Included as part of the PRECAUTIONS section.
Corneal Adverse Reactions
The presence of DURYSTA implants has been associated with corneal adverse reactions and increased risk of corneal endothelial cell loss. Administration of DURYSTA should be limited to a single implant per eye without retreatment. Caution should be used when prescribing DURYSTA in patients with limited corneal endothelial cell reserve.
Following administration with DURYSTA, the intracameral implant is intended to settle within the inferior angle. DURYSTA should be used with caution in patients with narrow iridocorneal angles (Shaffer grade < 3) or anatomical obstruction (e.g., scarring) that may prohibit settling in the inferior angle.
Macular edema, including cystoid macular edema, has been reported during treatment with ophthalmic bimatoprost, including DURYSTA intracameral implant. DURYSTA should be used with caution in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema.
Prostaglandin analogs, including DURYSTA, have been reported to cause intraocular inflammation. DURYSTA should be used with caution in patients with active intraocular inflammation (e.g., uveitis) because the inflammation may be exacerbated.
Ophthalmic bimatoprost, including DURYSTA intracameral implant, has been reported to cause changes to pigmented tissues, such as increased pigmentation of the iris. Pigmentation of the iris is likely to be permanent. Patients who receive treatment should be informed of the possibility of increased pigmentation. The pigmentation change is due to increased melanin content in the melanocytes rather than to an increase in the number of melanocytes. While treatment with DURYSTA can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly.
Intraocular surgical procedures and injections have been associated with endophthalmitis. Proper aseptic technique must always be used with administering DURYSTA, and patients should be monitored following the administration.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Bimatoprost was not carcinogenic in either mice or rats when administered by oral gavage at doses up to 2 mg/kg/day and 1 mg/kg/day respectively for 104 weeks (approximately 3100 and 1700 times, respectively, the maximum human exposure [based on plasma Cmax levels; blood-to-plasma partition ratio of 0.858]).
Bimatoprost was not mutagenic or clastogenic in the Ames test, in the mouse lymphoma test, or in the in vivo mouse micronucleus tests.
Impairment Of Fertility
Bimatoprost did not impair fertility in male or female rats up to doses of 0.6 mg/kg/day (1770-times the maximum human exposure, based on plasma Cmax; blood-to-plasma partition ratio of 0.858).
Use In Specific Populations
There are no adequate and well-controlled studies of DURYSTA (bimatoprost implant) administration in pregnant women to inform a drug associated risk. Oral administration of bimatoprost to pregnant rats and mice throughout organogenesis did not produce adverse maternal or fetal effects at clinically relevant exposures. Oral administration of bimatoprost to rats from the start of organogenesis to the end of lactation did not produce adverse maternal, fetal or neonatal effects at clinically relevant exposures [see Animal Data].
In an embryofetal development rat study, oral administration of bimatoprost to pregnant rats during organogenesis produced abortion at 0.6 mg/kg/day (1770-times the human systemic exposure to bimatoprost from DURYSTA, based on Cmax and a blood-to plasma partition ratio of 0.858). The No Observed Adverse Effect Level (NOAEL) for abortion was 0.3 mg/kg/day (estimated at 470-times the human systemic exposure to bimatoprost from DURYSTA, based on Cmax). No fetal abnormalities were observed at doses up to 0.6 mg/kg/day.
In an embryofetal development mouse study, oral administration of bimatoprost to pregnant mice during organogenesis produced abortion and early delivery at 0.3 mg/kg/day (2240-times the human systemic exposure to bimatoprost from DURYSTA, based on plasma Cmax level; blood-to plasma partition ratio of 0.858). The NOAEL for abortion and early delivery was 0.1 mg/kg/day (400-times the human systemic exposure to bimatoprost from DURYSTA, based on Cmax). No fetal abnormalities were observed at doses up to 0.6 mg/kg/day (5200-times the human systemic exposure to bimatoprost from DURYSTA, based on Cmax).
In a pre/postnatal development study, oral administration of bimatoprost to pregnant rats from gestation day 7 through lactation resulted in reduced gestation length, increased late resorptions, fetal deaths, and postnatal pup mortality, and reduced pup body weight at 0.3 mg/kg/day (estimated 470-times the human systemic exposure to bimatoprost from DURYSTA, based plasma Cmax and 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 systemic exposure to bimatoprost from DURYSTA, based on plasma Cmax).
There is no information regarding the presence of bimatoprost in human milk, the effects on the breastfed infants, or the effects on milk production. In animal studies, topical bimatoprost has been shown to be excreted in breast milk. Because many drugs are excreted in human milk, caution should be exercised when DURYSTA is administered to a nursing woman.
The developmental and health benefits of breastfeeding should be considered, along with the mother's clinical need for DURYSTA and any potential adverse effects on the breastfed child from DURYSTA.
Safety and effectiveness of DURYSTA in pediatric patients have not been established.
No overall differences in safety or effectiveness have been observed between elderly and other adult patients.