U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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 of CLOBAZAM

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

Description
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

Curator's Comment:: Has a central nervous system (CNS) depressant effect

Originator

Curator's Comment:: Discovery of Clobazam at the Maestretti Research Laboratories was first published in 1969. Maestretti Research Laboratories became part of Sanofi.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Secondary
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
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
641 μg/L
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

AUC

ValueDoseCo-administeredAnalytePopulation
13741 μg × h/L
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
36 h
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
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
10%
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

Doses

DosePopulationAdverse 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: Page: p. 69-70
healthy
n = 70
Health Status: healthy
Population Size: 70
Sources: 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: 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: Page: p. 69
healthy
n = 24
Health Status: healthy
Population Size: 24
Sources: Page: p. 69
Disc. AE: Transaminases increased...
AEs leading to
discontinuation/dose reduction:
Transaminases increased (1 patient)
Sources: 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: Page: p. 69
healthy
n = 24
Health Status: healthy
Population Size: 24
Sources: Page: p. 69
Disc. AE: Transaminases increased...
AEs leading to
discontinuation/dose reduction:
Transaminases increased (1 patient)
Sources: 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: Page: p. 70
healthy
n = 70
Health Status: healthy
Population Size: 70
Sources: Page: p. 70
Disc. AE: Transaminases increased...
AEs leading to
discontinuation/dose reduction:
Transaminases increased (2 patients)
Sources: 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: Page: p. 69
healthy
n = 24
Health Status: healthy
Population Size: 24
Sources: Page: p. 69
Disc. AE: Somnolence...
AEs leading to
discontinuation/dose reduction:
Somnolence (1 patient)
Sources: 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: Page: p. 69
healthy
n = 24
Health Status: healthy
Population Size: 24
Sources: Page: p. 69
Disc. AE: Dizziness, Somnolence...
AEs leading to
discontinuation/dose reduction:
Dizziness (1 patient)
Somnolence (1 patient)
Sources: Page: p. 69
AEs

