Medications mostly associated with priapism events: assessment of the 2015–2020 Food and Drug Administration (FDA) pharmacovigilance database entries

Schifano, Nicolò; Capogrosso, Paolo; Boeri, Luca; Fallara, Giuseppe; Çakır, Ömer Onur; Castiglione, Fabio; Alnajjar, Hussain M.; Muneer, Asıf; Dehò, Federico; Schifano, Fabrizio; Montorsi, Francesco; Salonia, Andrea

doi:10.1038/s41443-022-00583-3

Cited by 17 publications

(8 citation statements)

References 34 publications

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“…To the best of our knowledge, this is the first study documenting the misuse and abuse potential of semaglutide in comparison with both remaining GLP-1 analogues (dulaglutide, liraglutide, exenatide, lixisenatide, tirzepatide, and albiglutide) and the phentermine–topiramate combination. The comparison was carried out here with the help of a range of worldwide, valuable [ 34 , 35 ], pharmacovigilance data, namely those derived from the FAERS. AERs related to semaglutide showed steady and progressive increasing levels during the years 2018–2022; conversely, the phentermine–topiramate-related AERs remained roughly stable, and AERs related to the remaining GLP-1 mimetics appeared to have decreased during the same years.…”

Section: Discussionmentioning

confidence: 99%

Is There a Risk for Semaglutide Misuse? Focus on the Food and Drug Administration’s FDA Adverse Events Reporting System (FAERS) Pharmacovigilance Dataset

et al. 2023

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Recent media reports commented about a possible issue of the misuse of antidiabetics related to molecules promoted as a weight-loss treatment in non-obese people. We evaluated here available pharmacovigilance misuse/abuse signals related to semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, in comparison to other GLP-1 receptor agonists (albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, and tirzepatide) and the phentermine–topiramate combination. To acheieve that aim, we analyzed the Food and Drug Administration’s FDA Adverse Events Reporting System (FAERS) dataset, performing a descriptive analysis of adverse event reports (AERs) and calculating related pharmacovigilance measures, including the reporting odds ratio (ROR) and the proportional reporting ratio (PRR). During January 2018–December 2022, a total of 31,542 AERs involving the selected molecules were submitted to FAERS; most involved dulaglutide (n = 11,858; 37.6%) and semaglutide (n = 8249; 26.1%). In comparing semaglutide vs. the remaining molecules, the respective PRR values of the AERs ‘drug abuse’, ‘drug withdrawal syndrome’, ‘prescription drug used without a prescription’, and ‘intentional product use issue’ were 4.05, 4.05, 3.60, and 1.80 (all < 0.01). The same comparisons of semaglutide vs. the phentermine–topiramate combination were not associated with any significant differences. To the best of our knowledge, this is the first study documenting the misuse/abuse potential of semaglutide in comparison with other GLP1 analogues and the phentermine–topiramate combination. The current findings will need to be confirmed by further empirical investigations to fully understand the safety profile of those molecules.

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Section: Discussionmentioning

confidence: 99%

Is There a Risk for Semaglutide Misuse? Focus on the Food and Drug Administration’s FDA Adverse Events Reporting System (FAERS) Pharmacovigilance Dataset

et al. 2023

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“…This suggests that normally, PDE5is do not tend to induce priapism if prescribed in therapeutic dosages and under medical control. Harmoniously, a recent pharmacovigilance analysis of the FDA Adverse Event Reporting System database (2015–2020) showed a significant signal for tadalafil regarding priapism while indicating none for sildenafil 26 . Further, by sub‐analyzing the characteristics of priapism cases related to PDE5i, they showed that the majority of these cases were associated with excessive dosage ingestion, unusual indications, and/or concomitant medication/recreational drug use and concluded that PDE5i consumption could not cause priapism without the presentation of precipitating factors.…”

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Adverse reactions of PDE5 inhibitors: An analysis of the World Health Organization pharmacovigilance database

et al. 2023

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BackgroundDespite their efficacy and general safety, rare but devastating adverse drug reactions have been associated with phosphodiesterase type 5 inhibitors.ObjectivesTo determine the safety profile of oral phosphodiesterase type 5 inhibitors with a particular focus on priapism and malignant melanoma.Materials and methodsIn this case–non‐case study, we queried the individual case safety reports for phosphodiesterase type 5 inhibitors within the World Health Organization global database of individual case safety reports (VigiBase) between 1983 and 2021. We included all individual case safety reports for sildenafil, tadalafil, vardenafil, and avanafil in men. For comparison, we also extracted the safety data from the Food and Drug Administration trials for these drugs. We assessed the safety profile of phosphodiesterase type 5 inhibitors by disproportionality analysis by measuring reporting odds ratio for their most commonly reported adverse drug reactions, once for all phosphodiesterase type 5 inhibitor reports and once for reports of oral phosphodiesterase type 5 inhibitor use in adult men (≥18 years old) with sexual dysfunction.ResultsA total of 94,713 individual case safety reports for phosphodiesterase type 5 inhibitors were extracted. A total of 31,827 individual case safety reports were identified relating to adult men taking oral sildenafil, tadalafil, vardenafil, or avanafil for sexual dysfunction. The most common adverse drug reactions included poor drug efficacy (42.5%), headache (10.4% vs. 8.5%–27.6% [Food and Drug Administration]), abnormal vision (8.4% vs. ≤4.6% [Food and Drug Administration]), flushing (5.2% vs. 5.1%–16.5% [Food and Drug Administration]), and dyspepsia (4.2% vs. 3.4%–11.1% [Food and Drug Administration]). Priapism showed significant signals for sildenafil (reporting odds ratio = 13.81, 95% confidence interval: 11.75–16.24), tadalafil (reporting odds ratio = 14.54, 95% confidence interval: 11.56–18.06), and vardenafil (reporting odds ratio = 14.12, 95% confidence interval: 8.36–22.35). Comparing with other medications in VigiBase, sildenafil (reporting odds ratio = 8.73, 95% confidence interval: 7.63–9.99) and tadalafil (reporting odds ratio = 4.25, 95% confidence interval: 3.19–5.55) had significantly higher reporting odds ratios for malignant melanoma.ConclusionPhosphodiesterase type 5 inhibitors show significant signals correlating with priapism among a large international cohort. Further clinical study is needed to elucidate whether this is from proper or inappropriate use or other confounding conditions, as analysis of pharmacovigilance data does not allow for quantifying the clinical risk. Also, there appears to be a relationship between phosphodiesterase type 5 inhibitor use and malignant melanoma, which warrants additional study to better understand causation.

