(244) Population Pharmacokinetic and Economic Analysis of On-Demand Sildenafil vs. Daily Tadalafil for Erectile Dysfunction in High-Income Countries

Abstract Introduction Erectile dysfunction (ED) risk is strongly associated with increasing age and the prevalence of non-communicable chronic diseases, such as diabetes, hypertension, dyslipidemia, and cardiovascular disease. The global prevalence of ED in 2019 varied from 37.2% to 48.6% with 16%–45% affected in Europe and 52% affected in the United States of America, impacting men’s overall well-being, interpersonal relationships, and self-esteem. Sildenafil (100 mg and 50 mg), typically administered as on-demand doses, and tadalafil (5 mg), commonly prescribed in daily doses, represent two of the widely utilized medications approved by the European Medicines Agency and US Food and Drug Administration. Mulhall JP et al. (2018) reported that the median frequency of sexual activity ranged from 4 to 10 times/month, with ED medication taken 3–8 times/month. Thus, a daily-dosing regimen might lead to unnecessary pharmacological exposure and increased treatment expenses, especially when considering the out-of-pocket (OoP) expenditure. Objective The objective of the study was to evaluate the pharmacokinetic (PK) and cost-utility outcomes of on-demand sildenafil vs. daily dosing of tadalafil. Methods A population-based PK model for on-demand sildenafil (50 mg and 100 mg) and daily-dose tadalafil (5 mg) was developed to assess interindividual variability in PKs and overall management of ED in high-income countries. Data from published literature and advanced modeling techniques were used to simulate a hypothetical cohort of 10,000 self-paying adults with varying degrees of ED across different age groups, over a 1-year horizon, to assess the impacts on real-world treatment scenarios. Concurrently, a cost-utility analysis was conducted considering drug acquisition costs, healthcare resource utilization, and patient outcomes from a societal perspective. Results After 1 year, sildenafil 100 mg (327 ng/ml) demonstrated a higher maximum plasma concentration compared with tadalafil 5 mg (254 ng/ml). The time to reach peak concentration was shorter for sildenafil (sildenafil 100 mg, 1.17 hours, sildenafil 50 mg 1.04 hours) than for tadalafil (1.99 hours), indicating a more rapid absorption. In contrast, tadalafil exhibited a substantially higher systemic exposure, as reflected by a higher area under the concentration-time curve (AUC), suggesting a longer drug exposure compared to sildenafil (sildenafil 100 mg, sildenafil 50 mg and tadalafil 5 mg was 1957.08 ng·h ml-¹, 950.8 ng·h ml-¹, 3700.17 ng·h ml-¹ respectively). Although annual OoP expenditures were comparable, the quality-adjusted life years (QALY) gained were higher with sildenafil compared with tadalafil, resulted in a favorable incremental cost-effectiveness ratio and cost-effective therapy for ED patients compared with tadalafil. Conclusions The PK model and cost-utility analysis demonstrated that with on-demand sildenafil therapy the QALY gained were higher than tadalafil, highlighting a more favorable PK profile and economic advantage of sildenafil. However, this study was constrained by limited data availability, potentially limiting the extent to which variability in real-world patient behavior and adherence could be analyzed. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Viatris