AEs

AESignificanceDosePopulation
Depressed mood 1 patient
Disc. AE
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: Page: p. 69-70
healthy
n = 70
Health Status: healthy
Population Size: 70
Sources: Page: p. 69-70
Dizziness 1 patient
Disc. AE
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: Page: p. 69-70
healthy
n = 70
Health Status: healthy
Population Size: 70
Sources: Page: p. 69-70
Dysarthria 1 patient
Disc. AE
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: Page: p. 69-70
healthy
n = 70
Health Status: healthy
Population Size: 70
Sources: Page: p. 69-70
Erectile dysfunction 1 patient
Disc. AE
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: Page: p. 69-70
healthy
n = 70
Health Status: healthy
Population Size: 70
Sources: Page: p. 69-70
Insomnia 1 patient
Disc. AE
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: Page: p. 69-70
healthy
n = 70
Health Status: healthy
Population Size: 70
Sources: Page: p. 69-70
Libido decreased 1 patient
Disc. AE
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: Page: p. 69-70
healthy
n = 70
Health Status: healthy
Population Size: 70
Sources: Page: p. 69-70
Somnolence 1 patient
Disc. AE
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: Page: p. 69-70
healthy
n = 70
Health Status: healthy
Population Size: 70
Sources: Page: p. 69-70
Unsteady gait 1 patient
Disc. AE
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: Page: p. 69-70
healthy
n = 70
Health Status: healthy
Population Size: 70
Sources: Page: p. 69-70
Delirium 2 patients
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: Page: p. 69-70
healthy
n = 70
Health Status: healthy
Population Size: 70
Sources: Page: p. 69-70
Transaminases increased 1 patient
Disc. AE
10 mg 2 times / day steady, oral
Dose: 10 mg, 2 times / day
Route: oral
Route: steady
Dose: 10 mg, 2 times / day
Sources: Page: p. 69
healthy
n = 24
Health Status: healthy
Population Size: 24
Sources: Page: p. 69
Transaminases increased 1 patient
Disc. AE
15 mg 2 times / day steady, oral
Dose: 15 mg, 2 times / day
Route: oral
Route: steady
Dose: 15 mg, 2 times / day
Sources: Page: p. 69
healthy
n = 24
Health Status: healthy
Population Size: 24
Sources: Page: p. 69
Transaminases increased 2 patients
Disc. AE
20 mg 2 times / day steady, oral
Dose: 20 mg, 2 times / day
Route: oral
Route: steady
Dose: 20 mg, 2 times / day
Sources: Page: p. 70
healthy
n = 70
Health Status: healthy
Population Size: 70
Sources: Page: p. 70
Somnolence 1 patient
Disc. AE
60 mg 2 times / day steady, oral
Dose: 60 mg, 2 times / day
Route: oral
Route: steady
Dose: 60 mg, 2 times / day
Sources: Page: p. 69
healthy
n = 24
Health Status: healthy
Population Size: 24
Sources: Page: p. 69
Dizziness 1 patient
Disc. AE
70 mg 2 times / day steady, oral
Dose: 70 mg, 2 times / day
Route: oral
Route: steady
Dose: 70 mg, 2 times / day
Sources: Page: p. 69
healthy
n = 24
Health Status: healthy
Population Size: 24
Sources: Page: p. 69
Somnolence 1 patient
Disc. AE
70 mg 2 times / day steady, oral
Dose: 70 mg, 2 times / day
Route: oral
Route: steady
Dose: 70 mg, 2 times / day
Sources: Page: p. 69
healthy
n = 24
Health Status: healthy
Population Size: 24
Sources: Page: p. 69
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
yes (co-administration study)
Comment: clobazam increased dextromethorphan cmax 90%, auc 59%
Page: 16.0
weak
weak
yes (co-administration study)
Comment: clobazam decreased midazolam auc 27%, cmax 24%
Page: 9.0
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
yes (co-administration study)
Comment: ketoconazole increased clobazam auc 54%, no effect on cmax
Page: 15.0
minor
minor
yes (co-administration study)
Comment: omeprazole increased clobazam auc 30-36%, no effect on cmax
Page: 15.0
no
yes
yes (co-administration study)
Comment: verapamil reduced clobazam transport >96%
Page: 17.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Antipentylenetetrazol action of clobazam in developing rats.
1999
[Psychomotor slowness of a mentally retarded woman].
2001
Epileptic encephalopathy.
2001
[A pharmacological profile of clobazam (Mystan), a new antiepileptic drug].
2001 Aug
[Rolandic discharges in childhood epilepsy: magnetoencephalographic diagnosis].
2001 Aug 16-31
Determination of the antiepileptics vigabatrin and gabapentin in dosage forms and biological fluids using Hantzsch reaction.
2001 Feb
Induction of hypersensitivity to a previously tolerated antiepileptic drug by a second antiepileptic drug.
2001 Mar
[Epileptic crisis after antimalaria chemoprophylaxis with chloroquine].
2001 Nov 24
On the use of tranquillisers in epilepsy.
2002
Long-term neuropsychological follow-up and nosological considerations in five patients with continuous spikes and waves during slow sleep.
2002 Dec
Successful treatment of severe infantile hyperekplexia with low-dose clobazam.
2002 Feb
Clobazam shows a different antiepileptic action profile from clonazepam and zonisamide in Ihara epileptic rats.
2002 May
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
A case of nonconvulsive status epilepticus associated with focal cortical dysplasia.
2003 Apr
Mechanism of clobazam-induced thyroidal oncogenesis in male rats.
2003 Dec 10
Direct injection HPLC method for the determination of selected benzodiazepines in plasma using a Hisep column.
2003 Dec 4
Prophylactic use of clobazam in hot water epilepsy.
2003 Jan
Mechanism-based pharmacokinetic/pharmacodynamic modeling of the electroencephalogram effects of GABAA receptor modulators: in vitro-in vivo correlations.
2003 Jan
Effects of antiepileptic drugs on refractory seizures in the intact immature corticohippocampal formation in vitro.
2003 Nov
Development of a whole body physiologically based model to characterise the pharmacokinetics of benzodiazepines. 1: Estimation of rat tissue-plasma partition ratios.
2004 Aug
Sporadic major hyperekplexia in neonates and infants: clinical manifestations and outcome.
2004 Jul
Forensic intoxication with clobazam: HPLC/DAD/MSD analysis.
2004 Jul 16
Affinity of various benzodiazepine site ligands in mice with a point mutation in the GABA(A) receptor gamma2 subunit.
2004 Oct 15
Substrate depletion approach for determining in vitro metabolic clearance: time dependencies in hepatocyte and microsomal incubations.
2004 Sep
The difficulty in diagnosing non-convulsive status epilepticus during routine medical practice.
2004 Sep
Stiripentol: new preparation. Severe myoclonic epilepsy of infancy: promising.
2005 Apr
A case of toxic epidermal necrolysis with lesions mostly on sun-exposed skin.
2005 Apr
Molecular regulation of glutamate and GABA transporter proteins by clobazam during epileptogenesis in Fe(+++)-induced epileptic rats.
2005 Dec 14
Clobazam as add-on therapy for temporal lobe epilepsy and hippocampal sclerosis.
2005 Feb
Effect of antiepileptic drug polytherapy on crystalluria.
2005 Feb
Intermittent clobazam therapy in febrile seizures.
2005 Jan
Stiripentol.
2005 Jul
Neuroembryopathic effect of clobazam in rat: a histological study.
2005 Jun
Simultaneous determination of clobazam and its major metabolite in human plasma by a rapid HPLC method.
2005 Sep 5
Levetiracetam in idiopathic generalised epilepsy and porphyria cutanea tarda.
2006
Landau-Kleffner syndrome is not an eponymic badge of ignorance.
2006 Aug
Effects of some antiepileptics on septal-kindled seizures in rats.
2006 Dec
[Epilepsy: which therapy in acute care?].
2006 Dec 8
Anticonvulsant hypersensitivity syndrome to lamotrigine confirmed by lymphocyte stimulation in vitro.
2006 Feb
Eye rolling as a manifestation of clobazam toxicity in a child with epilepsy.
2006 Jul
Benign angiopathy of the central nervous system associated with phenytoin intoxication.
2006 Jun
Oxidative stress in children receiving valproic acid.
2006 Nov
Treatment in the pediatric emergency department is evidence based: a retrospective analysis.
2006 Oct 6
Effectiveness of clobazam as add-on therapy in children with refractory focal epilepsy.
2006 Sep
Clobazam.
2007 Jan
Stiripentol.
2007 Jan
Patents

