Recommended Spironolactone Dosing for Resistant Hypertension
Start spironolactone at 25 mg once daily, with the option to increase to 50 mg daily after 4-8 weeks if blood pressure remains uncontrolled and the medication is well-tolerated. 1, 2
Initial Dose
- Begin with 25 mg once daily as the standard starting dose for resistant hypertension 1, 2
- Some guidelines suggest 12.5-25 mg once daily as acceptable starting range, but 25 mg is the most commonly recommended initial dose 1, 2
- This patient is already on maximum doses of candesartan (an ARB) and atenolol (a beta blocker), making spironolactone the preferred fourth-line agent 3, 2
Pre-Treatment Requirements
Before initiating spironolactone, you must verify:
- Serum potassium is <4.5 mmol/L (ideally <5.0 mEq/L) 1, 2
- eGFR is >45 mL/min/1.73m² (some guidelines use >50 mL/min/1.73m² as the threshold) 1, 2
- The patient is not taking both an ACE inhibitor AND an ARB simultaneously, as triple therapy (ACEI + ARB + aldosterone antagonist) is potentially harmful 1
Monitoring Schedule
Critical safety monitoring is mandatory:
- Check serum potassium and creatinine 5-7 days after initiation 2
- Recheck at 1 week and 4 weeks after starting treatment 1
- Continue monitoring at 1,2,3, and 6 months after achieving maintenance dose 1
- Then monitor every 3-6 months thereafter 2
Dose Titration
- Consider increasing to 50 mg once daily after 4-8 weeks if blood pressure remains uncontrolled and potassium remains <5.5 mmol/L 1
- The target maintenance dose is 25-50 mg once daily based on tolerability and blood pressure response 1
- Recheck potassium and creatinine 1 and 4 weeks after any dose increase 1
Expected Blood Pressure Reduction
The evidence strongly supports spironolactone's efficacy:
- Office blood pressure typically decreases by 15-25/6-12 mmHg within 6 weeks to 6 months 4, 5, 6, 7, 8
- The PATHWAY-2 trial and multiple meta-analyses confirm spironolactone as the most effective fourth-line agent for resistant hypertension 3, 2
Safety Thresholds and Dose Adjustments
If potassium rises to 5.5-6.0 mmol/L:
- Halve the dose (e.g., reduce to 25 mg every other day or 12.5 mg daily) 1
- Monitor blood chemistry closely 1
If potassium rises above 6.0 mmol/L:
- Stop spironolactone immediately 1
- Monitor blood chemistry closely and provide specific treatment for hyperkalemia if needed 1
If creatinine rises to >220 μmol/L (2.5 mg/dL):
- Halve the dose and monitor closely 1
If creatinine rises to >310 μmol/L (3.5 mg/dL):
- Stop spironolactone immediately 1
Special Consideration for This Patient
Given the history of recurrent epistaxis, this patient may have underlying bleeding tendency or be on anticoagulation. While this doesn't contraindicate spironolactone, ensure:
- Blood pressure is adequately controlled to reduce epistaxis risk 2
- Monitor for any worsening of bleeding symptoms, though spironolactone itself doesn't increase bleeding risk 2
- The epistaxis history doesn't suggest secondary hypertension from conditions like hereditary hemorrhagic telangiectasia 3
Common Pitfalls to Avoid
- Do not start spironolactone if potassium is already >5.0 mEq/L - this is a contraindication 1, 2
- Do not use in patients with eGFR <30 mL/min/1.73m² without extreme caution and very close monitoring 1
- Do not combine with both an ACE inhibitor and ARB - use only one renin-angiotensin system blocker 1
- Do not skip the mandatory potassium monitoring - hyperkalemia occurs in approximately 4% of patients and can be life-threatening 2, 6
- Be aware that approximately 5-10% of male patients develop gynecomastia, which may require switching to eplerenone 1, 6