Identification
- Summary
Lifitegrast is a medication used to treat dry eye disease.
- Brand Names
- Xiidra
- Generic Name
- Lifitegrast
- DrugBank Accession Number
- DB11611
- Background
Lifitegrast is a FDA approved drug for the treatment of keratoconjunctivitis sicca (dry eye syndrome). It is a tetrahydroisoquinoline derivative and lymphocyte function-associated antigen-1 ( LFA-1) antagonist that was discovered through the rational design process. The ophthalmic solution was approved in July, 2016 under the trade name Xiidra. It has shown to protect the corneal surface and alleviate the symptoms of dry eye syndrome with fast onset of action and well tolerated profile in both local and systemic setting 2.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Lifitegrast (DB11611)
- Weight
- Average: 615.48
Monoisotopic: 614.0681277 - Chemical Formula
- C29H24Cl2N2O7S
- Synonyms
- Lifitegrast
- External IDs
- SAR 1118
- SAR-1118
- SHP-606
- SHP606
Pharmacology
- Indication
For the treatment of signs and symptoms of keratoconjunctivitis sicca (dry eye syndrome).
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Symptomatic treatment of Dry eye disease •••••••••••• •••••••••• - Contraindications & Blackbox Warnings
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Lifitegrast addresses both the symptoms and the resulting ocular surface damage by interfering with ocular inflammatory cycle 2. Lifitegrast is a lymphocyte function–associated antigen-1 antagonist through direct competitive antagonism and sequentially inhibits the T-cell recruitment, activation, and proinflammatory cytokine release associated with dry eye syndrome 4.
- Mechanism of action
Lifitegrast binds to the integrin lymphocyte function-associated antigen-1 (LFA-1), a cell surface protein found on leukocytes and blocks the interaction of LFA-1 with its cognate ligand intercellular adhesion molecule-1 (ICAM-1). ICAM-1 may be overexpressed in corneal and conjunctival tissues in dry eye disease. LFA-1/ICAM-1 interaction can contribute to the formation of an immunological synapse resulting in T-cell proliferation/activation and migration to target tissues. In vitro studies demonstrated that lifitegrast may inhibit T-cell adhesion to ICAM-1 in a human T-cell line and may inhibit secretion of inflammatory cytokines, inflammatory mediators, chemokines, TNF-α, and IL-1 in human peripheral blood mononuclear cells.
Target Actions Organism AIntegrin alpha-L antagonistHumans - Absorption
The mean peak plasma concentration (Cmax) of 1.70ng/mL was reached within 15 minutes of application. Quantifiable trough plasma concentrations ranged from 0.55 ng/mL to 3.74 ng/mL 6. Observations show limited systemic exposure that produces significant clinical outcomes.
- Volume of distribution
Not Available
- Protein binding
Human plasma protein binding of lifitegrast was approximately 99%, independent of concentration (50 to 1000ng/mL). Binding to isolated human serum albumin was 95% to 98%, and 31.6% to 51.1% to human α1-acid glycoprotein 6.
- Metabolism
Based on the findings of an in vitro metabolism study using fresh human hepatocytes, lifitegrast does not appear to undergo significant metabolism 6.
- Route of elimination
Not possible to perform mass balance study to determine the main route of elimination 6.
- Half-life
Not possible to calculate plasma elimination half-life based on plasma concentrations of lifitegrast, but reported to be relatively short in rat I.V. pharmacokinetics study 5.
- Clearance
Not possible to calculate clearance rate based on plasma concentrations of lifitegrast, but reported to be relatively fast in rat I.V. pharmacokinetics study 5. It is predicted that lifitegrast is cleared via nasal and subsequently gastrointestinal tract 6.
