CLOBAZAM

Details

Stereochemistry	ACHIRAL
Molecular Formula	C16H13ClN2O2
Molecular Weight	300.7402
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=CXOXHMZGEKVPMT-UHFFFAOYSA-N

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

HIDE SMILES / InChI

Molecular Formula	C16H13ClN2O2
Molecular Weight	300.7402
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/202067s003,203993s003lbl.pdf
Curator's Comment:: Description was created based on several sources, including https://www.drugs.com/cdi/clobazam.html; http://www.epilepsy.com/medications/clobazam https://www.ncbi.nlm.nih.gov/pubmed/?term=23318278

Clobazam belongs to the 1,5-benzodiazepine class of drugs with antiepileptic properties. It has been used to treat anxiety and epilepsy since 1970s. In the US clobazam was approved for marketing in October of 2011 for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome. It is also approved for adjunctive therapy for epilepsy in patients who have not responded to first-line drugs and in children who are refractory to first-line drugs. The mechanism of action for clobazam is not fully understood but is thought to involve what is known as potentiation of GABAergic neurotransmission resulting from binding at a benzodiazepine site at the GABA(A) receptor. Possible side effects: constipation, fever, drowsiness, sedation, ataxia, aggressive behavior, lethargy, drooling, and irritability. Other side effects include: urinary tract infection, pneumonia, cough, dysphagia, dysarthria, bronchitis, insomnia, fatigue, decreased appetite, and increased appetite.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
GABA-A receptor; anion channel 189 Target ID: CHEMBL2093872 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22145708	Activator 1343

Conditions

Condition	Modality	Targets	Highest Phase	Product
Lennox-Gastaut syndrome 4 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202067s002,203993s002lbl.pdf	Secondary		Approved 8043	ONFI Approved Use Indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients 2 years of age or older. Launch Date 1.31915514E12

C_max

Value	Dose	Co-administered	Analyte	Population
641 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6529527/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:		CLOBAZAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
13741 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6529527/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:		CLOBAZAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
36 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/202067s005,203993s007lbl.pdf	30 mg 1 times / day unknown, oral dose: 30 mg route of administration: Oral experiment type: UNKNOWN co-administered:		CLOBAZAM plasma	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
10% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/202067s005,203993s007lbl.pdf	30 mg 1 times / day unknown, oral dose: 30 mg route of administration: Oral experiment type: UNKNOWN co-administered:		CLOBAZAM plasma	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
80 mg 2 times / day steady, oral Highest studied dose Dose: 80 mg, 2 times / day Route: oral Route: steady Dose: 80 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 69-70	healthy n = 70 Health Status: healthy Population Size: 70 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 69-70	Disc. AE: Somnolence, Depressed mood... Other AEs: Delirium... AEs leading to discontinuation/dose reduction: Somnolence (1 patient) Depressed mood (1 patient) Libido decreased (1 patient) Erectile dysfunction (1 patient) Insomnia (1 patient) Dysarthria (1 patient) Unsteady gait (1 patient) Dizziness (1 patient) Other AEs: Delirium (2 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 69-70
10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 69	healthy n = 24 Health Status: healthy Population Size: 24 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 69	Disc. AE: Transaminases increased... AEs leading to discontinuation/dose reduction: Transaminases increased (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 69
15 mg 2 times / day steady, oral Dose: 15 mg, 2 times / day Route: oral Route: steady Dose: 15 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 69	healthy n = 24 Health Status: healthy Population Size: 24 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 69	Disc. AE: Transaminases increased... AEs leading to discontinuation/dose reduction: Transaminases increased (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 69
20 mg 2 times / day steady, oral Dose: 20 mg, 2 times / day Route: oral Route: steady Dose: 20 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 70	healthy n = 70 Health Status: healthy Population Size: 70 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 70	Disc. AE: Transaminases increased... AEs leading to discontinuation/dose reduction: Transaminases increased (2 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 70
60 mg 2 times / day steady, oral Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 69	healthy n = 24 Health Status: healthy Population Size: 24 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 69	Disc. AE: Somnolence... AEs leading to discontinuation/dose reduction: Somnolence (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 69
70 mg 2 times / day steady, oral Dose: 70 mg, 2 times / day Route: oral Route: steady Dose: 70 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 69	healthy n = 24 Health Status: healthy Population Size: 24 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 69	Disc. AE: Dizziness, Somnolence... AEs leading to discontinuation/dose reduction: Dizziness (1 patient) Somnolence (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 69

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 707 substrate 1601 inhibitor 1467	inhibitor 1604	inhibitor 1702	inhibitor 1475

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1383 CYP2C8 818 CYP2C19 1325 UGT1A1 192 UGT1A4 74 UGT1A6 104 UGT2B4 18 P-gp 1330	CYP2C19 910 CYP2B6 616 P-gp 1400 OAT 1	UGT1A1 65

