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{{DrugProjectFormSinglePage
|authorTag={{SG}}
|genericName=Clobazam
|aOrAn=a
|drugClass=Benzodiazepine
|indicationType=treatment
|indication=adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients 2 years of age or older
|adverseReactions=[[constipation]], [[somnolence]] or [[sedation]], [[pyrexia]], [[lethargy]], and [[drooling]]
|blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b>
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)
|fdaLIADAdult=====Seizures associated with Lennox-Gastaut syndrome (LGS)====
*A daily dose of ONFI greater than 5 mg should be administered in divided doses twice daily
*5 mg daily dose can be administered as a single dose.
*Dose patients according to body weight.
[[File:Clobazam Dosage.png|none|500px]]
*Do not proceed with dose escalation more rapidly than weekly, because serum concentrations of clobazam and its active metabolite require 5 and 9 days, respectively, to reach steady-state.
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Clobazam in adult patients.
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Clobazam in adult patients.
|fdaLIADPed=====Seizures associated with Lennox-Gastaut syndrome (LGS) (2 years of age or older)====
*A daily dose of ONFI greater than 5 mg should be administered in divided doses twice daily
*5 mg daily dose can be administered as a single dose.
*Dose patients according to body weight.
[[File:Clobazam Dosage.png|none|500px]]
*Do not proceed with dose escalation more rapidly than weekly, because serum concentrations of clobazam and its active metabolite require 5 and 9 days, respectively, to reach steady-state.
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Clobazam in pediatric patients.
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Clobazam in pediatric patients.
|useInGeri=Plasma concentrations at any given dose are generally higher in the elderly: proceed slowly with dose escalation. The starting dose should be 5 mg/day for all elderly patients. Then titrate elderly patients according to weight, but to half the dose presented in Table 1, as tolerated. If necessary and based upon clinical response, an additional titration to the maximum dose (20 mg/day or 40 mg/day, depending on weight) may be started on day 21 [see Use in Specific Populations (8.5)].
|useInRenalImpair=No dose adjustment is required for patients with mild and moderate renal impairment. There is no experience with ONFI in patients with severe renal impairment or end stage renal disease (ESRD). It is not known if clobazam or its active metabolite, N-desmethylclobazam, is dialyzable [see Use in Specific Populations (8.7), Clinical Pharmacology (12.3)].
|useInHepaticImpair=ONFI is hepatically metabolized; however, there are limited data to characterize the effect of hepatic impairment on the pharmacokinetics of ONFI. For this reason, proceed slowly with dosing escalations. For patients with mild to moderate hepatic impairment (Child-Pugh score 5-9), the starting dose should be 5 mg/day in both weight groups. Then titrate patients according to weight, but to half the dose presented in Table 1, as tolerated. If necessary and based upon clinical response, start an additional titration on day 21 to the maximum dose (20 mg/day or 40 mg/day, depending on the weight group). There is inadequate information about metabolism of ONFI in patients with severe hepatic impairment. Therefore no dosing recommendation in those patients can be given [see Use in Specific Populations (8.8), Clinical Pharmacology (12.3)].
|othersTitle=Dosage Adjustments in CYP2C19 Poor Metabolizers
|useInOthers=In CYP2C19 poor metabolizers, levels of N-desmethylclobazam, clobazam's active metabolite, will be increased. Therefore, in patients known to be CYP2C19 poor metabolizers, the starting dose should be 5 mg/day and dose titration should proceed slowly according to weight, but to half the dose presented in Table 1, as tolerated. If necessary and based upon clinical response, an additional titration to the maximum dose (20 mg/day or 40 mg/day, depending on the weight group) may be started on day 21 [see Use in Specific Populations (8.6), Clinical Pharmacology (12.5)].
|administration=*Oral
=====Important Administration Instructions=====
Instruct patients to read the "Instructions for Use" carefully for complete directions on how to properly dose and administer ONFI oral suspension.
ONFI Tablet Oral Administration
ONFI tablets can be taken with or without food.
ONFI tablets can be administered whole, broken in half along the score, or crushed and mixed in applesauce.
ONFI Oral Suspension Oral Administration
ONFI oral suspension can be taken with or without food [see Clinical Pharmacology (12.3)].
Shake ONFI Oral Suspension well before every administration. When administering the oral suspension, use only the oral dosing syringe provided with the product. Each carton includes two syringes, but only one syringe should be used for dosing. The second oral syringe is reserved as a replacement in case the first syringe is damaged or lost. Insert the provided adapter firmly into the neck of the bottle before first use and keep the adapter in place for the duration of the usage of the bottle. To withdraw the dose, insert the dosing syringe into the adapter and invert the bottle then slowly pull back the plunger to prescribed dose. After removing the syringe from the bottle adapter, slowly squirt ONFI Oral Suspension into the corner of the patient's mouth. Replace the cap after each use. The cap fits over the adapter when the adapter is properly placed. See ONFI Oral Suspension "Instructions for Use" for complete instruction on how to properly dose and administer the ONFI Oral Suspension.
|alcohol=Alcohol-Clobazam interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
}}
{{Drugbox|
{{Drugbox|
| IUPAC_name = ''7-Chloro-1,5-dihydro-1-methyl-5-phenyl-<BR>1,5-benzodiazepine-2,4(3H)-dione''
| IUPAC_name = ''7-Chloro-1,5-dihydro-1-methyl-5-phenyl-<BR>1,5-benzodiazepine-2,4(3H)-dione''

