nepafenac 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
anti-inflammatory agents, ibufenac derivatives 1899 78281-72-8

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • nepafenac
  • nevanac
penetrates the cornea and is converted by ocular tissue hydrolases to amfenac, a nonsteroidal anti-inflammatory drug, amfenac is thought to inhibit the action of prostaglandin H synthase (cyclooxygenase), an enzyme required for prostaglandin production
  • Molecular weight: 254.29
  • Formula: C15H14N2O2
  • CLOGP: 1.38
  • LIPINSKI: 0
  • HAC: 4
  • HDO: 2
  • TPSA: 86.18
  • ALOGS: -4.11
  • ROTB: 4
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.17 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 1.252 Moderate 0.65
caco2-efflux Caco-2 efflux ratio (BA/AB) 1.153 Moderate 0.65
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 47.534 10^-6 cm/s Moderate 0.65
dh-clint Dog hepatocyte intrinsic clearance 4.276 uL/min/10^6 cells Moderate 0.65
dppb Dog plasma protein binding (% unbound) 41.620 % Moderate 0.65
fcs-ppb Fetal calf serum protein binding (% unbound) 46.040 % Moderate 0.65
herg hERG pIC50 4.177 pIC50 Moderate 0.65
hh-clint Human hepatocyte intrinsic clearance 2.576 uL/min/10^6 cells Moderate 0.65
hlm-clint Human liver microsomal intrinsic clearance 3.076 uL/min/mg protein Moderate 0.65
hppb Human plasma protein binding (% unbound) 39.730 % Moderate 0.65
kinase-safety-class ACVR2A,ACVR2B,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK5,CDK9,DDR1,DYRK1B,EGFR,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,ITK,JAK2,MAP3K1,MAP3K21,MAP3K7,MAPK10,MAPK12,MAPK7,MAPK9,MAPKAPK2,MARK4,MET,NTRK2,PDK1,PDK2,PDK4,PDPK1,PIK3CB,PIK3CG,PIM2,PRKCD,PRKDC,SIK2,SIK3,STK33,TEK,TTK 45
kinase-selectivity-class AXL,EIF2AK3,GRK2,SIK2,STK33 5
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 5.035 Moderate 0.65
mh-clint Mouse hepatocyte intrinsic clearance 9.078 Moderate 0.65
mppb Mouse plasma protein binding (% unbound) 41 Moderate 0.65
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 8.472 Moderate 0.65
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 50.230 % Moderate 0.65
rat-kpuu-brain Rat brain Kpuu 0.060 % Moderate 0.65
rh-clint Rat hepatocyte intrinsic clearance 5.035 uL/min/10^6 cells Moderate 0.65
rh-fuinc Rat hepatocyte fraction unbound in incubation 92.300 % Moderate 0.65
rppb Rat plasma protein binding (% unbound) 36.690 % Moderate 0.65
solubility-dd Solubility at pH 7.4 in DMSO 414.954 uM Moderate 0.65

Approvals:

