Included as part of the PRECAUTIONS section.
Use of corticosteroids may result in posterior subcapsular cataract formation.
Based on clinical trials with RETISERT, during the 3-year post implantation
period , nearly all phakic eyes are expected to develop cataracts and require
Endophthalmitis and Surgical Complications
Late onset endophthalmitis has been observed. These events are often related
to the integrity of the surgical wound site. Careful attention to assure tight
closure of the scleral wound and the integrity of the overlying conjunctiva
at the wound site is important.
Potential complications accompanying intraocular surgery to place RETISERT
into the vitreous cavity may include, but are not limited to, the following:
cataract formation, choroidal detachment, endophthalmitis, hypotony, increased
intraocular pressure, exacerbation of intraocular inflammation, retinal detachment,
vitreous hemorrhage, vitreous loss, and wound dehiscence.
Following implantation of RETISERT, nearly all patients will experience an
immediate and temporary decrease in visual acuity in the implanted eye which
lasts for approximately one to four weeks post-operatively.
Increase in Intraocular Pressure
Prolonged use of corticosteroids may result in elevated IOP and/or 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. Patients must
be monitored for elevated IOP.
Based on clinical trials with RETISERT, within 3-years post implantation, approximately
77% of patients will require IOP lowering medications to control intraocular
pressure and 37% of patients will require filtering procedures to control intraocular
pressure. (see Clinical Trials Experience - Ocular Events section).
Separation of Implant Components
In vitro stability studies show that the strength of the adhesive bond between
the silicone cup reservoir and the suture tab is reduced with prolonged hydration,
indicating a potential for the separation of these components. The suture tab
composition is a silicone elastomer reinforced with a polyester mesh. Physicians
should periodically monitor the integrity of the implant by visual inspection.
Other Corticosteroid Induced Adverse Reactions
RETISERT should be used with caution in patients with a history of a viral,
bacterial, mycobacterial or fungal infection of the cornea and conjunctiva including
epithelial herpes simplex keratitis (dendritic keratitis), vaccinia and varicella.
Use of ocular steroids may prolong the course and may exacerbate the severity
of many viral infections of the eye (including herpes simplex). Employment of
a corticosteroid medication in the treatment of patients with a history of herpes
simplex requires great caution.
Prolonged use of corticosteroids may suppress the host response and thus increase
the hazard of secondary ocular infections (bacterial, fungal, and viral). In
acute purulent conditions of the eye, steroids may mask infection or enhance
existing infection. Fungal and viral infections of the cornea are particularly
prone to develop coincidentally with long-term application of steroids. The
possibility of fungal invasion should be considered in any persistent corneal ulceration where steroid treatment has been used.
Since resistance to infections is known to be reduced by corticosteroids, simultaneous
bilateral implantation should not be carried out, in order to limit the potential
for bilateral post-operative infection.
Ocular administration of corticosteroids has also been associated with delayed
wound healing and perforation of the globe where there is thinning of the sclera.
The use of steroids after cataract surgery may delay healing and increase the
incidence of bleb formation.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Long-term animal studies have not been performed on RETISERT to evaluate the
carcinogenic potential or the effect on fertility of fluocinolone acetonide.
Fluocinolone acetonide was not genotoxic in vitro in the Ames test,
the mouse lymphoma TK assay, or in vivo in the mouse bone marrow micronucleus
Use In Specific Populations
Pregnancy Category C
No adequate animal reproduction studies have been conducted with fluocinolone
acetonide. Corticosteroids are generally teratogenic in laboratory animals when
administered systemically at relatively low dosage levels. Fluocinolone acetonide
when administered subcutaneously at a dose of 0.13 mg/kg/day (approximately
10,000 times the daily clinical dose of RETISERT), during days 6 to 18 of pregnancy
in the rabbit, induced abortion at the end of the third and at the beginning
of the fourth gestational week. When administered subcutaneously to rats and
rabbits during gestation at a maternal toxic dose of 50 μg/kg/day (approximately
4,000 times the clinical dose of RETISERT), fluocinolone acetonide caused abortions
and malformations in a few surviving fetuses.
There are no adequate and well-controlled studies in pregnant women. RETISERT
should be used during pregnancy only if the potential benefit justifies the
potential risk to the fetus.
It is not known whether ocular administration of corticosteroids could result
in sufficient systemic absorption to produce detectable quantities in human
milk. Systemic steroids appear in human milk and could suppress growth, interfere
with endogenous corticosteroid production, or cause other untoward effects.
Caution should be exercised when RETISERT is implanted in a nursing woman.
Safety and effectiveness in pediatric patients below the age of 12 years have
not been established.
No overall differences in safety and effectiveness have been observed between
elderly and younger patients.