Nepafenac

Identification

Name
Nepafenac
Accession Number
DB06802
Description

Nepafenac is a non-steroidal anti-inflammatory prodrug (NSAID) usually sold as a prescription eye drop. It is used to treat pain and inflammation associated with cataract surgery.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 254.2839
Monoisotopic: 254.105527702
Chemical Formula
C15H14N2O2
Synonyms
  • 2-amino-3-benzoylbenzeneacetamide
  • Nepafenac
  • Népafénac
  • Nepafenaco
  • Nepafenacum
External IDs
  • AHR 9434
  • AHR-9434
  • AL 6515
  • AL-6515

Pharmacology

Pharmacology
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Indication

For the treatment of pain and inflammation associated with cataract surgery.

Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Low but quantifiable plasma concentrations of nepafenac and amfenac were observed in the majority of subjects 2 and 3 hours postdose, respectively, following bilateral topical ocular TID dosing of nepafenac ophthalmic suspension, 0.1%. The mean steady-state Cmax for nepafenac and for amfenac were 0.310 ± 0.104 ng/ml and 0.422 ± 0.121 ng/ml, respectively, following ocular administration.

Mechanism of action

Nepafenac is a prodrug. After penetrating the cornea, nepafenac undergoes rapid bioactivation to amfenac, which is a potent NSAID that uniformly inhibits the COX1 and COX2 activity.

TargetActionsOrganism
UProstaglandin G/H synthase 1
inhibitor
Humans
UProstaglandin G/H synthase 2
inhibitor
Humans
Absorption

Nepafenac rapidly cross the cornea (6 times faster than diclofenac in vitro).

Volume of distribution
Not Available
Protein binding

Amfenac has high affinity toward serum albumin proteins. In vitro, the percent bound to human albumin and human serum was 95.4% and 99.1% respectively.

Metabolism

Nepafenac (prodrug) is deaminated to amfenac (active compound) in the ciliary body epithelium, retina, and choroid by intraocular hydrolases. Subsequently, amfenac undergoes extensive metabolism to more polar metabolites involving hydroxylation of the aromatic ring leading to glucuronide conjugate formation.

Route of elimination

After oral administration of 14C-nepafenac to healthy volunteers, urinary excretion was found to be the major route of radioactivity elimination, accounting for approximately 85% of the dose, while fecal excretion represented approximately 6% of the dose. Nepafenac (prodrug) and amfenac (active compound) were not quantifiable in the urine.

Half-life
Not Available
Clearance
Not Available
Adverse Effects
Medicalerrors
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Toxicity

Ocularly applied non-steroidal anti-inflammatory drugs may cause increased bleeding of ocular tissues (including hyphemas) in conjunction with ocular surgery.

Affected organisms
Not Available
Pathways
PathwayCategory
Nepafenac Action PathwayDrug action
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.
DrugInteraction
AceclofenacThe risk or severity of adverse effects can be increased when Nepafenac is combined with Aceclofenac.
AcemetacinThe risk or severity of adverse effects can be increased when Nepafenac is combined with Acemetacin.
Acetylsalicylic acidThe therapeutic efficacy of Acetylsalicylic acid can be decreased when used in combination with Nepafenac.
AlclofenacThe risk or severity of adverse effects can be increased when Nepafenac is combined with Alclofenac.
AminophenazoneThe risk or severity of adverse effects can be increased when Nepafenac is combined with Aminophenazone.
Aminosalicylic acidThe therapeutic efficacy of Aminosalicylic acid can be decreased when used in combination with Nepafenac.
AmitriptylineThe risk or severity of gastrointestinal bleeding can be increased when Amitriptyline is combined with Nepafenac.
AmitriptylinoxideThe risk or severity of gastrointestinal bleeding can be increased when Amitriptylinoxide is combined with Nepafenac.
AmoxapineThe risk or severity of gastrointestinal bleeding can be increased when Amoxapine is combined with Nepafenac.
AntipyrineThe risk or severity of adverse effects can be increased when Nepafenac is combined with Antipyrine.
Interactions
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Food Interactions
No interactions found.