DateAgencyCompanyOrphan
Aug. 19, 2005 FDA ALCON PHARMS LTD

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Ulcerative keratitis 116.64 38.33 24 1789 3429 90623205
Cataract 111.79 38.33 45 1768 72047 90554587
Toxic anterior segment syndrome 108.22 38.33 21 1792 2229 90624405
Corneal opacity 106.22 38.33 18 1795 893 90625741
Eye pain 106.20 38.33 38 1775 44130 90582504
Corneal epithelium defect 102.41 38.33 16 1797 475 90626159
Visual acuity reduced 99.70 38.33 31 1782 23379 90603255
Product container issue 96.60 38.33 19 1794 2162 90624472
Corneal oedema 93.00 38.33 18 1795 1883 90624751
Uveitis 80.23 38.33 24 1789 15879 90610755
Liquid product physical issue 77.82 38.33 15 1798 1535 90625099
Vision blurred 72.72 38.33 38 1775 110255 90516379
Macular oedema 70.79 38.33 17 1796 4892 90621742
Intraocular pressure increased 69.41 38.33 18 1795 7075 90619559
Product quality issue 69.01 38.33 33 1780 79292 90547342
Anterior chamber inflammation 67.99 38.33 11 1802 409 90626225
Cystoid macular oedema 67.42 38.33 14 1799 2086 90624548
Product administration error 64.45 38.33 23 1790 26400 90600234
Product physical consistency issue 58.98 38.33 11 1802 943 90625691
Product delivery mechanism issue 58.80 38.33 10 1803 506 90626128
Corneal infiltrates 54.08 38.33 8 1805 163 90626471
Eye inflammation 53.61 38.33 15 1798 7836 90618798
Product packaging quantity issue 53.29 38.33 11 1802 1591 90625043
Ocular hypertension 52.77 38.33 11 1802 1669 90624965
Endophthalmitis 51.26 38.33 13 1800 4672 90621962
Foreign body sensation in eyes 50.54 38.33 12 1801 3288 90623346
Vitreous floaters 49.62 38.33 14 1799 7535 90619099
Ocular hyperaemia 48.52 38.33 20 1793 33778 90592856
Corneal scar 47.25 38.33 7 1806 144 90626490
Treatment failure 45.61 38.33 42 1771 303886 90322748
Corneal disorder 45.07 38.33 10 1803 2032 90624602
Ocular vascular disorder 43.66 38.33 8 1805 622 90626012
Visual impairment 43.25 38.33 29 1784 132336 90494298
Punctate keratitis 41.79 38.33 8 1805 788 90625846
Fibroadenoma of breast 41.09 38.33 8 1805 861 90625773
Wrong technique in product usage process 39.66 38.33 22 1791 71549 90555085
Eye irritation 38.48 38.33 17 1796 33961 90592673

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Ulcerative keratitis 100.82 33.50 21 1290 2067 42617957
Corneal oedema 89.00 33.50 18 1293 1530 42618494
Toxic anterior segment syndrome 84.59 33.50 17 1294 1399 42618625
Endophthalmitis 60.47 33.50 16 1295 4417 42615607
Intraocular pressure increased 59.01 33.50 17 1294 6416 42613608
Cystoid macular oedema 53.40 33.50 11 1300 1022 42619002
Visual impairment 52.93 33.50 26 1285 43087 42576937
Corneal opacity 51.98 33.50 10 1301 655 42619369
Macular oedema 49.24 33.50 13 1298 3556 42616468
Ocular hyperaemia 47.44 33.50 18 1293 15945 42604079
Glaucoma 46.53 33.50 15 1296 8233 42611791
Visual acuity reduced 45.78 33.50 18 1293 17532 42602492
Eye irritation 45.69 33.50 16 1295 11302 42608722
Haemolytic uraemic syndrome 43.81 33.50 11 1300 2468 42617556
Eye pain 42.78 33.50 17 1294 17013 42603011
Cataract 42.20 33.50 20 1291 30584 42589440
Vision blurred 42.07 33.50 24 1287 53675 42566349
Pseudoendophthalmitis 40.04 33.50 6 1305 85 42619939
Product quality issue 38.57 33.50 16 1295 17866 42602158
Foreign body sensation in eyes 36.91 33.50 8 1303 947 42619077
Anterior chamber cell 36.34 33.50 7 1304 461 42619563
Corneal disorder 36.09 33.50 8 1303 1051 42618973
Renal colic 35.66 33.50 9 1302 2059 42617965
Hypopyon 35.41 33.50 7 1304 528 42619496
Product delivery mechanism issue 33.61 33.50 6 1305 260 42619764

