Details
Stereochemistry | ACHIRAL |
Molecular Formula | C10H8F2N4O |
Molecular Weight | 238.1935 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
NC(=O)C1=CN(CC2=C(F)C=CC=C2F)N=N1
InChI
InChIKey=POGQSBRIGCQNEG-UHFFFAOYSA-N
InChI=1S/C10H8F2N4O/c11-7-2-1-3-8(12)6(7)4-16-5-9(10(13)17)14-15-16/h1-3,5H,4H2,(H2,13,17)
DescriptionCurator's Comment: description was created based on several sources, including:
http://www.rxlist.com/banzel-drug.htm
https://www.drugs.com/mtm/rufinamide.html
Curator's Comment: description was created based on several sources, including:
http://www.rxlist.com/banzel-drug.htm
https://www.drugs.com/mtm/rufinamide.html
Rufinamide is an anti-epileptic drug that is FDA approved for the treatment of lennox-gastaut syndrome (LGS). The principal mechanism of action of rufinamide is modulation of the activity of sodium channels and, in particular, prolongation of the inactive state of the channel. Hormonal contraceptives may be less effective with rufinamide. Patients on valproate should begin at a rufinamide dose lower than 10 mg/kg per day (pediatric patients) or 400 mg per day (adults). Common adverse reactions include headache, dizziness, fatigue, somnolence, and nausea.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL4296 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23221868 |
3.8 µM [EC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Palliative | BANZEL Approved UseI NDICATIONS AND USAGE BANZEL is indicated for adjunctive treatment of seizures associated with Lennox-Gastaut Syndrome in pediatric patients 1 year of age and older and in adults. BANZEL is indicated for adjunctive treatment of seizures associated with Lennox-Gastaut Syndrome (LGS) in pediatric patients 1 year of age and older, and in adults (1) Launch Date2008 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3.8 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18503564/ |
800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered: |
RUFINAMIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
70.3 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18503564/ |
800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered: |
RUFINAMIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
7.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18503564/ |
800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered: |
RUFINAMIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
10 h |
200 mg 2 times / day unknown, oral dose: 200 mg route of administration: Oral experiment type: UNKNOWN co-administered: |
RUFINAMIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
66% |
200 mg 2 times / day unknown, oral dose: 200 mg route of administration: Oral experiment type: UNKNOWN co-administered: |
RUFINAMIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
3600 mg 2 times / day multiple, oral MTD Dose: 3600 mg, 2 times / day Route: oral Route: multiple Dose: 3600 mg, 2 times / day Sources: Page: p.1125, p.1139 |
healthy n = 15 Health Status: healthy Population Size: 15 Sources: Page: p.1125, p.1139 |
|
22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Lennox-Gastaut Syndrome Sources: Page: p.1 |
Other AEs: Depression worsened, Suicidal behavior... Other AEs: Depression worsened Sources: Page: p.1Suicidal behavior (serious) Leukopenia (serious) Mood change Central nervous system disorder NOS Hypersensitivity reaction |
22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: Page: p.4 |
unhealthy Health Status: unhealthy Condition: Lennox-Gastaut Syndrome Sources: Page: p.4 |
Disc. AE: Fatigue... Other AEs: QT shortened... AEs leading to discontinuation/dose reduction: Fatigue (1-2) Other AEs:QT shortened (serious) Sources: Page: p.4 |
22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: Page: p.7 |
unhealthy Health Status: unhealthy Condition: Lennox-Gastaut Syndrome Sources: Page: p.7 |
Disc. AE: Convulsion, Rash... AEs leading to discontinuation/dose reduction: Convulsion (2%) Sources: Page: p.7Rash (2%) |
22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: Page: p.8 |
unhealthy Health Status: unhealthy Condition: Lennox-Gastaut Syndrome Sources: Page: p.8 |
Disc. AE: Vomiting, Dizziness... AEs leading to discontinuation/dose reduction: Vomiting (1%) Sources: Page: p.8Dizziness (3%) Headache (2%) Nausea (1%) Ataxia (1%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Central nervous system disorder NOS | 22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Lennox-Gastaut Syndrome Sources: Page: p.1 |
|
Depression worsened | 22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Lennox-Gastaut Syndrome Sources: Page: p.1 |
|
