Click below to learn more about the use of CYP2C19 genetics in the prescribing of clobazam.
Clobazam is metabolized by the liver to an inactive metabolite. Clobazam is metabolized to norclobazam, an active metabolite, primarily by the cytochrome p450 liver enzyme CYP3A4. Norclobazam is then primarily metabolized by CYP2C19 to an inactive metabolite. Of note, norclobazam (active metabolite) has a longer half-life (71-82 hours) than clobazam (36-42 hours).
Across populations, CYP2C19 protein alleles can have different genetic variants that impact its ability to metabolize clobazam. The different alleles can produce five different metabolism phenotypes: ultrarapid, rapid, normal, intermediate and poor metabolism. The poor metabolism phenotype has been shown to decrease norclobazam metabolism, resulting in increased norclobazam levels and a higher risk of side effects.
Patients who are CYP2C19 poor metabolizers have reduced metabolism of norclobazam leading to higher drug levels. This may increase the risk of side effects and toxicity (e.g. sedation) and lower doses may be needed. The FDA has provided dosing recommendations for CYP2C19 poor metabolizers being prescribed clobazam. Please see the table below for these recommendations.
At UCHealth the use of pharmacogenetics when prescribing clobazam will occur in patients who meet the following conditions:
1) Provided a blood or saliva sample to the Colorado Biobank and this sample has undergone genotyping. 2) Have consented for the return of their results. 3) Are prescribed clobazam.
This process takes a minimum of 4-6 weeks, but may take several years. Therefore, results will not be available at initial presentation if a patient has not previously enrolled in the Biobank.
If you are a provider AND your patient is a CYP2C19 poor metabolizer, an inline medication warning will appear if you attempt to prescribe or refill clobazam in UCHealth's EHR. If the inline medication warning is visible, links to resources will be listed for your reference. There is patient education text available for UCHealth providers to use in discharge paperwork or the after visit summary (AVS).
Visit our Provider FAQs page here. For immediate questions, secure chat Groups: Pharmacogenomics Service in UCHealth's EHR.