Revision as of 21:09, 13 January 2015

Clobazam
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Stefano Giannoni [2]

Disclaimer

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Overview

Clobazam is a Benzodiazepine that is FDA approved for the treatment of adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients 2 years of age or older. Common adverse reactions include constipation, somnolence or sedation, pyrexia, lethargy, and drooling.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Seizures associated with Lennox-Gastaut syndrome (LGS)

  • A daily dose of ONFI greater than 5 mg should be administered in divided doses twice daily
  • 5 mg daily dose can be administered as a single dose.
  • Dose patients according to body weight.
  • Do not proceed with dose escalation more rapidly than weekly, because serum concentrations of clobazam and its active metabolite require 5 and 9 days, respectively, to reach steady-state.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Clobazam in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Clobazam in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Seizures associated with Lennox-Gastaut syndrome (LGS) (2 years of age or older)

  • A daily dose of ONFI greater than 5 mg should be administered in divided doses twice daily
  • 5 mg daily dose can be administered as a single dose.
  • Dose patients according to body weight.
  • Do not proceed with dose escalation more rapidly than weekly, because serum concentrations of clobazam and its active metabolite require 5 and 9 days, respectively, to reach steady-state.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Clobazam in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Clobazam in pediatric patients.

Contraindications

There is limited information regarding Clobazam Contraindications in the drug label.

Warnings

There is limited information regarding Clobazam Warnings' in the drug label.

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Clobazam Clinical Trials Experience in the drug label.

Postmarketing Experience

There is limited information regarding Clobazam Postmarketing Experience in the drug label.

Drug Interactions

There is limited information regarding Clobazam Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Clobazam in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Clobazam in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Clobazam during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Clobazam in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Clobazam in pediatric settings.

Geriatic Use

Plasma concentrations at any given dose are generally higher in the elderly: proceed slowly with dose escalation. The starting dose should be 5 mg/day for all elderly patients. Then titrate elderly patients according to weight, but to half the dose presented in Table 1, as tolerated. If necessary and based upon clinical response, an additional titration to the maximum dose (20 mg/day or 40 mg/day, depending on weight) may be started on day 21 [see Use in Specific Populations (8.5)].

Gender

There is no FDA guidance on the use of Clobazam with respect to specific gender populations.

Race

There is no FDA guidance on the use of Clobazam with respect to specific racial populations.

Renal Impairment

No dose adjustment is required for patients with mild and moderate renal impairment. There is no experience with ONFI in patients with severe renal impairment or end stage renal disease (ESRD). It is not known if clobazam or its active metabolite, N-desmethylclobazam, is dialyzable [see Use in Specific Populations (8.7), Clinical Pharmacology (12.3)].

Hepatic Impairment

ONFI is hepatically metabolized; however, there are limited data to characterize the effect of hepatic impairment on the pharmacokinetics of ONFI. For this reason, proceed slowly with dosing escalations. For patients with mild to moderate hepatic impairment (Child-Pugh score 5-9), the starting dose should be 5 mg/day in both weight groups. Then titrate patients according to weight, but to half the dose presented in Table 1, as tolerated. If necessary and based upon clinical response, start an additional titration on day 21 to the maximum dose (20 mg/day or 40 mg/day, depending on the weight group). There is inadequate information about metabolism of ONFI in patients with severe hepatic impairment. Therefore no dosing recommendation in those patients can be given [see Use in Specific Populations (8.8), Clinical Pharmacology (12.3)].