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Ulcerative keratitis 178.52 31.42 36 2145 4730 110582388
Corneal oedema 161.65 31.42 31 2150 3142 110583976
Toxic anterior segment syndrome 152.91 31.42 30 2151 3424 110583694
Intraocular pressure increased 128.61 31.42 32 2149 10844 110576274
Endophthalmitis 121.89 31.42 29 2152 8158 110578960
Visual acuity reduced 118.47 31.42 38 2143 32135 110554983
Eye pain 94.71 31.42 36 2145 50063 110537055
Macular oedema 89.92 31.42 22 2159 6944 110580174
Cataract 88.24 31.42 39 2142 79446 110507672
Corneal opacity 87.68 31.42 16 2165 1235 110585883
Corneal epithelium defect 85.96 31.42 15 2166 897 110586221
Vision blurred 78.66 31.42 42 2139 128980 110458138
Cystoid macular oedema 74.82 31.42 16 2165 2784 110584334
Visual impairment 71.53 31.42 40 2141 134388 110452730
Ocular hypertension 71.43 31.42 15 2166 2393 110584725
Blindness unilateral 63.90 31.42 18 2163 9768 110577350
Corneal scar 63.05 31.42 10 2171 332 110586786
Ocular hyperaemia 55.87 31.42 23 2158 39263 110547855
Hypopyon 54.61 31.42 11 2170 1429 110585689
Uveitis 53.57 31.42 19 2162 21691 110565427
Corneal disorder 53.56 31.42 12 2169 2585 110584533
Vitreous floaters 51.56 31.42 15 2166 9119 110577999
Eye inflammation 51.50 31.42 15 2166 9156 110577962
Ocular vascular disorder 48.36 31.42 9 2172 773 110586345
Eye irritation 45.58 31.42 19 2162 33433 110553685
Punctate keratitis 44.48 31.42 9 2172 1195 110585923
Pseudoendophthalmitis 42.77 31.42 6 2175 84 110587034
Fibroadenoma of breast 42.71 31.42 8 2173 711 110586407
Glaucoma 41.85 31.42 16 2165 22501 110564617
Haemolytic uraemic syndrome 41.02 31.42 11 2170 4974 110582144
Foreign body sensation in eyes 40.33 31.42 10 2171 3324 110583794
Anterior chamber cell 38.49 31.42 8 2173 1213 110585905
Iris atrophy 37.54 31.42 6 2175 209 110586909
Anterior chamber inflammation 35.91 31.42 7 2174 768 110586350
Renal colic 35.56 31.42 9 2172 3249 110583869
Electric shock sensation 34.78 31.42 8 2173 1936 110585182
Corneal perforation 34.45 31.42 7 2174 949 110586169
Corneal infiltrates 34.35 31.42 6 2175 360 110586758
Photophobia 32.97 31.42 14 2167 25757 110561361
Vitritis 32.31 31.42 8 2173 2645 110584473

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC S01BC10 SENSORY ORGANS
OPHTHALMOLOGICALS
ANTIINFLAMMATORY AGENTS
Antiinflammatory agents, non-steroids
FDA CS M0001335 Anti-Inflammatory Agents, Non-Steroidal
FDA MoA N0000000160 Cyclooxygenase Inhibitors
MeSH PA D000700 Analgesics
MeSH PA D000893 Anti-Inflammatory Agents
MeSH PA D000894 Anti-Inflammatory Agents, Non-Steroidal
MeSH PA D018373 Peripheral Nervous System Agents
MeSH PA D018501 Antirheumatic Agents
MeSH PA D018689 Sensory System Agents
MeSH PA D018712 Analgesics, Non-Narcotic
FDA EPC N0000175722 Nonsteroidal Anti-inflammatory Drug
CHEBI has role CHEBI:35475 non-steroidal anti-inflammatory drug
CHEBI has role CHEBI:35481 non-narcotic analgesic
CHEBI has role CHEBI:35493 antipyretic
CHEBI has role CHEBI:50629 cyclooxygenase 2 inhibitor
CHEBI has role CHEBI:50630 cyclooxygenase 1 inhibitor
CHEBI has role CHEBI:35480 analgesic
CHEBI has role CHEBI:50266 prodrug
CHEBI has role CHEBI:66981 ophthalmology drug
CHEBI has role CHEBI:67079 anti-inflammatory agent

