CLASSES
Ophthalmological Non-steroidal Anti-inflammatories
DESCRIPTION
Ophthalmic NSAID
Used for the treatment of pain and inflammation associated with cataract surgery
May cause increased bleeding of ocular tissues when used in conjunction with ocular surgery
COMMON BRAND NAMES
ILEVRO, Nevanac
HOW SUPPLIED
ILEVRO/Nepafenac/Nevanac Ophthalmic Susp: 0.1%, 0.3%
DOSAGE & INDICATIONS
For the treatment of ocular pain and postoperative ocular inflammation following cataract surgery.
Ophthalmic dosage (0.1% ophthalmic suspension)
Adults, Adolescents, and Children >= 10 years
One drop into 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, Adolescents, and Children >= 10 years
One 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—120 minutes prior to surgery.
MAXIMUM DOSAGE
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 years: 3 drops/day 0.1% ophthalmic suspension in each affected eye; 1 drop/day 0.3% ophthalmic suspension in each affected eye.
< 10 years: Safety and efficacy have not been established.
Infants
Safety and efficacy have not been established.
Neonates
Safety and efficacy have not been established.
DOSING CONSIDERATIONS
Hepatic Impairment
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Renal Impairment
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
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.
STORAGE
ILEVRO:
- Protect from light
- Store between 36 to 77 degrees F
- Store in a cool, dry place
Nevanac:
- Store between 36 to 77 degrees F
- Store in a cool, dry place
CONTRAINDICATIONS / PRECAUTIONS
NSAID hypersensitivity, salicylate hypersensitivity
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.
Anticoagulant therapy, coagulopathy, diabetes mellitus, hemophilia, ocular disease, ocular surgery, rheumatoid arthritis
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. 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.
Children, infants, neonates
The safety and efficacy of nepafenac ophthalmic suspension has not been established for neonates, infants and children < 10 years old.
Pregnancy
Nepafenac ophthalmic suspension is classified as an FDA pregnancy risk category C drug. No adequate and well-controlled studies in pregnant women have been performed. 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.
Breast-feeding
According to the manufacturer, caution should be exercised if nepafenac ophthalmic solution is given to a woman who is 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. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Asthma
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.
Contact lenses
Contact lenses should not be worn during treatment. Nepafenac ophthalmic suspension contains the preservative benzalkonium chloride, which may be absorbed by soft contact lenses.
ADVERSE REACTIONS
Severe
ocular hypertension / Delayed / 5.0-10.0
visual impairment / Early / 5.0-10.0
corneal erosion / Delayed / Incidence not known
keratitis / Delayed / Incidence not known
Moderate
photophobia / Early / 1.0-5.0
conjunctival hyperemia / Early / 1.0-5.0
edema / Delayed / 1.0-5.0
hypertension / Early / 1.0-4.0
contact dermatitis / Delayed / Incidence not known
erythema / Early / Incidence not known
impaired wound healing / Delayed / Incidence not known
bleeding / Early / Incidence not known
Mild
foreign body sensation / Rapid / 5.0-10.0
ocular pain / Early / 1.0-5.0
xerophthalmia / Early / 1.0-5.0
lacrimation / Early / 1.0-5.0
ocular irritation / Rapid / 1.0-5.0
ocular pruritus / Rapid / 1.0-5.0
vomiting / Early / 1.0-4.0
headache / Early / 1.0-4.0
nausea / Early / 1.0-4.0
sinusitis / Delayed / 1.0-4.0
DRUG INTERACTIONS
There are no drug interactions associated with Nepafenac products.
PREGNANCY AND LACTATION
Pregnancy
Nepafenac ophthalmic suspension is classified as an FDA pregnancy risk category C drug. No adequate and well-controlled studies in pregnant women have been performed. 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.
According to the manufacturer, caution should be exercised if nepafenac ophthalmic solution is given to a woman who is 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. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
MECHANISM OF ACTION
Mechanism of Action: 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).
PHARMACOKINETICS
Nepafenac is administered topically to the eye. The clinical significance of the systemic absorption of nepafenac after ophthalmic administration is unknown.
Other Route(s)
Ophthalmic Route
The pro-drug structure allows nepafenac to rapidly penetrate the cornea and reach its target sites, while minimizing surface accumulation and reducing ocular surface complications. Two to three hours after bilateral 0.1% nepafenac ophthalmic administration, given three times daily, low but quantifiable plasma concentrations of nepafenac and amfenac were observed in the majority of subjects. 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. The clinical significance of the systemic absorption of nepafenac after ophthalmic administration is unknown.