Adverse Event Reporting Patterns Associated with Concomitant Use of 5-HT3 and NK-1 Receptor Antagonists: A Large-Scale Spontaneous-Reporting Analysis

Background/Objectives: Chemotherapy-induced nausea and vomiting (CINV) is common and compromises quality of life and adherence. 5-HT3 receptor antagonists (RAs) and NK-1 RAs are cornerstones, yet adverse event patterns associated with their concomitant use are not well characterized. Methods: We queried the US Food and Drug Administration Adverse Event Reporting System (FAERS) from 2004 Q1–2025 Q1 and deduplicated reports per Food and Drug Administration (FDA) guidance. Five algorithms—the Ω shrinkage measure, additive model, multiplicative model, combination risk ratio, and chi-square model—detected disproportionate reporting signals associated with concomitant use. We also performed time-to-onset (TTO) analysis and logistic regression. Results: We identified 965 concurrent use cases with a mean age of 58 years and a mean weight of 70 kg, with 59.7% (n = 575) of these cases being female. These reports included 366 preferred terms (PTs). Forty-nine PTs were significant across all five algorithms, mainly skin and subcutaneous disorders, hypersensitivity reactions, blood pressure abnormalities, hepatic and renal impairment, and nervous system disorders, with additional signals for abnormal antidiuretic hormone secretion, respiratory disorders, and oropharyngeal disorders. TTO showed most adverse drug events (ADEs) occurred within 20 days of therapy initiation. Logistic regression indicated that older age was associated with higher odds of classification as an important medical event (IME). Conclusions: Beyond prescribing information, we detected previously unrecognized adverse event terms that were disproportionately reported with concomitant use and that merit attention in practice.