Skip to Content

The originating document has been archived. We cannot confirm the completeness, accuracy and currency of the content.

Spironolactone / Hydrochlorothiazide

Pronunciation: spir-ON-oh-LAK-tone/HYE-droe-KLOR-oh-THYE-a-zide
Class: Diuretic combination

Trade Names

- Tablets, oral spironolactone 25 mg/hydrochlorothiazide 25 mg
- Tablets, oral spironolactone 50 mg/hydrochlorothiazide 50 mg

Aldactazide 25 (Canada)
Aldactazide 50 (Canada)
Novo-Spirozine (Canada)



Competitively inhibits aldosterone in distal tubules, resulting in increased excretion of sodium and water and decreased excretion of potassium.


Increases chloride, sodium, and water excretion by interfering with transport of sodium ions across renal tubular epithelium.

Indications and Usage

For the management of edema and sodium retention in CHF when the patient is only partially responsive to, or is intolerant of, other therapeutic measures; treatment of diuretic-induced hypokalemia in patients with CHF when other measures are considered inappropriate; treatment of patients with CHF taking digitalis when other therapies are considered inadequate or inappropriate; maintenance therapy in cirrhosis of the liver accompanied by edema and/or ascites; for nephrotic patients when treatment of the underlying disease, restriction of fluid and sodium intake, and the use of other diuretics do not provide an adequate response; for the treatment of essential hypertension; for the treatment of a diuretic-induced hypokalemia in hypertensive patients when other measures are considered inappropriate.


Anuria; acute renal insufficiency; significant impairment of renal excretory function; severe or acute hepatic failure; hyperkalemia; allergy to thiazide diuretics or to other sulfonamide-derived drugs.

Dosage and Administration


PO 1 to 8 tablets daily of spironolactone 25 mg/hydrochlorothiazide 25 mg or 1 to 4 tablets daily of spironolactone 50 mg/hydrochlorothiazide 50 mg.


PO 2 to 4 tablets daily of spironolactone 25 mg/hydrochlorothiazide 25 mg or 1 to 2 tablets daily of spironolactone 50 mg/hydrochlorothiazide 50 mg.

General Advice

  • Administer without regard to meals in single or divided daily doses.
  • Fixed-dose combination drugs are not indicated for initial therapy of edema or hypertension.


Store at 68° to 77°F. Protect from light, moisture, and freezing.

Drug Interactions

No drug interaction studies have been conducted between spironolactone/hydrochlorothiazide and other drugs. The following interactions are based on drug interactions involving each component of the spironolactone/hydrochlorothiazide combination.

Hydrochlorothiazide ACE inhibitors (eg, captopril)

The risk of acute renal dysfunction may be increased. Monitor renal function, especially in high-risk patients (eg, renally impaired). If an interaction is suspected, stop 1 or both agents. (See Spironolactone/ACE inhibitors.)

Alcohol, barbiturates, narcotics

Potentiation of orthostatic hypotension may occur. Monitor BP.

Antineoplastic agents (eg, cyclophosphamide)

Hydrochlorothiazide may prolong antineoplastic-induced myelosuppression. If coadministration cannot be avoided, use with caution.

Cholestyramine, colestipol resins

The pharmacologic effects of hydrochlorothiazide may be decreased because of impaired GI absorption. Separate the administration times by at least 4 h.

Corticosteroids, corticotropin

Electrolyte depletion may be intensified, particularly hypokalemia. Closely monitor serum potassium.


The pharmacologic effects of both drugs may be increased. Hyperglycemia, hyperuricemia, and hypotension may occur. Closely monitor BP, blood and urine glucose, and serum uric acid. If coadministration cannot be avoided, a decreased dosage of 1 or both agents may be required.


Hydrochlorothiazide-induced electrolyte disturbances may predispose to digitalis-induced arrhythmias. Measure plasma concentrations of potassium and magnesium; supplement low levels. Monitor patients for digoxin toxicity. (See Spironolactone/Digoxin.)


Plasma concentrations of dofetilide may be elevated. Prolongation of the QT interval may occur, increasing the risk of torsades de pointes. Coadministration is contraindicated.

Hypoglycemic agents, oral (eg, sulfonylureas)

Hydrochlorothiazide may increase fasting blood glucose. The effect of oral hypoglycemic agents may be decreased. Monitor blood glucose and adjust the hypoglycemic dose as needed.