- Adverse Effects
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Some adverse effects in 5-25% of the patients include instillation site irritation, dysgeusia and reduced visual acuity. There is no evidence or reports of potential carcinogenic, mutagenic or fertility-altering effects of this drug.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Lifitegrast sodium QG18FLP1KP 1119276-80-0 BPWOKOSRORLLIN-BQAIUKQQSA-M - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Xiidra Solution / drops 50 mg/1mL Ophthalmic Bausch & Lomb Incorporated 2024-01-02 Not applicable US 
Xiidra Solution / drops 50 mg/1mL Ophthalmic Novartis Pharmaceuticals Corporation 2016-07-11 Not applicable US Xiidra Solution / drops 50 mg/1mL Ophthalmic Takeda Pharmaceuticals America, Inc. 2016-07-11 2023-03-31 US Xiidra Solution 5 % w/v Ophthalmic Novartis 2018-02-12 Not applicable Canada 
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Lifitegrast For solution 50 mg/1mL Ophthalmic Aurobindo Pharma Limited 2023-11-07 Not applicable US
Categories
- ATC Codes
- S01XA25 — Lifitegrast
- Drug Categories
- Amino Acids
- Amino Acids, Aromatic
- Amino Acids, Cyclic
- Amino Acids, Peptides, and Proteins
- Anti-Inflammatory Agents
- Anti-inflammatory Agents, Miscellaneous
- Compounds used in a research, industrial, or household setting
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
- Cytochrome P-450 Enzyme Inhibitors
- Lymphocyte Function-Associated Antigen-1
- Lymphocyte Function-Associated Antigen-1 Antagonist
- Lymphocyte Function-Associated Antigen-1 Antagonists
- OATP2B1/SLCO2B1 substrates
- Ophthalmic Solutions
- Ophthalmologicals
- Pharmaceutical Preparations
- Pharmaceutical Solutions
- Sensory Organs
- Solutions
- Sulfur Compounds
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenylalanine and derivatives. These are compounds containing phenylalanine or a derivative thereof resulting from reaction of phenylalanine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Phenylalanine and derivatives
- Alternative Parents
- N-acyl-alpha amino acids / Phenylpropanoic acids / Tetrahydroisoquinolines / 2-halobenzoic acids and derivatives / Amphetamines and derivatives / Benzenesulfonyl compounds / Benzofurans / Aryl chlorides / Vinylogous halides / Tertiary carboxylic acid amides show 13 more
- Substituents
- 2-halobenzoic acid or derivatives / 3-phenylpropanoic-acid / Amphetamine or derivatives / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenesulfonyl group / Benzenoid / Benzofuran show 28 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 038E5L962W
- CAS number
- 1025967-78-5
- InChI Key
- JFOZKMSJYSPYLN-QHCPKHFHSA-N
- InChI
- InChI=1S/C29H24Cl2N2O7S/c1-41(38,39)20-4-2-3-16(11-20)12-23(29(36)37)32-27(34)25-22(30)13-19-15-33(9-7-21(19)26(25)31)28(35)18-6-5-17-8-10-40-24(17)14-18/h2-6,8,10-11,13-14,23H,7,9,12,15H2,1H3,(H,32,34)(H,36,37)/t23-/m0/s1
- IUPAC Name
- (2S)-2-{[2-(1-benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinolin-6-yl]formamido}-3-(3-methanesulfonylphenyl)propanoic acid
- SMILES
- CS(=O)(=O)C1=CC(C[C@H](NC(=O)C2=C(Cl)C3=C(CN(CC3)C(=O)C3=CC=C4C=COC4=C3)C=C2Cl)C(O)=O)=CC=C1
References
- General References
- Tauber J, Karpecki P, Latkany R, Luchs J, Martel J, Sall K, Raychaudhuri A, Smith V, Semba CP: Lifitegrast Ophthalmic Solution 5.0% versus Placebo for Treatment of Dry Eye Disease: Results of the Randomized Phase III OPUS-2 Study. Ophthalmology. 2015 Dec;122(12):2423-31. doi: 10.1016/j.ophtha.2015.08.001. Epub 2015 Sep 11. [Article]
- Abidi A, Shukla P, Ahmad A: Lifitegrast: A novel drug for treatment of dry eye disease. J Pharmacol Pharmacother. 2016 Oct-Dec;7(4):194-198. doi: 10.4103/0976-500X.195920. [Article]
- Paton DM: Lifitegrast: First LFA-1/ICAM-1 antagonist for treatment of dry eye disease. Drugs Today (Barc). 2016 Sep;52(9):485-493. [Article]
- Holland EJ, Luchs J, Karpecki PM, Nichols KK, Jackson MA, Sall K, Tauber J, Roy M, Raychaudhuri A, Shojaei A: Lifitegrast for the Treatment of Dry Eye Disease: Results of a Phase III, Randomized, Double-Masked, Placebo-Controlled Trial (OPUS-3). Ophthalmology. 2017 Jan;124(1):53-60. doi: 10.1016/j.ophtha.2016.09.025. Epub 2016 Oct 27. [Article]