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Clobazam in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Clobazam in patients who are immunocompromised.

Dosage Adjustments in CYP2C19 Poor Metabolizers

In CYP2C19 poor metabolizers, levels of N-desmethylclobazam, clobazam's active metabolite, will be increased. Therefore, in patients known to be CYP2C19 poor metabolizers, the starting dose should be 5 mg/day and dose titration should proceed slowly according to weight, but to half the dose presented in Table 1, as tolerated. If necessary and based upon clinical response, an additional titration to the maximum dose (20 mg/day or 40 mg/day, depending on the weight group) may be started on day 21 [see Use in Specific Populations (8.6), Clinical Pharmacology (12.5)].

Administration and Monitoring

Administration

  • Oral
Important Administration Instructions

Instruct patients to read the "Instructions for Use" carefully for complete directions on how to properly dose and administer ONFI oral suspension.

ONFI Tablet Oral Administration ONFI tablets can be taken with or without food. ONFI tablets can be administered whole, broken in half along the score, or crushed and mixed in applesauce.

ONFI Oral Suspension Oral Administration ONFI oral suspension can be taken with or without food [see Clinical Pharmacology (12.3)].

Shake ONFI Oral Suspension well before every administration. When administering the oral suspension, use only the oral dosing syringe provided with the product. Each carton includes two syringes, but only one syringe should be used for dosing. The second oral syringe is reserved as a replacement in case the first syringe is damaged or lost. Insert the provided adapter firmly into the neck of the bottle before first use and keep the adapter in place for the duration of the usage of the bottle. To withdraw the dose, insert the dosing syringe into the adapter and invert the bottle then slowly pull back the plunger to prescribed dose. After removing the syringe from the bottle adapter, slowly squirt ONFI Oral Suspension into the corner of the patient's mouth. Replace the cap after each use. The cap fits over the adapter when the adapter is properly placed. See ONFI Oral Suspension "Instructions for Use" for complete instruction on how to properly dose and administer the ONFI Oral Suspension.

Monitoring

There is limited information regarding Clobazam Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Clobazam and IV administrations.

Overdosage

There is limited information regarding Clobazam overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Clobazam Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Clobazam Mechanism of Action in the drug label.

Structure

There is limited information regarding Clobazam Structure in the drug label.

Pharmacodynamics

There is limited information regarding Clobazam Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Clobazam Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Clobazam Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Clobazam Clinical Studies in the drug label.

How Supplied

There is limited information regarding Clobazam How Supplied in the drug label.

Storage

There is limited information regarding Clobazam Storage in the drug label.

Images

Drug Images

{{#ask: Page Name::Clobazam |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}

Package and Label Display Panel

{{#ask: Label Page::Clobazam |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}

Patient Counseling Information

There is limited information regarding Clobazam Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Clobazam interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Clobazam Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Clobazam Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

Clobazam
File:Clobazam-2D-skeletal.png
File:Clobazam3d.png
Clinical data
Pregnancy
category
  • ?
Routes of
administration		Oral
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability90%
MetabolismHepatic
Elimination half-life18 hours
ExcretionRenal
Identifiers
CAS Number
PubChem CID
DrugBank
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC16H13ClN2O2
Molar mass300.74

Clobazam is a drug which is a benzodiazepine derivative. It has been marketed as an anxiolytic since 1975[2] and an anticonvulsant since 1984.[3]

Pharmacology

Clobazam is a 1,5-benzodiazepine, meaning that its diazepine ring has nitrogen atoms at the 1 and 5 positions (instead of the usual 1 and 4). Like other 1,5-benzodiazepines (arfendazam, lofendazam, e.g.), it has less affinity for the ω1-allosteric binding site on the GABAA receptor compared to the 1,4-benzodiazepines. It has selective affinity for the ω2 site, where it has agonistic activity.[4]

In a double-blind placebo-controlled trial published in 1990 comparing it to clonazepam, 10mg or 20 mg of clobazam was shown to be much less sedating than either 0.5mg or 1 mg of clonazepam.[5]

The ω1-receptor, which is found on the α1 subtype of the GABAA receptor, was shown to be responsible for the sedative effects of diazepam by McKernan et al in 2000, who also showed that its anxiolytic and anticonvulsant properties could still be seen in mice whose α1 receptors were insensitive to diazepam.[6] It would seem, then, that the anticonvulsant properties of clobazam are due to its selective affinity for ω2.