Hydrochlorothiazide may increase fasting blood glucose and decrease insulin secretion and insulin tissue sensitivity. The effect of insulin may be decreased. Monitor blood glucose and adjust the insulin dose as needed.


Lithium Cl may be decreased, increasing lithium concentrations and the risk of lithium toxicity. Lithium generally should not be given with hydrochlorothiazide.

Loop diuretics (eg, furosemide)

Hydrochlorothiazide and furosemide have synergistic effects that may result in profound diuresis and serious electrolyte abnormalities. Monitor for dehydration and electrolyte abnormalities during combined therapy. Titrate dosage with small or intermittent doses.

Nondepolarizing muscle relaxants (eg, tubocurarine)

Possible increased responsiveness to the muscle relaxant due to diuretic-induced hypokalemia. If hypokalemia cannot be corrected, a lower dosage of nondepolarizing muscle relaxants may be needed.

NSAIDs (eg, ibuprofen, indomethacin), salicylates (eg, aspirin)

The diuretic, natriuretic, and antihypertensive effects of hydrochlorothiazide may be reduced. Monitor BP and the diuretic response. If an interaction is suspected, it may be necessary to discontinue the NSAID or increase the salicylate dosage. Rarely, coadministration may also result in deterioration of renal function. Monitor renal function. (See Spironolactone/Hydrochlorothiazide.)

Pressor amines (eg, norepinephrine)

Response to pressor amines may be decreased. Use with caution.


The risk of phototoxicity may be increased if these agents are coadministered. Avoid coadministration.

Spironolactone ACE inhibitors (eg, captopril), angiotensin II receptor antagonists (eg, losartan)

The risk of hyperkalemia is increased. Closely monitor serum potassium and adjust therapy as needed. (See Hydrochlorothiazide/ACE inhibitors.)


The risk of hyperkalemia is increased. If coadministration cannot be avoided, closely monitor serum potassium.

Anticoagulants (eg, warfarin)

The hypoprothrombinemic effect of anticoagulants may be decreased. Monitor prothrombin activity and adjust the dose accordingly.


Spironolactone may alter the plasma concentrations and pharmacologic effects of digoxin; it may attenuate the inotropic action of digoxin. If an interaction is suspected (eg, worsening symptoms), adjust dosage accordingly. Digoxin levels are not useful in this interaction. (See Hydrochlorothiazide/Digoxin.)


The risk of hyperkalemia and associated serious, sometimes fatal, arrhythmias is increased. Coadministration is contraindicated.


Pharmacologic effects of mitotane may be decreased. If an interaction is suspected, it may be necessary to stop spironolactone.

NSAIDs (eg, ibuprofen, indomethacin)

The antihypertensive effects of spironolactone may be reduced. Monitor BP and the diuretic response. If an interaction is suspected, it may be necessary to discontinue the NSAID. Coadministration of spironolactone and indomethacin may be associated with increased potassium levels. Monitor serum potassium. (See Hydrochlorothiazide/NSAIDs.)

Other potassium-sparing diuretics (eg, amiloride, triamterene)

Hyperkalemia with the potential for cardiac arrhythmias may result. Coadministration is contraindicated.

Potassium preparations (eg, potassium chloride)

May result in severe hyperkalemia, possibly leading to cardiac arrhythmias or arrest. Avoid concomitant use, especially in renally impaired patients. If coadministration cannot be avoided, closely monitor serum potassium.


The risk of hyperkalemia may be increased. Coadministration is not recommended.

Laboratory Test Interactions

May decrease serum protein-bound iodine levels without evidence of alteration of thyroid function. Spironolactone or its metabolites may interfere with digoxin radioimmunoassays.

Adverse Reactions


Hypotension (including orthostatic).


Ataxia; dizziness; drowsiness; headache; lethargy; mental confusion; paresthesia; restlessness; vertigo.


Erythema multiforme; pruritus.


Transient blurred vision; xanthopsia.


Anorexia; constipation; diarrhea and cramping; gastric bleeding; gastric irritation; gastritis; nausea; pancreatitis; sialadenitis; ulceration; vomiting.


Amenorrhea; glycosuria; gynecomastia; inability to achieve and maintain erection; interstitial nephritis; irregular menses; postmenopausal bleeding; renal dysfunction; renal failure.


Agranulocytosis; aplastic anemia; leukopenia; hemolytic anemia; thrombocytopenia.