Hypersensitivity reaction | 22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Lennox-Gastaut Syndrome Sources: Page: p.1 |
|
Mood change | 22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Lennox-Gastaut Syndrome Sources: Page: p.1 |
|
Leukopenia | serious | 22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Lennox-Gastaut Syndrome Sources: Page: p.1 |
Suicidal behavior | serious | 22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Lennox-Gastaut Syndrome Sources: Page: p.1 |
Fatigue | 1-2 Disc. AE |
22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: Page: p.4 |
unhealthy Health Status: unhealthy Condition: Lennox-Gastaut Syndrome Sources: Page: p.4 |
QT shortened | serious | 22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: Page: p.4 |
unhealthy Health Status: unhealthy Condition: Lennox-Gastaut Syndrome Sources: Page: p.4 |
Convulsion | 2% Disc. AE |
22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: Page: p.7 |
unhealthy Health Status: unhealthy Condition: Lennox-Gastaut Syndrome Sources: Page: p.7 |
Rash | 2% Disc. AE |
22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: Page: p.7 |
unhealthy Health Status: unhealthy Condition: Lennox-Gastaut Syndrome Sources: Page: p.7 |
Ataxia | 1% Disc. AE |
22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: Page: p.8 |
unhealthy Health Status: unhealthy Condition: Lennox-Gastaut Syndrome Sources: Page: p.8 |
Nausea | 1% Disc. AE |
22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: Page: p.8 |
unhealthy Health Status: unhealthy Condition: Lennox-Gastaut Syndrome Sources: Page: p.8 |
Vomiting | 1% Disc. AE |
22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: Page: p.8 |
unhealthy Health Status: unhealthy Condition: Lennox-Gastaut Syndrome Sources: Page: p.8 |
Headache | 2% Disc. AE |
22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: Page: p.8 |
unhealthy Health Status: unhealthy Condition: Lennox-Gastaut Syndrome Sources: Page: p.8 |
Dizziness | 3% Disc. AE |
22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: Page: p.8 |
unhealthy Health Status: unhealthy Condition: Lennox-Gastaut Syndrome Sources: Page: p.8 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021911Orig1s000ClinPharmR_P1.pdf Page: 21, 56 |
inconclusive | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021911Orig1s000ClinPharmR_P1.pdf Page: 56.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021911Orig1s000ClinPharmR_P1.pdf Page: 21.0 |
weak | yes (co-administration study) Comment: coadministration with triazolam resulted in a 37% decrease in AUC and 23% decrease in Cmax of triazolam Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021911Orig1s000ClinPharmR_P1.pdf Page: 21.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021911Orig1s000ClinPharmR_P1.pdf Page: 21, 56 |
yes [Ki 450 uM] |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021911Orig1s000ClinPharmR_P1.pdf Page: 20.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021911Orig1s000ClinPharmR_P1.pdf Page: 40, 56 |
no |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 39.0 |
PubMed
Title | Date | PubMed |
---|---|---|
Practice of solid-phase extraction and protein precipitation in the 96-well format combined with high-performance liquid chromatography-ultraviolet detection for the analysis of drugs in plasma and brain. | 2001 Apr 15 |
|
Progress report on new antiepileptic drugs: a summary of the Fifth Eilat Conference (EILAT V). | 2001 Jan |
|
Rufinamide. | 2006 |
|
New antiepileptic drugs that are second generation to existing antiepileptic drugs. | 2006 Jun |
|
Diverse mechanisms of antiepileptic drugs in the development pipeline. | 2006 Jun |
|
Gateways to clinical trials. | 2006 Oct |
|
Rufinamide: a new anti-epileptic medication. | 2007 Aug |
|
Progress report on new antiepileptic drugs: a summary of the Eigth Eilat Conference (EILAT VIII). | 2007 Jan |
|
Rufinamide. | 2007 Jul |
|
Physicochemical characterization of solid dispersions of three antiepileptic drugs prepared by solvent evaporation method. | 2007 May |
|
Pregabalin for the management of partial epilepsy. | 2008 Dec |
|
Treatment of Lennox-Gastaut syndrome: overview and recent findings. | 2008 Dec |
|
Rufinamide: clinical pharmacokinetics and concentration-response relationships in patients with epilepsy. | 2008 Jul |
|
The anticonvulsant profile of rufinamide (CGP 33101) in rodent seizure models. | 2008 Jul |
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Rufinamide for generalized seizures associated with Lennox-Gastaut syndrome. | 2008 May 20 |
|
[Rufinamide. A review of its pharmacokinetic and pharmacodynamic properties]. | 2008 Oct 1-15 |
|
Product: Banzel. | 2009 Feb |
|