Sample Use Guides

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.
Name Type Language
CLOBAZAM
DASH   EP   INN   JAN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
INN   USAN  
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
Created by admin on Fri Jun 25 21:15:48 UTC 2021 , Edited by admin on Fri Jun 25 21:15:48 UTC 2021
FDA ORPHAN DRUG 248307
Created by admin on Fri Jun 25 21:15:48 UTC 2021 , Edited by admin on Fri Jun 25 21:15:48 UTC 2021
LIVERTOX 218
Created by admin on Fri Jun 25 21:15:48 UTC 2021 , Edited by admin on Fri Jun 25 21:15:48 UTC 2021
WHO-ATC N05BA09
Created by admin on Fri Jun 25 21:15:48 UTC 2021 , Edited by admin on Fri Jun 25 21:15:48 UTC 2021
NCI_THESAURUS C28197
Created by admin on Fri Jun 25 21:15:48 UTC 2021 , Edited by admin on Fri Jun 25 21:15:48 UTC 2021
WHO-VATC QN05BA09
Created by admin on Fri Jun 25 21:15:48 UTC 2021 , Edited by admin on Fri Jun 25 21:15:48 UTC 2021
NDF-RT N0000175694
Created by admin on Fri Jun 25 21:15:48 UTC 2021 , Edited by admin on Fri Jun 25 21:15:48 UTC 2021
Code System Code Type Description
CAS
22316-47-8
Created by admin on Fri Jun 25 21:15:48 UTC 2021 , Edited by admin on Fri Jun 25 21:15:48 UTC 2021
PRIMARY
WIKIPEDIA
CLOBAZAM
Created by admin on Fri Jun 25 21:15:48 UTC 2021 , Edited by admin on Fri Jun 25 21:15:48 UTC 2021
PRIMARY
MESH
C012255
Created by admin on Fri Jun 25 21:15:48 UTC 2021 , Edited by admin on Fri Jun 25 21:15:48 UTC 2021
PRIMARY
EPA CompTox
22316-47-8
Created by admin on Fri Jun 25 21:15:48 UTC 2021 , Edited by admin on Fri Jun 25 21:15:48 UTC 2021
PRIMARY
PUBCHEM
2789
Created by admin on Fri Jun 25 21:15:48 UTC 2021 , Edited by admin on Fri Jun 25 21:15:48 UTC 2021
PRIMARY
INN
3055
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PRIMARY
DRUG BANK
DB00349
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PRIMARY
EVMPD
SUB06673MIG
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PRIMARY
ChEMBL
CHEMBL70418
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PRIMARY
HSDB
8343
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PRIMARY
FDA UNII
2MRO291B4U
Created by admin on Fri Jun 25 21:15:48 UTC 2021 , Edited by admin on Fri Jun 25 21:15:48 UTC 2021
PRIMARY
NCI_THESAURUS
C81615
Created by admin on Fri Jun 25 21:15:48 UTC 2021 , Edited by admin on Fri Jun 25 21:15:48 UTC 2021
PRIMARY
ECHA (EC/EINECS)
244-908-7
Created by admin on Fri Jun 25 21:15:48 UTC 2021 , Edited by admin on Fri Jun 25 21:15:48 UTC 2021
PRIMARY
LACTMED
Clobazam
Created by admin on Fri Jun 25 21:15:48 UTC 2021 , Edited by admin on Fri Jun 25 21:15:48 UTC 2021
PRIMARY
RXCUI
21241
Created by admin on Fri Jun 25 21:15:48 UTC 2021 , Edited by admin on Fri Jun 25 21:15:48 UTC 2021
PRIMARY RxNorm
MERCK INDEX
M3626
Created by admin on Fri Jun 25 21:15:48 UTC 2021 , Edited by admin on Fri Jun 25 21:15:48 UTC 2021
PRIMARY Merck Index
NDF-RT
N0000182137
Created by admin on Fri Jun 25 21:15:48 UTC 2021 , Edited by admin on Fri Jun 25 21:15:48 UTC 2021
PRIMARY Cytochrome P450 2D6 Inhibitors [MoA]
IUPHAR
7149
Created by admin on Fri Jun 25 21:15:48 UTC 2021 , Edited by admin on Fri Jun 25 21:15:48 UTC 2021
PRIMARY
DRUG CENTRAL
682
Created by admin on Fri Jun 25 21:15:48 UTC 2021 , Edited by admin on Fri Jun 25 21:15:48 UTC 2021
PRIMARY