Spironolactone (Aldactone)

Indications

Acne Vulgaris (see Acne Vulgaris, Acne Vulgaris)

  • xxx

Congestive Heart Failure (CHF) (see Congestive Heart Failure, Congestive Heart Failure)

Clinical Efficacy

  • Randomized Aldactone Evaluation Study (RALES) (NEJM, 1999) [MEDLINE]
    • Spironolactone (25-50 mg qday) Decreased Mortality Rate in Severe CHF

Diuretic-Induced Hypokalemia (see Hypokalemia, Hypokalemia)

  • xxx

Edema

Hirsutism (see Hirsutism, Hirsutism)

  • xxxx

Hypertension (see Hypertension, Hypertension)

Clinical Efficacy

  • Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) Trial (Hypertension, 2007) [MEDLINE]
    • xxxx

Primary Hyperaldosteronism (see Hyperaldosteronism, Hyperaldosteronism)

  • Clinical Efficacy
    • xxxx

Pharmacology

  • Aldosterone Receptor Antagonist

Administration

  • PO (Congestive Heart Failure): 25-50 mg qday
  • PO (Edema): 25-200 mg qday (divided qday-BID)
  • PO (Hyperaldosteronism Maintenance Treatment): 100-200 mg qday (divided qday-BID)
  • PO (Hypertension): 25-50 mg qday (divided qday-BID)

Dose Adjustment

  • Hepatic
    • Cautious Use
  • Renal
    • CrCl <10 or Anuria: contraindicated

Use in Pregnancy (see Pregnancy, Pregnancy)

  • Avoid Use

Use in Lactation

  • Probable Safe

Drug Interactions

Agents Which are Associated with Drug-Induced Hypoaldosteronism (see Hypoaldosteronism, Hypoaldosteronism)


Adverse Effects

Cardiovascular Adverse Effects

Endocrinologic Adverse Effects

Hematologic/Oncologic Adverse Effects

  • Tumorigenic (in Chronic Use Studies in Rats): FDA black box warning

Renal Adverse Effects

Hyponatremia (see Hyponatremia, Hyponatremia)

  • Epidemiology
    • Spironolactone-Induced Hyponatremia Has Been Reported Mainly in Two Treatment Scenarios
      • Treatment of Congestive Heart Failure
      • Treatment of Resistant Hypertension Which is Unrelated to Hyperaldosteronism
    • Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) Trial (Hypertension, 2007) [MEDLINE]
      • Spironolactone was Associated with Mild Hyponatremia (Pre-Spironolactone Serum Sodium 140 mEq/L -> Post-Spironolactone Serum Sodium 138 mEq/L)L however, the median dose of spironolactone used in the trial was low (only 25 mg qday)
  • Physiologic Mechanisms
    • Impairment of Aldosterone-Mediated Renal Sodium Resorption: with increased natriuresis

Hyperkalemia (see Hyperkalemia, Hyperkalemia)

  • Epidemiology
    • Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) Trial (Hypertension, 2007) [MEDLINE]
      • Spironolactone was Associated with Hyperkalemia (Pre-Spironolactone Serum Potassium 4.13 mEq/L -> Post-Spironolactone Serum Potassium 4.54 mEq/L)
  • Physiology
    • Decreased Renal Potassium Excretion
  • Clinical
    • Caution Should Be Exercised When Using Spironolactone in Conjunction with Other Agents Which Also Impair Renal Potassium Excretion (ACE Inhibitors, etc)

Other Adverse Effects

  • xxx

References

  • Spironolactone-associated hyponatremic coma. Nephron. 1994;67(4):503 [MEDLINE]
  • The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999;341: 709-17 [MEDLINE]
  • Interaction of spironolactone with ACE inhibitors or angiotensin receptor blockers: analysis of 44 cases. BMJ. 2003 Jul 19;327(7407):147-9 [MEDLINE]
  • Effect of spironolactone on blood pressure in subjects with resistant hypertension. Hypertension. 2007 Apr;49(4):839-45. Epub 2007 Feb 19 [MEDLINE]
  • Well tolerated spironolactone-related hyponatremia. J Clin Hypertens (Greenwich). 2008 Apr;10(4):317-21 [MEDLINE]