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“…This finding is consistent with that of Schifano et al, who found disproportionate reporting for tadalafil among drugs that are associated with priapism. 28 However, most reports for PDE5Is were related to concomitant drugs known to cause priapism, which were taken at the same time and/or at an inappropriate intake or excessive dosage, such as trazodone, various antipsychotics, intracavernosal prostaglandin injections, and alcohol. This is consistent with the suggestion by Rezaee and Gross that drugs with a higher risk of priapism are commonly taken concomitantly with PDE5Is.…”

Section: Discussionmentioning

confidence: 99%

Safety profile and signal detection of phosphodiesterase type 5 inhibitors for erectile dysfunction: a Food and Drug Administration Adverse Event Reporting System analysis

Shin,

Rojanasarot,

Hincapie

et al. 2023

Sexual Medicine

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Background Phosphodiesterase type 5 inhibitors (PDE5Is) are generally well tolerated but have been associated with uncommon and significant adverse events (AEs). Aim This study aims to investigate and compare the characteristics of AEs associated with PDE5Is used for erectile dysfunction and identify any safety signals in a postmarketing surveillance database between 2010 and 2021. Methods A descriptive analysis was conducted for all AEs reported to the Food and Drug Administration Adverse Event Reporting System for 4 PDE5Is—avanafil, sildenafil, tadalafil, and vardenafil—indicated for erectile dysfunction between January 2010 and December 2021. The frequency of the most reported AEs and outcomes were identified. A disproportionality analysis based on proportional reporting ratio (PRR) and reporting odds ratio (ROR) was conducted for the most common and clinically important AEs to identify signals to gain insights into potential differences in safety profiles. Outcomes The outcome measures of the study are frequency of reported AEs and outcomes following AE. Results A total of 29 236 AEs were reported for PDE5Is during the study period. The most reported AE was “drug ineffective” with 7115 reports (24.3%). Eight safety signals were detected across the 4 drugs. Key signals were sexual disorders (PRR, 3.13 [95% CI, 2.69-3.65]; ROR, 3.24 [95% CI, 2.77-3.79]) and death (PRR, 3.17 [2.5-4.01]; ROR, 3.211 [2.52-4.06]) for sildenafil, priapism (PRR, 3.63 [2.11-6.24]; ROR, 3.64 [2.12-6.26]) for tadalafil, and drug administration error (PRR, 2.54 [1.84-3.52]; ROR, 2.6 [1.86-3.63]) for vardenafil. The most reported outcomes were other serious events with 6685 events (67.2%) and hospitalization with 1939 events (19.5%). Clinical Implications The commonly reported AEs and detected signals may guide clinicians in treatment decision making for men with erectile dysfunction. Strengths and Limitations This is the first comprehensive report and disproportionality analysis on all types of AEs associated with PDE5Is used for erectile dysfunction in the United States. The findings should be interpreted cautiously due to limitations in the Adverse Event Reporting System, which includes self-reports, duplicate and incomplete reports, and biases in reporting and selection. Therefore, establishing a causal relationship between the reported AEs and the use of PDE5Is is uncertain, and the data may be confounded by other medications and indications. Conclusion PDE5Is demonstrate significantly increased risks of reporting certain clinically important AEs. While these events are not common, it is imperative to continually monitor PDE5I use at the levels of primary care to national surveillance to ensure safe utilization.

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Medications mostly associated with priapism events: assessment of the 2015–2020 Food and Drug Administration (FDA) pharmacovigilance database entries

Cited by 17 publications

References 34 publications

Is There a Risk for Semaglutide Misuse? Focus on the Food and Drug Administration’s FDA Adverse Events Reporting System (FAERS) Pharmacovigilance Dataset

Is There a Risk for Semaglutide Misuse? Focus on the Food and Drug Administration’s FDA Adverse Events Reporting System (FAERS) Pharmacovigilance Dataset

Adverse reactions of PDE5 inhibitors: An analysis of the World Health Organization pharmacovigilance database

Safety profile and signal detection of phosphodiesterase type 5 inhibitors for erectile dysfunction: a Food and Drug Administration Adverse Event Reporting System analysis

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