ALDACTAZIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ALDACTAZIDE (ALDACTAZIDE).
Combination of spironolactone (aldosterone antagonist) and hydrochlorothiazide (thiazide diuretic). Spironolactone competitively inhibits aldosterone binding at mineralocorticoid receptors in distal renal tubules, increasing sodium and water excretion while retaining potassium. Hydrochlorothiazide inhibits sodium-chloride symporter in distal convoluted tubule, reducing sodium reabsorption and promoting diuresis.
| Metabolism | Spironolactone is extensively metabolized in the liver primarily via CYP3A4 to active metabolites (canrenone, 7α-thiomethylspironolactone). Hydrochlorothiazide is not extensively metabolized and is largely excreted unchanged in urine. |
| Excretion | Renal: spironolactone ~50% (metabolites), canrenone ~36%; fecal: spironolactone ~22% (metabolites). Hydrochlorothiazide: ~95% unchanged in urine. |
| Half-life | Spironolactone: 78–84 min (parent), canrenone: 10–35 h; hydrochlorothiazide: 6–15 h. Steady-state diuresis in 3–4 days. |
| Protein binding | Spironolactone: >90% (albumin, alpha-1-acid glycoprotein); canrenone: ~75%; hydrochlorothiazide: ~68% (albumin). |
| Volume of Distribution | Spironolactone: 12–24 L/kg (extensive tissue binding, long terminal half-life); hydrochlorothiazide: 3–4 L/kg. |
| Bioavailability | Spironolactone: ~60–90% (oral, food increases); hydrochlorothiazide: 65–75% (oral, variable). |
| Onset of Action | Oral: diuresis within 2–3 h, peak antihypertensive effect 2–3 weeks. |
| Duration of Action | Diuresis persists 2–3 days after discontinuation; antihypertensive effect may persist for 1–2 weeks. |
One tablet (spironolactone 25 mg / hydrochlorothiazide 25 mg) orally once daily initially; may increase to 2 tablets once daily or 1 tablet twice daily as needed.
| Dosage form | TABLET |
| Renal impairment | Contraindicated if GFR < 30 mL/min. For GFR 30-60 mL/min, use with caution and monitor electrolytes; no specific dose adjustment recommended. |
| Liver impairment | Contraindicated in Child-Pugh Class C (severe hepatic impairment). For Child-Pugh A or B, use with caution; start with lowest dose and monitor fluid/electrolyte balance. |
| Pediatric use | Safety and efficacy not established; no standard dosing available. Use only if clearly needed and with extreme caution. |
| Geriatric use | Start with initial lowest dose (e.g., 1 tablet once daily) and titrate slowly due to increased risk of electrolyte imbalance, hypotension, and renal impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ALDACTAZIDE (ALDACTAZIDE).
| Breastfeeding | Spironolactone and its metabolite canrenone are excreted into breast milk; M/P ratio not established. Hydrochlorothiazide is excreted in low amounts (M/P ratio ~0.1). Monitor infant for electrolyte disturbances and diuretic effects. Avoid use in breastfeeding if possible, or use lowest effective dose. |
| Teratogenic Risk | First trimester: Crosses placenta; potential risk of fetal electrolyte disturbances and growth restriction. Second and third trimesters: Risk of fetal hypoaldosteronism, hyponatremia, and adverse metabolic effects. Spironolactone component: Anti-androgenic effects may cause feminization of male fetuses. Hydrochlorothiazide component: Associated with fetal or neonatal jaundice, thrombocytopenia, and electrolyte imbalances. |
■ FDA Black Box Warning
Spironolactone has been shown to be a tumorigen in chronic toxicity studies in rats. Unnecessary use should be avoided.
| Serious Effects |
["Anuria","Acute or chronic renal insufficiency","Hyperkalemia (serum potassium >5.5 mEq/L)","Addison's disease (adrenal insufficiency)","Concurrent use of eplerenone or other potassium-sparing diuretics","Hypersensitivity to spironolactone, hydrochlorothiazide, or sulfonamide-derived drugs"]
| Precautions | ["Hyperkalemia: Risk increased with renal impairment, diabetes, or concomitant potassium supplements/ACE inhibitors/ARBs. Monitor potassium levels.","Hypotension and electrolyte imbalance (hyponatremia, hypomagnesemia, hypochloremia).","Azotemia: May precipitate in patients with renal disease.","Sulfonamide allergy: Hydrochlorothiazide is a sulfonamide derivative; cross-reactivity possible.","Acute myopia/secondary angle-closure glaucoma: Rare with thiazides.","Non-melanoma skin cancer: Increased risk with hydrochlorothiazide; photosensitivity."] |
| Food/Dietary | Avoid high-potassium foods (bananas, oranges, tomatoes, spinach, potatoes, avocados, dried fruits, nuts, and salt substitutes containing potassium chloride). Limit alcohol intake as it may increase dizziness and hypotension. Maintain adequate fluid intake unless otherwise instructed. |
Loading safety data…
| Fetal Monitoring | Monitor maternal blood pressure, serum electrolytes (especially potassium, sodium), renal function, and uric acid. Fetal monitoring: serial ultrasound for growth parameters and amniotic fluid volume; consider umbilical artery Doppler if intrauterine growth restriction suspected. Neonatal monitoring: assess for electrolyte imbalances, jaundice, and thrombocytopenia. |
| Fertility Effects | Spironolactone may cause menstrual irregularities, anovulation, and anti-androgenic effects that could impair fertility in women. In men, spironolactone can reduce spermatogenesis and libido. Hydrochlorothiazide has no known direct effects on fertility. |
| Clinical Pearls | Monitor serum potassium closely, especially in elderly, renal impairment, or concomitant ACEi/ARB use. Avoid use in patients with anuria, acute renal failure, or hyperkalemia. Combination therapy with spironolactone and hydrochlorothiazide can cause hyponatremia and azotemia. Consider dose adjustment in hepatic impairment due to spironolactone metabolism. |
| Patient Advice | Take this medication exactly as prescribed, usually once daily in the morning with food to reduce stomach upset. · Avoid potassium supplements, salt substitutes containing potassium, and high-potassium foods (e.g., bananas, oranges, tomatoes, spinach). · Be aware of signs of hyperkalemia: muscle weakness, fatigue, irregular heartbeat, or numbness/tingling. Report these immediately. · This medication may cause dizziness or lightheadedness; avoid driving if affected. · Do not use if you have severe kidney disease or are unable to urinate. · Inform all healthcare providers you are taking this medication, especially before surgery or any new prescription. · May cause increased sensitivity to sunlight; use sunscreen and protective clothing. · If you miss a dose, take it as soon as remembered unless close to next dose; do not double dose. · Keep out of reach of children and store at room temperature away from moisture. |