(C-104) Trends in Spironolactone Incidence by Indication among Young Women and Girls in the United States: Quantifying Patterns of On-label and Off-label Prescribing

Background: Spironolactone is a cardiovascular disease medication widely prescribed off-label for androgen-related conditions such as acne in young women and girls, with these prescriptions frequently exceeding on-label doses. Use of spironolactone was cited as a potential cause of vulvar pain in a case series, yet the trajectory of off-label use across all androgen-related conditions is needed to inform population-level safety studies.

Objectives: To examine trends in spironolactone incidence stratified by indication among insured young women and girls in the United States (US).

Methods: We used the Merative MarketScan Commercial Claims and Encounters Database, a US-based data warehouse with claims from private employers. Patients were assessed for eligibility each month from 2000 to 2020 using the following criteria: female, aged 12 to 40, at least 3 months of continuous insurance coverage, and no prior spironolactone prescription fill during the time enrolled. Prescription fills were identified with National Drug Codes. Potential indications for spironolactone (acne, polycystic ovary syndrome (PCOS), hirsutism, hidradenitis suppurativa, hypertension, and congestive heart failure) were assessed with International Classification of Diseases codes recorded 30 days before to 3 days after the first prescription fill and patients could have more than one indication. Monthly incidence was calculated as the number eligible with a new prescription fill for a specific indication divided by the total number eligible, standardized to the age group and region of the eligible population in January 2010.

Results: Out of 38 million eligible patients, 451,234 (1.2%) initiated spironolactone. Over half (55%) were diagnosed with acne, with this proportion highest (70%) among those aged 12 to 18. Prescriptions for acne rose steadily from 2000 to 2020 beyond use for any other indication, with the standardized average monthly incidence increasing by 52.5 initiators per 100,000. After acne, hirsutism (8.3%) and PCOS (8.1%) were the most common, with a modest absolute increase in monthly incidence of around 5 per 100,000 over the 20 years. On-label indications of hypertension and heart failure were most frequent among those aged 33 to 40 compared to younger groups, though overall they applied to only 4% and 1% of all initiators, respectively. New prescriptions for hypertension, congestive heart failure, and hidradenitis suppurativa were less than 3 per 100,000 eligible per month throughout the study period.

Conclusions: Given the rapid acceleration in spironolactone prescribing for acne relative to on-label indications, including among adolescents, safety studies on off-label use requiring higher doses may be warranted.