Nepafenac ophthalmic suspension is a topical non-steroidal anti-inflammatory pro-drug for the treatment of the pain and inflammation associated with cataract surgery in adults and pediatric patients 10 years and older. Nepafenac is the first ophthalmic NSAID pro-drug. Topical nepafenac readily penetrates the cornea and is then metabolized to amfenac, which inhibits the action of prostaglandin H synthase (cyclooxygenase), an enzyme required for prostaglandin production. Use may result in increased bleeding time, delayed healing, and keratitis.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Ophthalmic Administration
-For topical application to the eye only.
-Shake the container well before use.
-If more than 1 medicine is to be administered in the eye, the medicines should be given 5 minutes apart.
-Do not administer while wearing contact lens.
Keratitis, which appears to be reversible with discontinuation of the drug, has been reported in patients receiving ophthalmic NSAIDs, such as nepafenac. Ophthalmic administration of nepafenac may result in impaired wound healing. Corneal erosion that can lead to ulceration or perforation has been associated with ophthalmic administration of NSAIDs. Patients with evidence of corneal breakdown should immediately discontinue use of nepafenac ophthalmic solution and should be closely monitored, as these events may be sight threatening. Adherence to the dosing regimen may reduce the risk of serious adverse events. Contact dermatitis had been known to occur after the use of topical anti-inflammatory medications, including nepafenac. Eyelid excoriation and erythema have also been associated with the use of nepafenac ophthalmic solution.
Most adverse effects of ocular nepafenac administration are related to the eye, but systemic adverse reactions can occur. For example, headache, hypertension, nausea and vomiting, and sinusitis occurred in 1% to 4% of patients.
The most frequently reported ocular adverse events in clinical studies with nepafenac following cataract surgery, reported in 5% to 10% of patients, included capsular opacity, visual impairment (decreased visual acuity), foreign body sensation, ocular hypertension, and sticky sensation. Approximately 1% to 5% of patients experienced conjunctival or corneal edema, xerophthalmia, lid margin crusting, ocular irritation, conjunctival hyperemia, ocular pain, ocular pruritus, photophobia, lacrimation (tearing), and vitreous detachment. Some of these events may have been a result of the cataract surgical procedure as opposed to nepafenac administration.
Like other NSAIDs, nepafenac can potentially prolong bleeding time. There have been reports that ocularly applied NSAIDs may cause increased bleeding of ocular tissues (including hyphemas) in conjunction with ocular procedures.
Nepafenac ophthalmic suspension is contraindicated in patients with NSAID hypersensitivity. Use caution when administering nepafenac to patients who have previously exhibited sensitivities to phenylacetic acid derivatives and salicylate hypersensitivity as the potential for cross-sensitivity exists.
Nepafenac should be used with caution in patients who are receiving other medications that may prolong bleeding time (e.g., anticoagulant therapy), and in patients with known bleeding tendencies, preexisting coagulopathy, or hemophilia. Like other NSAIDs, nepafenac can prolong bleeding time. There have been reports that ocularly applied NSAIDs may cause increased bleeding of ocular tissues (including hyphemas) in conjunction with ocular procedures.
There are no adequate and well-controlled studies with nepafenac use during pregnancy. The use of nepafenac in pregnant women is only justified if the benefits outweigh the possible risks to the fetus. Because of the possibility of closure of the ductus arteriosus, the use of nepafenac ophthalmic suspension should be avoided in late pregnancy.
Systemic absorption of ophthalmic NSAIDs through the nasal mucosa has been reported to cause exacerbation of bronchial asthma in at least three patients. Two of the three patients had a previous history of mild to moderate asthma. The third patient experienced acute asthma attacks following each administration of the ophthalmic NSAID. The attacks ceased following discontinuation of the drug and reappeared following re-challenge with the drug. It may be prudent to avoid administration of nepafenac ophthalmic suspension in asthmatic patients until further information is known.
According FDA-labeling, caution should be exercised if nepafenac ophthalmic solution is administered during breast-feeding. It is not known whether nepafenac is excreted in human milk. Systemic concentrations are low after ophthalmic use; therefore, breast milk concentrations are likely to be very low, if present at all. Although nepafenac has not been evaluated by the American Academy of Pediatrics (AAP), other NSAIDs such as ibuprofen, indomethacin, and naproxen are considered to be usually compatible with breast-feeding by the AAP.
Contact lenses should not be worn during treatment. Nepafenac ophthalmic suspension contains the preservative benzalkonium chloride, which may be absorbed by soft contact lenses.