Related Drugs by ATC class:

S01BC Antiinflammatory agents, non-steroids 10 drugs
bendazacbromfenacdiclofenacflurbiprofenindomethacinketorolacoxyphenbutazonepiroxicampranoprofensalicylic acid

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Post-Op Ocular Inflammation indication
Postoperative Ocular Pain indication
Keratitis contraindication 5888003 DOID:4677
Tear film insufficiency contraindication 46152009
Corneal erosion contraindication 50792001
Blood coagulation disorder contraindication 64779008 DOID:1247
Rheumatoid arthritis contraindication 69896004 DOID:7148
Diabetes mellitus contraindication 73211009 DOID:9351
Perforation of cornea contraindication 74895004
Corneal ulcer contraindication 91514001 DOID:8463
Corneal epithelial degeneration contraindication 231929005
Impaired wound healing contraindication 271618001
Decreased Corneal Sensitivity contraindication
Ocular Bleeding contraindication




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 13.34 acidic
pKa2 2.94 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
0.1% NEVANAC HARROW EYE N021862 Aug. 19, 2005 RX SUSPENSION/DROPS OPHTHALMIC 7834059 Jan. 31, 2027 METHOD OF TREATING OCULAR INFLAMMATION

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Prostaglandin G/H synthase 2 Enzyme INHIBITOR IC50 6.82 WOMBAT-PK KEGG DRUG
Prostaglandin G/H synthase 1 Enzyme INHIBITOR IC50 6.60 WOMBAT-PK KEGG DRUG
Cyclooxygenase Enzyme IC50 6.70 CHEMBL
Cyclooxygenase Enzyme IC50 7 CHEMBL

External reference:

IDSource
4024931 VUID
N0000171607 NUI
D05143 KEGG_DRUG
4024931 VANDF
C0961209 UMLSCUI
CHEBI:75922 CHEBI
CHEMBL1021 ChEMBL_ID
DB06802 DRUGBANK_ID
C414203 MESH_SUPPLEMENTAL_RECORD_UI
151075 PUBCHEM_CID
7564 IUPHAR_LIGAND_ID
7685 INN_ID
0J9L7J6V8C UNII
DB15911 DRUGBANK_ID
298665 RXNORM
196661 MMSL
20485 MMSL
71034 MMSL
010980 NDDF
419460005 SNOMEDCT_US
419829002 SNOMEDCT_US
C0051572 UMLSCUI
CHEMBL25146 ChEMBL_ID
51579-82-9 SECONDARY_CAS_RN
2136 PUBCHEM_CID
7565 IUPHAR_LIGAND_ID
4363 INN_ID
C014285 MESH_SUPPLEMENTAL_RECORD_UI
28O5C1J38A UNII
CHEBI:75915 CHEBI
0J9L7J6V8C INXIGHT DRUGS
28O5C1J38A INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
ILEVRO HUMAN PRESCRIPTION DRUG LABEL 1 0078-0743 SUSPENSION/ DROPS 3 mg OPHTHALMIC NDA 22 sections
NEVANAC HUMAN PRESCRIPTION DRUG LABEL 1 0078-0778 SUSPENSION/ DROPS 1 mg OPHTHALMIC NDA 23 sections
Nevanac HUMAN PRESCRIPTION DRUG LABEL 1 54868-6302 SUSPENSION 1 mg OPHTHALMIC NDA 22 sections
ILEVRO HUMAN PRESCRIPTION DRUG LABEL 1 82667-400 SUSPENSION/ DROPS 3 mg OPHTHALMIC NDA 22 sections
NEVANAC HUMAN PRESCRIPTION DRUG LABEL 1 82667-500 SUSPENSION/ DROPS 1 mg OPHTHALMIC NDA 23 sections
NEVANAC HUMAN PRESCRIPTION DRUG LABEL 1 82667-500 SUSPENSION/ DROPS 1 mg OPHTHALMIC NDA 23 sections