LUMIGAN^®
(bimatoprost ophthalmic solution) 0.03%

LUMIGAN^® (bimatoprost ophthalmic solution) 0.03% is a synthetic prostamide analog with ocular hypotensive activity. Its chemical name is (Z)-7-[(1R,2R,3R,5S)-3,5-Dihydroxy-2-[1E,3S)-3-hydroxy-5-phenyl-1-pentenyl]cyclopentyl]-5-N-ethylheptenamide, and its molecular weight is 415.58. Its molecular formula is C₂₅H₃₇NO₄. Its chemical structure is:

Bimatoprost is a powder, which is very soluble in ethyl alcohol and methyl alcohol and slightly soluble in water. LUMIGAN^® is a clear, isotonic, colorless, sterile ophthalmic solution with an osmolality of approximately 290 mOsmol/kg.

Contains: Active: bimatoprost 0.3 mg/mL; Preservative: Benzalkonium chloride 0.05 mg/mL; Inactives: Sodium chloride; sodium phosphate, dibasic; citric acid; and purified water. Sodium hydroxide and/or hydrochloric acid may be added to adjust pH. The pH during its shelf life ranges from 6.8-7.8.

Bimatoprost is a prostamide, a synthetic structural analog of prostaglandin with ocular hypotensive activity. It selectively mimics the effects of naturally occurring substances, prostamides. Bimatoprost is believed to lower intraocular pressure (IOP) in humans by increasing outflow of aqueous humor through both the trabecular meshwork and uveoscleral routes. Elevated IOP presents a major risk factor for glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss.

In clinical studies of patients with open angle glaucoma or ocular hypertension with a mean baseline IOP of 26 mmHg, the IOP-lowering effect of LUMIGAN^® (bimatoprost ophthalmic solution) 0.03% once daily (in the evening) was 7-8 mmHg.

Results of dosing for up to five years with products in this drug class showed that the onset of noticeable increased iris pigmentation occurred within the first year of treatment for the majority of the patients who developed noticeable increased iris pigmentation. Patients continued to show signs of increasing iris pigmentation throughout the five years of the study. Observation of increased iris pigmentation did not affect the incidence, nature or severity of adverse events (other than increased iris pigmentation) recorded in the study. IOP reduction was similar regardless of the development of increased iris pigmentation during the study.

In patients with a history of liver disease or abnormal ALT, AST and/or bilirubin at baseline, LUMIGAN^® had no adverse effect on liver function over 48 months.

LUMIGAN^® (bimatoprost ophthalmic solution) 0.03% is indicated for the reduction of elevated intraocular pressure in patients with open angle glaucoma or ocular hypertension.

LUMIGAN^® (bimatoprost ophthalmic solution) 0.03% is contraindicated in patients with hypersensitivity to bimatoprost or any other ingredient in this product.

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.

In clinical trials, the most frequent events associated with the use of LUMIGAN^® (bimatoprost ophthalmic solution) 0.03% occurring in approximately 15% to 45% of patients, in descending order of incidence, included conjunctival hyperemia, growth of eyelashes, and ocular pruritus. Approximately 3% of patients discontinued therapy due to conjunctival hyperemia.

Ocular adverse events occurring in approximately 3 to 10% of patients, in descending order of incidence, included ocular dryness, visual disturbance, ocular burning, foreign body sensation, eye pain, pigmentation of the periocular skin, blepharitis, cataract, superficial punctate keratitis, eyelid erythema, ocular irritation, and eyelash darkening. The following ocular adverse events reported in approximately 1 to 3% of patients, in descending order of incidence, included: eye discharge, tearing, photophobia, allergic conjunctivitis, asthenopia, increases in iris pigmentation, and conjunctival edema. In less than 1% of patients, intraocular inflammation was reported as iritis.

Systemic adverse events reported in approximately 10% of patients were infections (primarily colds and upper respiratory tract infections). The following systemic adverse events reported in approximately 1 to 5% of patients, in descending order of incidence, included headaches, abnormal liver function tests, asthenia and hirsutism.

No information is available on overdosage in humans. If overdose with LUMIGAN^® (bimatoprost ophthalmic solution) 0.03% occurs, treatment should be symptomatic.

In oral (by gavage) mouse and rat studies, doses up to 100 mg/kg/day did not produce any toxicity. This dose expressed as mg/m² is at least 70 times higher than the accidental dose of one bottle of LUMIGAN^® for a 10 kg child.

The recommended dosage is one drop in the affected eye(s) once daily in the evening. The dosage of LUMIGAN^® (bimatoprost ophthalmic solution) 0.03% should not exceed once daily since it has been shown that more frequent administration may decrease the intraocular pressure lowering effect.

Reduction of the intraocular pressure starts approximately 4 hours after the first administration with maximum effect reached within approximately 8 to 12 hours.

LUMIGAN^® may be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart.

LUMIGAN^® (bimatoprost ophthalmic solution) 0.03% is supplied sterile in opaque white low density polyethylene ophthalmic dispenser bottles and tips with turquoise polystyrene caps in the following sizes:

•  2.5 mL fill in 5 mL container – NDC 0023-9187-03
•  5 mL fill in 10 mL container – NDC 0023-9187-05
•  7.5 mL fill in 10 mL container – NDC 0023-9187-07

Storage: LUMIGAN^® should be stored in the original container at 2°to 25°C (36° to 77°F).

Rx only

Revised September 2006

©2006 Allergan, Inc.
Irvine, CA 92612

^® marks owned by Allergan, Inc.

US Patents 5,688,819 and 6,403,649.
9106X
71669US11T