caution in patients with mild renal impairment; contraindicated with anuria, acute renal insufficiency, renal decompensation, or significant impairment of renal excretory function.

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

Special populations:

• Older adult: Avoid use of spironolactone doses >25 mg/day in older adult patients with heart failure or with reduced renal function (eg, CrCl <30 mL/minute or eGFR ≤30 mL/minute/1.73 m2) (AHA/ACC/HFSA [Heidenreich 2022]).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Aldactazide: Hydrochlorothiazide 25 mg and spironolactone 25 mg [DSC]

Aldactazide: Hydrochlorothiazide 50 mg and spironolactone 50 mg [DSC] [scored]

Generic: Hydrochlorothiazide 25 mg and spironolactone 25 mg

Generic Equivalent Available: US

Yes

Pricing: US

Tablets (Spironolactone-HCTZ Oral)

25-25 mg (per each): $1.24 - $1.54

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:

Generic: Hydrochlorothiazide 25 mg and spironolactone 25 mg, Hydrochlorothiazide 50 mg and spironolactone 50 mg

Extemporaneous Preparations

Hydrochlorothiazide 5 mg/mL and Spironolactone 5 mg/mL Oral Suspension

An oral suspension containing hydrochlorothiazide 5 mg and spironolactone 5 mg per mL may be made with tablets. Crush twenty-four 25 mg/25 mg hydrochlorothiazide-spironolactone tablets and reduce to a fine powder. Add ~25 mL of a 1:1 mixture of Ora-Sweet and Ora-Plus or Ora Sweet SF and Ora-Plus or cherry syrup and mix to a uniform paste; mix while adding the vehicle in equal proportions to almost 120 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add sufficient quantity of vehicle to make 120 mL. Label "shake well" and "protect from light." Stable 60 days under refrigeration or at room temperature.

Allen LV Jr, Erickson MA 3rd. Stability of labetalol hydrochloride, metoprolol tartrate, verapamil hydrochloride, and spironolactone with hydrochlorothiazide in extemporaneously compounded oral liquids. Am J Health Syst Pharm. 1996;53(19):2304-2309. doi:10.1093/ajhp/53.19.23048893069
Nahata MC, Pai VB. Pediatric Drug Formulations. 6th ed. Cincinnati, OH: Harvey Whitney Books Co; 2014.
Administration: Pediatric

Oral: May be taken with or without food.

Administration: Adult

Oral: Administer in single or divided doses with or without food.

Hazardous Drugs Handling Considerations

Spironolactone is a hazardous agent (NIOSH 2024 [table 2]).

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).

Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.

Storage/Stability

Store below 25°C (77°F).

Use

Treatment of edematous conditions associated with congestive heart failure, cirrhosis of the liver accompanied by edema and/or ascites, and nephrotic syndrome (FDA approved in adults); treatment of essential hypertension (FDA approved in adults).

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

Aldactazide may be confused with Aldactone

Older Adult: High-Risk Medication:

Beers Criteria: Diuretics (hydrochlorothiazide and spironolactone) 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

Refer to individual components.

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.

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

Abiraterone Acetate: Spironolactone may decrease therapeutic effects of Abiraterone Acetate. Management: Consider alternatives to the combined use of spironolactone and abiraterone. If combined, monitor the clinical response to abiraterone closely, looking specifically for signs of clinical failure and/or disease progression. Risk D: Consider Therapy Modification

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

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

Alcohol (Ethyl): May increase orthostatic hypotensive effects of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor

Alfuzosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Aliskiren: Potassium-Sparing Diuretics may increase hyperkalemic effects of Aliskiren. Risk C: Monitor

Allopurinol: Thiazide and Thiazide-Like Diuretics may increase hypersensitivity effects of Allopurinol. Risk C: Monitor

Alpha-/Beta-Agonists: Spironolactone may decrease vasoconstricting effects of Alpha-/Beta-Agonists. Risk C: Monitor

Amifostine: Blood Pressure Lowering Agents may increase hypotensive effects 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 increase photosensitizing effects of Aminolevulinic Acid (Systemic). Risk X: Avoid

Aminolevulinic Acid (Topical): Photosensitizing Agents may increase photosensitizing effects of Aminolevulinic Acid (Topical). Risk C: Monitor

Ammonium Chloride: Potassium-Sparing Diuretics may increase adverse/toxic effects of Ammonium Chloride. Specifically the risk of systemic acidosis. Risk C: Monitor

