Eyeworld

Brief Summary of Safety Consult the full Prescribing Information for complete product information. INDICATIONS AND USAGE OXERVATE™ (cenegermin-bkbj) ophthalmic solution 0.002% is indicated for the treatment of neurotrophic keratitis. DOSAGE AND ADMINISTRATION Contact lenses should be removed before applying OXERVATE and may be reinserted 15 minutes after administration. If a dose is missed, treatment should be continued as normal, at the next scheduled administration. If more than one topical ophthalmic product is being used, administer the eye drops at least 15 minutes apart to avoid diluting products. Administer OXERVATE 15 minutes prior to using any eye ointment, gel or other viscous eye drops. Recommended Dosage and Dose Administration Instill one drop of OXERVATE in the affected eye(s), 6 times a day at 2-hour intervals for eight weeks. ADVERSE REACTIONS Clinical Studies Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. In two clinical trials of patients with neurotrophic keratitis, a total of 101 patients received cenegermin-bkbj eye drops at 20 mcg/mL at a frequency of 6 times daily in the affected eye(s) for a duration of 8 weeks. The mean age of the population was 61 to 65 years of age (18 to 95). The majority of the treated patients were female (61%). The most common adverse reaction was eye pain following instillation which was reported in approximately 16% of patients. Other adverse reactions occurring in 1-10% of OXERVATE patients and more frequently than in the vehicle-treated patients included corneal deposits, foreign body sensation, ocular hyperemia, ocular inflammation and tearing. USE IN SPECIFIC POPULATIONS Pregnancy Risk Summary There are no data from the use of OXERVATE in pregnant women to inform any drug associated risks. Administration of cenegermin-bkbj to pregnant rats or rabbits during the period of organogenesis did not produce adverse fetal effects at clinically relevant doses. In a pre- and postnatal development study, administration of cenegermin-bkbj to pregnant rats throughout gestation and lactation did not produce adverse effects in offspring at clinically relevant doses. Animal Data In embryofetal development studies, daily subcutaneous administration of cenegermin-bkbj to pregnant rats and rabbits throughout the period of organogenesis produced a slight increase in post-implantation loss at doses greater than or equal to 42 mcg/kg/day (267 times the MRHOD). A no observed adverse effect level (NOAEL) was not established for post-implantation loss in either species. In rats, hydrocephaly and ureter anomalies were each observed in one fetus at 267 mcg/kg/day (1709 times the MRHOD). In rabbits, cardiovascular malformations, including ventricular and atrial septal defects, enlarged heart and aortic arch dilation were each observed in one fetus at 83 mcg/kg/day (534 times the MRHOD). No fetal malformations were observed in rats and rabbits at doses of 133 mcg/kg/day and 42 mcg/kg/day, respectively. In a pre- and postnatal development study, daily subcutaneous administration of cenegermin-bkbj to pregnant rats during the period of organogenesis and lactation did not affect parturition and was not associated with adverse toxicity in offspring at doses up to 267 mcg/kg/day. In parental rats and rabbits, an immunogenic response to cenegermin-bkbj was observed. Given that cenegermin-bkbj is a heterologous protein in animals, this response may not be relevant to humans. Lactation There are no data on the presence of OXERVATE in human milk, the effects on 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 OXERVATE, and any potential adverse effects on the breastfed infant from OXERVATE. Pediatric Use The safety and effectiveness of OXERVATE have been established in the pediatric population. Use of OXERVATE in this population is supported by evidence from adequate and well-controlled trials of OXERVATE in adults with additional safety data in pediatric patients from 2 years of age and older [see Clinical Studies (14)]. Geriatric Use Of the total number of subjects in clinical studies of OXERVATE, 43.5 % were 65 years old and over. No overall differences in safety or effectiveness were observed between elderly and younger adult patients. NONCLINICAL TOXICOLOGY Carcinogenesis and Mutagenesis Animal studies have not been conducted to determine the carcinogenic and mutagenic potential of cenegermin-bkbj. Impairment of fertility Daily subcutaneous administration of cenegermin-bkbj to male and female rats for at least 14 days prior to mating, and at least 18 days post-coitum had no effect on fertility parameters in male or female rats at doses up to 267 mcg/kg/day (1709 times the MRHOD). In general toxicology studies, subcutaneous and ocular administration of cenegermin-bkbj in females was associated with ovarian findings including persistent estrus, ovarian follicular cysts, atrophy/reduction of corpora lutea, and changes in ovarian weight at doses greater than or equal to 19 mcg/kg/day (119 times the MRHOD). © 2019 Dompé U.S. Inc. All rights reserved. US-OXE-1900010 06/19

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