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1532	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 16.0	no
CYP2C19 1392	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 16.0	no
CYP2C8 865	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 16.0	no
CYP2C9 1648	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 16.0	no
CYP3A4 1772	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 16.0	no
P-gp 1514	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 17.0	no
UGT1A1 240	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 16.0	no
UGT1A4 77	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 16.0	no
UGT1A6 136	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 16.0	no
UGT2B4 18	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 16.0	no
CYP2D6 1738	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 16.0	no	yes (co-administration study) Comment: clobazam increased dextromethorphan cmax 90%, auc 59% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 16.0
UGT1A1 240	inducer 1440 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 17.0	weak
CYP3A4 1772	inducer 1440 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 9.0	weak	yes (co-administration study) Comment: clobazam decreased midazolam auc 27%, cmax 24% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 9.0

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1601	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 15.0	major	yes (co-administration study) Comment: ketoconazole increased clobazam auc 54%, no effect on cmax Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 15.0
CYP2B6 616	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 15.0	minor
CYP2C19 910	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 15.0	minor	yes (co-administration study) Comment: omeprazole increased clobazam auc 30-36%, no effect on cmax Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 15.0
OAT 1	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000ClinPharmR.pdf Page: 96.0	no
P-gp 1400	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 17.0	yes	yes (co-administration study) Comment: verapamil reduced clobazam transport >96% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 17.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1507	inhibitor 1489 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000CrossR.pdf Page: 20.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:31413	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:31413
ZINC	ZINC000000001175	http://zinc15.docking.org/substances/ZINC000000001175
eMolecules	536528	https://www.emolecules.com/cgi-bin/more?vid=536528

PubMed

Title	Date	PubMed
[Psychomotor slowness of a mentally retarded woman].	2001	12116722
Management strategies for refractory localization-related seizures.	2001	11520319
Epileptic encephalopathy.	2001	11520318
[A pharmacological profile of clobazam (Mystan), a new antiepileptic drug].	2001 Aug	11530681
[Rolandic discharges in childhood epilepsy: magnetoencephalographic diagnosis].	2001 Aug 16-31	11588728
Induction of hypersensitivity to a previously tolerated antiepileptic drug by a second antiepileptic drug.	2001 Mar	11442165
[Epileptic crisis after antimalaria chemoprophylaxis with chloroquine].	2001 Nov 24	11769070
Infantile spasms: diagnosis and assessment of treatment response by video-EEG.	2001 Oct	11665822
Atypical evolution in childhood epilepsy with occipital paroxysms (Panayiotopoulos type).	2001 Sep	11679309
Psychosomatic reactions to a stressful environment and an attempt at pharmacological modification.	2001 Sep-Oct	11535941
Long-term neuropsychological follow-up and nosological considerations in five patients with continuous spikes and waves during slow sleep.	2002 Dec	12600810
Treatment of trigeminal neuralgia: letter to editor.	2002 Jun	12134205
Anti-epileptic drugs.	2002 May	12418630
Clobazam shows a different antiepileptic action profile from clonazepam and zonisamide in Ihara epileptic rats.	2002 May	12076840
[Long-term efficacy and tolerance of stiripentaol in severe myoclonic epilepsy of infancy (Dravet's syndrome)].	2002 Nov	12503502
Vagus nerve stimulation in a case of epilepsy with CSWSS: respiratory side effects during sleep.	2002 Oct	12366745
A casuistic rationale for the treatment of spastic and myocloni in a childhood neurodegenerative disease: neuronal ceroid lipofuscinosis of the type Jansky-Bielschowsky.	2002 Oct-Dec	12500158
A case of nonconvulsive status epilepticus associated with focal cortical dysplasia.	2003 Apr	12689702
Phenytoin toxicity due to fluoropyrimidines (5FU/capecitabine): three case reports.	2003 Aug 18	12915866
Mechanism of clobazam-induced thyroidal oncogenesis in male rats.	2003 Dec 10	14580900
Use of clobazam for the treatment of refractory complex partial seizures.	2003 Jul	12810340
Clobazam monotherapy in drug naïve adult patients with epilepsy.	2003 Jun	12763470
[A case of intractable epilepsy showing frequent gelastic seizures by administration of clobazam].	2003 Sep	13677950
Clobazam as a new antiepileptic drug and clorazepate dipotassium as an alternative antiepileptic drug in Japan.	2004	15610190
Hypersensitivity to topiramate sprinkle capsules does not preclude the use of topiramate tablets.	2004	15035654
Screening, library-assisted identification and validated quantification of 23 benzodiazepines, flumazenil, zaleplone, zolpidem and zopiclone in plasma by liquid chromatography/mass spectrometry with atmospheric pressure chemical ionization.	2004 Aug	15329838
A major influence of CYP2C19 genotype on the steady-state concentration of N-desmethylclobazam.	2004 Dec	15533655
Unusual side-effects due to clobazam: a case report with genetic study of CYP2C19.	2004 Jan	14729419
Miconazole and clobazam; a useful interaction in Dravet's syndrome?	2004 Jan	14709525
[Idiopathic epilepsies: some therapeutic aspects].	2004 Jan 16-31	14752722
Sporadic major hyperekplexia in neonates and infants: clinical manifestations and outcome.	2004 Jul	15246489
Forensic intoxication with clobazam: HPLC/DAD/MSD analysis.	2004 Jul 16	15240045
In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19.	2004 Nov	15483195
Affinity of various benzodiazepine site ligands in mice with a point mutation in the GABA(A) receptor gamma2 subunit.	2004 Oct 15	15451405
The difficulty in diagnosing non-convulsive status epilepticus during routine medical practice.	2004 Sep	15315926
Photosensitivity in idiopathic generalized epilepsies.	2005	16302877
Levetiracetam in the treatment of infantile spasms.	2005	15701562
A case of toxic epidermal necrolysis with lesions mostly on sun-exposed skin.	2005 Apr	15752129
[Subacute encephalitis with anti-glutamate receptor antibodies presented with epilepsia partialis continua].	2005 Aug	16180713
Intermittent clobazam therapy in febrile seizures.	2005 Jan	15684445
[Antiepileptic drugs in the treatment of autistic regression syndromes].	2005 Jan 15	15736083
Neuroembryopathic effect of clobazam in rat: a histological study.	2005 Jun	16295712
A common variable immunodeficient patient who developed acute disseminated encephalomyelitis followed by the Lennox-Gastaut syndrome.	2005 Jun	15943601
Levetiracetam in idiopathic generalised epilepsy and porphyria cutanea tarda.	2006	17163270
[Epilepsy: which therapy in acute care?].	2006 Dec 8	17136662
Benign angiopathy of the central nervous system associated with phenytoin intoxication.	2006 Jun	16376047
Treatment in the pediatric emergency department is evidence based: a retrospective analysis.	2006 Oct 6	17022829
Effectiveness of clobazam as add-on therapy in children with refractory focal epilepsy.	2006 Sep	17057871
Clobazam.	2007 Jan	17199029
Stiripentol.	2007 Jan	17199026

