Chemical: Drug
clobazam

PharmGKB contains no dosing guidelines for this . To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.


last updated 06/02/2016

1. FDA Label for clobazam and CYP2C19

Actionable PGx

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.

Full label available at DailyMed

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.

? = Mouse-over for quick help

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
No VIP available CA VA CYP2C19 *1 N/A N/A N/A
No VIP available CA VA CYP2C19 *2 N/A N/A N/A
No VIP available CA VA CYP2C19 *3 N/A N/A N/A
No VIP available No Clinical Annotations available VA
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
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

Overview

Generic Names
  • clobazam
Trade Names
  • Chlorepin
  • Clorepin
  • Frisium
  • Mystan
  • Urbadan
  • Urbanyl
Brand Mixture Names

PharmGKB Accession Id

PA10888

Type(s):

Drug

Description

Clobazam is a drug which is a benzodiazepine derivative. It has been marketed as an anxiolytic since 1975 and an anticonvulsant since 1984. Wikipedia

Source: Drug Bank

Indication

For treatment and management of epilepsy and anxiety disorder.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Clobazam binds at a distinct binding site associated with a Cl - ionopore at the GABA-A receptor, increasing the duration of time for which the Cl - ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is prolonged as a result.

Source: Drug Bank

Pharmacology

Clobazam is a barbiturate used in combination with acetaminophen or aspirin and caffeine for its sedative and relaxant effects in the treatment of tension headaches, migraines, and pain.

Source: Drug Bank

Food Interaction

Alcohol increases clobazam absorption by 50%.|Take without regard to meals.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic. Clobazam has two major metabolites: N-desmethyl-clobazam and 4'-hydroxyclobazam, the former of which is active. The demethylation is facilitated by CYP2C19, CYP3A4, and CYP2B6 and the 4'-hydroxyclobazam by CYP2C18 and CYP2C19.

Source: Drug Bank

Protein Binding

83%

Source: Drug Bank

Absorption

Bioavailability is 90%.

Source: Drug Bank

Half-Life

18 hours

Source: Drug Bank

Chemical Properties

Chemical Formula

C16H13ClN2O2

Source: Drug Bank

Isomeric SMILES

CN1c2ccc(cc2N(C(=O)CC1=O)c3ccccc3)Cl

Source: OpenEye

Canonical SMILES

CN1C2=C(C=C(Cl)C=C2)N(C2=CC=CC=C2)C(=O)CC1=O

Source: Drug Bank

Average Molecular Weight

300.74

Source: Drug Bank

Monoisotopic Molecular Weight

300.066555377

Source: Drug Bank

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)

Drug Interactions

Interaction Description
clobazam - clozapine Increased risk of toxicity (source: Drug Bank)
clobazam - clozapine Increased risk of toxicity (source: Drug Bank)
clozapine - clobazam Increased risk of toxicity (source: Drug Bank)
clozapine - clobazam Increased risk of toxicity (source: Drug Bank)
telithromycin - clobazam Telithromycin may reduce clearance of Clobazam. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Clobazam if Telithromycin is initiated, discontinued or dose changed. (source: Drug Bank)
ticlopidine - clobazam Ticlopidine may decrease the metabolism and clearance of Clobazam. Consider alternate therapy or monitor for adverse/toxic effects of Clobazam if Ticlopidine is initiated, discontinued or dose changed. (source: Drug Bank)
tipranavir - clobazam Tipranavir may decrease the metabolism and clearance of Clobazam. Consider alternate therapy or monitor for Clobazam toxic effects if Tipranavir is initiated or dose increased. (source: Drug Bank)
triprolidine - clobazam The CNS depressants, Triprolidine and Clobazam, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy. (source: Drug Bank)
triprolidine - clobazam The CNS depressants, Triprolidine and Clobazam, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy. (source: Drug Bank)
voriconazole - clobazam Voriconazole may increase the serum concentration of clobazam by decreasing its metabolism. Monitor for clobazam toxicity if voriconazole is initiated or dose increased. (source: Drug Bank)

Curated Information ?

Publications related to clobazam: 16

No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Effect of CYP2C19 polymorphisms on the clinical outcome of low-dose clobazam therapy in Japanese patients with epilepsy. European journal of clinical pharmacology. 2015. Hashi Sachiyo, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Effects of CYP2C19 and P450 oxidoreductase polymorphisms on the population pharmacokinetics of clobazam and N-desmethylclobazam in japanese patients with epilepsy. Therapeutic drug monitoring. 2014. Saruwatari Junji, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Influence of CYP2C19 polymorphism and concomitant antiepileptic drugs on serum clobazam and N-desmethyl clobazam concentrations in patients with epilepsy. Therapeutic drug monitoring. 2013. Yamamoto Yoshiaki, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Challenges in pharmacogenetics. European journal of clinical pharmacology. 2013. Cascorbi Ingolf, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Gene-wide tagging study of the association between ABCC2, ABCC5 and ABCG2 genetic polymorphisms and multidrug resistance in epilepsy. Pharmacogenomics. 2011. Kwan Patrick, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Gene-wide tagging study of association between ABCB1 polymorphisms and multidrug resistance in epilepsy in Han Chinese. Pharmacogenomics. 2009. Kwan Patrick, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Impact of CYP2C19 polymorphisms on the efficacy of clobazam therapy. Pharmacogenomics. 2008. Seo Takayuki, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ABCB1 polymorphisms influence the response to antiepileptic drugs in Japanese epilepsy patients. Pharmacogenomics. 2006. Seo Takayuki, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
A major influence of CYP2C19 genotype on the steady-state concentration of N-desmethylclobazam. Brain & development. 2004. Kosaki Kenjiro, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The benzodiazepine site of the GABAA receptor: an old target with new potential?. Sleep medicine. 2004. Bateson Alan N. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19. Drug metabolism and disposition: the biological fate of chemicals. 2004. Giraud Carole, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Unusual side-effects due to clobazam: a case report with genetic study of CYP2C19. Brain & development. 2004. Parmeggiani Antonia, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Evidence of polymorphic CYP2C19 involvement in the human metabolism of N-desmethylclobazam. Therapeutic drug monitoring. 2002. Contin Manuela, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Mapping of the benzodiazepine recognition site on GABA(A) receptors. Current topics in medicinal chemistry. 2002. Sigel Erwin. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
New insights into the role of the GABA(A)-benzodiazepine receptor in psychiatric disorder. The British journal of psychiatry : the journal of mental science. 2001. Nutt D J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The benzodiazepine binding site of GABAA receptors. Trends in pharmacological sciences. 1997. Sigel E, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB00349
ChEBI:
31413
KEGG Drug:
D01253
PubChem Compound:
2789
PubChem Substance:
46506115
Drugs Product Database (DPD):
2247230
ChemSpider:
2687
Therapeutic Targets Database:
DAP000672

Clinical Trials

These are trials that mention clobazam and are related to either pharmacogenetics or pharmacogenomics.

No trials loaded.

NURSA Datasets

provided by nursa.org

No NURSA datasets available.

Common Searches

Search PubMed
Search Medline Plus
Search PubChem
Search CTD

Sources for PharmGKB drug information: DrugBank, PubChem.