vigabatrin Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
gabamimetic agents	2819	68506-86-5

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: vigabatrin (+/-)-4-Amino-5-hexenoic acid sabril vigabatrin hydrochloride vigabatrin HCl	The precise mechanism of vigabatrin's anti-seizure effect is unknown, but it is believed to be the result of its action as an irreversible inhibitor of gamma-aminobutyric acid transaminase (GABA-T), the enzyme responsible for the metabolism of the inhibitory neurotransmitter GABA. This action results in increased levels of GABA in the central nervous system. Molecular weight: 129.16 Formula: C6H11NO2 CLOGP: -2.22 LIPINSKI: 0 HAC: 3 HDO: 2 TPSA: 63.32 ALOGS: -0.13 ROTB: 4 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

vigabatrin
(+/-)-4-Amino-5-hexenoic acid
sabril
vigabatrin hydrochloride
vigabatrin HCl

The precise mechanism of vigabatrin's anti-seizure effect is unknown, but it is believed to be the result of its action as an irreversible inhibitor of gamma-aminobutyric acid transaminase (GABA-T), the enzyme responsible for the metabolism of the inhibitory neurotransmitter GABA. This action results in increased levels of GABA in the central nervous system.

Molecular weight: 129.16
Formula: C6H11NO2
CLOGP: -2.22
LIPINSKI: 0
HAC: 3
HDO: 2
TPSA: 63.32
ALOGS: -0.13
ROTB: 4

Status: OFP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

Dose	Unit	Route
2	g	O

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	3	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	60 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	442.42 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	99 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Approvals:

Date	Agency	Company	Orphan
Aug. 21, 2009	FDA	LUNDBECK LLC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Seizure	1559.26	32.46	576	5209	122478	46557799
Drug withdrawal convulsions	605.69	32.46	110	5675	1231	46679046
Infantile spasms	391.43	32.46	60	5725	203	46680074
Product dose omission issue	273.29	32.46	199	5586	168321	46511956
Retinogram abnormal	209.21	32.46	32	5753	106	46680171
Drug ineffective	195.60	32.46	319	5466	677519	46002758
Death	192.61	32.46	221	5564	335327	46344950
Epilepsy	184.40	32.46	79	5706	23659	46656618
Status epilepticus	176.35	32.46	66	5719	13913	46666364
Irritability	138.98	32.46	69	5716	28877	46651400
Visual field defect	123.74	32.46	41	5744	6042	46674235
Somnolence	109.88	32.46	115	5670	156406	46523871
Brain operation	98.10	32.46	20	5765	422	46679855
Aggression	77.14	32.46	43	5742	22701	46657576
Change in seizure presentation	70.46	32.46	14	5771	258	46680019
Tonic convulsion	69.97	32.46	18	5767	1088	46679189
Focal dyscognitive seizures	69.46	32.46	22	5763	2806	46677471
Partial seizures	64.38	32.46	24	5761	4986	46675291
Drug resistance	62.08	32.46	34	5751	17334	46662943
Generalised tonic-clonic seizure	57.63	32.46	38	5747	27084	46653193
Respiratory distress	56.63	32.46	40	5745	31876	46648401
Optic atrophy	55.64	32.46	15	5770	1087	46679190
Abnormal behaviour	53.42	32.46	33	5752	21025	46659252
Seizure cluster	51.25	32.46	10	5775	167	46680110
Infantile spitting up	49.16	32.46	8	5777	43	46680234
Retinal injury	49.04	32.46	10	5775	211	46680066
Intellectual disability	47.57	32.46	12	5773	670	46679607
Temporal lobe epilepsy	43.56	32.46	10	5775	373	46679904
Pneumonia	43.44	32.46	123	5662	376197	46304080
Epidural lipomatosis	42.80	32.46	8	5777	105	46680172
Pneumonia aspiration	41.33	32.46	33	5752	31572	46648705
Coma blister	40.28	32.46	8	5777	147	46680130
Ophthalmological examination abnormal	38.85	32.46	7	5778	74	46680203
Nausea	38.06	32.46	19	5766	687435	45992842
Hypotonia	37.62	32.46	19	5766	8210	46672067
Bronchiolitis	37.05	32.46	13	5772	2272	46678005
Blindness	36.20	32.46	24	5761	17245	46663032
Respiratory failure	35.75	32.46	51	5734	94765	46585512
Visual impairment	34.65	32.46	42	5743	66647	46613630
Rhinovirus infection	34.58	32.46	14	5771	3622	46676655
Respiratory syncytial virus bronchiolitis	34.38	32.46	8	5777	317	46679960
Pain	33.38	32.46	9	5776	476939	46203338
Therapeutic product effective for unapproved indication	32.60	32.46	6	5779	72	46680205

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Seizure	1539.48	40.74	597	4912	97878	29849091
Drug withdrawal convulsions	547.18	40.74	105	5404	1054	29945915
Infantile spasms	503.24	40.74	80	5429	219	29946750
Product dose omission issue	340.03	40.74	210	5299	91421	29855548
Drug ineffective	226.74	40.74	293	5216	340094	29606875
Visual field defect	203.32	40.74	61	5448	4375	29942594
Retinogram abnormal	175.38	40.74	28	5481	79	29946890
Status epilepticus	162.51	40.74	65	5444	11007	29935962
Brain operation	109.99	40.74	22	5487	276	29946693
Death	98.08	40.74	207	5302	357076	29589893
Infantile spitting up	96.91	40.74	15	5494	32	29946937
Somnolence	91.03	40.74	100	5409	96663	29850306
Visual impairment	83.45	40.74	58	5451	30380	29916589
Epilepsy	78.78	40.74	48	5461	20121	29926848
Ophthalmological examination abnormal	68.38	40.74	11	5498	33	29946936
Sudden unexplained death in epilepsy	68.34	40.74	16	5493	434	29946535
Irritability	63.33	40.74	44	5465	23006	29923963
Aggression	60.85	40.74	52	5457	36855	29910114
Optic atrophy	59.68	40.74	16	5493	760	29946209
Postictal paralysis	55.36	40.74	11	5498	133	29946836
Respiratory distress	53.42	40.74	46	5463	32926	29914043
Partial seizures	51.37	40.74	21	5488	3746	29943223
Respiratory syncytial virus infection	46.69	40.74	19	5490	3349	29943620
Crying	46.39	40.74	22	5487	5587	29941382
Abnormal behaviour	46.13	40.74	38	5471	25585	29921384
Seizure cluster	44.62	40.74	9	5500	118	29946851