Amphetamines: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor

Angiotensin II Receptor Blockers: Potassium-Sparing Diuretics may increase hyperkalemic effects of Angiotensin II Receptor Blockers. Risk C: Monitor

Angiotensin-Converting Enzyme Inhibitors: Potassium-Sparing Diuretics may increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor

Angiotensin-Converting Enzyme Inhibitors: Thiazide and Thiazide-Like Diuretics may increase hypotensive effects of Angiotensin-Converting Enzyme Inhibitors. Thiazide and Thiazide-Like Diuretics may increase nephrotoxic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor

Antidiabetic Agents: Hyperglycemia-Associated Agents may decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor

Antidiabetic Agents: Thiazide and Thiazide-Like Diuretics may decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may increase hypotensive effects of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor

Arginine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Arsenic Trioxide: Thiazide and Thiazide-Like Diuretics may increase hypotensive effects of Arsenic Trioxide. Thiazide and Thiazide-Like Diuretics may increase QTc-prolonging effects 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

Aspirin: May decrease therapeutic effects of Spironolactone. Risk C: Monitor

Barbiturates: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Benperidol: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Beta2-Agonists: May increase hypokalemic effects of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor

Bile Acid Sequestrants: May decrease absorption of Thiazide and Thiazide-Like Diuretics. Management: Separate administration of bile acid sequestrants and oral 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 decrease antihypertensive effects of Antihypertensive Agents. Brigatinib may increase bradycardic effects of Antihypertensive Agents. Risk C: Monitor

Brimonidine (Topical): May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Bromperidol: May decrease hypotensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase hypotensive effects of Bromperidol. Risk X: Avoid

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

Cardiac Glycosides: Spironolactone may increase serum concentration of Cardiac Glycosides. Spironolactone (and/or its metabolites) may also interfere with the assays used to determine Digoxin concentrations, falsely increasing or decreasing Digoxin concentrations. Risk C: Monitor

Ciprofloxacin (Systemic): Spironolactone may increase arrhythmogenic effects of Ciprofloxacin (Systemic). Risk C: Monitor

Corticosteroids (Systemic): May increase hypokalemic effects of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor

Cosyntropin: Coadministration of Spironolactone and Cosyntropin may alter diagnostic results. Management: Patients receiving spironolactone should omit their pre-test dose on the day selected for cosyntropin testing. Risk D: Consider Therapy Modification

CycloPHOSphamide: Thiazide and Thiazide-Like Diuretics may increase adverse/toxic effects of CycloPHOSphamide. Specifically, granulocytopenia may be enhanced. Risk C: Monitor

CycloSPORINE (Systemic): Potassium-Sparing Diuretics may increase hyperkalemic effects of CycloSPORINE (Systemic). Risk X: Avoid

CYP2C8 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors): Spironolactone may increase serum concentration of CYP2C8 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors): Spironolactone may increase serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

Desmopressin: Hyponatremia-Associated Agents may increase hyponatremic effects of Desmopressin. Risk C: Monitor

Dexketoprofen: May increase adverse/toxic effects of Sulfonamides. Risk C: Monitor

Dexmethylphenidate: May decrease therapeutic effects of Antihypertensive Agents. Risk C: Monitor

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

Diazoxide Choline: May increase adverse/toxic effects of Thiazide and Thiazide-Like Diuretics. Specifically, the hyperglycemic and hyperuricemic effects may be increased. Risk C: Monitor

Diazoxide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Diazoxide: Thiazide and Thiazide-Like Diuretics may increase adverse/toxic effects of Diazoxide. Risk C: Monitor

Dichlorphenamide: Thiazide and Thiazide-Like Diuretics may increase hypokalemic effects of Dichlorphenamide. Risk C: Monitor

Digitoxin: Potassium-Sparing Diuretics may increase adverse/toxic effects of Digitoxin. Potassium-Sparing Diuretics may decrease therapeutic effects of Digitoxin. Risk C: Monitor

Dofetilide: HydroCHLOROthiazide may increase QTc-prolonging effects of Dofetilide. HydroCHLOROthiazide may increase serum concentration of Dofetilide. Risk X: Avoid

Drospirenone-Containing Products: May increase hyperkalemic effects of Potassium-Sparing Diuretics. Risk C: Monitor

DULoxetine: Blood Pressure Lowering Agents may increase hypotensive effects of DULoxetine. Risk C: Monitor

EPINEPHrine (Systemic): Diuretics may increase arrhythmogenic effects of EPINEPHrine (Systemic). Diuretics may decrease vasopressor effects of EPINEPHrine (Systemic). Risk C: Monitor

