Persistent Hypersomnolence Following Clobazam in a Child With Epilepsy and Undiagnosed CYP2C19 Polymorphism

Area of Science:

• Pharmacogenomics
• Clinical Neurology
• Drug Metabolism

Background:

• Clobazam (CLB) is an anticonvulsant medication used to treat seizures.
• Adverse drug reactions, such as hypersomnolence, can occur with CLB treatment.
• Individual variability in drug response necessitates understanding underlying mechanisms.

Observation:

• An 11-year-old female experienced severe hypersomnolence after one week of modest clobazam (CLB) dosage.
• Serum concentrations of CLB and its active metabolite are influenced by cytochrome-dependent metabolism.
• Drug-drug interactions were excluded as the cause of hypersomnolence.

Findings:

• DNA analysis revealed the patient possessed a CYP2C19 *2/*2 genotype, indicating poor metabolizer enzyme activity.
• This genetic polymorphism likely contributed to the accumulation of CLB and subsequent hypersomnolence.
• The findings underscore a pharmacogenomic basis for clobazam-induced hypersomnolence.

Implications:

• While routine genetic testing for all CLB patients is impractical, it should be considered for those experiencing adverse effects.
• Pharmacokinetic models and CLB dose/concentration ratios may help manage treatment in at-risk individuals.
• This case emphasizes the clinical relevance of pharmacogenomics in optimizing drug therapy and preventing adverse events.