Identification
- Summary
Nepafenac is an ophthalmic NSAID used for the symptomatic treatment of pain and inflammation associated with cataract surgery.
- Brand Names
- Ilevro, Nevanac
- Generic Name
- Nepafenac
- DrugBank Accession Number
- DB06802
- Background
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
Structure for Nepafenac (DB06802)
- 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
- Indication
For the treatment of pain and inflammation associated with cataract surgery.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Inflammation •••••••••••• Management of Pain •••••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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.
Target Actions Organism UProstaglandin G/H synthase 1 inhibitorHumans UProstaglandin G/H synthase 2 inhibitorHumans - 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
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Ocularly applied non-steroidal anti-inflammatory drugs may cause increased bleeding of ocular tissues (including hyphemas) in conjunction with ocular surgery.
- Pathways
Pathway Category Nepafenac Action Pathway Drug 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAceclofenac The risk or severity of adverse effects can be increased when Aceclofenac is combined with Nepafenac. Acemetacin The risk or severity of adverse effects can be increased when Nepafenac is combined with Acemetacin. Acetylsalicylic acid The therapeutic efficacy of Acetylsalicylic acid can be decreased when used in combination with Nepafenac. Alclofenac The risk or severity of adverse effects can be increased when Nepafenac is combined with Alclofenac. Aminophenazone The risk or severity of adverse effects can be increased when Aminophenazone is combined with Nepafenac. - 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.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ilevro Suspension 0.3 % w/v Ophthalmic Novartis 2014-06-01 Not applicable Canada 
Ilevro Suspension / drops 3 mg/1mL Ophthalmic Novartis Pharmaceuticals Corporation 2012-12-20 Not applicable US 
Ilevro Suspension 3 mg/1mL Ophthalmic ALCON LABORATORIES, INC. 2012-12-20 2021-11-30 US Nevanac Suspension / drops 1 mg/ml Ophthalmic Novartis Europharm Limited 2020-12-23 Not applicable EU 
Nevanac Suspension / drops 1 mg/1mL Ophthalmic ALCON LABORATORIES, INC. 2005-09-06 2023-04-30 US
Categories
- ATC Codes
- S01BC10 — Nepafenac
- Drug Categories
- Acetamides
- Acetates
- Acids, Acyclic
- Acids, Carbocyclic
- Agents causing hyperkalemia
- Amides
- Analgesics
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)
- Antirheumatic Agents
- Benzene Derivatives
- Central Nervous System Agents
- Cyclooxygenase Inhibitors
- Nephrotoxic agents
- Ophthalmologicals
- Peripheral Nervous System Agents
- Selective Cyclooxygenase 2 Inhibitors (NSAIDs)
- Sensory Organs
- Sensory System Agents
- 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)
- Affected organisms
- Not Available
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
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- FDA Approved Drug Products: NEVANAC (nepafenac) suspension [Link]
- External Links
- Human Metabolome Database
- HMDB0015678
- KEGG Drug
- D05143
- PubChem Compound
- 151075
- PubChem Substance
- 99443294
- ChemSpider
- 133160
- BindingDB
- 50228731
- 298665
- ChEBI
- 75922
- ChEMBL
- CHEMBL1021
- ZINC
- ZINC000005162311
- PharmGKB
- PA165958407
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Nepafenac
- FDA label
- Download (119 KB)
- MSDS
- Download (58.1 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Not Available Cataract Surgery 1 4 Completed Not Available Cataracts 1 4 Completed Not Available Intraocular Pressure (IOP) 1 4 Completed Not Available Vitrectomy therapy 1 4 Completed Prevention Cataracts 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Suspension / drops Ophthalmic 0.1 % Suspension Ophthalmic 0.3 % w/v Suspension Ophthalmic 3 mg/1mL Suspension / drops Ophthalmic 3 mg/1mL Suspension Ophthalmic Suspension Conjunctival; Ophthalmic 3 mg Suspension Ophthalmic 3 mg Suspension Conjunctival; Ophthalmic 1 mg Solution / drops Ophthalmic Solution / drops Ophthalmic 1 MG/ML Solution / drops Ophthalmic 3 MG/ML Suspension Ophthalmic 0.1 % w/v Suspension Ophthalmic 1 mg/1mL Suspension Ophthalmic 1.000 mg Suspension / drops Ophthalmic 1 mg/ml Suspension / drops Ophthalmic 1 mg/1mL Suspension / drops Ophthalmic 3 mg/ml Suspension Ophthalmic 0.1 % Suspension Ophthalmic 1.0 mg/ml Suspension Ophthalmic 1.00 mg Suspension Ophthalmic 1 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US7834059 No 2010-11-16 2027-01-31 US US8071648 No 2011-12-06 2025-12-02 US US8324281 No 2012-12-04 2025-12-02 US US7947295 No 2011-05-24 2024-06-08 US US6403609 No 2002-06-11 2018-07-17 US US8921337 No 2014-12-30 2032-03-31 US US9662398 No 2017-05-30 2030-12-01 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0197 mg/mL ALOGPS logP 1.53 ALOGPS logP 2.08 Chemaxon logS -4.1 ALOGPS pKa (Strongest Acidic) 15.82 Chemaxon pKa (Strongest Basic) 1.83 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 86.18 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 74.46 m3·mol-1 Chemaxon Polarizability 26.67 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9624 Blood Brain Barrier + 0.9918 Caco-2 permeable + 0.5581 P-glycoprotein substrate Non-substrate 0.7608 P-glycoprotein inhibitor I Non-inhibitor 0.5471 P-glycoprotein inhibitor II Non-inhibitor 0.9209 Renal organic cation transporter Non-inhibitor 0.8641 CYP450 2C9 substrate Non-substrate 0.8471 CYP450 2D6 substrate Non-substrate 0.827 CYP450 3A4 substrate Non-substrate 0.6542 CYP450 1A2 substrate Inhibitor 0.6993 CYP450 2C9 inhibitor Inhibitor 0.547 CYP450 2D6 inhibitor Non-inhibitor 0.882 CYP450 2C19 inhibitor Inhibitor 0.5714 CYP450 3A4 inhibitor Non-inhibitor 0.7118 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7441 Ames test Non AMES toxic 0.6193 Carcinogenicity Non-carcinogens 0.6932 Biodegradation Not ready biodegradable 0.719 Rat acute toxicity 2.0064 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9797 hERG inhibition (predictor II) Non-inhibitor 0.7681
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 168.1336793 predictedDarkChem Lite v0.1.0 [M-H]- 167.8211793 predictedDarkChem Lite v0.1.0 [M-H]- 156.12404 predictedDeepCCS 1.0 (2019) [M+H]+ 167.7066793 predictedDarkChem Lite v0.1.0 [M+H]+ 167.9239793 predictedDarkChem Lite v0.1.0 [M+H]+ 158.48204 predictedDeepCCS 1.0 (2019) [M+Na]+ 167.9283793 predictedDarkChem Lite v0.1.0 [M+Na]+ 168.3339793 predictedDarkChem Lite v0.1.0 [M+Na]+ 164.57518 predictedDeepCCS 1.0 (2019)
Targets
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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
- 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. [Article]
- 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
- 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. [Article]
Drug created at September 14, 2010 16:21 / Updated at April 16, 2024 12:20