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

Stem definition	Drug id	CAS RN
integrin antagonists	5174	1025967-78-5

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: lifitegrast SAR 1118-023 SAR 1118 SAR-1118 xiidra	a lymphocyte function-associated antigen-1 ( LFA-1) antagonist, blocks the interaction of LFA-1 with its cognate ligand intercellular adhesion molecule-1 (ICAM-1), LFA-1/ICAM-1 interaction can contribute to the formation of an immunological synapse resulting in T-cell activation and migration to target tissues Molecular weight: 615.48 Formula: C29H24Cl2N2O7S CLOGP: 2.28 LIPINSKI: 1 HAC: 9 HDO: 2 TPSA: 133.99 ALOGS: -5.03 ROTB: 7 Status: ONP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

lifitegrast
SAR 1118-023
SAR 1118
SAR-1118
xiidra

a lymphocyte function-associated antigen-1 ( LFA-1) antagonist, blocks the interaction of LFA-1 with its cognate ligand intercellular adhesion molecule-1 (ICAM-1), LFA-1/ICAM-1 interaction can contribute to the formation of an immunological synapse resulting in T-cell activation and migration to target tissues

Molecular weight: 615.48
Formula: C29H24Cl2N2O7S
CLOGP: 2.28
LIPINSKI: 1
HAC: 9
HDO: 2
TPSA: 133.99
ALOGS: -5.03
ROTB: 7

Status: ONP

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

Drug dosage:

None

ADMET properties:

None

Approvals:

Date	Agency	Company	Orphan
July 11, 2016	FDA	SHIRE DEV 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
Instillation site pain	2914.69	48.53	400	4982	508	46680172
Instillation site reaction	2288.01	48.53	300	5082	180	46680500
Eye irritation	1074.82	48.53	270	5112	16344	46664336
Vision blurred	1071.92	48.53	384	4998	79324	46601356
Dysgeusia	621.15	48.53	216	5166	40275	46640405
Instillation site irritation	599.62	48.53	78	5304	37	46680643
Instillation site pruritus	558.08	48.53	71	5311	17	46680663
Instillation site erythema	517.60	48.53	67	5315	28	46680652
Instillation site lacrimation	427.63	48.53	54	5328	9	46680671
Eye pain	318.64	48.53	120	5262	27820	46652860
Dry eye	263.58	48.53	107	5275	30215	46650465
Instillation site discharge	258.40	48.53	33	5349	9	46680671
Lacrimation increased	228.48	48.53	81	5301	15780	46664900
Ocular hyperaemia	225.77	48.53	85	5297	19625	46661055
Instillation site swelling	217.91	48.53	27	5355	0	46680680
Eye discharge	188.22	48.53	53	5329	4875	46675805
Product container issue	181.43	48.53	42	5340	1757	46678923
Instillation site discomfort	169.47	48.53	21	5361	0	46680680
Product quality issue	159.17	48.53	79	5303	35569	46645111
Eye pruritus	131.39	48.53	50	5332	11848	46668832
Visual impairment	120.30	48.53	82	5300	66607	46614073
Product use complaint	99.70	48.53	26	5356	1786	46678894
Instillation site dryness	93.38	48.53	12	5370	4	46680676
Ocular discomfort	90.76	48.53	27	5355	3008	46677672
Instillation site inflammation	88.76	48.53	11	5371	0	46680680
Eyelid margin crusting	85.35	48.53	19	5363	664	46680016
Eye disorder	83.24	48.53	41	5341	18100	46662580
Inappropriate schedule of product administration	83.22	48.53	65	5317	64948	46615732
Instillation site foreign body sensation	78.07	48.53	10	5372	3	46680677
Instillation site burn	72.62	48.53	9	5373	0	46680680
Product packaging quantity issue	70.65	48.53	18	5364	1126	46679554
Taste disorder	65.93	48.53	25	5357	5853	46674827
Eye swelling	62.44	48.53	35	5347	20068	46660612
Foreign body sensation in eyes	61.84	48.53	18	5364	1858	46678822
Instillation site hypersensitivity	56.48	48.53	7	5375	0	46680680

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
Instillation site reaction	613.65	120.68	67	840	22	29951549
Instillation site pain	505.70	120.68	58	849	61	29951510
Vision blurred	444.99	120.68	122	785	41694	29909877
Eye irritation	359.44	120.68	71	836	5625	29945946
Instillation site lacrimation	131.78	120.68	14	893	0	29951571

Pharmacologic Action:

Source	Code	Description
ATC	S01XA25	SENSORY ORGANS OPHTHALMOLOGICALS OTHER OPHTHALMOLOGICALS Other ophthalmologicals
MeSH PA	D009883	Ophthalmic Solutions
MeSH PA	D019999	Pharmaceutical Solutions
FDA MoA	N0000192700	Lymphocyte Function-Associated Antigen-1 Antagonists
FDA EPC	N0000192701	Lymphocyte Function-Associated Antigen-1 Antagonist
CHEBI has role	CHEBI:35472	anti-inflammatory drugs
CHEBI has role	CHEBI:133024	lfa-1 antagonist

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Tear film insufficiency	indication	46152009

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	3.42	acidic
pKa2	12.3	acidic

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
5%	XIIDRA	NOVARTIS	N208073	July 11, 2016	RX	SOLUTION/DROPS	OPHTHALMIC	July 11, 2021	NEW CHEMICAL ENTITY

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Integrin alpha-L/beta-2	Adhesion	P05107 P20701	ITAL_HUMAN ITB2_HUMAN	ANTAGONIST	IC50	8.05		SCIENTIFIC LITERATURE	DRUG LABEL
Intercellular adhesion molecule 1	Unclassified	P05362	ICAM1_HUMAN		IC50	8.53		CHEMBL

External reference:

ID	Source
D10374	KEGG_DRUG
4035938	VANDF
C3713860	UMLSCUI
CHEBI:133023	CHEBI
CHEMBL2048028	ChEMBL_ID
CHEMBL2048409	ChEMBL_ID
DB11611	DRUGBANK_ID
C575157	MESH_SUPPLEMENTAL_RECORD_UI
7533	IUPHAR_LIGAND_ID
9584	INN_ID
038E5L962W	UNII
11965427	PUBCHEM_CID
1801820	RXNORM
243704	MMSL
31873	MMSL
016935	NDDF
720489009	SNOMEDCT_US
763569006	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Xiidra	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0911	SOLUTION/ DROPS	50 mg	OPHTHALMIC	NDA	24 sections
Xiidra	HUMAN PRESCRIPTION DRUG LABEL	1	54092-606	SOLUTION/ DROPS	50 mg	OPHTHALMIC	NDA	23 sections