Safety profile of clobazam in the real world: an analysis of FAERS database and systematic review of case reports

Background Most of the safety data of clobazam came from well-designed clinical trials, while the real-world information is insufficient.Research design and methods We performed a disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database through OpenVigil 2 and conducted a systematic review of case reports regarding adverse drug reactions (ADR) linked to clobazam.Results The analysis of FAERS identified 595 ADR signals. Nervous system disorders cantains the most positive signals among all system organ classes (SOCs). Except for seizure (n = 1696) and somnolence (n = 813), drug interactions (n = 492) were the most frequently reported positive signals. A total of 502 unique citations were initially retrieved and 31 individual cases from 28 publications were included. Skin reactions were the most reactions (n = 9), containing three types of severe reactions not alerted in the instruction. Five cases were caused by interactions between clobazam and other antiepileptic drugs, etravirine-based antiretroviral therapy, omeprazole, or meropenem. One patient died of aspiration pneumonia.Conclusions Clinicians must pay attention to severe skin reactions and monitor the signs of suspicious respiratory infections/inflammations and central sedation. Patients with skin reactions will benefit from the withdrawal of clobazam and the treatment with glucocorticoids. The drug reactions between clobazam with severe or moderate cytochrome P450 (CYP) 3A4 or CYP2C19 inhibitors or other antiepileptic drugs should also be alerted.