Included as part of the PRECAUTIONS section.
Increased Bleeding Time
With some nonsteroidal anti-inflammatory drugs including NEVANAC®, there exists the potential for increased bleeding time due to interference with thrombocyte aggregation. There have been reports that ocularly applied nonsteroidal anti-inflammatory drugs may cause increased bleeding of ocular tissues (including hyphemas) in conjunction with ocular surgery.
It is recommended that NEVANAC® ophthalmic suspension be used with caution in patients with known bleeding tendencies or who are receiving other medications which may prolong bleeding time.
Topical nonsteroidal anti-inflammatory drugs (NSAIDs) including NEVANAC®, may slow or delay healing. Topical corticosteroids are also known to slow or delay healing. Concomitant use of topical NSAIDs and topical steroids may increase the potential for healing problems.
Use of topical NSAIDs may result in keratitis. In some susceptible patients, continued use of topical NSAIDs may result in epithelial breakdown, corneal thinning, corneal erosion, corneal ulceration or corneal perforation. These events may be sight threatening. Patients with evidence of corneal epithelial breakdown should immediately discontinue use of topical NSAIDs including NEVANAC® and should be closely monitored for corneal health.
Postmarketing experience with topical NSAIDs suggests that patients with complicated
ocular surgeries, corneal denervation, corneal epithelial defects, diabetes
mellitus, ocular surface diseases (e.g., dry eye syndrome), rheumatoid arthritis,
or repeat ocular surgeries within a short period of time may be at increased
risk for corneal adverse events which may become sight threatening. Topical
NSAIDs should be used with caution in these patients.
Postmarketing experience with topical NSAIDs also suggests that use more than 1 day prior to surgery or use beyond 14 days post surgery may increase patient risk and severity of corneal adverse events.
Contact Lens Wear
NEVANAC should not be administered while using contact lenses.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Nepafenac has not been evaluated in long-term carcinogenicity studies. Increased
chromosomal aberrations were observed in Chinese hamster ovary cells exposed
in vitro to nepafenac suspension. Nepafenac was not mutagenic in the
Ames assay or in the mouse lymphoma forward mutation assay. Oral doses up to
5,000 mg/kg did not result in an increase in the formation of micronucleated
polychromatic erythrocytes in vivo in the mouse micronucleus assay in
the bone marrow of mice.
Nepafenac did not impair fertility when administered orally to male and female rats at 3 mg/kg (approximately 90 and 380 times the plasma exposure to the parent drug, nepafenac, and the active metabolite, amfenac, respectively, at the recommended human topical ophthalmic dose).
Use In Specific Populations
Pregnancy Category C: Reproduction studies performed with nepafenac
in rabbits and rats at oral doses up to 10 mg/kg/day have revealed no evidence
of teratogenicity due to nepafenac, despite the induction of maternal toxicity.
At this dose, the animal plasma exposure to nepafenac and amfenac was approximately
260 and 2400 times human plasma exposure at the recommended human topical ophthalmic
dose for rats and 80 and 680 times human plasma exposure for rabbits, respectively.
In rats, maternally toxic doses ≥ 10 mg/kg were associated with dystocia,
increased postimplantation loss, reduced fetal weights and growth, and reduced
Nepafenac has been shown to cross the placental barrier in rats. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, NEVANAC® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Because of the known effects of prostaglandin biosynthesis inhibiting drugs on the fetal cardiovascular system (closure of the ductus arteriosus), the use of NEVANAC® during late pregnancy should be avoided.
NEVANAC® is excreted in the milk of lactating rats. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when NEVANAC® ophthalmic suspension is administered to a nursing woman.
The safety and effectiveness of NEVANAC® in pediatric patients below the age of 10 years have not been established.
No overall differences in safety and effectiveness have been observed between elderly and younger patients.