1 INDICATIONS AND USAGE LATISSE ® (bimatoprost ophthalmic solution) 0.03% is indicated to treat hypotrichosis of the eyelashes by increasing their growth including length, thickness and darkness. LATISSE ® is a prostaglandin analog, indicated to treat hypotrichosis of the eyelashes by increasing their growth including length, thickness and darkness. (1)
3 DOSAGE FORMS AND STRENGTHS Bimatoprost ophthalmic solution 0.3 mg/mL. Bimatoprost ophthalmic solution 0.3 mg/mL. (3)
4 CONTRAINDICATIONS None None (4)
5 WARNINGS AND PRECAUTIONS Concurrent administration of LATISSE ® and IOP-lowering prostaglandin analogs in ocular hypertensive patients may decrease the IOP-lowering effect. Patients using these products concomitantly should be closely monitored for changes to their intraocular pressure. (5.1) Pigmentation of the eyelids and iris may occur. Iris pigmentation is likely to be permanent. (5.2, 5.3) 5.1 Effects on Intraocular Pressure Bimatoprost ophthalmic solution (LUMIGAN ®) lowers intraocular pressure (IOP) when instilled directly to the eye in patients with elevated IOP. In clinical trials, in patients with or without elevated IOP, LATISSE ® lowered IOP, however, the magnitude of the reduction was not cause for clinical concern. In ocular hypertension studies with LUMIGAN ®, it has been shown that exposure of the eye to more than one dose of bimatoprost daily may decrease the intraocular pressure lowering effect. In patients using LUMIGAN ® or other prostaglandin analogs for the treatment of elevated intraocular pressure, the concomitant use of LATISSE ® may interfere with the desired reduction in IOP. Patients using prostaglandin analogs including LUMIGAN ® for IOP reduction should only use LATISSE ® after consulting with their physician and should be monitored for changes to their intraocular pressure [see Patient Counseling Information (17.3)]. 5.2 Iris Pigmentation Increased iris pigmentation has occurred when bimatoprost solution was administered. Patients should be advised about the potential for increased brown iris pigmentation which is likely to be permanent [see Adverse Reactions (6.2) and Patient Counseling Information (17.5)]. The pigmentation change is due to increased melanin content in the melanocytes rather than to an increase in the number of melanocytes. The long term effects of increased pigmentation are not known. Iris color changes seen with administration of bimatoprost ophthalmic solution may not be noticeable for several months to years. Typically, the brown pigmentation around the pupil spreads concentrically towards the periphery of the iris and the entire iris or parts of the iris become more brownish. Neither nevi nor freckles of the iris appear to be affected by treatment. Treatment with LATISSE ® solution can be continued in patients who develop noticeably increased iris pigmentation. 5.3 Lid Pigmentation Bimatoprost has been reported to cause pigment changes (darkening) to periorbital pigmented tissues and eyelashes. The pigmentation is expected to increase as long as bimatoprost is administered, but has been reported to be reversible upon discontinuation of bimatoprost in most patients [see Patient Counseling Information (17.4)]. 5.4 Hair Growth Outside the Treatment Area There is the potential for hair growth to occur in areas where LATISSE ® solution comes in repeated contact with the skin surface. It is important to apply LATISSE ® only to the skin of the upper eyelid margin at the base of the eyelashes using the accompanying sterile applicators, and to carefully blot any excess LATISSE ® from the eyelid margin to avoid it running onto the cheek or other skin areas [see Patient Counseling Information (17.6)]. 5.5 Intraocular Inflammation LATISSE ® solution should be used with caution in patients with active intraocular inflammation (e.g., uveitis) because the inflammation may be exacerbated. 5.6 Macular Edema Macular edema, including cystoid macular edema, has been reported during treatment with bimatoprost ophthalmic solution (LUMIGAN ®) for elevated IOP. LATISSE ® 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. 5.7 Contamination of LATISSE ® or Applicators The LATISSE ® bottle must be kept intact during use. It is important to use LATISSE ® solution as instructed, by placing one drop on the single-use-per-eye applicator. The bottle tip should not be allowed to contact any other surface since it could become contaminated. The accompanying sterile applicators should only be used on one eye and then discarded since reuse of applicators increases the potential for contamination and infections. There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products [see Patient Counseling Information (17.2)]. 5.8 Use with Contact Lenses LATISSE ® contains benzalkonium chloride, which may be absorbed by and cause discoloration of soft contact lenses. Contact lenses should be removed prior to application of solution and may be reinserted 15 minutes following its administration [see Patient Counseling Information (17.8)].
