Nepafenac

S01B - Antiinflammatory agents ATC S01BC10 Small molecule approved 2005 Topical Prodrug Natural product

Active form: Amfenac.

JFDA label: Nevanac Eye Drops,Suspension 1.0mg/ml

Mechanism of Action

Inhibitor of Cyclooxygenase — Cyclooxygenase inhibitor

Target	Action	Gene / class
Cyclooxygenase efficacy	INHIBITOR

Indications

Approved

Ocular pain and inflammation associated with cataract surgery

Contraindications

Source: Lexicomp

Additional contraindications (not in US labeling): Asthma, urticarial, or acute rhinitis precipitated by acetylsalicylic acid or other NSAIDs Absolute
Hypersensitivity to nepafenac, other NSAIDs, or any component of the formulation Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (1)

Common Hypertension

Nervous system disorders (2)

Common Foreign body sensation of eye · headache

Gastrointestinal disorders (2)

Common Nausea · vomiting

Eye disorders (14)

Common conjunctival edema · corneal edema · crusting of eyelid · Decreased visual acuity · eye discomfort · eye pain · eye pruritus · increased intraocular pressure · lacrimation · ocular hyperemia · photophobia · sticky sensation of eye · vitreous detachment · xerophthalmia

Respiratory, thoracic and mediastinal disorders (1)

Common Sinusitis

Dosing

Source: Lexicomp

Ocular pain and inflammation associated with cataract surgery: Ophthalmic: 0.1% suspension: Instill 1 drop into affected eye(s) 3 times daily, beginning 1 day prior to surgery, the day of surgery, and through the first 2 weeks of the postoperative period 0.3% suspension: Instill 1 drop into affected eye(s) once daily, beginning 1 day prior to surgery, the day of surgery, and through the first 2 weeks of the postoperative period. Instill 1 additional drop 30 to 120 minutes prior to surgery.

Ocular pain and inflammation associated with cataract surgery: Ophthalmic: Children ≥10 years and Adolescents: Refer to adult dosing.

Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer's labeling.

Warnings & Precautions

Source: Lexicomp

Aspirin/NSAID sensitivity

Use with caution in patients with previous sensitivity to acetylsalicylic acid and phenylacetic acid derivatives, including patients who experience bronchospasm, asthma, rhinitis, or urticaria following NSAID or aspirin.

Keratitis

May cause keratitis; continued use in a patient with keratitis may cause severe corneal adverse reactions, potentially resulting in loss of vision. Immediately discontinue use in patients with evidence of corneal epithelial damage. Disease-related concerns:

Bleeding disorders

Use with caution in patients with a predisposition to bleeding (bleeding tendencies or medications which interfere with coagulation).

Diabetes

Use with caution in patients with diabetes mellitus; may be at risk of corneal adverse events, potentially resulting in loss of vision.

Ocular disease

Use with caution in patients with complicated ocular surgeries, corneal denervation, corneal epithelial defects, ocular surface disease, or repeat ocular surgeries (within a short timeframe); may be at risk of corneal adverse events, potentially resulting in loss of vision.

Rheumatoid arthritis

Use with caution in patients with rheumatoid arthritis; may be at risk of corneal adverse events, potentially resulting in loss of vision. Special populations:

Surgery patients

May slow/delay healing or prolong bleeding time following surgery. Increased intraocular bleeding (including hyphema) has been reported. To minimize the risk of infection following surgery of both eyes, two separate bottles of eye drops (one for each eye) should be used; instruct patients not to use the same bottle for both eyes. Other warnings/precautions:

Contact lenses

May contain benzalkonium chloride which may be absorbed by soft contact lenses; contact lenses should not be worn during treatment.

Duration of therapy

Use for more than 1 day prior to surgery or for 14 days beyond surgery may increase risk and severity of corneal adverse events.

Pregnancy & Lactation

Pregnancy

FDA category C Teratogenic

Teratogenic events were not observed in animal reproduction studies. Exposure to nonsteroidal anti-inflammatory drugs late in pregnancy may lead to premature closure of the ductus arteriosus.

Lactation

It is not known if nepafenac is excreted in breast milk; the manufacturer recommends that caution be exercised when administering to nursing women.

Chemistry & Properties

Formula	C15H14N2O2
Molecular weight	254.29 g/mol
IUPAC name	2-(2-amino-3-benzoylphenyl)acetamide
CAS	78281-72-8
PubChem CID	151075
InChIKey	`QEFAQIPZVLVERP-UHFFFAOYSA-N`
logP	1.53 (XLogP 1.9)
Polar surface area	86.18 Å²
H-bond acceptors / donors	3 / 2
Drug-likeness (QED)	0.64
Lipinski violations	0

SMILES

NC(=O)Cc1cccc(C(=O)c2ccccc2)c1N

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	10.0%
Half-life	1.672 h
Volume of distribution	0.483 L/kg
Protein binding	99.0%
BBB penetrant	Yes

Enzyme interactions

Enzyme	Role	Detail
CYP1A2	Inhibitor	—
CYP2C19	Inhibitor	—
CYP2C8	Inhibitor	—
CYP2C9	Inhibitor	—
CYP3A4	Inhibitor	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Registered Products (1)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Nevanac Eye Drops,Suspension	Suspension 1 mg/ml	5 ml	The Jordan Drugstore Co	5.100