Post-Marketing Disproportionality Analysis of Adverse Events Associated with the Novel Drug Suzetrigine Using the FAERS Database

Objective: The ongoing opioid crisis in the United States underscores the need for safer non-opioid analgesics due to the risks of dependence and serious adverse effects. Suzetrigine, a newly approved selective NaV1.8 (Voltage-gated sodium channel 1.8) inhibitor by the U. S. Food and Drug Administration, represents a novel mechanism-based therapy for acute pain. While clinical data are promising, its real-world safety profile remains limited. Therefore, this study utilizes the FDA Adverse Event Reporting System (FAERS) to identify emerging adverse event signals through disproportionality analysis. Methods: A retrospective pharmacovigilance study was conducted using data from the FDA Adverse Event Reporting System to assess adverse events associated with Suzetrigine. Reports from post approval period (January-December 2025) were analyzed, including only cases where the drug was the primary suspect, with duplicates removed. The data were downloaded/extracted in March 2026, at which time the Q4 2025 FAERS file was publicly available on the FDA website. Adverse events with ≥ 30 reports were included for analysis. Disproportionality measures, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and chi-square test, were applied. A signal was considered significant if ROR>1 with a 95% C I excluding 1, PRR ≥ 2, and χ² ≥ 4. All analyses were conducted using Microsoft Excel to identify and rank potential safety signals. Results: A total of 633 adverse event reports associated with Suzetrigine were identified, of which 64 (10.1%) were serious, including three reported fatalities. Disproportionality analysis using the FDA Adverse Event Reporting System identified six significant safety signals meeting predefined criteria. The strongest signals were paresthesia (ROR 13.72) and muscle spasms (ROR 8.68), suggesting a potential mechanism-related effect linked to NaV1.8 inhibition. Moderate signals included pruritus, dizziness, nausea, and rash, with pruritus being the most frequently reported event (n = 71). Overall, neurological and dermatological events predominated, with paresthesia and muscle spasms emerging as the most prominent signals. Conclusion: Post-marketing FAERS data for Suzetrigine reveal strong neurological signals, notably paresthesia and muscle spasms, and frequent pruritus, consistent with its selective NaV1.8 mechanism. Moderate signals for dizziness, nausea, and rash were also observed. These early findings provide the first real-world safety profile for this novel analgesic, although confirmatory studies are needed.