Is pitolisant safe for clinical use? A retrospective pharmacovigilance study focus on the post‐marketing safety

Abstract

Pitolisant, a novel histamine H3‐receptor antagonist, holds significant promise for treating narcolepsy. However, a petition, which highlighted that pitolisant was associated with deaths during clinical trials, has propelled it into the spotlight of widespread societal attention on April 3, 2023. Till now, the clinical safety of pitolisant remains a heatedly debated topic. This study aimed to offer a comprehensive assessment of the safety profile of pitolisant in real‐world clinical settings. Adverse event reports where pitolisant was the primary suspect drug were extracted from the FDA Adverse Event Reporting System database. The clinical characteristics and concomitant drugs of the pitolisant‐associated adverse events were analyzed. The potential adverse event signals of pitolisant were explored using four disproportionality analysis methods. Furthermore, the difference in pitolisant‐associated adverse event signals was investigated concerning sex, age, weight, and dose. A total of 526 reports and 1695 adverse events with pitolisant as the primary suspected drug were identified. The most significant adverse event signals were generally mild and of short duration. The concomitant drugs of pitolisant were highly intricate, mainly included drugs for treating narcolepsy as well as antidepressants. Seven new significant adverse event signals emerged. The safety profile of pitolisant exhibited no significant differences across age and dose groups, although slight variations were observed in relation to sex and weight. The findings from reports of death and life‐threatening outcomes underscore the importance of enhanced monitoring for cardiac and respiratory adverse reactions when utilizing pitolisant. This study provided a broader understanding of the safety profile of pitolisant.

A real-world pharmacovigilance study of FDA adverse event reporting system events for Capmatinib

“…The data for this retrospective drug vigilance study were extracted from the FAERS database, covering the third quarter of 2020 to the fourth quarter of 2022. Five types of datasets were used, including patient demographic and administrative information (DEMO), drug information (DRUG), the start and end dates of treatment with the reported drug (THER), adverse event encodings (REAC), and indication/diagnosis for use (INDI) 32 – 34 . Cases of capmatinib as the PS drug were identified using the generic name (prod_ai column as CAPMATINIB).…”

“…Descriptive analysis methods were used to thoroughly characterize the clinical features of capmatinib-related adverse events after removing missing data, including reporting year and quarter, occurred country, reporter type, sex, age, weight, dose, frequency, and onset time 32 – 34 . Spearman correlation coefficient was used to explore correlations between typical clinical features, including sex, age, weight, dose, frequency, and onset time.…”

“…As dose and frequency are critical factors for the rational use of capmatinib, the ANOVA test and sunburst plot were applied to analyzing the correlation of dose and frequency, as well as their distributions across countries. The concomitant drugs of the capmatinib-associated adverse event reports were then analyzed 32 . In the same report, if capmatinib was identified as the PS drug, the other drugs labeled as ‘secondary suspect’, ‘concomitant’, or ‘interacting’ were considered concomitant drugs 32 .…”

“…The concomitant drugs of the capmatinib-associated adverse event reports were then analyzed 32 . In the same report, if capmatinib was identified as the PS drug, the other drugs labeled as ‘secondary suspect’, ‘concomitant’, or ‘interacting’ were considered concomitant drugs 32 .…”

“…The adverse events were coded using PTs, which were mapped to the corresponding primary SOC level based on the standardized Medical Dictionary for Regulatory Activities (MedDRA) version 25.1. The adverse event signals of capmatinib were investigated by profiling the frequency and intensity at the SOC and PT levels 32 – 34 . Four disproportionality analysis methods were used, including ROR 35 , 36 , PRR 29 , 33 , BCPNN 23 , 29 , 33 , and MGPS 23 , 29 , 33 .…”