Included as part of the PRECAUTIONS section.
Increased Bleeding Time
With some nonsteroidal anti-inflammatory drugs including
ILEVRO (nepafenac ophthalmic suspension), 0.3%, 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 hyphema) in
conjunction with ocular surgery.
It is recommended that ILEVRO (nepafenac ophthalmic
suspension), 0.3% be used with caution in patients with known bleeding
tendencies or who are receiving other medications which may prolong bleeding
Topical nonsteroidal anti-in_ammatory drugs (NSAIDs)
including ILEVRO (nepafenac ophthalmic suspension), 0.3%, 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 ILEVRO (nepafenac ophthalmic suspension), 0.3% 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
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
ILEVRO (nepafenac ophthalmic suspension), 0.3% 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.
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 70 and 630 times human plasma exposure at the recommended human
topical ophthalmic dose for rats and 20 and 180 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 fetal survival.
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, ILEVRO (nepafenac ophthalmic suspension), 0.3% 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 ILEVRO (nepafenac ophthalmic suspension), 0.3% during
late pregnancy should be avoided.
Nepafenac 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 ILEVRO (nepafenac ophthalmic
suspension), 0.3% is administered to a nursing woman.
The safety and effectiveness of ILEVRO (nepafenac
ophthalmic suspension), 0.3% 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.