CAROSPIR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CAROSPIR (CAROSPIR).
Aldosterone antagonist; competitively inhibits aldosterone binding to mineralocorticoid receptors in renal distal tubules, increasing sodium and water excretion while retaining potassium. Also has weak antagonistic activity at androgen receptors.
| Metabolism | Hepatic metabolism via deacetylation, dethiolation, and S-methylation; major metabolites: canrenone, 7α-thiomethylspironolactone. CYP450 not significantly involved. |
| Excretion | Approximately 50-60% of the dose is excreted in urine as active metabolites (primarily canrenone) and unchanged drug, with about 10-20% as unchanged spironolactone. Fecal excretion accounts for 20-30%, mainly as metabolites. |
| Half-life | Spironolactone has a short half-life of 1.3-2.0 hours, but its active metabolite canrenone has a prolonged half-life of 13-24 hours (mean 18 hours), leading to a sustained pharmacodynamic effect requiring 2-3 days to reach steady state. |
| Protein binding | Spironolactone is 98-99% bound to plasma proteins (primarily albumin and alpha-1-acid glycoprotein); canrenone is 90-95% bound. |
| Volume of Distribution | 0.05-0.1 L/kg for spironolactone; canrenone 0.2-0.4 L/kg. Indicates extensive tissue distribution and binding to receptors. |
| Bioavailability | Oral bioavailability of spironolactone is approximately 60-70% (first-pass metabolism). Canrenone bioavailability after spironolactone is about 25%. |
| Onset of Action | Oral: 24-48 hours for diuretic effect; 2-4 weeks for maximum antihypertensive effect. No parenteral route available. |
| Duration of Action | Diuretic effect persists 2-3 days after discontinuation due to active metabolites. Antihypertensive effect lasts 24 hours, allowing once-daily dosing. |
Spironolactone 25-100 mg orally once daily. Initial: 25 mg once daily; titrate at 4-week intervals based on response and potassium levels. Maximum: 100 mg/day.
| Dosage form | SUSPENSION |
| Renal impairment | eGFR ≥30 mL/min: No adjustment. eGFR 30-49 mL/min: Use with caution; consider reducing dose (e.g., 25 mg every 48 hours) and monitor potassium. eGFR <30 mL/min: Contraindicated due to risk of hyperkalemia. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Use with caution; consider dose reduction (e.g., initial 12.5 mg once daily) and monitor. Child-Pugh Class C: Contraindicated due to risk of hepatic encephalopathy and electrolyte disturbances. |
| Pediatric use | Neonates and infants: 1-3 mg/kg/day orally divided every 12-24 hours. Children: 1-3 mg/kg/day orally divided every 12-24 hours; maximum 3 mg/kg/day up to 100 mg/day. For heart failure: initial 1 mg/kg/day, titrate up to 3 mg/kg/day if tolerated. |
| Geriatric use | Start at lowest dose (12.5-25 mg once daily) with slow titration. Monitor renal function, electrolytes, and blood pressure closely due to increased risk of hyperkalemia, hyponatremia, and hypotension. Avoid doses >50 mg/day unless necessary. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CAROSPIR (CAROSPIR).
| Breastfeeding | Spironolactone and its active metabolite canrenone are excreted into breast milk. M/P ratio not definitively established; limited data suggest low levels (<0.2 mg/L for canrenone). Risk to infant unlikely at maternal therapeutic doses, but monitor for electrolyte disturbances, diuresis, antiandrogenic effects. Caution in preterm or ill infants. |
| Teratogenic Risk | First trimester: Spironolactone has antiandrogenic effects; animal studies show feminization of male fetuses. Human data limited; risk not quantified but avoid due to potential endocrine disruption. Second/third trimester: No known structural teratogenicity; may cause electrolyte imbalances in neonate if used near term. Risk of fetal hypotension, hyponatremia, hyperkalemia. Use only if clearly needed. |
■ FDA Black Box Warning
Spironolactone has been shown to be a tumorigen in chronic toxicity studies in rats. Use only when other treatments are not available or inadequate.
| Serious Effects |
Anuria, acute renal insufficiency, significant renal impairment (eGFR <30 mL/min), hyperkalemia (serum potassium >5.5 mEq/L), concomitant use with eplerenone, Addison's disease.
| Precautions | Hyperkalemia (risk increases with renal impairment, concurrent potassium supplements, or ACE inhibitors), hypotension, electrolyte imbalances, gynecomastia (dose-dependent), reversible upon discontinuation, caution with hepatic impairment. |
| Food/Dietary | Avoid high-potassium foods (bananas, oranges, spinach, tomatoes, potatoes, avocados, dried fruits, salt substitutes with potassium chloride). Grapefruit juice may alter drug metabolism. Limit sodium intake to reduce fluid retention. |
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| Fetal Monitoring | Monitor maternal blood pressure, serum electrolytes (especially potassium), renal function periodically. Monitor fetal growth and amniotic fluid volume via ultrasound if used in pregnancy. Assess neonatal electrolytes and blood pressure at birth if used near term. |
| Fertility Effects | May cause menstrual irregularities, amenorrhea, or gynecomastia in women due to antiandrogenic effects. Reversible upon discontinuation. No adverse effects on ovarian reserve reported. In men, may cause decreased libido, gynecomastia. Effects on spermatogenesis not well studied but generally reversible. |
| Clinical Pearls | CAROSPIR (spironolactone) is a potassium-sparing diuretic with antiandrogen properties. Monitor serum potassium and renal function closely, especially in elderly or those on ACE inhibitors/ARBs. Use cautiously in diabetes due to risk of hyperkalemia. Effective for heart failure with reduced ejection fraction (NYHA III-IV) and resistant hypertension. Onset of diuresis is 2-3 days, with maximal effect at 48-72 hours. Contraindicated in anuria, acute renal insufficiency, and hyperkalemia. |
| Patient Advice | Take with food to reduce stomach upset. · Avoid potassium supplements and salt substitutes containing potassium. · Monitor for signs of hyperkalemia: muscle weakness, fatigue, irregular heartbeat. · May cause gynecomastia (breast tenderness/enlargement) in men; usually reversible upon discontinuation. · Avoid alcohol and NSAIDs (ibuprofen, naproxen) as they may increase risk of kidney problems or hyperkalemia. · Report symptoms of dehydration: excessive thirst, dry mouth, decreased urination. |