From the Guidelines
For resistant hypertension, spironolactone is typically started at a low dose, as recommended by the 2020 international society of hypertension global hypertension practice guidelines 1. The initial dose is usually 25 mg once daily and can be titrated up to 50 mg daily if needed and tolerated. Before initiating therapy, baseline potassium and renal function should be checked, as spironolactone works as an aldosterone antagonist, blocking sodium reabsorption and promoting potassium retention, making it particularly effective for resistant hypertension which often involves aldosterone excess. Regular monitoring of potassium levels and renal function is essential during treatment, as hyperkalemia is a potential side effect, especially in patients with reduced kidney function or those taking other potassium-sparing medications or supplements. Some studies, such as the 2017 acc/aha/aapa/abc/acpm/ags/apha/ash/aspc/nma/pcna guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1, provide evidence for the use of spironolactone in resistant hypertension, but the most recent and highest quality study, the 2020 international society of hypertension global hypertension practice guidelines 1, recommends adding a low dose of spironolactone as the 4th line agent in those whose serum potassium is <4.5 mmol/L and whose eGFR is >45 ml/min/1.73m2 to achieve BP targets. Patients should be advised about possible side effects including gynecomastia in men and menstrual irregularities in women. Spironolactone should be used cautiously in patients with significant renal impairment (eGFR <45 mL/min) and is contraindicated in those with severe kidney disease, anuria, or hyperkalemia. The PATHWAY-2 study 1 demonstrated the superiority of spironolactone over alpha and beta blockers, providing substantial evidence for its use in resistant hypertension. Key points to consider when using spironolactone for resistant hypertension include:
- Starting with a low dose and titrating up as needed and tolerated
- Monitoring potassium levels and renal function regularly
- Being aware of potential side effects, including gynecomastia and menstrual irregularities
- Using cautiously in patients with significant renal impairment and avoiding use in those with severe kidney disease, anuria, or hyperkalemia.
From the FDA Drug Label
2.3 Treatment of Essential Hypertension The recommended initial daily dose is 25 mg to 100 mg of spironolactone tablets administered in either single or divided doses is recommended. Dosage can be titrated at two-week intervals. Doses greater than 100 mg/day generally do not provide additional reductions in blood pressure. The recommended dose of spironolactone for resistant hypertension is not explicitly stated, but for essential hypertension, the dose is 25 mg to 100 mg daily.
- The dose can be titrated at two-week intervals.
- Doses greater than 100 mg/day are not recommended as they do not provide additional reductions in blood pressure 2.
From the Research
Spironolactone Dose for Resistant Hypertension
- The recommended dose of spironolactone for resistant hypertension is 25 to 50mg daily 3, 4, 5, 6.
- Studies have shown that spironolactone is effective in reducing blood pressure in patients with resistant hypertension, with a mean decrease in systolic blood pressure of 21.7 mmHg and diastolic blood pressure of 8.5 mmHg 4.
- A network meta-analysis found that spironolactone had the highest ranking probability and was considered the most effective treatment to reduce office systolic blood pressure and 24-hour systolic blood pressure in patients with resistant hypertension 7.
- The addition of spironolactone to a multidrug regimen has been shown to provide significant additive blood pressure reduction in subjects with resistant hypertension, with and without primary aldosteronism 6.
- The most common adverse effects of spironolactone in the treatment of resistant hypertension are hyperkalemia, gynecomastia, and renal insufficiency, which warrant monitoring 5.