e host response and thus increase the hazard of secondary ocular infection. in acute purulent conditions, steroids may mask infection or enhance existing infection. ( 5.4 ) • viral infections – 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). ( 5.5 ) • fungal infections – 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. ( 5.6 ) 5.1 intraocular pressure (iop) increase prolonged use of corticosteroids, including loteprednol etabonate ophthalmic gel, 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. 5.2 cataracts use of corticosteroids may result in posterior subcapsular cataract formation. 5.3 delayed healing 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. 5.4 bacterial infections 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. 5.5 viral infections 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). 5.6 fungal infections 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. 5.7 contact lens wear patients should not wear contact lenses during their course of therapy with loteprednol etabonate ophthalmic gel.

n. 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. data animal data 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 doses ≥ 0.1 mg/kg (1.2 times the recommended human ophthalmic dose (rhod) based on body surface area, assuming 100% absorption). spina bifida (including meningocele) was observed at doses ≥ 0.1 mg/kg, and exencephaly and craniofacial malformations were observed at doses ≥ 0.4 mg/kg (4.9 times the rhod). at 3 mg/kg (36 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 doses ≥ 6 mg/kg (73 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 doses ≥ 5 mg/kg (30 times the rhod); and cleft palate, agnathia, cardiovascular defects, umbilical hernia, decreased fetal body weight and decreased skeletal ossification at doses ≥ 50 mg/kg (304 times the rhod). embryofetal lethality (resorption) was observed at 100 mg/kg (608 times the rhod). the noael for developmental toxicity in rats was 0.5 mg/kg (3 times the rhod). loteprednol etabonate was maternally toxic (reduced body weight gain) at doses of ≥ 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 doses ≥ 0.5 mg/kg (3 times the clinical dose), reduced survival was observed in live-born offspring. doses ≥ 5 mg/kg (30 times the rhod) caused umbilical hernia/incomplete gastrointestinal tract. doses ≥ 50 mg/kg (304 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. 8.2 lactation 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 and any potential adverse effects on the breastfed infant from lotemax. 8.4 pediatric use the safety and effectiveness of lotemax have been established in the pediatric population. use of lotemax in this population is supported by evidence from adequate and well-controlled trials of lotemax in adults with additional data from a safety and efficacy trial in pediatric patients from birth to 11 years of age [see clinical studies (14) ]. 8.5 geriatric use no overall differences in safety and effectiveness have been observed between elderly and younger patients.

k 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. data animal data 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 doses ≥ 0.1 mg/kg (1.2 times the recommended human ophthalmic dose (rhod) based on body surface area, assuming 100% absorption). spina bifida (including meningocele) was observed at doses ≥ 0.1 mg/kg, and exencephaly and craniofacial malformations were observed at doses ≥ 0.4 mg/kg (4.9 times the rhod). at 3 mg/kg (36 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 doses ≥ 6 mg/kg (73 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 doses ≥ 5 mg/kg (30 times the rhod); and cleft palate, agnathia, cardiovascular defects, umbilical hernia, decreased fetal body weight and decreased skeletal ossification at doses ≥ 50 mg/kg (304 times the rhod). embryofetal lethality (resorption) was observed at 100 mg/kg (608 times the rhod). the noael for developmental toxicity in rats was 0.5 mg/kg (3 times the rhod). loteprednol etabonate was maternally toxic (reduced body weight gain) at doses of ≥ 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 doses ≥ 0.5 mg/kg (3 times the clinical dose), reduced survival was observed in live-born offspring. doses ≥ 5 mg/kg (30 times the rhod) caused umbilical hernia/incomplete gastrointestinal tract. doses ≥ 50 mg/kg (304 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.

d upon in vivo and in vitro preclinical metabolism studies, loteprednol etabonate undergoes extensive metabolism to the inactive carboxylic acid metabolites, pj-91 and pj-90. the systemic exposure to loteprednol etabonate following ocular administration of loteprednol etabonate ophthalmic gel has not been studied in humans.

mic gel (54 patients) or prednisolone acetate ophthalmic suspension 1% (53 patients) four times daily for 14 days. at day 14, the percentages of patients with complete clearing of anterior chamber inflammation were 57% in the loteprednol etabonate ophthalmic gel group and 63% in the prednisolone group.