Patents

Sample Use Guides

In Vivo Use Guide

Patients ≤30 kg body weight: Initiate at 5 mg daily and titrate as tolerated up to 20 mg daily. Patients > 30 kg body weight: Initiate at 10 mg daily and titrate as tolerated up to 40 mg daily. For doses above 5 mg/day administer in two divided doses. Dosage adjustment needed in following groups: Geriatric patients. Known CYP2C19 poor metabolizers. Mild or moderate hepatic impairment; no information for severe hepatic impairment.

Route of Administration: Oral

In Vitro Use Guide

Recurrent ictal-like seizures (ILEs, four per hour) were generated in intact corticohippocampal formations (CHFs) of P7-8 rats, and extracellular recordings were performed in the hippocampus and neocortex. Clobazam was applied at clinically relevant concentrations (at least two), during 30 min after the third ILE. Clobazam prevented the occurrence of seizures in recurrent ictal-like seizures.

Substance Class	Chemical Created by `admin` on `Fri Jun 25 21:15:48 UTC 2021` Edited by `admin` on `Fri Jun 25 21:15:48 UTC 2021`
Record UNII	2MRO291B4U
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CLOBAZAM

Official Name

English

CLOBAZAM [MI]

Common Name

English

CLOBAZAM [JAN]

Common Name

English

URBADAN

Brand Name

English

1H-1,5-BENZODIAZEPINE-2,4(3H,5H)-DIONE, 7-CHLORO-1-METHYL-5-PHENYL-

Systematic Name

English

CLOBAZAM [ORANGE BOOK]

Common Name

English

CLOBAZAM [VANDF]

Common Name

English

FRISIUM

Brand Name

English

URBANYL

Brand Name

English

ONFI

Brand Name

English

LM 2717

Code

English

LM-2717

Code

English

COLBAZAM [VANDF]

Common Name

English

NSC-336279

Code

English

HR-376

Code

English

MYSTAN

Brand Name

English

H 4723

Code

English

HR 376

Code

English

CLOBAZAM [EP MONOGRAPH]

Common Name

English

CLOBAZAM [MART.]

Common Name

English

7-CHLORO-1-METHYL-5-PHENYL-1H-1,5-BENZODIAZEPINE-2,4-(3H,5H)-DIONE

Common Name

English

SYMPAZAN

Brand Name

English

H-4723

Code

English

CLOBAZAM [INN]

Common Name

English

CLOBAZAM [USAN]

Common Name

English

CLOBAZAM [WHO-DD]

Common Name

English

Classification Tree Code System Code

DEA NO.

2751