- Zhong M, Gadek TR, Bui M, Shen W, Burnier J, Barr KJ, Hanan EJ, Oslob JD, Yu CH, Zhu J, Arkin MR, Evanchik MJ, Flanagan WM, Hoch U, Hyde J, Prabhu S, Silverman JA, Wright J: Discovery and Development of Potent LFA-1/ICAM-1 Antagonist SAR 1118 as an Ophthalmic Solution for Treating Dry Eye. ACS Med Chem Lett. 2012 Jan 31;3(3):203-6. doi: 10.1021/ml2002482. eCollection 2012 Mar 8. [Article]
- FDA Clinical Pharmacology and Biopharmaceutics Review [Link]
- FDA Approved Drug Products: Xiidra (lifitegrast) ophthalmic solution [Link]
- External Links
- KEGG Drug
- D10374
- PubChem Compound
- 11965427
- PubChem Substance
- 347828006
- ChemSpider
- 10139520
- BindingDB
- 50386331
- 1801820
- ChEBI
- 133023
- ChEMBL
- CHEMBL2048028
- ZINC
- ZINC000084668739
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Lifitegrast
- FDA label
- Download (1.22 MB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Supportive Care Contact Lens Discomfort (CLD) / Contact Lens Related Dry Eye / Contact Lenses 1 4 Completed Treatment Dry Eye Syndrome (DES) 1 4 Completed Treatment Dry Eyes 3 4 Recruiting Treatment Corneal Diseases 1 4 Recruiting Treatment Dry Eyes 2
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength For solution Ophthalmic 50 mg/1mL Solution Ophthalmic 5 % w/v Solution Ophthalmic 50.00 mg Solution / drops Ophthalmic 50 mg/1mL - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8927574 No 2015-01-06 2030-11-12 US US7928122 No 2011-04-19 2024-11-05 US US9085553 No 2015-07-21 2033-07-25 US US9353088 No 2016-05-31 2030-10-21 US US9216174 No 2015-12-22 2024-11-05 US US7314938 No 2008-01-01 2025-03-10 US US8084047 No 2011-12-27 2026-05-17 US US8367701 No 2013-02-05 2029-04-15 US US8168655 No 2012-05-01 2029-05-09 US US8592450 No 2013-11-26 2026-05-17 US US7790743 No 2010-09-07 2024-11-05 US US7745460 No 2010-06-29 2024-11-05 US US9447077 No 2016-09-20 2029-04-15 US US9890141 No 2018-02-13 2030-10-21 US US10124000 No 2018-11-13 2024-11-05 US US11058677 No 2021-07-13 2033-12-18 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility Soluble FDA Label - Predicted Properties
Property Value Source Water Solubility 0.00571 mg/mL ALOGPS logP 3.96 ALOGPS logP 4.02 Chemaxon logS -5 ALOGPS pKa (Strongest Acidic) 3.27 Chemaxon pKa (Strongest Basic) -1.3 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 133.99 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 154.48 m3·mol-1 Chemaxon Polarizability 59.49 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 228.20387 predictedDeepCCS 1.0 (2019) [M+H]+ 230.36162 predictedDeepCCS 1.0 (2019) [M+Na]+ 236.23138 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Metal ion binding
- Specific Function
- Integrin alpha-L/beta-2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4. It is involved in a variety of immune phenomena including leukocyte-endothelial cell interaction, cytotoxic T-cell mediated ...
- Gene Name
- ITGAL
- Uniprot ID
- P20701
- Uniprot Name
- Integrin alpha-L
- Molecular Weight
- 128768.495 Da
References
- Paton DM: Lifitegrast: First LFA-1/ICAM-1 antagonist for treatment of dry eye disease. Drugs Today (Barc). 2016 Sep;52(9):485-493. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- FDA Clinical Pharmacology and Biopharmaceutics Review [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibit...
- Gene Name
- SLCO1A2
- Uniprot ID
- P46721
- Uniprot Name
- Solute carrier organic anion transporter family member 1A2
- Molecular Weight
- 74144.105 Da
References
- FDA Clinical Pharmacology and Biopharmaceutics Review [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost.
- Gene Name
- SLCO2B1
- Uniprot ID
- O94956
- Uniprot Name
- Solute carrier organic anion transporter family member 2B1
- Molecular Weight
- 76709.98 Da
References
- FDA Clinical Pharmacology and Biopharmaceutics Review [Link]
Drug created at July 13, 2016 15:57 / Updated at April 23, 2024 11:38