LUMIGAN

Allergan, Inc.

HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use LUMIGAN 0.01% and 0.03% (bimatoprost ophthalmic solution) safely and effectively. See full prescribing information for LUMIGAN. LUMIGAN 0.01% and 0.03% (bimatoprost ophthalmic solution)Initial U.S. Approval: 2001 INDICATIONS AND USAGE LUMIGAN ® is a prostaglandin analog indicated for the reduction of elevated intraocular pressure in patients with open angle glaucoma or ocular hypertension. (1) DOSAGE AND ADMINISTRATIONOne drop in the affected eye(s) once daily in the evening. (2) DOSAGE FORMS AND STRENGTHSSolution containing 0.1 mg/mL bimatoprost (LUMIGAN ® 0.01%) or containing 0.3 mg/mL bimatoprost (LUMIGAN ® 0.03%). (3) CONTRAINDICATIONSNone (4) WARNINGS AND PRECAUTIONS Pigmentation.   Pigmentation of the iris, periorbital tissue (eyelid) and eyelashes can occur. Iris pigmentation is likely to be permanent. (5.1) Eyelash Changes.   Gradual change to eyelashes including increased length, thickness and number of lashes. Usually reversible. (5.2) Side EffectsMost common adverse reaction (range 25%-45%) is conjunctival hyperemia. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Allergan at 1-800-433-8871 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. USE IN SPECIFIC POPULATIONSUse in pediatric patients below the age of 16 years is not recommended because of potential safety concerns related to increased pigmentation following long-term chronic use. (8.4)

FULL PRESCRIBING INFORMATION: CONTENTS*

• 1 LUMIGAN INDICATIONS AND USAGE
• 2 LUMIGAN DOSAGE AND ADMINISTRATION
• 3 DOSAGE FORMS AND STRENGTHS
• 4 LUMIGAN CONTRAINDICATIONS
• 5 WARNINGS AND PRECAUTIONS
  • 5.1 Pigmentation
  • 5.2 Eyelash Changes
  • 5.3 Intraocular Inflammation
  • 5.4 Macular Edema
  • 5.5 Angle-closure, Inflammatory, or Neovascular Glaucoma
  • 5.6 Bacterial Keratitis
  • 5.7 Use with Contact Lenses
• 6 LUMIGAN ADVERSE REACTIONS
  • 6.1 Clinical Studies Experience
  • 6.2 Postmarketing Experience
• 8 USE IN SPECIFIC POPULATIONS
  • 8.1 Pregnancy
  • 8.3 Nursing Mothers
  • 8.4 Pediatric Use
  • 8.5 Geriatric Use
  • 8.6 Hepatic Impairment
• 10 OVERDOSAGE
• 11 LUMIGAN DESCRIPTION
• 12 CLINICAL PHARMACOLOGY
  • 12.1 Mechanism of Action
  • 12.3 Pharmacokinetics
• 13 NONCLINICAL TOXICOLOGY
  • 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
• 14 CLINICAL STUDIES
• 16 HOW SUPPLIED/STORAGE AND HANDLING
• 17 PATIENT COUNSELING INFORMATION
  • 17.1 Potential for Pigmentation
  • 17.2 Potential for Eyelash Changes
  • 17.3 Handling the Container
  • 17.4 When to Seek Physician Advice
  • 17.5 Use with Contact Lenses
  • 17.6 Use with Other Ophthalmic Drugs

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

LUMIGAN ^® 0.01% and 0.03% (bimatoprost ophthalmic solution) is indicated for the reduction of elevated intraocular pressure in patients with open angle glaucoma or ocular hypertension.

2 DOSAGE AND ADMINISTRATION

The recommended dosage is one drop in the affected eye(s) once daily in the evening. LUMIGAN ^® 0.01% and 0.03% (bimatoprost ophthalmic solution) should not be administered more than once daily since it has been shown that more frequent administration of prostaglandin analogs 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.

3 DOSAGE FORMS AND STRENGTHS

Ophthalmic solution containing bimatoprost 0.1 mg/mL (LUMIGAN ^® 0.01%) or containing bimatoprost 0.3 mg/mL (LUMIGAN ^® 0.03%).

