Drug-induced liver injury associated with atypical generation antipsychotics from the FDA Adverse Event Reporting System (FAERS).

Recent studies have shown that liver enzyme abnormalities were not only seen with typical antipsychotics (APs) but also with atypical antipsychotics (AAPs). During the last 20 years, the hepatotoxicity of various antipsychotics received much attention. However, systematic evaluations of hepatotoxicity associated with APs are limited. All drug related hepatic disorders cases were retrieved from the FDA Adverse Event Reporting System (FAERS) database using standardized MedDRA queries (SMQ) from the first quarter of 2017 to the first quarter of 2022. Patient characteristics and prognosis were assessed. In this study, a case/non-case approach was used to calculate reporting odds ratio (RORs) and 95% confidence intervals (CIs). We calculated the drug-induced liver injury (DILI) RORs for each AAPs. A total of 408 DILI cases were attributed to AAPs during the study period. 18.6% of these were designated as serious adverse event (SAE), which include death (19.74%), hospitalization (68.42%), disability (2.63%), and life-threatening (9.21%) outcomes. The RORs values in descending order were: quetiapine (ROR = 0.782), clozapine (ROR = 0.665), aripiprazole (ROR = 0.507), amisulpride (ROR = 0.308), paliperidone (ROR = 0.212), risperidone (ROR = 0.198), ziprasidone (0.131). The result found in our study was that all AAPs didn't have a significant correlation with increased hepatotoxicity. Future analysis of the FAERS database in conjunction with other data sources will be essential for continuous monitoring of DILI.

He S ，Chen B ，Li C 《BMC Pharmacology & Toxicology》

Comparative Safety Signal Assessment of Hospitalization Associated With the Use of Atypical Antipsychotics.

Persons with symptoms of psychosis receiving treatment with atypical antipsychotics (AAPs) can experience serious adverse events (AEs) requiring admission to the hospital. The comparative likelihood of AE-related hospitalization following the use of all AAPs has not been fully characterized. Therefore, we evaluated the safety signals of hospitalizations associated with the use of AAPs. We conducted a cross-sectional analysis using the FDA Adverse Event Reporting System (FAERS) database (from January 1, 2004, to December 31, 2021) to examine disproportionality in reporting hospitalizations suspected to be associated with 12 AAPs (aripiprazole, asenapine, brexpiprazole, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, and pimavanserin, quetiapine, risperidone, and ziprasidone). Hospitalization in the FAERs database is an outcome that is recorded as a result of an AE occurring at any drug dose. We estimated reporting odds ratios (RORs) by comparing the odds of hospitalization occurring with a particular AAP to the odds of its occurrence with other drugs. In addition, we considered the presence of a significant safety signal when the lower limit of the 95% confidence interval (CI) of the ROR is >1. A total of 204,287 cases of hospitalizations were reported to the FDA for individuals treated with AAPs. There were significant safety signals of hospitalization associated with using clozapine (ROR, 2.88; 95% CI, 2.84-2.92), olanzapine (ROR, 2.61; 95% CI, 2.57-2.64), quetiapine (ROR, 1.87; 95% CI, 1.85-1.89), risperidone (ROR, 1.41; 95% CI, 1.39-1.43), aripiprazole (ROR, 1.34; 95% CI, 1.32-1.35), and ziprasidone (ROR, 1.14; 95% CI, 1.10-1.18). However, no hospitalization-related safety signals were observed with the use of paliperidone, pimavanserin, iloperidone, asenapine, lurasidone, and brexpiprazole. The ROR estimates were numerically higher among older adults than younger adults. This cross-sectional assessment of data from FAERs (2004-2021) suggested that users of clozapine, olanzapine, quetiapine, risperidone, aripiprazole, and ziprasidone were more likely to report being hospitalized than users of other AAPs. Given that the FAERs database only contains spontaneous reports of AEs experienced by persons exposed to a drug but without information on exposed persons who did not have an event, a cohort study comparing hospitalizations among new users of individual AAPs against each other is needed to delineate these safety signals further.

