Safety profile and signal detection of tadalafil: a real-world analysis based on the Food and Drug adverse event reporting system.

Abstract

Background: Tadalafil, a phosphodiesterase type 5 inhibitor, is widely used for erectile dysfunction and benign prostatic hyperplasia. Although generally well tolerated, concerns have emerged regarding uncommon but potentially clinically relevant adverse event (AE) reports and safety signals, particularly involving ocular, auditory, and cardiovascular systems.

Aim: To characterize the post-marketing safety profile of tadalafil and identify potential safety signals using a real-world pharmacovigilance database.

Methods: All AE reports with tadalafil as the primary suspected drug were retrieved from the FDA Adverse Event Reporting System (FAERS) from Q1 2004 to Q1 2024. After data deduplication and Medical Dictionary for Regulatory Activities (MedDRA, version 26.0) recoding, descriptive analyses were conducted to summarize demographic characteristics and AE distributions. Disproportionality analyses-including reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and empirical Bayes geometric mean-were applied to detect safety signals at system organ class (SOC) and preferred term (PT) levels.

Outcomes: Primary outcomes included frequencies of reported AEs and identification of statistically significant signals across multiple signal-detection algorithms.

Results: Among 85 927 reports, 9304 identified tadalafil as the primary suspect drug. Reported AEs involving tadalafil spanned 23 SOCs. Using 4 signal detection algorithms, 135 PTs were found to show statistically significant disproportionality. In addition, several potential safety signals not listed in the current drug labeling-such as retinal hemorrhage, elevated intraocular pressure, and ejaculatory dysfunction-were detected.

Clinical significance: The identified signals highlight the importance of clinical vigilance, particularly in patients with potential vascular or sensory risk factors, and these findings contribute to raising clinical awareness and will guide future pharmacological epidemiological studies.

Strengths and limitations: This study provides the most comprehensive real-world safety evaluation of tadalafil using FAERS up to 2024, employing 4 complementary algorithms to improve signal robustness. However, intrinsic limitations of spontaneous reporting-such as under-reporting, reporting bias, incomplete information, and inability to infer causality-necessitate cautious interpretation. Confounding by comorbidities and co-medications cannot be fully excluded.

Conclusion: This systematic pharmacovigilance analysis characterizes the post-marketing safety signal spectrum of tadalafil and identifies several potential safety signals that warrant further investigation, and these findings are informative and may serve as a reference for future controlled studies and post-marketing safety surveillance.