LI Fang, XU Yin-peng, WANG Ya-ling, ZHANG Sa-sa, XIAO Lei, FENG Yan-ru-yu, LI Min
Objective: To systematically analyze adverse event signals and clinical characteristics of drug-related hyperhomocysteinemia (HHcy) based on the Food and Drug Administration Adverse Event Reporting System (FAERS), and to identify potential drug safety risks. Methods: Reports related to HHcy in the FAERS database from the first quarter of 2004 to the second quarter of 2025 were retrieved. Data were cleaned using the deduplication method recommended by the FDA, and signal mining was performed using the reporting odds ratio (ROR), proportional reporting ratio (PRR), and information component (IC) methods. Patient demographic characteristics, drug distribution, outcomes, time to onset (TTO), and event duration were analyzed, and TTO data were fitted using a Weibull distribution model. Results: A total of 249 valid reports were obtained. The sex distribution was balanced (45.0% male and 42.6% female), and patients aged 18-64 years accounted for the largest proportion (55.0%). Hospitalization accounted for 35.7%, and serious outcomes (life-threatening events, disability, and death) accounted for 10.8%. 16 drugs with HHcy risk signals were identified, involving 8 anatomical therapeutic chemical classes. Nitrous oxide (ROR=1679.54), guvisorin (ROR=853.11), and rofecoxib (ROR=47.56) showed the strongest associations. Notably, HHcy was not listed as an adverse reaction in the prescribing information for several drugs. TTO analysis showed a mean TTO of 89.1 days, consistent with an early failure-type risk curve. The mean duration of adverse events was 47.7 days, and 74.4% resolved within 30 days. Conclusion: Multiple drugs were statistically associated with HHcy, and some associations have not yet been documented in the prescribing information, suggesting potential new drug safety signals. Clinicians should pay attention to the risks associated with nitrous oxide, guvisorin, rofecoxib, and related drugs; strengthen early monitoring of plasma homocysteine levels; and provide folic acid or vitamin B12 intervention when necessary. Future prospective studies and mechanistic investigations are needed to further clarify the causal relationship between these drugs and HHcy.
