Objective To identify post-marketing adverse event (AE) signals associated with isotretinoin using real-world data from the U.S. Food and Drug Administration (FDA) AE Reporting System (FAERS), aiming to provide references for clinical safety and further research.

Methods AE reports from the first quarter of 2004 to the third quarter of 2024 were extracted from the FAERS database. Four signal detection methods were employed: the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Medicines and Healthcare products Regulatory Agency (MHRA) comprehensive criteria, Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS).

Results A total of 142,160 AE reports involving isotretinoin were collected, corresponding to 50,519 patients. The four methods identified 469 common AE signals. The top five AEs ranked by descending ROR values were: inflammatory bowel disease (ROR=579.14; 95% CI: 554.95-604.39), gastrointestinal injury (ROR=412.80; 95% CI: 381.18-447.04), fulminant acne (ROR=321.42; 95% CI: 236.39-437.04), ulcerative proctitis (ROR=241.56; 95% CI: 201.70-289.30), and premature epiphyseal closure (ROR=221.22; 95% CI: 172.47-283.74). Among the top 30 AE signals, several conditions, including nasal vestibulitis, anal papilla hypertrophy, neonatal neuroblastoma, diverticular hernia, SAPHO syndrome, somatic delusional disorder, hypersomnia-bulimia syndrome, and hemihypertrophy, were not listed in the drug’s prescribing information. The AE signals involved 25 system organ classes, predominantly psychiatric disorders (75, 15.99%), gastrointestinal disorders (58, 12.37%), and various congenital, familial, and genetic disorders (50, 10.66%). Additionally, strong signals related to pregnancy events were detected, notably unintended pregnancy (ROR=91.39; 95% CI: 86.78-96.26).

Conclusion AE signals associated with isotretinoin involve a broad spectrum of system organ classes. Comprehensive monitoring during clinical use is essential, particularly concerning psychiatric and gastrointestinal disorders. Given the strong signals regarding teratogenicity and pregnancy-related events, strengthening preventive measures for pregnancy risks in patients is recommended.

The authors have declared no competing interest.

The author(s) received no specific funding for this work.

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