What are the possible side effects of spironolactone?

Common Side Effects of Spironolactone

Spironolactone has numerous potential side effects, with the most common being hyperkalemia, menstrual irregularities (15-30%), diuresis (29%), breast tenderness (3-5%), dizziness (3-4%), nausea (2-4%), and gynecomastia in men. 1, 2

Major Side Effect Categories

Electrolyte and Metabolic Abnormalities

• Hyperkalemia: The most clinically significant and potentially dangerous side effect 2, 3
  • Requires monitoring, especially in patients with renal impairment, diabetes, liver disorders, elderly patients, or those taking other medications that can increase potassium levels 1
  • The American College of Cardiology recommends checking electrolytes and renal function at 1 week, 1 month, and then every 3 months 1
• Other electrolyte disturbances: Hyponatremia and hypovolemia 2

Endocrine and Reproductive Effects

• In women:

  • Menstrual irregularities (15-30% of patients) 1
  • Amenorrhea or postmenopausal bleeding 2
  • Risk increases significantly with higher doses (relative risk of 4.12 for women taking 200mg/day) 1

• In men:

  • Gynecomastia (breast enlargement) 2, 4
  • Decreased libido 2
  • Erectile dysfunction 2, 4

Gastrointestinal Effects

• Nausea and vomiting (2-4%) 1, 2
• Diarrhea and abdominal cramping 2
• Gastric bleeding, ulceration, and gastritis 2

Neurological Effects

• Dizziness (3-4%) 1, 2
• Headache, drowsiness, lethargy 2
• Mental confusion, ataxia 2
• Risk of impaired neurological function/coma in patients with hepatic impairment 2

Dermatological Effects

• Serious skin reactions (rare but severe):
  • Stevens-Johnson Syndrome (SJS)
  • Toxic epidermal necrolysis (TEN)
  • Drug rash with eosinophilia and systemic symptoms (DRESS) 2
• Alopecia and pruritus 2

Hematologic Effects

• Leukopenia (including agranulocytosis)
• Thrombocytopenia 2

Special Considerations and Monitoring

Pregnancy and Breastfeeding

• Pregnancy category C - should be discontinued if pregnancy is planned or detected
• Potential for feminization of male fetuses due to anti-androgenic activity 1, 2
• Limited data on breastfeeding, but active metabolite (canrenone) is present in breast milk in low amounts 2

Monitoring Requirements

• Potassium monitoring:
  • Not routinely necessary in young, healthy women without risk factors
  • Required in older patients or those with comorbidities 1
  • Serum potassium levels exceeding 5.5 mEq/L are concerning 1
• Renal function monitoring, especially in elderly patients or those with impaired renal function 2

Drug Interactions

• Avoid concurrent use with:
  • Potassium supplements
  • Other potassium-sparing diuretics
  • ACE inhibitors or ARBs
  • NSAIDs
  • Potent CYP3A4 inhibitors 5, 1

Practical Considerations

• Side effects are more common in clinical practice than reported in clinical trials 6
• Withdrawal rates of approximately 25% have been observed in heart failure patients, primarily due to hyperkalemia (17.1%) and renal function deterioration (14.5%) 6
• Patients should avoid high-potassium foods (low-sodium processed foods, coconut water) 1
• Lower doses (50mg twice daily) may have fewer side effects than higher doses (100mg twice daily) 7

By understanding these potential side effects and implementing appropriate monitoring, the risks associated with spironolactone therapy can be minimized while maintaining its therapeutic benefits.