Products

Products
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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
IlevroSuspension3 mg/1mLOphthalmicALCON LABORATORIES, INC.2012-12-20Not applicableUS flag
IlevroSuspension0.3 %OphthalmicNovartis2014-06-01Not applicableCanada flag
IlevroSuspension / drops3 mg/1mLOphthalmicNovartis Pharmaceuticals Corporation2012-12-20Not applicableUS flag
NevanacSuspension0.1 %OphthalmicNovartis2008-08-21Not applicableCanada flag
NevanacSuspension / dropsOphthalmicNovartis Europharm Limited2020-12-23Not applicableEU flag
NevanacSuspension / dropsOphthalmicNovartis Europharm Limited2020-12-23Not applicableEU flag
NevanacSuspension / drops1 mg/1mLOphthalmicALCON LABORATORIES, INC.2005-09-06Not applicableUS flag
NevanacSuspension / dropsOphthalmicNovartis Europharm Limited2020-12-23Not applicableEU flag
NevanacSuspension1 mg/1mLOphthalmicPhysicians Total Care, Inc.2011-08-31Not applicableUS flag

Categories

ATC Codes
S01BC10 — Nepafenac
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as benzophenones. These are organic compounds containing a ketone attached to two phenyl groups.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzophenones
Direct Parent
Benzophenones
Alternative Parents
Diphenylmethanes / Aryl-phenylketones / Phenylacetamides / Benzoyl derivatives / Aniline and substituted anilines / Vinylogous amides / Primary carboxylic acid amides / Amino acids and derivatives / Primary amines / Organopnictogen compounds
show 2 more
Substituents
Amine / Amino acid or derivatives / Aniline or substituted anilines / Aromatic homomonocyclic compound / Aryl ketone / Aryl-phenylketone / Benzophenone / Benzoyl / Carbonyl group / Carboxamide group
show 14 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
monocarboxylic acid amide (CHEBI:75922)

Chemical Identifiers

UNII
0J9L7J6V8C
CAS number
78281-72-8
InChI Key
QEFAQIPZVLVERP-UHFFFAOYSA-N
InChI
InChI=1S/C15H14N2O2/c16-13(18)9-11-7-4-8-12(14(11)17)15(19)10-5-2-1-3-6-10/h1-8H,9,17H2,(H2,16,18)
IUPAC Name
2-(2-amino-3-benzoylphenyl)acetamide
SMILES
NC(=O)CC1=CC=CC(C(=O)C2=CC=CC=C2)=C1N