In 1996, Nakamura et al reported that clobazam and its active metabolite, N-desmethylclobazam (norclobazam), work by enhancing GABA-activated chloride currents at GABAA-receptor-coupled Cl- channels. It was also reported that these effects were inhibited by the GABA antagonist flumazenil, and that clobazam acts most efficiently in GABA-deficient brain tissue.[7]

Nine years earlier, Kilpatrick et al noted that there was a correlation between plasma levels of norclobazam and therapeutic effects, although this was not true with the parent compound.[8]

According to Valli and colleagues in 1984, clobazam lowered prolactin levels elevated by sulpiride, a typical antipsychotic[9]. Hyperprolactinemia (i.e. elevated blood prolactin) occurs occasionally in people using antipsychotics, (particularly the typical ones), and can lead to cardiovascular disease, breast cancer, galactorrhea, infertility, amenorrhea, dysmenorrhea, osteopenia, osteoporosis, loss of libido, impotence,[10] and hypogonadism.[11]

Antipsychotics block type 2 dopamine receptors and at least 65% of central D2 receptors need to be occupied to produce a response; >72% D2 receptor occupancy was found to be associated with development of hyperprolactinemia.[12]

Peak plasma protein binding occurs around 83%.

Metabolism

Clobazam has two major metabolites: N-desmethyl-clobazam and 4'-hydroxyclobazam, the former of which is active.[13] The demethylation is facilitated by CYP2C19, CYP3A4, and CYP2B6 and the 4'-hydroxyclobazam by CYP2C18 and CYP2C19.[14]

Dependence

Clobazam as with other benzodiazepine drugs can lead to physical dependence, addiction and what is known as the benzodiazepine withdrawal syndrome. Withdrawal from clobazam or other benzodiazepines after regular use often leads to withdrawal symptoms which are similar to those seen during alcohol and barbiturate withdrawal. The higher the dose and the longer the drug is taken for, the greater the risk of experiencing unpleasant withdrawal symptoms. Withdrawal symptoms can however occur from standard dosages and also after short term use. Benzodiazepine treatment should be discontinued as soon as possible via a slow and gradual dose reduction regime.[15]

Uses

Canada

As of 2005, clobazam (Frisium®) is approved in Canada for adjunctive use in tonic-clonic, complex partial, and myoclonic seizures.[16]

France

Clobazam (Urbanyl®[17]) is approved for adjunctive therapy in complex partial seizures[18] certain types of status epilepticus, specifically the myoclonic, myoclonic-absent, simple partial, complex partial, and tonic varieties[19], and non-status absence seizures.[20] It is also approved for treatment of anxiety.

India

Clobazam (Frisium®, Aventis Pharma India, Ltd.) is approved for use as an adjunctive therapy in epilepsy and in acute and chronic anxiety.[21]

Japan

Clobazam (Mystan®[4]) is approved for adjunctive therapy in treatment-resistant epilepsy featuring complex partial seizures.[22]

New Zealand

Marketed as: Frisium®[23]

United Kingdom

Clobazam (Frisium®) is approved in the United Kingdom for short-term (2-4 weeks) relief of acute anxiety in patients who have not responded to other drugs, with or without insomnia and without uncontrolled clinical depression.[24]

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. It is not recommended for use in children between the ages of six months and three years, unless there is a compelling need.[24]

In addition to epilepsy and severe anxiety, clobazam is also approved as an adjunctive agent in schizophrenia and other psychotic disorders.[24]

Clobazam is sometimes used for refractory epilepsies however, long term prophylactic treatment of epilepsy has considerable drawbacks, most importantly loss of antiepileptic effects due to tolerance which may render long term therapy useless.[25] Other antiepileptic drugs may therefore be preferred for the long term management of epielpsy. Also benzodiazepines have the draw back after long term use of causing rebound seizures upon abrupt or over-rapid discontinuation of therapy forming part of the benzodiazepine withdrawal syndrome.