Jaundice (intrahepatic cholestatic jaundice); mixed cholestatic/hepatocellular toxicity.


Anaphylaxis; fever; necrotizing angiitis (vasculitis, cutaneous vasculitis); maculopapular or erythematous cutaneous eruptions; photosensitivity; purpura; rash; respiratory distress, including pneumonitis and pulmonary edema; urticaria.


Electrolyte imbalance; hyperglycemia; hyperuricemia.


Muscle spasm; weakness.



Spironolactone has been shown to be a tumorigen in chronic toxicity studies in rats. Use only as prescribed. Avoid unnecessary use of this drug.

Fixed-dose combination drugs are not indicated for initial therapy of edema or hypertension. Edema or hypertension requires therapy to be titrated to the individual patient. If the fixed combination represents the dosage so determined, its use may be more convenient in patient management. The treatment of hypertension and edema is not static but must be reevaluated as conditions in each patient warrant.


Observe patients for signs of fluid or electrolyte imbalance (eg, hyponatremia, hypochloremic alkalosis, hypokalemia, hyperkalemia, hypomagnesemia). Periodically determine serum electrolytes at appropriate intervals. Monitor serum potassium levels at frequent intervals, especially during initial dosages, when dosages are changed, or with any illness that may influence renal function. Patients with mild renal impairment and diabetes should receive frequent and continued monitoring of serum electrolytes. Frequently monitor acid/base balance and serum electrolytes in severely ill patients in whom respiratory or metabolic acidosis may occur. Periodic BUN and creatinine determinations should be made, especially for elderly patients and patients with confirmed or suspected hepatic or renal insufficiencies. Monitor blood glucose in diabetic patients when drug is started or dose is changed.


Category C . Spironolactone and thiazides cross the placental barrier and appear in cord blood. There is a risk of fetal or neonatal jaundice, pancreatitis, thrombocytopenia, and possibly other adverse reactions that have occurred in adults.




Safety and efficacy not established.


May occur, especially in patients with a history of allergy or bronchial asthma.

Renal Function

Contraindicated in patients with anuria, acute and chronic renal insufficiency, or significant renal impairment. Cumulative drug effects may be observed. Thiazides may precipitate azotemia in patients with renal disease.

Hepatic Function

Use with caution in patients with impaired hepatic function because minor alternations of fluid and electrolyte balance may precipitate hepatic coma.


Avoid use if possible. May require adjustments of insulin or oral hypoglycemic agents; hyperglycemia may occur and diabetes mellitus may manifest during administration.

Electrolyte imbalance

Hyperkalemia, hypokalemia, hypercalcemia, hypophosphatemia, hypochloremic alkalosis, hypomagnesemia, and/or hyponatremia may occur. Hyperkalemia is more likely to occur in renally impaired, diabetic, elderly, or severely ill patients.


May develop in association with the use of spironolactone. In rare instances, some breast enlargement may persist when spironolactone is discontinued.


May occur, or acute gout may be precipitated.

Lipid effects

Increases in cholesterol and triglyceride levels may occur.

Ocular effects

Hydrochlorothiazide can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma within hours to weeks of drug initiation.


Antihypertensive effect may be enhanced.

Renal effects

Elevated BUN and/or creatinine may occur.

Systemic lupus erythematosus

May be activated or exacerbated.



CNS depression, dehydration, diarrhea, dizziness, drowsiness, electrolyte imbalance (eg, hypokalemia, hyperkalemia, hyponatremia), hypotension, lethargy progressing to coma, maculopapular or erythematous rash, mental confusion, nausea, vomiting.

Patient Information

  • Caution patients that light-headedness can occur, especially during the first days of therapy, and it should be reported to their health care provider.
  • Caution patients that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to excessive fall in BP, resulting in light-headedness or fainting.
  • Instruct diabetic patients to monitor blood glucose more frequently when drug is started or dose is changed, and to inform their health care provider of significant changes in readings.
  • Caution patients to avoid unnecessary exposure to UV light (sunlight, tanning booths), use sunscreen, and wear protective clothing when exposed to UV light to avoid photosensitivity reaction.
  • Instruct patients to stop taking drug and immediately report any of the following symptoms to their health care provider: fainting; swelling of the face, lips, eyelids, or tongue.
  • Caution patients to not take any prescription or OTC medications, potassium salt substitutes, or potassium dietary supplements unless advised by their health care provider.

Copyright © 2009 Wolters Kluwer Health.