b"31The following additional adverse drug reactions occurred in less than 1% of patients: hyphema, iridocyclitis, uveitis, corneal opacity, product administered at inappropriate site, corneal decompensation, cystoid macular edema, and drug hypersensitivity.The most common nonocular adverse reaction was headache, which was observed in 5% of patients. Brief SummaryPlease see the DURYSTA package insert for USE IN SPECIFIC POPULATIONSfull Prescribing Information Pregnancy: There are no adequate and well-controlled studies of DURYSTA INDICATIONS AND USAGE administration in pregnant women to inform a drug associated risk. Oral DURYSTA is a prostaglandin analog indicated for the reduction of intraocularadministration of bimatoprost to pregnant rats and mice throughout pressure (IOP) in patients with open angle glaucoma (OAG) or ocularorganogenesis did not produce adverse maternal or fetal effects at clinically hypertension (OHT). relevant exposures. Oral administration of bimatoprost to rats from the start of organogenesis to the end of lactation did not produce adverse maternal, CONTRAINDICATIONS fetal or neonatal effects at clinically relevant exposures.DURYSTA is contraindicated in patients with active or suspected ocularIn embryo/fetal developmental studies in pregnant mice and rats, abortion was or periocular infections; corneal endothelial cell dystrophy; prior cornealobserved at oral doses of bimatoprost which achieved at least 1770 times the transplantation, or endothelial cell transplants; absent or ruptured posteriormaximum human bimatoprost exposure following a single administration of lens capsule, due to the risk of implant migration into the posterior segment;DURYSTA (based on plasma C maxlevels; blood-to-plasma partition ratio of 0.858).or hypersensitivity to bimatoprost or any other components of the product. WARNINGS AND PRECAUTIONS In a pre/postnatal development study, oral administration of bimatoprost Corneal Adverse Reactions: The presence of DURYSTA implants has beento pregnant rats from gestation day 7 through lactation resulted in reduced associated with corneal adverse reactions and increased risk of cornealgestation length, increased late resorptions, fetal deaths, and postnatal pupmortality, and reduced pup body weight at 0.3 mg/kg/day (estimated 470-times endothelial cell loss. Administration of DURYSTAshould be limited to a singleimplant per eye without retreatment. Caution should be used when prescribingthe human systemic exposure to bimatoprost from DURYSTA, based plasma DURYSTA in patients with limited corneal endothelial cell reserve. C maxand a blood-to plasma partition ratio of 0.858). No adverse effects were observed in rat offspring at 0.1 mg/kg/day (estimated 350-times the human Iridocorneal Angle: Following administration with DURYSTAsystemic exposure to bimatoprost from DURYSTAmax )., the intracameral, based on plasma Cimplant is intended to settle within the inferior angle. DURYSTA should beLactation: There is no information regarding the presence of bimatoprost used with caution in patients with narrow iridocorneal angles (Shaffer gradein human milk, the effects on the breastfed infants, or the effects on milk 3) or anatomical obstruction (e.g., scarring) that may prohibit settling in theproduction. In animal studies, topical bimatoprost has been shown to inferior angle.be excreted in breast milk. Because many drugs are excreted in human Macular Edema: Macular edema, including cystoid macular edema, has beenmilk, caution should be exercised when DURYSTA is administered to a reported during treatment with ophthalmic bimatoprost, including DURYSTAnursing woman.intracameral implant. DURYSTA should be used with caution in aphakic patients,The developmental and health benefits of breastfeeding should be considered, in pseudophakic patients with a torn posterior lens capsule, or in patients withalong with the mother's clinical need for DURYSTA and any potential adverse known risk factors for macular edema. effects on the breastfed child from DURYSTA.Intraocular Inflammation: Prostaglandin analogs, including DURYSTA , havePediatric Use: Safety and effectiveness of DURYSTAin pediatric patients been reported to cause intraocular inflammation. DURYSTAshould be usedhave not been established.with caution in patients with active intraocular inflammation (e.g., uveitis) because the inflammation may be exacerbated. Geriatric Use: No overall differences in safety or effectiveness have been Pigmentation: Ophthalmic bimatoprost, including DURYSTA intracameralobserved between elderly and other adult patients.implant, has been reported to cause changes to pigmented tissues, suchNONCLINICAL TOXICOLOGYas increased pigmentation of the iris. Pigmentation of the iris is likely to beCarcinogenesis, Mutagenesis, Impairment of Fertilitypermanent. Patients who receive treatment should be informed of the possibilityBimatoprost was not carcinogenic in either mice or rats when administered of increased pigmentation. The pigmentation change is due to increasedby oral gavage at doses up to 2 mg/kg/day and 1 mg/kg/day respectively for melanin content in the melanocytes rather than to an increase in the number104 weeks (approximately 3100 and 1700 times, respectively, the maximum of melanocytes. While treatment with DURYSTA can be continued in patientshuman exposure [based on plasma C maxlevels; blood-to-plasma partition ratio who develop noticeably increased iris pigmentation, these patients should beof 0.858]).examined regularly. Bimatoprost was not mutagenic or clastogenic in the Ames test, in the mouse Endophthalmitis: Intraocular surgical procedures and injections have beenlymphoma test, or in the in vivo mouse micronucleus tests.associated with endophthalmitis. Proper aseptic technique must always beBimatoprost did not impair fertility in male or female rats up to doses of used with administering DURYSTA, and patients should be monitored following0.6 mg/kg/day (1770-times the maximum human exposure, based on plasma the administration.C maxlevels; blood-to-plasma partition ratio of 0.858).ADVERSE REACTIONS PATIENT COUNSELING INFORMATIONBecause clinical trials are conducted under widely varying conditions, adverseTreatment-related Effects: Advise patients about the potential risk for reaction rates observed in the clinical trials of a drug cannot be directly comparedcomplications including, but not limited to, the development of corneal adverse to rates in the clinical trials of another drug and may not reflect the ratesevents, intraocular inflammation or endophthalmitis.observed in practice. Potential for Pigmentation: Advise patients about the potential for increased The most common ocular adverse reaction observed in two randomized, active-controlled clinical trials with DURYSTA in patients with OAG or OHTbrown pigmentation of the iris, which may be permanent.was conjunctival hyperemia, which was reported in 27% of patients. OtherWhen to Seek Physician Advice: Advise patients that if the eye becomes red, common ocular adverse reactions reported in 5-10% of patients were foreignsensitive to light, painful, or develops a change in vision, they should seek body sensation, eye pain, photophobia, conjunctival hemorrhage, dry eye, eyeimmediate care from an ophthalmologist. irritation, intraocular pressure increased, corneal endothelial cell loss, visionRx onlyblurred, and iritis. Ocular adverse reactions occurring in 1-5% of patients were anterior chamber cell, lacrimation increased, corneal edema, aqueous humor leakage, iris adhesions, ocular discomfort, corneal touch, iris hyperpigmentation, anterior chamber flare, anterior chamber inflammation, and macular edema.DUR133688-v2 02/21 based on v1.0USPI9652014084 DUR Journal Ad_US Medicine_ST.indd 2 4/15/22 4:39 PM"