A comprehensive study on drug-related Raynaud’s phenomenon based on the FDA adverse event reporting system

Raynaud's phenomenon (RP) is often an overlooked adverse event, mainly secondary RP, where drug induction or exacerbation is a controllable and preventable factor. This study aimed to systematically evaluate the association between drugs and RP using the FDA adverse event reporting system (FAERS) database. Utilizing disproportionality analysis, we quantified the risk of RP-associated drugs based on large-scale FAERS case data. Drugs were categorized by ATC classification, and descriptive analyses were conducted to assess population characteristics and reporting patterns. Secondary analyses and Weibull shape parameter testing were performed to verify the reliability of the results and the temporal patterns of adverse event onset. A total of 562 drugs and 4303 cases were linked to RP. Significant signals were identified across 8 ATC categories, predominantly nervous system agents (21 drugs, n = 632), cardiovascular drugs (20 drugs, n = 403), and immunomodulators (14 drugs, n = 185). Pharmacologically, CGRP inhibitors, triptans, non-selective β-blockers, interferons, and antineoplastic/immunomodulatory agents demonstrated high mechanistic relevance to RP. Indications such as rheumatoid arthritis (256 cases, 5.95%), narcolepsy (149 cases, 3.46%), and attention-deficit hyperactivity disorder (117 cases, 2.72%) were frequently associated with RP. Cases were concentrated in individuals aged 25-59, with a female predominance (ratio 3.13:1). This study systematically reports drug-RP associations. Clinicians should consider RP risk when prescribing CGRP inhibitors, triptans, non-selective β-blockers, interferons, or antineoplastic/immunomodulatory agents. Middle-aged and elderly females, particularly those with rheumatoid arthritis, warrant heightened vigilance for drug-induced RP.