Spironolactone Side Effects
Spironolactone can cause several significant side effects including hyperkalemia, worsening renal function, menstrual irregularities, breast tenderness/enlargement in men, and various other metabolic and neurological effects. 1, 2
Common Side Effects
Cardiovascular and Renal Effects
- Hyperkalemia is one of the most common and potentially serious side effects, especially in elderly patients and those with renal impairment 1
- Worsening renal function can occur, particularly in patients with pre-existing kidney disease 1
- Hypotension may develop, especially when combined with other antihypertensive medications 2
Endocrine and Reproductive Effects
- Menstrual irregularities occur in 15-30% of women, with higher risk at doses of 200mg/day 1
- Breast tenderness affects 3-5% of women and up to 10% of men compared to placebo 1
- Gynecomastia (breast enlargement) in men is dose-dependent and may necessitate switching to eplerenone 1
- Decreased libido and erectile dysfunction may occur in men 2
Gastrointestinal Effects
- Nausea (2-4%), vomiting, and abdominal discomfort 1, 2
- Diarrhea, which can exacerbate risk of hyperkalemia 3
- Gastric bleeding, ulceration, and gastritis have been reported 2
Neurological Effects
- Headache (2%), dizziness (3-4%), drowsiness, and fatigue (1-2%) 1, 2
- Mental confusion, lethargy, and ataxia can occur, particularly in patients with hepatic impairment 2
Other Side Effects
- Polyuria (1-2%) due to diuretic effect 1, 4
- Skin reactions including rash, Stevens-Johnson Syndrome, and toxic epidermal necrolysis (rare) 2
- Hematologic effects including leukopenia, agranulocytosis, and thrombocytopenia (rare) 2
Risk Factors and Monitoring
Hyperkalemia Risk
- Highest risk in patients with:
Monitoring Recommendations
- Check renal function and serum electrolytes before starting treatment 1
- Recheck at 1 and 4 weeks after initiation and after any dose increase 1
- Continue monitoring at 1,2,3, and 6 months after achieving maintenance dose, then every 6 months 1
- Routine potassium monitoring may not be necessary in young, healthy women without risk factors 1, 6
Management of Side Effects
Hyperkalemia Management
- If potassium rises to >5.5 mmol/L: halve the dose and monitor closely 1
- If potassium rises to ≥6.0 mmol/L: stop spironolactone immediately and treat hyperkalemia 1
Worsening Renal Function
- If creatinine rises to >220 μmol/L (2.5 mg/dL): halve the dose 1
- If creatinine rises to >310 μmol/L (3.5 mg/dL): discontinue spironolactone 1
Gynecomastia
- For men with breast tenderness or enlargement: consider switching to eplerenone 1
Menstrual Irregularities
- Consider concomitant use of combined oral contraceptives or hormonal IUD to minimize menstrual side effects 1
- Consider cyclical administration (days 4-21 of menstrual cycle) rather than continuous dosing 7
Special Populations
Pregnancy Considerations
- Pregnancy category C; potential risk to male fetus due to anti-androgenic properties 1, 2
- Avoid in pregnancy or counsel women about potential risks 2
Hepatic Impairment
- Can cause sudden alterations in fluid and electrolyte balance 2
- May precipitate impaired neurological function or hepatic encephalopathy 2
- Start with lowest dose and titrate slowly in patients with cirrhosis 2
Long-term Safety
- Long-term studies (up to 8 years) in women with acne have not shown serious illnesses attributable to spironolactone 4
- Despite black box warning about tumorigenicity (based on animal studies), large cohort studies with over 30 million person-years of follow-up have not confirmed increased cancer risk 1
Common Pitfalls
- Failing to monitor electrolytes and renal function in high-risk patients 1, 3
- Not advising patients to stop spironolactone if diarrhea develops, which can precipitate hyperkalemia 3
- Overlooking drug interactions, particularly with potassium-sparing medications 1
- Inadequate counseling about contraception for women of childbearing potential 1, 2