LOTEMAX SM(loteprednol etabonate ophthalmic gel)0.38%, fortopical ophthalmic(三)
e (including herpes simplex).
5.6 Fungal Infections
Fungal infections of the cornea are particularly prone to develop coincidentally with long-term local steroidapplication. Fungus invasion must be considered in any persistent corneal ulceration where a steroid has beenused or is in use. Fungal cultures should be taken when appropriate.
5.7 Contact Lens Wear
Contact lenses should not be worn when the eyes are inflamed.
6 ADVERSE REACTIONS
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in theclinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may notreflect the rates observed in practice.
Adverse reactions associated with ophthalmic steroids include elevated intraocular pressure, which may beassociated with infrequent optic nerve damage, visual acuity and field defects, posterior subcapsular cataractformation, delayed wound healing and secondary ocular infection from pathogens including herpes simplex,and perforation of the globe where there is thinning of the cornea or sclera.
There were no treatment-emergent adverse drug reactions that occurred in more than 1% of subjects in the threetimes daily group compared to vehicle.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
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 whenadministered orally during pregnancy. Loteprednol etabonate produced malformations when administered orallyto pregnant rabbits at doses 4.2 times the recommended human ophthalmic dose (RHOD) and to pregnant rats atdoses 106 times the RHOD. In pregnant rats receiving oral doses of loteprednol etabonate during the periodequivalent to the last trimester of pregnancy through lactation in humans, survival of offspring was reduced atdoses 10.6 times the RHOD. Maternal toxicity was observed in rats at doses 1066 times the RHOD, and amaternal 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 to20%, of clinically recognized pregnancies.
Data
Animal Data
Embryofetal studies were conducted in pregnant rabbits administered loteprednol etabonate by oral gavage ongestation days 6 to 18, to target the period of organogenesis. Loteprednol etabonate produced fetalmalformations at 0.1 mg/kg (4.2 times the recommended human ophthalmic dose (RHOD) based on bodysurface area, assuming 100% absorption).
Spina bifida (including meningocele) was observed at 0.1 mg/kg, andexencephaly 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 leftcommon carotid artery, limb flexures, umbilical hernia, scoliosis, and delayed ossification. Abortion andembryofetal lethality (resorption) occurred at 6 mg/kg (256 times the RHOD). A NOAEL for developmentaltoxicity 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 ongestation days 6 to 15 |
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