Yunusa I ，Teng C ，Karaye IM ，Crounse E ，Alsahali S ，Maleki N ... -  《Frontiers in Psychiatry》

Drug-induced liver injury associated with antiseizure medications from the FDA Adverse Event Reporting System (FAERS).

Treatment with antiseizure medications (ASMs) confers a risk of drug-induced liver injury (DILI), especially for older ASMs. We sought to quantify recent reports of DILI attributed to both older and newer generation ASMs and survey newly marketed ASMs for hepatotoxicity in a large post-marketing database. We queried over 2.6 million adverse event reports made to the FDA Adverse Event Reporting System (FAERS) database between July 1, 2018 and March 31, 2020 for DILI due to ASMs commonly used in clinical practice. Patient characteristics and outcomes were assessed. We calculated the reporting odds ratio (ROR) of DILI for each individual ASM versus all non-ASM reports. A total of 2175 DILI cases were attributed to an ASM during the study period. 97.2% of these were designated as serious reactions, which include death, hospitalization, disability, and other life-threatening outcomes. A number of older and newer generation ASMs were associated with DILI, specifically: carbamazepine (ROR 2.92), phenobarbital (ROR 2.91), oxcarbazepine (ROR 2.58), phenytoin (ROR 2.40), valproate (ROR 2.22), lamotrigine (ROR 2.06), clobazam (ROR 1.67), levetiracetam (ROR 1.56), and diazepam (ROR 1.53). However, increased odds of DILI were not seen with zonisamide, perampanel, stiripentol, lacosamide, clonazepam, pregabalin, felbamate, eslicarbazepine, cannabidiol, topiramate, gabapentin, ethosuximide, brivaracetam, or primidone. Vigabatrin, tiagabine, and rufinamide all had zero reports of DILI. The majority of newer generation ASMs were not significantly associated with DILI. Future studies utilizing FAERS in conjunction with other data sources will be critical for the ongoing surveillance of DILI, particularly as newly marketed ASMs continue to enter into widespread clinical use.

Kamitaki BK ，Minacapelli CD ，Zhang P ，Wachuku C ，Gupta K ，Catalano C ，Rustgi V ... -  《-》

Drug-induced liver injury associated with elexacaftor/tezacaftor/ivacaftor: A pharmacovigilance analysis of the FDA adverse event reporting system (FAERS).

The efficacy and safety of elexacaftor/tezacaftor/ivacaftor (ETI) have been established in prospective clinical trials. Liver function test elevations were observed in a greater proportion of patients receiving ETI compared with placebo; however, the relatively small number of patients and short duration of study preclude detection of rare but clinically significant associations with drug-induced liver injury (DILI). To address this gap, we assessed the real-world risk of DILI associated with ETI through data mining of the FDA adverse event reporting system (FAERS). Disproportionality analyses were conducted on FAERS data from the fourth quarter of 2019 through the third quarter of 2022. Comparative patient demographics, onset time and outcomes for ETI-DILI were also obtained. 452 reports of DILI associated with ETI were found, representing 2.1 % of all adverse event reports for ETI. All disproportionality measures were significant for ETI-DILI at p < 0.05; the reporting odds ratio (ROR) (2.82) was comparable to that of drugs classified by FDA as "Most-DILI concern". The most notable demographic finding was a male majority (5:4 male to female ratio) for ETI-DILI compared to a female majority (4:5 male to female ratio) for non ETI-DILI. Median ETI-DILI onset time was 50.5 days, and hospitalization was the second most common complication. Using FAERS data, ETI was found to be disproportionately associated with DILI. Future research is needed to investigate the hepatotoxic mechanisms and assess potential mitigation strategies for ETI-induced hepatotoxicity.

Shi A ，Nguyen H ，Kuo CB ，Beringer PM ... -  《-》

A pharmacovigilance study on drug-induced liver injury associated with antibody-drug conjugates (ADCs) based on the food and drug administration adverse event reporting system.

Sun C ，Yang X ，Tang L ，Chen J ... -  《-》