This section contains excerpted
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information on gene-based dosing recommendations. Neither this section nor other parts of this review contain the complete recommendations from the sources.
2019 Statement from the US Food and Drug Administration (FDA)
2.5 Dosage Adjustments in CYP2C19 Poor Metabolizers
In CYP2C19 poor metabolizers, levels of N-desmethylclobazam, clobazam's active metabolite, will be increased. Therefore, in patients known to be CYP2C19 poor metabolizers, the starting dose should be 5 mg/day and dose titration should proceed slowly according to weight, but to half the dose presented in Table 1, as tolerated. If necessary and based upon clinical response, an additional titration to the maximum dose (20 mg/day or 40 mg/day, depending on the weight group) may be started on day 21.
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8.6 CYP2C19 Poor Metabolizers
Concentrations of clobazam's active metabolite, N-desmethylclobazam, are higher in CYP2C19 poor metabolizers than in normal metabolizers. For this reason, dosage modification is recommended
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12.5 Pharmacogenomics
The polymorphic CYP2C19 is the main enzyme that metabolizes the pharmacologically active N- desmethylclobazam. Compared with CYP2C19 normal metabolizers, N-desmethylclobazam AUC and Cmax are approximately 3–5 times higher in poor metabolizers (e.g., subjects with *2/*2 genotype) and 2 times higher in intermediate metabolizers (e.g., subjects with *1/*2 genotype). The prevalence of CYP2C19 poor metabolism differs depending on racial/ethnic background. Dosage in patients who are known CYP2C19 poor metabolizers may need to be adjusted.
The systemic exposure of clobazam is similar for both CYP2C19 poor and normal metabolizers.
Please review the complete therapeutic recommendations that are located here:
(1).
Table 1. The FDA (2019) Drug Label for Clobazam: Recommended Total Daily Dosing by Weight Group | Less than or equal to 30 kg body weight | Greater than 30 kg body weight | CYP2C19 poor metabolizers |
|---|
| Starting dose | 5 mg | 10 mg | In patients known to be CYP2C19 poor metabolizers, the starting dose should be 5 mg/day and dose titration should proceed slowly according to weight, but to half the recommended total daily doses presented in this table, as tolerated. If necessary, and based upon clinical response, an additional titration to the maximum dose (20 mg/day or 40 mg/day, depending on the weight group) may be started on day 21. |
| Starting day 7 | 10 mg | 20 mg |
| Starting day 14 | 20 mg | 40 mg |
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The FDA labels specific drug formulations. We have substituted the generic names for any drug labels in this excerpt. The FDA may not have labeled all formulations containing the generic drug. Certain terms, genes and genetic variants may be corrected in accordance to nomenclature standards, where necessary. We have given the full name of abbreviations, shown in square brackets, where necessary.