Included as part of the PRECAUTIONS section.
Intraocular Pressure (IOP) Increase
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 should be made by a physician only after examination of the
patient with the aid of magnification such as a 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 of the eye, steroids may mask infection or enhance existing
infection. If signs and symptoms fail to improve after 2 days, the patient
should be re-evaluated.
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 cultures should be taken when
Sensitivity to topically applied aminoglycosides may
occur in some patients. If hypersensitivity develops with this product,
discontinue use and institute appropriate therapy.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term animal studies have not been conducted to
evaluate the carcinogenic potential of loteprednol etabonate or tobramycin.
Loteprednol etabonate was not genotoxic in vitro in the Ames test, the mouse
lymphoma TK assay, a chromosome aberration test in human lymphocytes, or in an in
vivo mouse micronucleus assay.
Oral treatment of male and female rats at 50 mg/kg/day
and 25 mg/kg/day of loteprednol etabonate, respectively, (500 and 250 times the
maximum clinical dose, respectively) prior to and during mating did not impair
fertility in either gender. No impairment of fertility was noted in studies of
subcutaneous tobramycin in rats at 100 mg/kg/day (1700 times the maximum daily
Use In Specific Populations
Pregnancy Category C. Loteprednol etabonate has been
shown to be embryotoxic (delayed ossification) and teratogenic (increased
incidence of meningocele, abnormal left common carotid artery, and limb
fixtures) when administered orally to rabbits during organogenesis at a dose of
3 mg/kg/day (35 times the maximum daily clinical dose), a dose which caused no
maternal toxicity. The no-observed-effect-level (NOEL) for these effects was
0.5 mg/kg/day (6 times the maximum daily clinical dose). Oral treatment of rats
during organogenesis resulted in teratogenicity (absent innominate artery at
≥ 5 mg/kg/day doses, and cleft palate and umbilical hernia at ≥ 50
mg/kg/day) and embryotoxicity (increased post-implantation losses at 100
mg/kg/day and decreased fetal body weight and skeletal ossification with
≥ 50 mg/kg/day). Treatment of rats at 0.5 mg/kg/day (6 times the maximum
daily clinical dose) during organogenesis did not result in any reproductive
toxicity. Loteprednol etabonate was maternally toxic (significantly reduced
body weight gain during treatment) when administered to pregnant rats during
organogenesis at doses of ≥ 5 mg/kg/day. Oral exposure of female rats to
50 mg/kg/day of loteprednol etabonate from the start of the fetal period
through the end of lactation, a maternally toxic treatment regimen
(significantly decreased body weight gain), gave rise to decreased growth and
survival and retarded development in the offspring during lactation; the NOEL
for these effects was 5 mg/kg/day. Loteprednol etabonate had no effect on the
duration of gestation or parturition when administered orally to pregnant rats
at doses up to 50 mg/kg/day during the fetal period.
Reproductive studies have been performed in rats and
rabbits with tobramycin at doses up to 100 mg/kg/day parenterally and have
revealed no evidence of impaired fertility or harm to the fetus. There are no
adequate and well controlled studies in pregnant women. Zylet should be used
during pregnancy only if the potential benefit justifies the potential risk to
It is not known whether topical ophthalmic administration
of corticosteroids could result in sufficient systemic absorption to produce
detectable quantities in human milk. Systemic steroids that appear in human
milk could suppress growth, interfere with endogenous corticosteroid
production, or cause other untoward effects. Caution should be exercised when
Zylet is administered to a nursing woman.
Two trials were conducted to evaluate the safety and
efficacy of Zylet® (loteprednol etabonate and tobramycin) Ophthalmic Suspension
in pediatric subjects age zero to six years; one was in subjects with lid
inflammation and the other was in subjects with blepharoconjunctivitis.
In the lid inflammation trial, Zylet with warm compresses
did not demonstrate efficacy compared to vehicle with warm compresses. Patients
received warm compress lid treatment plus Zylet or vehicle for 14 days. The
majority of patients in both treatment groups showed reduced lid inflammation.
In the blepharoconjunctivitis trial, Zylet did not
demonstrate efficacy compared to vehicle, loteprednol etabonate ophthalmic
suspension, or tobramycin ophthalmic solution. There was no difference between
treatment groups in mean change from baseline blepharoconjunctivitis score at
There were no differences in safety assessments between
the treatment groups in either trial.
No overall differences in safety and effectiveness have
been observed between elderly and younger patients.