Spironolactone for Acne: Timing of Response in Trials

What the SAFA trial measured

The SAFA trial randomized 410 women with facial acne persisting at least 6 months: 201 to spironolactone and 209 to placebo. Spironolactone was given at 50 mg daily to week 6, then 100 mg daily to week 24, and participants continued their usual topical treatments [2].

The quality-of-life (Acne-Specific Quality of Life symptom subscale) difference favoring spironolactone was 1.27 points at 12 weeks and 3.77 points at 24 weeks [2]. Investigator's Global Assessment success at week 12 was 18.5% versus 5.6%. At 24 weeks, 81.9% versus 63.3% rated themselves improved [2]. These are different measures taken at different time points.

Headache was reported by 20.4% on spironolactone and 12.0% on placebo, with no serious adverse reactions [2].

Is there evidence for higher doses?

A systematic review of 10 randomized trials and 21 case series rated all trials at high risk of bias and the evidence quality low or very low. One crossover trial showed that 200 mg daily beat placebo for inflamed lesions. Data from the remaining trials were unhelpful in establishing efficacy of lower doses. Menstrual side effects were more common at 200 mg and less frequent with a combined oral contraceptive [3].

Related factors in the label and studies

Potassium. The Aldactone label says to monitor potassium within 1 week of starting or titrating and regularly afterwards. It says to decrease the dose or stop and treat if hyperkalemia occurs [1]. In 974 healthy young women on spironolactone for acne, 13 of 1802 potassium values were abnormal (0.72%) vs 0.76% in 1165 comparison women. The authors concluded routine monitoring had low usefulness in that group, which excluded heart or kidney disease and renin-angiotensin drugs [4].

Food. Food raised spironolactone bioavailability by about 95%, and the label says it should be taken consistently with respect to food [1].

Other medicines. The label states NSAIDs can reduce the diuretic, natriuretic and antihypertensive effect of spironolactone, and that aspirin may reduce its efficacy [1]. It names no cytochrome P450 enzyme and lists no CYP-based interactions; it describes rapid, extensive metabolism to canrenone and sulfur-retaining metabolites [1].

What longer use looks like

An uncontrolled series of 403 adult women at one academic center (2008 to 2019) found that, among patients with available data at first follow-up, 75.5% had reduction or clearance of facial acne, 84.0% of chest acne and 80.2% of back acne. Mean drug survival was 470.7 days. Menstrual side effects were less common with combined oral contraception (OR 0.23, 95% CI 0.11 to 0.50) [5].