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 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
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 appropriate.
Contact Lens Wear
Contact lenses should not be worn when the eyes are inflamed.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Long-term animal studies have not been conducted to evaluate the carcinogenic potential of loteprednol
etabonate. Loteprednol etabonate was not genotoxic in vitro in the Ames test, the mouse lymphoma tk assay, or
in the chromosomal aberration test in human lymphocytes, or in vivo in the mouse micronucleus assay.
Treatment of male and female rats with 25 mg/kg/day of loteprednol etabonate (533 times the RHOD based on
body surface area, assuming 100% absorption) prior to and during mating caused preimplantation loss and
decreased the number of live fetuses/live births. The NOAEL for fertility in rats was 5 mg/kg/day (106 times
Use In Specific Populations
There are no adequate and well controlled studies with loteprednol etabonate in pregnant women.
Loteprednol etabonate produced teratogenicity at clinically relevant doses in the rabbit and rat when
administered orally during pregnancy. Loteprednol etabonate produced malformations when administered orally
to pregnant rabbits at doses 4.2 times the recommended human ophthalmic dose (RHOD) and to pregnant rats at
doses 106 times the RHOD. In pregnant rats receiving oral doses of loteprednol etabonate during the period
equivalent to the last trimester of pregnancy through lactation in humans, survival of offspring was reduced at
doses 10.6 times the RHOD. Maternal toxicity was observed in rats at doses 1066 times the RHOD, and a
maternal no observed adverse effect level (NOAEL) was established at 106 times the RHOD.
The background risk of major birth defects and miscarriage for the indicated population is unknown. However,
the background risk in the U.S. general population of major birth defects is 2 to 4%, and of miscarriage is 15 to
20%, of clinically recognized pregnancies.
Embryofetal studies were conducted in pregnant rabbits administered loteprednol etabonate by oral gavage on
gestation days 6 to 18, to target the period of organogenesis. Loteprednol etabonate produced fetal
malformations at 0.1 mg/kg (4.2 times the recommended human ophthalmic dose (RHOD) based on body
surface area, assuming 100% absorption). Spina bifida (including meningocele) was observed at 0.1 mg/kg, and
exencephaly and craniofacial malformations were observed at 0.4 mg/kg (17 times the RHOD). At 3 mg/kg
(128 times the RHOD), loteprednol etabonate was associated with increased incidences of abnormal left
common carotid artery, limb flexures, umbilical hernia, scoliosis, and delayed ossification. Abortion and
embryofetal lethality (resorption) occurred at 6 mg/kg (256 times the RHOD). A NOAEL for developmental
toxicity was not established in this study. The NOAEL for maternal toxicity in rabbits was 3 mg/kg/day.
Embryofetal studies were conducted in pregnant rats administered loteprednol etabonate by oral gavage on
gestation days 6 to 15, to target the period of organogenesis. Loteprednol etabonate produced fetal
malformations, including absent innominate artery at 5 mg/kg (106 times the RHOD); and cleft palate, agnathia,
cardiovascular defects, umbilical hernia, decreased fetal body weight and decreased skeletal ossification at 50
mg/kg (1066 times the RHOD). Embryofetal lethality (resorption) was observed at 100 mg/kg (2133 times the
RHOD). The NOAEL for developmental toxicity in rats was 0.5 mg/kg (10.6 times the RHOD). Loteprednol
etabonate was maternally toxic (reduced body weight gain) at 50 mg/kg/day. The NOAEL for maternal toxicity
was 5 mg/kg.
A peri-/postnatal study was conducted in rats administered loteprednol etabonate by oral gavage from gestation
day 15 (start of fetal period) to postnatal day 21 (the end of lactation period). At 0.5 mg/kg (10.6 times the
clinical dose), reduced survival was observed in live-born offspring. Doses ≥ 5 mg/kg (106 times the RHOD)
caused umbilical hernia/incomplete gastrointestinal tract. Doses ≥ 50 mg/kg (1066 times the RHOD) produced
maternal toxicity (reduced body weight gain, death), decreased number of live-born offspring, decreased birth
weight, and delays in postnatal development. A developmental NOAEL was not established in this study. The
NOAEL for maternal toxicity was 5 mg/kg.
There are no data on the presence of loteprednol etabonate in human milk, the effects on the breastfed infant, or
the effects on milk production. The developmental and health benefits of breastfeeding should be considered,
along with the mother's clinical need for LOTEMAX® SM and any potential adverse effects on the breastfed
infant from LOTEMAX® SM.
Safety and effectiveness of LOTEMAX® SM in pediatric patients have not been established.
No overall differences in safety and effectiveness have been observed between elderly and younger patients.