Dosage

Clobazam is available in oral form only, due to its insolubility in water.

Side effects

Common

Rare

Contraindications

Clobazam should be used with great care in patients with the following disorders:

Drug Interactions

Abuse potential

Clobazam in animal studies has been shown to increase reward seeking behaviours which may suggest an increased risk of addictive behavioural patterns.[28]

External links

References

  • Ochoa, Juan G. (2005). "GABA Receptor Agonists". Antiepileptic Drugs: An Overview. eMedicine.com, Inc. Retrieved 10 July. Unknown parameter |accessyear= ignored (|access-date= suggested) (help); Check date values in: |accessdate= (help)

End Notes

  1. ↑ "MISUSE OF DRUGS ACT 1975". Unknown parameter |accessyear= ignored (|access-date= suggested) (help); Unknown parameter |accessmonthday= ignored (help)
  2. ↑ Freche, C. (1975). "[Study of an anxiolytic, clobazam, in otorhinolaryngology in psychosomatic pharyngeal manifestations]". Semaine des Hopitaux. Therapeutique. 51 (4): 261–3. PMID 5777. [Article in French] [No abstract] List of Library Holdings Worldwide
  3. ↑ No authors listed (1991). "Clobazam in treatment of refractory epilepsy: the Canadian experience. A retrospective study. Canadian Clobazam Cooperative Group". Epilepsia. 32 (3): 407–16. PMID 2044502. List of Library Holdings
  4. ↑ 4.0 4.1 Nakajima H (2001). "[A pharmacological profile of clobazam (Mystan), a new antiepileptic drug]" (PDF). Nippon Yakurigaku Zasshi. 118 (2): 117–22. PMID 11530681. [Article in Japanese]
  5. ↑ Wildin JD, Pleuvry BJ, Mawer GE, Onon T, Millington L (1990). "Respiratory and sedative effects of clobazam and clonazepam in volunteers". British Journal of Clinical Pharmacology. 29 (2): 169–77. PMID 2106335.List of Library Holdings Worldwide
  6. ↑ McKernan RM, Rosahl TW, Reynolds DS, Sur C, Wafford KA, Atack JR, Farrar S, Myers J, Cook G, Ferris P, Garrett L, Bristow L, Marshall G, Macaulay A, Brown N, Howell O, Moore KW, Carling RW, Street LJ, Castro JL, Ragan CI, Dawson GR, Whiting PJ (2000). "Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABA(A) receptor alpha1 subtype". Nature Neuroscience. 3 (6): 587–92. doi:10.1038/75761. PMID 10816315.
  7. ↑ Nakamura, Fumihiro (1996). "Effects of clobazam and its active metabolite on GABA-activated currents in rat cerebral neurons in culture" (PDF). Epilepsia. 37 (8): 728–35. PMID 8764810. Retrieved 2006-08-03. Unknown parameter |coauthors= ignored (help)
  8. ↑ Kilpatrick C, Bury R, Fullinfaw R, Moulds R (1987). "Clobazam in the treatment of epilepsy". Clinical and Experimental Neurology. 23 (1): 139–44. PMID 3117456. List of Library Holdings Worldwide
  9. ↑ Valli M, Courtiere A, Tamalet C, Jadot G (1984). "[Activity of clobazam on plasma prolactin and gonadotropins after administration of sulpiride in the male rat]". Annales d'Endocrinologie. 45 (6): 409–11. [Article in French] PMID 6152598 List of Library Holdings Worldwide
  10. ↑ Halbreich, Uriel (2003). "Hyperprolactinemia and Schizophrenia: Mechanisms and Clinical Aspects". Journal of Psychiatric Practice. 9 (5): 344–53. PMID 15985953. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  11. ↑ Meaney, Anna Maria (2004). "Effects of long-term prolactin-raising antipsychotic medication on bone mineral density in patients with schizophrenia". British Journal of Psychiatry. 184: 503–508. PMID 15172944. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  12. ↑ Kapur, Shitij (2000). "Relationship Between Dopamine D2 Occupancy, Clinical Response, and Side Effects: A Double-Blind PET Study of First-Episode Schizophrenia". The American Journal of Psychiatry. 157 (4): 514–20. PMID 10739409. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  13. ↑ Contin M, Sangiorgi S, Riva R, Parmeggiani A, Albani F, Baruzzi A (2002). "Evidence of polymorphic CYP2C19 involvement in the human metabolism of N-desmethylclobazam". Therapeutic Drug Monitoring. 24 (6): 737–41. PMID 12451290. List of Library Holdings Worldwide