4 CONTRAINDICATIONS

None

5 WARNINGS AND PRECAUTIONS

5.1 Pigmentation

Bimatoprost ophthalmic solution 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. Pigmentation is expected to increase as long as bimatoprost is administered. The pigmentation change is due to increased melanin content in the melanocytes rather than to an increase in the number of melanocytes. After discontinuation of bimatoprost, 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 long term effects of increased pigmentation are not known.

Iris color change 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. While treatment with LUMIGAN ^® 0.01% and 0.03% (bimatoprost ophthalmic solution) can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly [see Patient Counseling Information (17.1)].

5.2 Eyelash Changes

LUMIGAN ^® 0.01% and 0.03% 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.

5.3 Intraocular Inflammation

LUMIGAN ^® 0.01% and 0.03% should be used with caution in patients with active intraocular inflammation (e.g., uveitis) because the inflammation may be exacerbated.

5.4 Macular Edema

Macular edema, including cystoid macular edema, has been reported during treatment with bimatoprost ophthalmic solution. LUMIGAN ^® 0.01% and 0.03% 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.

5.5 Angle-closure, Inflammatory, or Neovascular Glaucoma

LUMIGAN ^® 0.01% and 0.03% has not been evaluated for the treatment of angle-closure, inflammatory or neovascular glaucoma.

5.6 Bacterial Keratitis

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 Patient Counseling Information (17.3)].

5.7 Use with Contact Lenses

Contact lenses should be removed prior to instillation of LUMIGAN ^® 0.01% and 0.03% and may be reinserted 15 minutes following its administration.

6 ADVERSE REACTIONS

6.1 Clinical Studies Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

In clinical studies with bimatoprost ophthalmic solutions (0.01% or 0.03%) the most common adverse reaction was conjunctival hyperemia (range 25%–45%). Approximately 0.5% to 3% of patients discontinued therapy due to conjunctival hyperemia with 0.01% or 0.03% bimatoprost ophthalmic solutions. Other common reactions (>10%) included growth of eyelashes, and ocular pruritus.

Additional ocular adverse reactions (reported in 1 to 10% of patients) with bimatoprost ophthalmic solutions included ocular dryness, visual disturbance, ocular burning, foreign body sensation, eye pain, pigmentation of the periocular skin, blepharitis, cataract, superficial punctate keratitis, periorbital erythema, ocular irritation, eyelash darkening, eye discharge, tearing, photophobia, allergic conjunctivitis, asthenopia, increases in iris pigmentation, conjunctival edema, conjunctival hemorrhage, and abnormal hair growth. Intraocular inflammation, reported as iritis, was reported in less than 1% of patients.

Systemic adverse reactions reported in approximately 10% of patients with bimatoprost ophthalmic solutions were infections (primarily colds and upper respiratory tract infections). Other systemic adverse reactions (reported in 1 to 5% of patients) included headaches, abnormal liver function tests, and asthenia.

6.2 Postmarketing Experience

The following reactions have been identified during postmarketing use of LUMIGAN ^® 0.01% and 0.03% 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 LUMIGAN ^®, or a combination of these factors, include: dizziness, eyelid edema, hypertension, nausea, and periorbital and lid changes associated with a deepening of the eyelid sulcus.

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.

At doses at least 41 times the maximum 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 ^® 0.01% and 0.03% (bimatoprost ophthalmic solution) 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.

8.3 Nursing Mothers

It is not known whether LUMIGAN ^® 0.01% and 0.03% 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.

8.4 Pediatric Use

Use in pediatric patients below the age of 16 years is not recommended because of potential safety concerns related to increased pigmentation following long-term chronic use.

8.5 Geriatric Use

No overall clinical differences in safety or effectiveness have been observed between elderly and other adult patients.

8.6 Hepatic Impairment

In patients with a history of liver disease or abnormal ALT, AST and/or bilirubin at baseline, bimatoprost 0.03% had no adverse effect on liver function over 48 months.

10 OVERDOSAGE

No information is available on overdosage in humans. If overdose with LUMIGAN ^® 0.01% and 0.03% (bimatoprost ophthalmic solution) 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 ^® 0.03% for a 10 kg child.

11 DESCRIPTION

LUMIGAN ^® 0.01% and 0.03% (bimatoprost ophthalmic solution) 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: