Included as part of the PRECAUTIONS section.
Sulfite Allergic Reactions
Contains sodium sulfite, a sulfite that may cause
allergic type reactions including anaphylactic symptoms and life-threatening or
less severe asthmatic episodes in certain susceptible people. The overall
prevalence of sulfite sensitivity in the general population is unknown and probably
low. Sulfite sensitivity is seen more frequently in asthmatic than in
Slow or Delayed Healing
All topical nonsteroidal anti-inflammatory drugs
(NSAIDs), including bromfenac, 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.
Potential for Cross-Sensitivity
There is the potential for cross-sensitivity to
acetylsalicylic acid, phenylacetic acid derivatives, and other NSAIDs, including
bromfenac. Therefore, caution should be used when treating individuals who have
previously exhibited sensitivities to these drugs.
Increased Bleeding Time
With some NSAIDs, including bromfenac, there exists the potential
for increased bleeding time due to interference with platelet aggregation.
There have been reports that ocularly applied NSAIDs may cause increased
bleeding of ocular tissues (including hyphemas) in conjunction with ocular
It is recommended that PROLENSA ophthalmic solution be
used with caution in patients with known bleeding tendencies or who are
receiving other medications which may prolong bleeding time.
Keratitis and Corneal Reactions
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 bromfenac, and should be closely monitored for corneal health.
Post-marketing 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
Post-marketing experience with topical NSAIDs also suggests
that use more than 24 hours prior to surgery or use beyond 14 days post-surgery
may increase patient risk for the occurrence and severity of corneal adverse
Contact Lens Wear
PROLENSA should not be instilled while wearing contact
lenses. Remove contact lenses prior to instillation of PROLENSA. The
preservative in PROLENSA, benzalkonium chloride may be absorbed by soft contact
lenses. Lenses may be reinserted after 10 minutes following administration of
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term carcinogenicity studies in rats and mice given oral
doses of bromfenac up to 0.6 mg/kg/day (systemic exposure 30 times the systemic
exposure predicted from the recommended human ophthalmic dose [RHOD] assuming
the human systemic concentration is at the limit of quantification) and 5
mg/kg/day (340 times the predicted human systemic exposure), respectively,
revealed no significant increases in tumor incidence.
Bromfenac did not show mutagenic potential in various mutagenicity
studies, including the reverse mutation, chromosomal aberration, and
Bromfenac did not impair fertility when administered
orally to male and female rats at doses up to 0.9 mg/kg/day and 0.3 mg/kg/day,
respectively (systemic exposure 90 and 30 times the predicted human exposure,
Use In Specific Populations
Treatment of rats at oral doses up to 0.9 mg/kg/day (systemic
exposure 90 times the systemic exposure predicted from the recommended human
ophthalmic dose [RHOD] assuming the human systemic concentration is at the limit
of quantification) and rabbits at oral doses up to 7.5 mg/kg/day (150 times the
predicted human systemic exposure) produced no treatment-related malformations in
reproduction studies. However, embryo-fetal lethality and maternal toxicity
were produced in rats and rabbits at 0.9 mg/kg/day and 7.5 mg/kg/day,
respectively. In rats, bromfenac treatment caused delayed parturition at 0.3
mg/ kg/day (30 times the predicted human exposure), and caused dystocia,
increased neonatal mortality and reduced postnatal growth at 0.9 mg/kg/day.
There are no adequate and well-controlled studies in pregnant
women. Because animal reproduction studies are not always predictive of human
response, this drug should be used during pregnancy only if the potential
benefit justifies the potential risk to the fetus. Because of the known effects
of prostaglandin biosynthesisinhibiting drugs on the fetal cardiovascular
system (closure of ductus arteriosus), the use of PROLENSA™ ophthalmic solution
during late pregnancy should be avoided.
Caution should be exercised when PROLENSA ophthalmic solution
is administered to a nursing woman.
Safety and efficacy in pediatric patients below the age
of 18 years have not been established.
There is no evidence that the efficacy or safety profiles
for Prolensa differ in patients 70 years of age and older compared to younger