MIEBO

1 INDICATIONS AND USAGE MIEBO ® (perfluorohexyloctane ophthalmic solution) is indicated for the treatment of the signs and symptoms of dry eye disease (DED). MIEBO (perfluorohexyloctane ophthalmic solution) is a semifluorinated alkane indicated for treatment of the signs and symptoms of dry eye disease. ( 1 )

2 DOSAGE AND ADMINISTRATION Instill one drop of MIEBO four times daily into each eye. ( 2.1 ) 2.1 Recommended Dosage Instill one drop of MIEBO four times daily into affected eye(s). Contact lenses should be removed prior to and for at least 30 minutes after the administration of MIEBO. 2.2 Administration Instructions Step 1. Remove the cap from eye drop bottle. Step 2. Holding the bottle upright, gently squeeze the bottle. Step 3. While squeezing, turn the bottle upside down and release the pressure (drawing air into the bottle). Step 4. Keeping the bottle upside down, place the bottle above your eye and squeeze it again to release a drop into your eye. Repeat steps 1 - 4 for the second affected eye. Step 2. Step 3. Step 4.

4 CONTRAINDICATIONS Hypersensitivity. ( 4.1 ) 4.1 Hypersensitivity MIEBO is contraindicated in patients with a history of hypersensitivity reaction to perfluorohexyloctane [see Adverse Reactions ( 6.1 )] .

5 WARNINGS AND PRECAUTIONS 5.1 Use with Contact Lenses MIEBO should not be administered while wearing contact lenses. Advise patients that contact lenses should be removed prior to and for at least 30 minutes after administration of MIEBO.

6 ADVERSE REACTIONS Most common ocular adverse reaction was blurred vision. Blurred vision was reported in less than 4% of individuals. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bausch & Lomb Incorporated at 1-800-553-5340 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In patients with DED, 614 patients received at least one dose of MIEBO in two randomized controlled clinical trials across 68 sites in the United States. The most common ocular adverse reaction was blurred vision. Blurred vision and conjunctival redness were reported in 1-3% of individuals. In four premarketing studies (three open-label [n=127], one randomized [n=24 treated with at least one dose of perfluorohexyloctane]) the most common adverse reaction was hypersensitivity.

8.1 Pregnancy Risk Summary There are no adequate and well controlled studies with MIEBO in pregnant women. In animal reproduction studies with oral administration of perfluorohexyloctane during the period of organogenesis, no adverse maternal or developmental effects were observed in rats at doses up to 162 times the recommended human ophthalmic dose (RHOD) ( see Data ). Maternal toxicity, miscarriages and reduced fetal weights were observed in rabbits at all doses tested, with the lowest dose as 41 times the RHOD. All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects is 2 to 4%, and of miscarriage is 15 to 20%, of clinically recognized pregnancies. Data Animal Data An embryofetal study was conducted in pregnant rabbits administered perfluorohexyloctane by oral gavage on gestation days 6 to 19, to target the period of organogenesis. Perfluorohexyloctane produced maternal toxicity, characterized by reduced body weight gain and food consumption, and miscarriages at all doses tested, with the lowest dose as ≥ 250 mg/kg/day (41 times the RHOD based on body surface area). Reduced fetal weights were also observed at ≥ 250 mg/kg/day but no fetal mortality or malformations. A no observed adverse effect level (NOAEL) for maternal toxicity was not established in rabbits. An embryofetal study was conducted in pregnant rats administered perfluorohexyloctane by oral gavage on gestation days 6 to 17, to target the period of organogenesis. There was no evidence of embryofetal toxicity or teratogenicity at doses up to 2,000 mg/kg/day (162 times the RHOD).