Aldactone
Aldactone
Generic Name
Aldactone
Mechanism
Spironolactone is a non‑steroidal potassium‑sparing diuretic that acts primarily by antagonizing aldosterone at the epithelial sodium channel (ENaC) in the distal nephron.
• Aldosterone blockade → ↓ Na⁺ reabsorption, ↑ K⁺ retention, and ↑ water excretion.
• Antiandrogenic activity (competitively blocks androgen receptors) → useful for gynecomastia, hirsutism, and acne.
• Mild antimineralocorticoid effects at higher doses.
Pharmacokinetics
| Property | Details |
| Absorption | Oral bioavailability ~100 % after a 10 mg dose; peak plasma 3–4 h. |
| Distribution | Plasma protein bound ~45 %; large volume of distribution (7 L/kg). |
| Metabolism | Hepatic via CYP3A4/CYP2C9; active metabolites (e.g., 6‑α‑hydroxy‑spironolactone, canrenone) ~3–6 h. |
| Excretion | Renal (~50 %), biliary (~30 %). |
| Half‑life | Parent drug 5–6 h; active metabolites 13–17 h. |
| Special Populations | Reduced renal clearance in CKD; dose adjustment necessary. |
Indications
| Indication | Typical Dose |
| Heart failure (CHF) | 25–50 mg daily → titrate to 200 mg total/day. |
| Hypertension | 25–50 mg once or twice daily. |
| Edema (cardiorenal, hepatic, nephrotic) | 25–100 mg daily. |
| Hyperaldosteronism (primary) | 25–150 mg daily. |
| Acne & hirsutism (women) | 25–50 mg daily. |
| Benign Prostatic Hyperplasia (BPH) | 150 mg daily (off‑label). |
| Prevention of pre‑eclampsia (high‑risk pregnancies) | 50 mg daily (off‑label). |
> *Note:* Pregnancy category D – contraindicated in pregnancy.
Contraindications
- Contraindications:
- Hyperkalemia or renal failure (eGFR <30 mL/min).
- Addison’s disease or concomitant mineralocorticoid deficiency.
- Pregnancy & lactation.
- Warnings:
- Hyperkalemia, especially in CKD, diabetes, or concurrent ACEI/ARB.
- Adrenal suppression with prolonged use at high doses.
- Estimated GFR decline in long‑term therapy.
- Women of childbearing potential – avoid unless definitive contraception is used.
Dosing
- Initial: 25 mg once daily; increase by 25–50 mg increments every 2–4 weeks based on response.
- Maintenance: 200 mg/day (split as 100 mg bid) for CHF; 25–50 mg/d for hypertension or edema.
- Taper: Slowly reduce dose over 1–2 weeks to avoid rebound hypertension.
- Administration: Oral tablets; can be taken with or without food.
- Reformulation: Available lyophilized oral solution for non‑compliant patients.
Adverse Effects
Common
• Gynecomastia, breast tenderness (male).
• Menstrual irregularities, amenorrhea (female).
• Gastrointestinal upset (nausea, diarrhea).
• Headache, dizziness.
Serious
• Hyperkalemia → arrhythmias, syncope.
• Acute renal failure in susceptible patients.
• Hypersensitivity rash (e.g., Stevens–Johnson).
• Cushingoid features (rare).
• Adrenal insufficiency (long‑term high dose).
Monitoring
| Parameter | Frequency | Rationale |
| Serum potassium & creatinine | Baseline, then every 2–4 weeks until stable, then quarterly. | Detect hyperkalemia & renal impairment. |
| Albumin‑creatinine ratio | Baseline, annually. | Evaluate nephropathy progression. |
| Liver function tests (AST, ALT, ALP) | Baseline, annually. | Monitor hepatotoxicity. |
| Blood pressure | At each visit. | Effectiveness & safety. |
| Clinical exam | As needed. | Detect gynecomastia, acne, hirsutism. |
Clinical Pearls
- Gynecomastia is dose‑related: minimal at 25 mg but becomes prominent >50 mg daily; consider bicalutamide or eplerenone if bothersome.
- Use as a “loop kick‑start” in severe CHF: a brief 3‑day course of 200 mg/day can improve fluid status before initiating standard diuretics.
- Spironolactone vs. Eplerenone: Eplerenone has fewer endocrine side effects but is more expensive; both are effective in refractory ACEI/ARB‑treated heart failure.
- Hyperkalemia alert: In patients on ACEI/ARB + spironolactone, check potassium >3 days after dose changes.
- For acne: initiating 25 mg daily can reduce acne severity in 3–6 months; maintain for 6–12 months for lasting benefit.
- Timing of dose: Taking spironolactone in the evening may mitigate nocturia in CHF patients.
- Drug interactions: Strong CYP3A4 inducers (rifampin, carbamazepine) decrease efficacy; strong inhibitors (ketoconazole, clarithromycin) increase serum levels.
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