Included as part of the PRECAUTIONS section.
Prolonged use of corticosteroids may result in glaucoma
with damage to the optic nerve, defects in visual acuity and fields of vision.
Steroids should be used with caution in the presence of glaucoma. If this product
is used for 10 days or longer, intraocular pressure should be monitored.
Use of corticosteroids may result in posterior
subcapsular cataract formation.
The use of steroids after cataract surgery may delay
healing and increase the incidence of bleb formation. In those diseases causing
thinning of the cornea or sclera, perforations have been known to occur with
the use of topical steroids. The initial prescription and renewal of the
medication order beyond 28 days should be made by a physician only after
examination of the patient with the aid of magnification such as slit lamp
biomicroscopy and, where appropriate, fluorescein staining.
Prolonged use of corticosteroids may suppress the host
response and thus increase the hazard of secondary ocular infections. In acute
purulent conditions, steroids may mask infection or enhance existing infection.
If signs and symptoms fail to improve after 2 days, the patient should be
Employment of a corticosteroid medication in the
treatment of patients with a history of herpes simplex requires great caution.
Use of ocular steroids may prolong the course and may exacerbate the severity
of many viral infections of the eye (including herpes simplex).
Fungal infections of the cornea are particularly prone to
develop coincidentally with long-term local steroid application. Fungus
invasion must be considered in any persistent corneal ulceration where a steroid
has been used or is in use. Fungal culture should be taken when appropriate.
Topical Ophthalmic Use Only
DUREZOL is not indicated for intraocular administration.
Contact Lens Wear
DUREZOL should not be instilled while wearing contact
lenses. Remove contact lenses prior to instillation of DUREZOL. The
preservative in DUREZOL may be absorbed by soft contact lenses. Lenses may be
reinserted after 10 minutes following administration of DUREZOL.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
Difluprednate was not genotoxic in vitro in the Ames
test, and in cultured mammalian cells CHL/IU (a fibroblastic cell line derived
from the lungs of newborn female Chinese hamsters). An in vivo micronucleus
test of difluprednate in mice was also negative. Treatment of male and female
rats with subcutaneous difluprednate up to 10 mcg/kg/day prior to and during
mating did not impair fertility in either gender. Long term studies have not
been conducted to evaluate the carcinogenic potential of difluprednate.
Use In Specific Populations
Teratogenic Effects - Pregnancy Category C
Difluprednate has been shown to be
embryotoxic (decrease in embryonic body weight and a delay in embryonic
ossification) and teratogenic (cleft palate and skeletal) anomalies when administered
subcutaneously to rabbits during organogenesis at a dose of 1–10 mcg/kg/day.
The noobserved- effect-level (NOEL) for these effects was 1 mcg/kg/day, and 10
mcg/kg/day was considered to be a teratogenic dose that was concurrently found
in the toxic dose range for fetuses and pregnant females. Treatment of rats
with 10 mcg/kg/day subcutaneously during organogenesis did not result in any reproductive
toxicity, nor was it maternally toxic. At 100 mcg/kg/day after subcutaneous
administration in rats, there was a decrease in fetal weights and delay in
ossification, and effects on weight gain in the pregnant females. It is
difficult to extrapolate these doses of difluprednate to maximum daily human doses
of DUREZOL, since DUREZOL is administered topically with minimal systemic
absorption, and difluprednate blood levels were not measured in the
reproductive animal studies. However, since use of difluprednate during human
pregnancy has not been evaluated and cannot rule out the possibility of harm, DUREZOL
should be used during pregnancy only if the potential benefit justifies the
potential risk to the embryo or fetus.
It is not known whether topical ophthalmic administration
of corticosteroids could result in sufficient systemic absorption to produce
detectable quantities in breast milk. Systemically administered corticosteroids
appear in human milk and could suppress growth, interfere with endogenous
corticosteroid production, or cause other untoward effects. Caution should be
exercised when DUREZOL is administered to a nursing woman.
DUREZOL was evaluated in a 3-month, multicenter,
double-masked, trial in 79 pediatric patients (39 DUREZOL; 40 prednisolone
acetate) 0 to 3 years of age for the treatment of inflammation following
cataract surgery. A similar safety profile was observed in pediatric patients
comparing DUREZOL to prednisolone acetate ophthalmic suspension, 1%.
No overall differences in safety or effectiveness have
been observed between elderly and younger patients.