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

ABSTRACT

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.

KEYWORDS:

• Clobazam
• FAERS
• safety
• systematic review
• case reports

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One reviewer has received manuscript or speaker’s fees from Astellas, Eisai, Eli Lilly, Elsevier Japan, Janssen Pharmaceuticals, Kyowa Yakuhin, Lundbeck Japan, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, MSD, Nihon Medi-Physics, Novartis, Otsuka Pharmaceutical, Shionogi, Shire, Sumitomo Pharma, Takeda Pharmaceutical, Tsumura, Viatris, Wiley Japan, and Yoshitomi Yakuhin, and research grants from Eisai, Mochida Pharmaceutical, Meiji Seika Pharma, Shionogi and Sumitomo Pharma. The remaining reviewers have no other relevant financial or other relationships to disclose.

Author contributions

All authors have made direct contribution to the manuscript and approved the submission. P An, X Liu, and B Zhang organized the structure of the article. P An performed the literature search and the analysis of the FAERS database. P An and X Liu performed the literature screening. P An wrote the first draft, then X Liu and B Zhang corrected the draft. All authors approved the final version and contributed to the corrections indicated by the reviewers.

Ethical approval

All data used in the study are second-hand, coming from public databases.

Additional information

Funding

This study was supported by National High Level Hospital Clinical Research Funding (2022-PUMCH-B-059), the CAMS Innovation Fund for Medical Sciences (CIFMS 2021-I2M-1-003), the Fundamental Research Funds for the Central Universities (3332021003, 2021-RW310-001) and the Youth Research Fund of Peking Union Medical College Hospital (201911755)