Pharmacologic Action:

Source	Code	Description
ATC	N03AG04	NERVOUS SYSTEM ANTIEPILEPTICS ANTIEPILEPTICS Fatty acid derivatives
FDA EPC	N0000175753	Anti-epileptic Agent
MeSH PA	D000927	Anticonvulsants
MeSH PA	D002491	Central Nervous System Agents
MeSH PA	D004791	Enzyme Inhibitors
MeSH PA	D018682	GABA Agents
MeSH PA	D018377	Neurotransmitter Agents
CHEBI has role	CHEBI:35623	antiepileptic
CHEBI has role	CHEBI:63674	4-aminobutyrate transaminase inhibitors

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
West syndrome	indication	28055006
Epilepsy characterized by intractable complex partial seizures	indication	442481002
Suicidal thoughts	contraindication	6471006
Weight gain finding	contraindication	8943002
Visual field defect	contraindication	12184005
Reduced visual acuity	contraindication	13164000
Mood swings	contraindication	18963009
Kidney disease	contraindication	90708001	DOID:557
Edema	contraindication	267038008
Anemia	contraindication	271737000	DOID:2355
Pregnancy, function	contraindication	289908002
Peripheral nerve disease	contraindication	302226006
Breastfeeding (mother)	contraindication	413712001

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	3.94	acidic
pKa2	10.16	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
500MG	VIGABATRIN	DR REDDYS	A211539	Jan. 29, 2021	RX	TABLET	ORAL	July 31, 2021	COMPETITIVE GENERIC THERAPY

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
4-aminobutyrate aminotransferase, mitochondrial	Enzyme	P80404	GABT_HUMAN	INHIBITOR				CHEMBL	CHEMBL
Gamma-amino-N-butyrate transaminase	Unclassified		GABT_RAT		IC50	4.38		CHEMBL

External reference:

ID	Source
4025280	VUID
N0000171807	NUI
D00535	KEGG_DRUG
4025280	VANDF
C0592085	UMLSCUI
CHEBI:63638	CHEBI
CHEMBL89598	ChEMBL_ID
D020888	MESH_DESCRIPTOR_UI
5581	INN_ID
GR120KRT6K	UNII
5665	PUBCHEM_CID
4821	IUPHAR_LIGAND_ID
DB01080	DRUGBANK_ID
14851	RXNORM
15507	MMSL
36115	MMSL
52922	MMSL
d04669	MMSL
003774	NDDF
310283001	SNOMEDCT_US
322976008	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Vigabatrin for oral solution USP, 500 mg	HUMAN PRESCRIPTION DRUG LABEL	1	0054-0702	FOR SOLUTION	50 mg	ORAL	ANDA	33 sections
VIGADRONE	HUMAN PRESCRIPTION DRUG LABEL	1	0245-0556	POWDER, FOR SOLUTION	50 mg	ORAL	ANDA	35 sections
Vigabatrin	HUMAN PRESCRIPTION DRUG LABEL	1	0591-3851	TABLET, FILM COATED	500 mg	ORAL	ANDA	29 sections
vigabatrin	HUMAN PRESCRIPTION DRUG LABEL	1	0591-3955	POWDER, FOR SOLUTION	50 mg	ORAL	ANDA	30 sections
Vigabatrin	HUMAN PRESCRIPTION DRUG LABEL	1	16729-521	POWDER, FOR SOLUTION	500 mg	ORAL	ANDA	33 sections
vigabatrin for oral solution	HUMAN PRESCRIPTION DRUG LABEL	1	31722-009	POWDER, FOR SOLUTION	50 mg	ORAL	ANDA	36 sections
Vigabatrin	HUMAN PRESCRIPTION DRUG LABEL	1	43598-651	TABLET, FILM COATED	500 mg	ORAL	ANDA	32 sections
Vigabatrin	HUMAN PRESCRIPTION DRUG LABEL	1	43598-697	POWDER, FOR SOLUTION	50 mg	ORAL	ANDA	31 sections
VIGABATRIN	HUMAN PRESCRIPTION DRUG LABEL	1	49884-358	POWDER, FOR SOLUTION	50 mg	ORAL	ANDA	32 sections
SABRIL	HUMAN PRESCRIPTION DRUG LABEL	1	67386-111	TABLET, FILM COATED	500 mg	ORAL	NDA	32 sections
SABRIL	HUMAN PRESCRIPTION DRUG LABEL	1	67386-211	POWDER, FOR SOLUTION	50 mg	ORAL	NDA	33 sections
VIGABATRIN	Human Prescription Drug Label	1	67877-674	POWDER, FOR SOLUTION	50 mg	ORAL	ANDA	31 sections
VIGABATRIN	HUMAN PRESCRIPTION DRUG LABEL	1	69097-964	POWDER, FOR SOLUTION	500 mg	ORAL	ANDA	32 sections
Vigabatrin	HUMAN PRESCRIPTION DRUG LABEL	1	69238-1425	FOR SOLUTION	500 mg	ORAL	ANDA	30 sections