Finerenone: Potassium-Sparing Diuretics may increase hyperkalemic effects of Finerenone. Risk C: Monitor

Fludrocortisone: May decrease therapeutic effects of Mineralocorticoid (Aldosterone) Receptor Antagonists. Mineralocorticoid (Aldosterone) Receptor Antagonists may decrease therapeutic effects of Fludrocortisone. Risk C: Monitor

Flunarizine: May increase therapeutic effects of Antihypertensive Agents. Risk C: Monitor

Heparin: May increase hyperkalemic effects of Potassium-Sparing Diuretics. Risk C: Monitor

Heparins (Low Molecular Weight): May increase hyperkalemic effects of Potassium-Sparing Diuretics. Risk C: Monitor

Herbal Products with Blood Pressure Increasing Effects: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor

Herbal Products with Blood Pressure Lowering Effects: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Hypotension-Associated Agents: Blood Pressure Lowering Agents may increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor

Iloperidone: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Indoramin: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor

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

Isocarboxazid: May increase hypotensive effects of Diuretics. Risk X: Avoid

Ivabradine: Thiazide and Thiazide-Like Diuretics may increase arrhythmogenic effects of Ivabradine. Risk C: Monitor

Levodopa-Foslevodopa: Blood Pressure Lowering Agents may increase hypotensive effects of Levodopa-Foslevodopa. Risk C: Monitor

Levomethadone: May increase adverse/toxic effects of Spironolactone. Levomethadone may decrease therapeutic effects of Spironolactone. Spironolactone may decrease serum concentration of Levomethadone. Risk C: Monitor

Levosulpiride: Thiazide and Thiazide-Like Diuretics may increase adverse/toxic effects of Levosulpiride. Risk X: Avoid

Licorice: May increase hypokalemic effects of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor

Lithium: Thiazide and Thiazide-Like Diuretics may decrease 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 increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor

Lormetazepam: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Mecamylamine: Thiazide and Thiazide-Like Diuretics may increase adverse/toxic effects 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

Metergoline: May decrease antihypertensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase orthostatic hypotensive effects of Metergoline. Risk C: Monitor

Methenamine: Thiazide and Thiazide-Like Diuretics may decrease therapeutic effects of Methenamine. Risk C: Monitor

Methotrexate: HydroCHLOROthiazide may increase nephrotoxic effects of Methotrexate. Risk C: Monitor

Methoxsalen (Systemic): Photosensitizing Agents may increase photosensitizing effects of Methoxsalen (Systemic). Risk C: Monitor

Methylphenidate: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor

Mitotane: Spironolactone may decrease serum concentration of Mitotane. Risk X: Avoid

Molsidomine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Multivitamins/Fluoride (with ADE): May increase hypercalcemic effects of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor

Multivitamins/Minerals (with ADEK, Folate, Iron): Thiazide and Thiazide-Like Diuretics may increase hypercalcemic effects of Multivitamins/Minerals (with ADEK, Folate, Iron). Risk C: Monitor

Multivitamins/Minerals (with AE, No Iron): Thiazide and Thiazide-Like Diuretics may increase 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

Naftopidil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Neuromuscular-Blocking Agents (Nondepolarizing): Thiazide and Thiazide-Like Diuretics may increase neuromuscular-blocking effects of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor

Nicergoline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Nicorandil: May increase hyperkalemic effects of Potassium-Sparing Diuretics. Risk C: Monitor

Nicorandil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Nitroprusside: Blood Pressure Lowering Agents may increase hypotensive effects of Nitroprusside. Risk C: Monitor

Nonsteroidal Anti-Inflammatory Agents (Topical): May decrease therapeutic effects of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor

Nonsteroidal Anti-Inflammatory Agents: May decrease therapeutic effects of Thiazide and Thiazide-Like Diuretics. Thiazide and Thiazide-Like Diuretics may increase nephrotoxic effects of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor

Nonsteroidal Anti-Inflammatory Agents: May increase hyperkalemic effects of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may decrease antihypertensive effects of Potassium-Sparing Diuretics. Risk C: Monitor

Obinutuzumab: May increase hypotensive effects 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 increase adverse/toxic effects of Diuretics. Opioid Agonists may decrease therapeutic effects of Diuretics. Risk C: Monitor

Palopegteriparatide: Thiazide and Thiazide-Like Diuretics may increase therapeutic effects of Palopegteriparatide. Thiazide and Thiazide-Like Diuretics may decrease therapeutic effects of Palopegteriparatide. Risk C: Monitor