American Epilepsy Society--62nd Annual Meeting. 5-9 December 2008, Seattle, USA. | 2009 Feb |
|
Truly "rational" polytherapy: maximizing efficacy and minimizing drug interactions, drug load, and adverse effects. | 2009 Jun |
|
Effectiveness and tolerability of rufinamide in children and adults with refractory epilepsy: first European experience. | 2009 Mar |
|
Adopting an orphan drug: rufinamide for Lennox-Gastaut syndrome. | 2009 May-Jun |
|
New drugs: Febuxostat, lacosamide, and rufinamide. | 2009 May-Jun |
|
Gateways to clinical trials. | 2009 Nov |
|
The cost effectiveness of rufinamide in the treatment of Lennox-Gastaut syndrome in the UK. | 2010 |
|
First European long-term experience with the orphan drug rufinamide in childhood-onset refractory epilepsy. | 2010 Apr |
|
"Epileptic encephalopathy" of infancy and childhood: electro-clinical pictures and recent understandings. | 2010 Dec |
|
New drugs for pediatric epilepsy. | 2010 Dec |
|
Ethyl 1-(2,6-difluoro-benz-yl)-1H-1,2,3-triazole-4-carboxyl-ate. | 2010 Dec 15 |
|
Selected pharmacokinetic issues of the use of antiepileptic drugs and parenteral nutrition in critically ill patients. | 2010 Dec 31 |
|
New Drugs2010, PART 1. | 2010 Feb |
|
Simultaneous HPLC-UV analysis of rufinamide, zonisamide, lamotrigine, oxcarbazepine monohydroxy derivative and felbamate in deproteinized plasma of patients with epilepsy. | 2010 Feb 1 |
|
Lennox-Gastaut syndrome: An overview. | 2010 Jan |
|
Drug interactions involving the new second- and third-generation antiepileptic drugs. | 2010 Jan |
|
Cost-utility analysis of rufinamide versus topiramate and lamotrigine for the treatment of children with Lennox-Gastaut Syndrome in the United Kingdom. | 2010 Jan |
|
Update on anticonvulsant drugs. | 2010 Jul |
|
Stability of extemporaneously prepared rufinamide oral suspensions. | 2010 Mar |
|
Medical management of Lennox-Gastaut syndrome. | 2010 May |
|
Treating Lennox-Gastaut syndrome in epileptic pediatric patients with third-generation rufinamide. | 2010 Oct 5 |
|
Antiepileptic drug interactions - principles and clinical implications. | 2010 Sep |
|
Emerging drugs for partial onset seizures. | 2010 Sep |
|
Rufinamide for pediatric patients with Lennox-Gastaut syndrome: a comprehensive overview. | 2011 Apr 1 |
Patents
Sample Use Guides
Starting daily dose: 400-800 mg per day in two equally divided doses. Increase by 400-800 mg every other day until a maximum dose of 3200 mg per day, in two divided doses, is reached.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18503564
In vitro studies with human liver microsomes using con-centrations of rufinamide in the range of 10–300 µmol/L(2.4–72 µg/ml) found no significant inhibition of any ofeight major human CYP isozymes—CYP1A2, CYP2A6,CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4/5, andCYP4A9/11.
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Classification Tree | Code System | Code | ||
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WHO-ATC |
N03AF03
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NCI_THESAURUS |
C264
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WHO-VATC |
QN03AF03
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LIVERTOX |
NBK548457
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EU-Orphan Drug |
EU/3/04/240
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EMA ASSESSMENT REPORTS |
INOVELON (AUTHORIZED: EPILEPSY)
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FDA ORPHAN DRUG |
193504
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C079703
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7387
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RUFINAMIDE
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106308-44-5
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129228
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7470
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SUB10403MIG
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WFW942PR79
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CHEMBL1201754
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69036
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Rufinamide
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100000089186
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m9696
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1606401
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C75167
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SS-30
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DB06201
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3534
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ACTIVE MOIETY
METABOLITE (PARENT)