spironolactone
Brand: Aldactone
Prototype Drug
Drug Class: potassium-sparing diuretic / mineralocorticoid receptor antagonist
Drug Family: diuretic
Subclass: steroidal MRA
Organ Systems: cardiovascularrenal
Mechanism of Action
Competitively antagonizes aldosterone at its nuclear receptor in the collecting duct; promotes sodium/water excretion while retaining potassium; also blocks androgen receptors causing gynecomastia.
mineralocorticoid receptor (aldosterone receptor)
Indications
- heart failure (HFrEF — RALES trial)
- hyperaldosteronism
- hypertension (resistant)
- edema (cirrhosis, nephrotic syndrome)
- hypokalemia prevention
- acne/hirsutism (off-label, antiandrogen)
Contraindications
- hyperkalemia
- severe renal impairment (CrCl <30)
- Addison's disease
- concomitant eplerenone use
Adverse Effects
Common
- hyperkalemia
- gynecomastia
- menstrual irregularities
- breast tenderness
- GI upset
Serious
- life-threatening hyperkalemia
- androgen-related: gynecomastia, impotence
Pharmacokinetics (ADME)
| Absorption | 65-70% oral |
| Distribution | large Vd |
| Metabolism | hepatic to active metabolites (canrenone, 7-alpha-thiomethylspironolactone) |
| Excretion | renal |
| Half-life | ~1.4h (parent), 13-24h (active metabolites) |
| Onset | 2-3 days (peak effect) |
| Peak | 2-3 days |
| Duration | 2-3 days |
| Protein Binding | 91-98% |
| Vd | large |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| ACE inhibitors/ARBs | additive hyperkalemia — life-threatening | major |
| NSAIDs | reduced diuretic effect; worsened hyperkalemia | moderate |
| digoxin | spironolactone increases digoxin half-life | moderate |
Nursing Considerations
- Monitor K+ before initiation and 1 week after each dose increase; hold if K+ >5.0 mEq/L
- RALES trial: 30% relative risk reduction in mortality in HFrEF at low dose (25-50 mg)
- Warn male patients of gynecomastia (androgen receptor blockade) — irreversible in some cases
- Slow onset (2-3 days for full effect): not for acute diuresis
Clinical Pearls
- RALES trial: 25-50 mg reduces HFrEF mortality — use low dose in HF to minimize hyperkalemia risk
- Anti-androgenic effects: acne and hirsutism treatment; gynecomastia in men
- Steroidal MRA: crosses androgen/progesterone receptors — replaced by eplerenone or finerenone in HF where side effects problematic
Safety Profile
Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
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