Spironolactone Gains Foothold in Acne Amid Unresolved Safety Questions

With spironolactone (Aldactone) treatment for acne rising several-fold in recent decades, safety concerns persist for this off-label practice in understudied populations.

A database of U.S. insurance claims showed that among girls and women ages 12-40 years, new prescriptions of spironolactone increased from a standardized monthly mean of 17 per 100,000 covered individuals in 2000 to 88 per 100,000 in 2020.

Of the 38 million generally healthy young women and girls in the claims database, 1.2% initiated spironolactone.

While the rise in spironolactone initiation was observed across age subgroups, women ages 19-25 showed the greatest increase, reported a group led by Sarah Soppe, MPH, of University of North Carolina at Chapel Hill, in JAMA Network Open.

“Most initiators had androgen-related conditions, indications frequently requiring higher doses than those examined in clinical trials for cardiovascular disease,” Soppe and colleagues noted, adding that spironolactone users in the study were mostly diagnosed with acne (55.5%), followed by hirsutism (8.3%), and polycystic ovary syndrome (8.1%) — all off-label uses.

Spironolactone is only FDA approved for treatment of heart failure with reduced ejection fraction, adjunctive blood pressure lowering in hypertension, edema, and primary hyperaldosteronism.

Although the aldosterone antagonist is widely used by many dermatologists as a hormonal approach to acne — backed by various studies supporting efficacy — the application remains off label. The range of effective doses for acne spans 50 to 200 mg, while the heart failure dosage is set at 25 mg once daily.

Spironolactone’s established safety risks include hyperkalemia, hypotension, worsening renal function, electrolyte and metabolic abnormalities, and gynecomastia. Spironolactone is contraindicated in patients with hyperkalemia, Addison’s disease, or concomitant use of eplerenone (Inspra). According to its label, spironolactone recipients should undergo regular monitoring of serum potassium and renal function.

The American Academy of Dermatology does not recommend monitoring potassium in healthy young women being treated for acne, however.

Spironolactone’s safety profile had been primarily generated from trials of older people with heart failure, so its safety in relatively healthy young people with acne remains unresolved. As such, many prescribers of spironolactone for acne are still monitoring patients’ potassium levels despite the move to eliminate this practice.

Soppe’s group conducted the cohort study using the Merative MarketScan Commercial Claims and Encounters Database. New prescriptions, defined as prescription fills after 3 months without fills, were identified with National Drug Codes.

Of the spironolactone initiators captured in the study, 11.5% were ages 12-18 when they got their first spironolactone prescription. The initiators typically did not have hypertension (4.0%) or congestive heart failure (0.8%).

Nonetheless, it was possible that the analysis was affected by some misclassification of indication in the database.

“Despite these limitations, our findings indicate spironolactone among young women and girls is notable and growing, with the great majority having indications requiring higher doses than those examined in trials. Further investment in safety studies may be warranted,” the investigators concluded.

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