References

General References
  1. Gamache DA, Graff G, Brady MT, Spellman JM, Yanni JM: Nepafenac, a unique nonsteroidal prodrug with potential utility in the treatment of trauma-induced ocular inflammation: I. Assessment of anti-inflammatory efficacy. Inflammation. 2000 Aug;24(4):357-70. [PubMed:10850857]
  2. Ke TL, Graff G, Spellman JM, Yanni JM: Nepafenac, a unique nonsteroidal prodrug with potential utility in the treatment of trauma-induced ocular inflammation: II. In vitro bioactivation and permeation of external ocular barriers. Inflammation. 2000 Aug;24(4):371-84. [PubMed:10850858]
  3. Lane SS, Modi SS, Lehmann RP, Holland EJ: Nepafenac ophthalmic suspension 0.1% for the prevention and treatment of ocular inflammation associated with cataract surgery. J Cataract Refract Surg. 2007 Jan;33(1):53-8. [PubMed:17189793]
  4. Walters T, Raizman M, Ernest P, Gayton J, Lehmann R: In vivo pharmacokinetics and in vitro pharmacodynamics of nepafenac, amfenac, ketorolac, and bromfenac. J Cataract Refract Surg. 2007 Sep;33(9):1539-45. [PubMed:17720067]
  5. Bucci FA Jr, Waterbury LD: Re: Pharmacokinetics and pharmacodynamics of nepafenac, amfenac, ketorolac, and bromfenac. J Cataract Refract Surg. 2008 Aug;34(8):1226; author reply 1226-7. doi: 10.1016/j.jcrs.2008.05.019. [PubMed:18655957]
Human Metabolome Database
HMDB0015678
KEGG Drug
D05143
PubChem Compound
151075
PubChem Substance
99443294
ChemSpider
133160
BindingDB
50228731
RxNav
298665
ChEBI
75922
ChEMBL
CHEMBL1021
ZINC
ZINC000005162311
PharmGKB
PA165958407
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Nepafenac
AHFS Codes
  • 52:08.20 — Nonsteroidal Anti-inflammatory Agents
FDA label
Download (119 KB)
MSDS
Download (58.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedNot AvailableCataract Surgery1
4CompletedNot AvailableCataracts1
4CompletedNot AvailableIntraocular Pressure1
4CompletedNot AvailableVitrectomy therapy1
4CompletedPreventionCataracts1
4CompletedPreventionCystoid Macular Edema1
4CompletedPreventionEpiretinal Membrane1
4CompletedPreventionMacular Edema1
4CompletedTreatmentCataracts2
4CompletedTreatmentCataracts / Cystoid Macular Edema1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
SuspensionOphthalmic0.3 %
SuspensionOphthalmic3 mg/1mL
Suspension / dropsOphthalmic3 mg/1mL
SuspensionConjunctival; Ophthalmic3 mg
SuspensionOphthalmic
SuspensionConjunctival; Ophthalmic1 mg
Solution / dropsOphthalmic
SuspensionOphthalmic0.1 %
SuspensionOphthalmic1 mg/1mL
Suspension / dropsOphthalmic1 mg/1mL
Suspension / dropsOphthalmic
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US7834059No2010-11-162027-01-31US flag
US8071648No2011-12-062025-12-02US flag
US8324281No2012-12-042025-12-02US flag
US7947295No2011-05-242024-06-08US flag
US6403609No2002-06-112018-07-17US flag
US8921337No2014-12-302032-03-31US flag
US9662398No2017-05-302030-12-01US flag

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0197 mg/mLALOGPS
logP1.53ALOGPS
logP2.08ChemAxon
logS-4.1ALOGPS
pKa (Strongest Acidic)15.82ChemAxon
pKa (Strongest Basic)1.83ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area86.18 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity74.46 m3·mol-1ChemAxon
Polarizability26.63 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9624
Blood Brain Barrier+0.9918
Caco-2 permeable+0.5581
P-glycoprotein substrateNon-substrate0.7608
P-glycoprotein inhibitor INon-inhibitor0.5471
P-glycoprotein inhibitor IINon-inhibitor0.9209
Renal organic cation transporterNon-inhibitor0.8641
CYP450 2C9 substrateNon-substrate0.8471
CYP450 2D6 substrateNon-substrate0.827
CYP450 3A4 substrateNon-substrate0.6542
CYP450 1A2 substrateInhibitor0.6993
CYP450 2C9 inhibitorInhibitor0.547
CYP450 2D6 inhibitorNon-inhibitor0.882
CYP450 2C19 inhibitorInhibitor0.5714
CYP450 3A4 inhibitorNon-inhibitor0.7118
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7441
Ames testNon AMES toxic0.6193
CarcinogenicityNon-carcinogens0.6932
BiodegradationNot ready biodegradable0.719
Rat acute toxicity2.0064 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9797
hERG inhibition (predictor II)Non-inhibitor0.7681
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-03dr-1490000000-433d63cd52e5b86417da

Targets

Drugtargets
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Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
Molecular Weight
68685.82 Da
References
  1. Gamache DA, Graff G, Brady MT, Spellman JM, Yanni JM: Nepafenac, a unique nonsteroidal prodrug with potential utility in the treatment of trauma-induced ocular inflammation: I. Assessment of anti-inflammatory efficacy. Inflammation. 2000 Aug;24(4):357-70. [PubMed:10850857]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
Molecular Weight
68995.625 Da
References
  1. Gamache DA, Graff G, Brady MT, Spellman JM, Yanni JM: Nepafenac, a unique nonsteroidal prodrug with potential utility in the treatment of trauma-induced ocular inflammation: I. Assessment of anti-inflammatory efficacy. Inflammation. 2000 Aug;24(4):357-70. [PubMed:10850857]

Drug created on September 14, 2010 16:21 / Updated on April 23, 2021 04:04