6 ADVERSE REACTIONS Most common adverse reactions (incidence approximately 3% - 4%) are eye pruritus, conjunctival hyperemia, and skin hyperpigmentation. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Allergan at 1-800-433-8871 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Experience The following information is based on clinical trial results from a multicenter, double-masked, randomized, vehicle-controlled, parallel study including 278 adult patients for four months of treatment. The most frequently reported adverse reactions were eye pruritus, conjunctival hyperemia, skin hyperpigmentation, ocular irritation, dry eye symptoms, and periorbital erythema. These reactions occurred in less than 4% of patients. Adverse reactions reported with bimatoprost ophthalmic solution (LUMIGAN ®) for the reduction of intraocular pressure include, ocular dryness, visual disturbance, ocular burning, foreign body sensation, eye pain, blepharitis, cataract, superficial punctate keratitis, eye discharge, tearing, photophobia, allergic conjunctivitis, asthenopia, increases in iris pigmentation, conjunctival edema, abnormal hair growth, iritis, infections (primarily colds and upper respiratory tract infections), headaches, and asthenia. 6.2 Postmarketing Experience The following reactions have been identified during postmarketing use of LATISSE ® in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. The reactions, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to LATISSE ®, or a combination of these factors, include: eye swelling, eyelid edema, hypersensitivity (local allergic reactions), lacrimation increased, madarosis and trichorrhexis (temporary loss of a few lashes to loss of sections of eyelashes, and temporary eyelash breakage, respectively), periorbital and lid changes associated with a deepening of the eyelid sulcus, rash (including macular and erythematous), skin discoloration (periorbital), and vision blurred.
8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C Teratogenic effects: In embryo/fetal developmental studies in pregnant mice and rats, abortion was observed at oral doses of bimatoprost which achieved at least 33 or 97 times, respectively, the maximum intended human exposure (based on blood AUC levels after topical ophthalmic administration to the cornea or conjunctival sac). At doses at least 41 times the maximum intended human exposure, the gestation length was reduced in the dams, the incidence of dead fetuses, late resorptions, peri- and postnatal pup mortality was increased, and pup body weights were reduced. There are no adequate and well-controlled studies of bimatoprost ophthalmic solution 0.03% administration in pregnant women. Because animal reproductive studies are not always predictive of human response, LATISSE ® should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus. 8.3 Nursing Mothers It is not known whether LATISSE ® solution is excreted in human milk, although in animal studies, bimatoprost has been shown to be excreted in breast milk. Because many drugs are excreted in human milk, caution should be exercised when LATISSE ® is administered to a nursing woman. 8.4 Pediatric Use Use of LATISSE ® was evaluated in a sixteen week double-masked, randomized, vehicle-controlled study conducted in pediatric patients who were post-chemotherapy or had alopecia areata, and adolescents who had hypotrichosis with no associated medical condition. No new safety issues were observed. The results of the Global Eyelash Assessment are provided in Table 1. Table 1. Number (%) of subjects with at least a 1-grade increase from baseline at month 4 in Global Eyelash Assessment Age Range (years) LATISSE ® Vehicle Difference (95% CI) Adolescents with hypotrichosis (N=40) 15 - 17 19/26 (73%) 1/14 (7%) 66% (44%, 88%) Post Chemotherapy Pediatric Patients (N=16) 5 - 17 11/13 (85%) 3/3 (100%) -15% (-35%, 4%) Alopecia Areata Pediatric Patients (N=15) 5 - 17 4/9 (44%) 2/6 (33%) 11% (-39%, 61%) 8.5 Geriatric Use No overall clinical differences in safety or effectiveness have been observed between elderly and other adult patients.