  14. ↑ Giraud C, Tran A, Rey E, Vincent J, Treluyer JM, Pons G (2004). "In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19". Drug Metabolism and Disposition. 32 (11): 1279–86. PMID 15483195. List of Library Holdings Worldwide
  15. ↑ MacKinnon GL (1982). "Benzodiazepine withdrawal syndrome: a literature review and evaluation". The American journal of drug and alcohol abuse. 9 (1): 19–33. PMID 6133446. Unknown parameter |coauthors= ignored (help)
  16. ↑ Epilepsy Ontario (2005). "Clobazam". Medications. Retrieved March 4. Unknown parameter |accessyear= ignored (|access-date= suggested) (help); Check date values in: |accessdate= (help)
  17. ↑ "Liste des médicaments contenant la substance : Clobazam". Retrieved 28 September. Unknown parameter |accessyear= ignored (|access-date= suggested) (help); Check date values in: |accessdate= (help) Vidal.
  18. ↑ Larrieu JL, Lagueny A, Ferrer X, Julien J (1986). "[Epilepsy with continuous discharges during slow-wave sleep. Treatment with clobazam]". Revue d'Electroencephalographie et de Neurophysiologie Clinique. 16 (4): 383–94. [Article in French] PMID 3103177 List of Library Holdings Worldwide
  19. ↑ Gastaut, Henri (1984). "[Treatment of certain forms of status epilepticus by means of a single oral dose of clobazam]". Revue d'Electroencephalographie et de Neurophysiologie Clinique. 14 (3): 203–6. PMID 6528075. Unknown parameter |coauthors= ignored (help) (Article in French) List of Library Holdings Worldwide
  20. ↑ Biam Database (2001). "CLOBAZAM". Classes Chimiques: BENZODIAZEPINE. Retrieved 28 September. Unknown parameter |accessyear= ignored (|access-date= suggested) (help); Check date values in: |accessdate= (help)
  21. ↑ "Frisium Press Kit". Aventis Pharma India. Archived from the original on 2005-03-05. Retrieved 2006-08-02.
  22. ↑ Shimizu, Hisako (2003). "Use of clobazam for the treatment of refractory complex partial seizures". Seizure. 12 (5): 282–6. PMID 12810340. Unknown parameter |coauthors= ignored (help) List of Library Holdings Worldwide
  23. ↑ Epilepsy New Zealand (2000). "Antiepileptic Medication". Retrieved 11 July. Unknown parameter |accessyear= ignored (|access-date= suggested) (help); Check date values in: |accessdate= (help)
  24. ↑ 24.0 24.1 24.2 sanofi-aventis (2002). "Frisium Tablets 10 mg, Summary of Product Characteristics from eMC". electronic Medicines Compendium. Medicines.org.uk. Retrieved 11 July. Unknown parameter |accessyear= ignored (|access-date= suggested) (help); Check date values in: |accessdate= (help)
  25. ↑ Isojärvi, JI (1998). "Benzodiazepines in the treatment of epilepsy in people with intellectual disability". J Intellect Disabil Res. 42 (1): 80–92. PMID 10030438. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  26. ↑ Iwasaki T (2003). "[A case of intractable epilepsy showing frequent gelastic seizures by administration of clobazam]". No To Hattatsu. 35 (5): 406–10. Unknown parameter |coauthors= ignored (help) [Article in Japanese] PMID 13677950 List of Library Holdings Worldwide
  27. ↑ Monjanel-Mouterde S, Antoni M, Bun H, Botta-Frindlund D, Gauthier A, Durand A, Cano JP (1994). "Pharmacokinetics of a single oral dose of clobazam in patients with liver disease". Annual Review of Pharmacology and Toxicology. 74 (6): 345–50. PMID 7937568. List of Library Holdings Worldwide
  28. ↑ Thiébot MH (1985). "Benzodiazepines reduce the tolerance to reward delay in rats". Psychopharmacology (Berl). 86 (1–2): 147–52. PMID 2862657. Unknown parameter |coauthors= ignored (help)

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