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)
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.
Therefore, caution should be used when treating individuals who have previously
exhibited sensitivities to these drugs.
Increased Bleeding Time
With some NSAIDs, 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 surgery.
It is recommended that Xibrom 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
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 events.
Contact Lens Wear
Xibrom should not be administered while wearing contact
lenses. Remove contact lenses prior to instillation of Xibrom. The preservative
in Xibrom, benzalkonium chloride, may be absorbed by soft contact lenses.
Lenses may be reinserted after 10 minutes following administration of Xibrom.
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 micronucleus tests.
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
Pregnancy - Pregnancy Category C
There are no adequate and well-controlled studies with
Xibrom in pregnant women. No malformations were observed in reproduction
studies in rats and rabbits with oral doses of bromfenac at exposures up to 150
times (rats) and 90 times (rabbits) the predicted human systemic exposure;
however, both embryolethality and maternal toxicity were observed at the
highest dose exposures. The systemic concentration of bromfenac is estimated to
be below the limit of quantification (50 ng/mL) at steady-state in humans,
following ocular administration [see CLINICAL PHARMACOLOGY]. 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.
Premature closure of the ductus arteriosus in the fetus
has occurred with third trimester use of oral and injectable NSAIDs. Measurable
maternal and fetal plasma drug levels are available with oral and injectable
routes of NSAID administration. The maternal plasma level of Xibrom following
ocular administration is unknown [see CLINICAL PHARMACOLOGY].
Reproduction studies performed in rats at oral doses of
bromfenac 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 drug-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.
It is not known if Xibrom is present in human milk. The
systemic concentration of bromfenac is estimated to be below the limit of
quantification (50 ng/mL) at steady-state in humans, following ocular
administration [see CLINICAL PHARMACOLOGY]. Based on the low level of
systemic exposure, it is unlikely that Xibrom would be detected in human milk
using available assays. Caution should be exercised when Xibrom ophthalmic
solution is administered to a nursing woman.
Safety and efficacy in pediatric patients below the age
of 18 have not been established.
There is no evidence that the efficacy or safety profiles
for Xibrom differ in patients 65 years of age and older compared to younger