Post-marketing experience with ophthalmic NSAIDs suggests that patients with complicated ocular surgery, diabetes mellitus, ocular disease affecting the ocular surface (e.g., xerophthalmia, corneal denervation, or corneal epithelial defects), rheumatoid arthritis, or repeat ocular surgeries within a short period of time may be at increased risk for corneal adverse events that are potentially sight-threatening. Ocular NSAIDs should be used with caution in these patients. Post-marketing experience also suggests that nepafenac use more than 24 hours prior to or use beyond 14 days following ocular surgery may increase risk for the occurrence and severity of corneal adverse events.
For the treatment of ocular pain and postoperative ocular inflammation following cataract surgery:
Ophthalmic dosage (0.1% ophthalmic suspension):
Adults: Instill 1 drop in the affected eye(s) 3 times a day beginning 1 day prior to cataract surgery, continued on the day of surgery and through the first 2 weeks of the postoperative period.
Children and Adolescents 10 to 17 years: Instill 1 drop in the affected eye(s) 3 times a day beginning 1 day prior to cataract surgery, continued on the day of surgery and through the first 2 weeks of the postoperative period.
Ophthalmic dosage (0.3% ophthalmic suspension):
Adults: Instill 1 drop into the affected eye(s) once daily beginning 1 day prior to cataract surgery and continued through the first 2 weeks of the postoperative period. On the day of surgery, 1 drop should be administered as usual with an additional drop administered 30 to 120 minutes prior to surgery.
Children and Adolescents 10 to 17 years: Instill 1 drop into the affected eye(s) once daily beginning 1 day prior to cataract surgery and continued through the first 2 weeks of the postoperative period. On the day of surgery, 1 drop should be administered as usual with an additional drop administered 30 to 120 minutes prior to surgery.
Maximum Dosage Limits:
-Adults
3 drops/day 0.1% ophthalmic suspension in each affected eye; 1 drop/day 0.3% ophthalmic suspension in each affected eye.
-Geriatric
3 drops/day 0.1% ophthalmic suspension in each affected eye; 1 drop/day 0.3% ophthalmic suspension in each affected eye.
-Adolescents
3 drops/day 0.1% ophthalmic suspension in each affected eye; 1 drop/day 0.3% ophthalmic suspension in each affected eye.
-Children
10 to 12 years: 3 drops/day 0.1% ophthalmic suspension in each affected eye; 1 drop/day 0.3% ophthalmic suspension in each affected eye.
1 to 9 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
There are no drug interactions associated with Nepafenac products.
Following ophthalmic administration, nepafenac penetrates the cornea and is converted by ocular tissue hydrolases to amfenac, a nonsteroidal anti-inflammatory drug (NSAID). The anti-inflammatory and analgesic properties of amfenac are mediated through inhibition of prostaglandin H synthase (cyclooxygenase), an enzyme required for prostaglandin production. The prostaglandins play a role in the miotic response produced during and after ocular surgery by constricting the iris sphincter independently of cholinergic mechanisms. In the eye, prostaglandins also have been shown to disrupt the blood-aqueous humor barrier, cause vasodilation, increase vascular permeability, promote leukocytosis, and increase intraocular pressure (IOP). The degree of ocular inflammatory response is correlated with prostaglandin-induced increases in ciliary epithelium permeability. With ophthalmic administration, NSAIDs inhibit the synthesis of prostaglandins in the iris, ciliary body, and conjunctiva, and, thus, work to prevent manifestations of ocular inflammation and reduce pain. The pro-drug structure of nepafenac allows for rapid penetration to the cornea and distribution to target sites, while minimizing surface accumulation and reducing ocular surface complications. While not an FDA-approved indication, topical nepafenac appears to inhibit choroidal neovascularization (CNV) and ischemia-induced retinal neovascularization by decreasing production of vascular endothelial growth factor (VEGF).
Nepafenac is administered topically to the eye. The clinical significance of the systemic absorption of nepafenac after ophthalmic administration is unknown.
Affected cytochrome P450 isoenzymes: none
Nepafenac at concentrations up to 300 ng/mL did not inhibit the in vitro metabolism of 6 specific marker substrates of cytochrome P450 (CYP) isozymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4). Therefore, drug to drug interactions involving CYP-mediated metabolism of concomitantly administered drugs are unlikely. Drug-drug interactions mediated by protein binding are also unlikely.
-Route-Specific Pharmacokinetics
Other Route(s)
Ophthalmic Route
Low but quantifiable plasma concentrations of nepafenac and amfenac were observed in the majority of subjects 2 and 3 hours after bilateral 0.1% nepafenac ophthalmic administration, given three times daily. Following ocular administration, 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.