Stronger Safety Considerations Needed for Lumateprone Use, Especially for Women

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Lumateprone, while an important factor in the treatment landscape of schizophrenia, has an underestimated safety profile and should be used with special consideration for individuals that may be at risk for severe adverse events (AEs), namely females and individuals with bipolar 2 disorder.¹

“…like all medications, lumateperone is associated with potential AEs. The objective of the present study is to evaluate the safety properties of lumateperone by analyzing the most recent data from the FDA Adverse Event Reporting System (FAERS) database, which collects and analyzes adverse drug events for evaluating drug safety and efficacy.² This analysis aims to provide evidence-based guidance for its rational clinical use by evaluating severe AEs associated with the drug,” lead investigator Yanjing Zhang, Senior Researcher, Department of Clinical Pharmacy, and The Technology Innovation Center for Artificial Intelligence in Clinical Pharmacy of Hebei Province, First Hospital of Hebei Medical University, Shijiazhuang, China, and colleagues wrote.¹

The investigators analyzed AE reports in the FDA Adverse Event Reporting System (FAERS) from the fourth quarter of 2019, according to the FDA approval of lumateperone, to the first quarter of 2024. They evaluated the disproportionality in lumateperone-associated AEs using Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). They also conducted univariate and multivariate logistic regression analyses to identify risk factors for lumateperone-induced severe AEs.

Zhang and colleagues collected a total of 2,644 AE reports that defined lumateperone as the primary suspected drug, including 739 reports of severe AEs and 1905 reports of non-severe AEs. They found 130 preferred terms (PTs) with significant disproportionality based on the 4 measures, 67 (51.53%) of which were not included in the product labeling, affecting 6 systems and organs. They also found that dizziness (n = 81) was the most reported lumateperone-associated severe AE and tardive dyskinesia showed the strongest signal (ROR = 186.24).¹

Using logistic regression analysis, the investigators found that gender (female OR, 1.811 [95% CI, 1.302-2.519]; P = .000) bipolar II disorder (OR, 1.695 [95% CI, 1.320-2.178]; P = .000), and concomitant drug use were independent risk factors for lumateperone-associated severe AEs. On the other hand, concomitant use of CYP3A4 inhibitors or drugs metabolized by CYP3A4 was associated with a decreased risk of severe AEs (OR, 0.524 [95% CI, 0.434-0.633]; P = .000).¹

“These results underscore the need for healthcare providers to exercise heightened caution when prescribing lumateperone and to inform patients about these potential AEs. Logistic regression analysis indicated that the use of concomitant medications is a risk factor for severe AEs associated with lumateperone, while CYP3A4 enzyme inhibitors or substrates did not increase the risk of severe AEs. Despite the inherent limitations of the data, these preliminary findings provide valuable insights and reference points for future, more comprehensive studies and safety assessments,” Zhang and colleagues concluded.¹

REFERENCES
1. Zhang Y, Zhou C, Liu Y, et al. Adverse event signal mining and severe adverse event influencing factor analysis of Lumateperone based on FAERS database. Front Pharmacol. 2024;15:1472648. Published 2024 Sep 23. doi:10.3389/fphar.2024.1472648

2. Jiang, Y., Zhou, L., Shen, Y., Zhou, Q., Ji, Y., and Zhu, H. (2024). Safety assessment of Brexpiprazole: real-world adverse event analysis from the FAERS database. J. Affect Disord. 346, 223–229. doi:10.1016/j.jad.2023.11.025