Annotation of U.S. Food and Drug Administration (FDA) label information
for clobazam
and CYP2C19
Summary
In patients known to be CYP2C19 poor metabolizers, the drug label states that the initial dose of clobazam (ONFI) should be 5 mg/day. Patients can be titrated initially to 10 - 20 mg/day, and then titrated further to a maximum daily dose of 40 mg, if tolerated. This is due to an increase in levels of N-desmethylclobazam, the active metabolite of clobazam.
Annotation
Clobazam (ONFI) is indicated for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in patients 2 years of age or older. The FDA-approved drug label for clobazam highlights information regarding CYP2C19 poor metabolizers.
Excerpts from the clobazam (ONFI) label:
Concentrations of clobazam's active metabolite, N-desmethylclobazam, are higher in CYP2C19 poor metabolizers than in extensive metabolizers. For this reason, the initial dose in patients known to be CYP2C19 poor metabolizers should be 5 mg/day. These patients should be titrated initially to 10-20 mg/day, and may be titrated further to a maximum daily dose of 40 mg if tolerated...In CYP2C19 poor metabolizers, levels of N-desmethylclobazam were 5-fold higher in plasma and 2- to 3-fold higher in urine than in CYP2C19 extensive metabolizers.
For the complete drug label text with sections containing pharmacogenetic information highlighted, see the clobazam drug label.
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