Chemical: Drug
clobazam
PharmGKB contains no prescribing info for this . Contact us to report known genotype-based dosing guidelines, or if you are interested in developing guidelines.
1. Annotation of FDA Label 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.
*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.
Genes and/or phenotypes found in this label
-
CYP1A2
- Clinical pharmacology section
- source: U.S. Food and Drug Administration
-
CYP2B6
- metabolism/PK, Clinical pharmacology section
- source: U.S. Food and Drug Administration
-
CYP2C19
- dosage, metabolism/PK, Dosage & administration section, Drug interactions section, Clinical pharmacology section, Use in specific populations section
- source: U.S. Food and Drug Administration
-
CYP2C8
- Clinical pharmacology section
- source: U.S. Food and Drug Administration
-
CYP2C9
- Clinical pharmacology section
- source: U.S. Food and Drug Administration
-
CYP2D6
- metabolism/PK, Drug interactions section, Clinical pharmacology section
- source: U.S. Food and Drug Administration
-
CYP3A4
- other, metabolism/PK, Drug interactions section, Clinical pharmacology section
- source: U.S. Food and Drug Administration
-
UGT1A1
- Clinical pharmacology section
- source: U.S. Food and Drug Administration
-
UGT1A4
- Clinical pharmacology section
- source: U.S. Food and Drug Administration
-
UGT1A6
- Clinical pharmacology section
- source: U.S. Food and Drug Administration
-
UGT2B4
- Clinical pharmacology section
- source: U.S. Food and Drug Administration
PharmGKB contains no Clinical Variants that meet the highest level of criteria.
To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.
Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.
The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.
The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.
The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.
Links in the "Gene" column lead to PharmGKB Gene Pages.
List of all variant annotations for clobazam
| Gene ? |
Variant?
(147) |
Alternate Names ? | Chemicals ? |
Alleles
?
(+ chr strand) |
Function ? |
Amino Acid?
Translation |
|
|---|---|---|---|---|---|---|---|
CA
VA
|
CYP2C19 | *1 | N/A | N/A | N/A | ||
|
CA
VA
|
CYP2C19 | *2 | N/A | N/A | N/A | ||
|
CA
VA
|
CYP2C19 | *3 | N/A | N/A | N/A | ||
| rs1057868 | NC_000007.13:g.75615006C>T, NC_000007.14:g.75985688C>T, NG_008930.1:g.75587C>T, NM_000941.2:c.1508C>T, NP_000932.3:p.Ala503Val, NW_003871064.1:g.3514924C>T, XM_005250459.1:c.1508C>T, XM_005250460.1:c.1205C>T, XM_005250461.1:c.932C>T, XM_005277600.1:c.1508C>T, XM_005277601.1:c.1205C>T, XM_005277602.1:c.932C>T, XP_005250516.1:p.Ala503Val, XP_005250517.1:p.Ala402Val, XP_005250518.1:p.Ala311Val, XP_005277657.1:p.Ala503Val, XP_005277658.1:p.Ala402Val, XP_005277659.1:p.Ala311Val, rs17840495, rs17846082, rs17859083, rs3198400, rs57699079 |
C > T
|
SNP |
A503V
|
Overview
- clobazam
- Chlorepin
- Clorepin
- Frisium
- Mystan
- Urbadan
- Urbanyl
PharmGKB Accession Id
PA10888
Type(s):
Drug
Description
Source: Drug Bank
Other Vocabularies
- MeSH: clobazam (C012255)
- ATC: Benzodiazepine derivatives (N05BA)
- UMLS: clobazam (C0055891)
- RxNorm: clobazam (21241)
- NDFRT: CLOBAZAM (N0000176077)
Information pulled from DrugBank has not been reviewed by PharmGKB.
Pharmacology, Interactions, and Contraindications
Mechanism of Action
Source: Drug Bank
Pharmacology
Source: Drug Bank
Food Interaction
Source: Drug Bank
Absorption, Distribution, Metabolism, Elimination & Toxicity
Biotransformation
Source: Drug Bank
Chemical Properties
SMILES
CN1C2=C(C=C(Cl)C=C2)N(C2=CC=CC=C2)C(=O)CC1=O
Source: Drug Bank
InChI String
InChI=1S/C16H13ClN2O2/c1-18-13-8-7-11(17)9-14(13)19(16(21)10-15(18)20)12-5-3-2-4-6-12/h2-9H,10H2,1H3
Source: Drug Bank
Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.
Curated Information ?
Drug Targets
| Gene | Description |
|---|---|
| GABRA1 | (source: Drug Bank ) |
| GABRA2 | (source: Drug Bank ) |
| GABRA3 | (source: Drug Bank ) |
| GABRA4 | (source: Drug Bank ) |
| GABRA5 | (source: Drug Bank ) |
| GABRA6 | (source: Drug Bank ) |
| GABRB1 | (source: Drug Bank ) |
| GABRB2 | (source: Drug Bank ) |
| GABRB3 | (source: Drug Bank ) |
| GABRD | (source: Drug Bank ) |
| GABRE | (source: Drug Bank ) |
| GABRG1 | (source: Drug Bank ) |
| GABRG2 | (source: Drug Bank ) |
| GABRG3 | (source: Drug Bank ) |
| GABRP | (source: Drug Bank ) |
| GABRQ | (source: Drug Bank ) |
| GABRR1 | (source: Drug Bank ) |
| GABRR2 | (source: Drug Bank ) |
| GABRR3 | (source: Drug Bank ) |
Curated Information ?
| Evidence | Disease |
|---|---|
| Drug Toxicity | |
| Epilepsy |
Publications related to clobazam: 17
LinkOuts
Clinical Trials
These are trials that mention clobazam and are related to either pharmacogenetics or pharmacogenomics.
NURSA Datasets
No NURSA datasets available.