WARNINGS
LUMIGAN ® (bimatoprost ophthalmic solution) 0.03% has been reported to cause changes to pigmented tissues. The most frequently reported changes have been increased pigmentation of the iris, periorbital tissue (eyelid) and eyelashes, and growth of eyelashes. Pigmentation is expected to increase as long as LUMIGAN ® is administered. After discontinuation of LUMIGAN ® pigmentation of the iris is likely to be permanent while pigmentation of the periorbital tissue and eyelash changes have been reported to be reversible in some patients. Patients who receive treatment should be informed of the possibility of increased pigmentation. The effects of increased pigmentation beyond 5 years are not known.
PRECAUTIONS
General: LUMIGAN ® (bimatoprost ophthalmic solution) 0.03% may gradually increase the pigmentation of the iris. The eye color change is due to increased melanin content in the stromal melanocytes of the iris rather than to an increase in the number of melanocytes. This change may not be noticeable for several months to years (see WARNINGS ). 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. While treatment with LUMIGAN ® can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly.
During clinical trials, the increase in brown iris pigment has not been shown to progress further upon discontinuation of treatment, but the resultant color change may be permanent.
Eyelid skin darkening, which may be reversible upon discontinuation of the treatment has been reported in association with the use of LUMIGAN ®.
LUMIGAN ® may gradually change eyelashes and vellus hair in the treated eye; these changes include increased length, thickness and number of lashes. Eyelash changes are usually reversible upon discontinuation of treatment.
LUMIGAN ® (bimatoprost ophthalmic solution) 0.03% should be used with caution in patients with active intraocular inflammation (e.g., uveitis).
Macular edema, including cystoid macular edema, has been reported during treatment with bimatoprost ophthalmic solution. LUMIGAN ® 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.
LUMIGAN ® has not been evaluated for the treatment of angle closure, inflammatory or neovascular glaucoma.
There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface (see PRECAUTIONS, Information for Patients).
Contact lenses should be removed prior to instillation of LUMIGAN ® and may be reinserted 15 minutes following its administration (see PRECAUTIONS, Information for Patients).
Information for Patients: (see WARNINGS and PRECAUTIONS ): Patients should be advised about the potential for increased brown pigmentation of the iris, which may be permanent. Patients should also be informed about the possibility of eyelid skin darkening, which may be reversible after discontinuation of LUMIGAN ®.
Patients should also be informed of the possibility of eyelash and vellus hair changes in the treated eye during treatment with LUMIGAN ®. These changes may result in a disparity between eyes in length, thickness, pigmentation, number of eyelashes or vellus hairs, and/or direction of eyelash growth. Eyelash changes are usually reversible upon discontinuation of treatment.
Patients should be instructed to avoid allowing the tip of the dispensing container to contact the eye, surrounding structures, fingers, or any other surface in order to avoid contamination of the solution by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions.
Patients should also be advised that if they develop an intercurrent ocular condition (e.g., trauma or infection) or have ocular surgery, they should immediately seek their physician's advice concerning the continued use of the multidose container.
Patients should be advised that if they develop any ocular reactions, particularly conjunctivitis and eyelid reactions, they should immediately seek their physician's advice.
Patients should be advised that LUMIGAN ® contains benzalkonium chloride, which may be absorbed by soft contact lenses. Contact lenses should be removed prior to instillation of LUMIGAN ® and may be reinserted 15 minutes following its administration.
If more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes between applications.
Carcinogenesis, Mutagenesis, Impairment of fertility: Bimatoprost was not carcinogenic in either mice or rats when administered by oral gavage at doses of up to 2 mg/kg/day and 1 mg/kg/day respectively (approximately 192 times and 291 times the recommended human exposure based on blood AUC levels respectively) for 104 weeks.
Bimatoprost was not mutagenic or clastogenic in the Ames test, in the mouse lymphoma test, or in the in vivo mouse micronucleus tests.
Bimatoprost did not impair fertility in male or female rats up to doses of 0.6 mg/kg/day (approximately 103 times the recommended human exposure based on blood AUC levels).
Pregnancy: Teratogenic effects Pregnancy Category C. 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 intended human exposure based on blood AUC levels.
At doses 41 times the intended human exposure based on blood AUC levels, 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 LUMIGAN ® administration in pregnant women. Because animal reproductive studies are not always predictive of human response, LUMIGAN ® should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing mothers: It is not known whether LUMIGAN ® 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 LUMIGAN ® is administered to a nursing woman.
Pediatric Use: Safety and effectiveness in pediatric patients have not been established.
Geriatric Use: No overall clinical differences in safety or effectiveness have been observed between elderly and other adult patients.
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