Pentoxifylline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Perazine: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor

Pholcodine: Blood Pressure Lowering Agents may increase hypotensive effects of Pholcodine. Risk C: Monitor

Phosphodiesterase 5 Inhibitors: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Piperacillin: May increase hypokalemic effects of Diuretics. Risk C: Monitor

Polyethylene Glycol-Electrolyte Solution: Diuretics may increase nephrotoxic effects of Polyethylene Glycol-Electrolyte Solution. Risk C: Monitor

Porfimer: Photosensitizing Agents may increase photosensitizing effects of Porfimer. Risk X: Avoid

Potassium Salts: May increase hyperkalemic effects of Spironolactone. Risk X: Avoid

Potassium-Sparing Diuretics: May increase hyperkalemic effects of Potassium-Sparing Diuretics. Risk X: Avoid

Prazosin: Antihypertensive Agents may increase hypotensive effects of Prazosin. Risk C: Monitor

Promazine: Thiazide and Thiazide-Like Diuretics may increase QTc-prolonging effects of Promazine. Risk X: Avoid

Prostacyclin Analogues: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Quinagolide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Reboxetine: May increase hypokalemic effects of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor

Selective Serotonin Reuptake Inhibitor: May increase hyponatremic effects of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor

Silodosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

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

Sotagliflozin: HydroCHLOROthiazide may decrease therapeutic effects of Sotagliflozin. Sotagliflozin may decrease serum concentration of HydroCHLOROthiazide. Risk C: Monitor

Tacrolimus (Systemic): Potassium-Sparing Diuretics may increase hyperkalemic effects of Tacrolimus (Systemic). Risk C: Monitor

Terazosin: Antihypertensive Agents may increase hypotensive effects of Terazosin. Risk C: Monitor

Tolvaptan: May increase hyperkalemic effects of Potassium-Sparing Diuretics. Risk C: Monitor

Topiramate: Thiazide and Thiazide-Like Diuretics may increase hypokalemic effects of Topiramate. Thiazide and Thiazide-Like Diuretics may increase serum concentration of Topiramate. Risk C: Monitor

Toremifene: Thiazide and Thiazide-Like Diuretics may increase hypercalcemic effects of Toremifene. Risk C: Monitor

Trimethoprim: May increase hyperkalemic effects of Potassium-Sparing Diuretics. Risk C: Monitor

Urapidil: Antihypertensive Agents may increase hypotensive effects of Urapidil. Risk C: Monitor

Verteporfin: Photosensitizing Agents may increase photosensitizing effects of Verteporfin. Risk C: Monitor

Vitamin D Analogs: Thiazide and Thiazide-Like Diuretics may increase hypercalcemic effects of Vitamin D Analogs. Risk C: Monitor

Food Interactions

Excessive potassium intake may cause hyperkalemia. Management: Avoid food with high potassium content and potassium-containing salt substitutes.

Pregnancy Considerations

Animal reproduction studies have not been conducted with this combination product. See individual monographs.

Monitoring Parameters

Serum electrolytes, BUN, creatinine, blood pressure, heart rate, fluid balance, body weight.

Pharmacokinetics (Adult Data Unless Noted)

See individual agents.

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

  • (AR) Argentina: Aldactone HCT;
  • (AT) Austria: Deverol mit thiazid | Supracid;
  • (BE) Belgium: Docspirochlor | Nefrozide | Uractazide;
  • (BR) Brazil: Aldazida;
  • (CH) Switzerland: Spironothiazid;
  • (DE) Germany: Risicordin | Spironothiazid;
  • (EG) Egypt: Aldactazid | Aldactazide | Spirozide;
  • (ES) Spain: Miscidon;
  • (GB) United Kingdom: Nolaxen;
  • (IT) Italy: Aldactazide;
  • (KR) Korea, Republic of: Aldactazide | Durozide | Spirozide | Spiten;
  • (LU) Luxembourg: Docspirochlor;
  • (PK) Pakistan: Aldactazide;
  • (PR) Puerto Rico: Aldactazide | Spironolactone and hydrochlorothiazide;
  • (PT) Portugal: Ondolen forte;
  • (PY) Paraguay: Terotrom d;
  • (TR) Turkey: Aktazid | Aldactazide;
  • (TW) Taiwan: Slosat | Spilazide;
  • (VE) Venezuela, Bolivarian Republic of: Aldactazida
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