LACTATION SECTION.

8.2 Lactation There are no data on the presence of perfluorohexyloctane in human milk, the effects on the breastfed infant, or the effects on milk production. The lack of clinical data during lactation precludes clear determination of the risk of MIEBO to an infant during lactation; however, the developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for MIEBO.

DESCRIPTION SECTION.

11 DESCRIPTION MIEBO(TM) (perfluorohexyloctane ophthalmic solution) is sterile, clear and colorless liquid containing 100% perfluorohexyloctane, for topical ophthalmic use.The active ingredient is 1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluorotetradecane and is semifluorinated alkane. It has molecular formula of C14H17F13 and molecular weight of 432.26 g/mol. The chemical structure is:Perfluorohexyloctane is practically immiscible with water. It is miscible with ethanol and most organic solvents. Each multiple-dose bottle contains mL of perfluorohexyloctane, 1.338 g/mL as clear and colorless liquid.. chemstructure.

DOSAGE & ADMINISTRATION SECTION.

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 drop into your eye. Repeat steps - for the second affected eye. Step 2.. Step 3.. Step 4.

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING MIEBO(TM) (perfluorohexyloctane ophthalmic solution) is supplied as sterile, clear and colorless liquid in multiple-dose mL polypropylene bottles with dropper tips and screw caps, packaged in carton NDC 24208-377-05.StorageStore MIEBO at 15oC to 25oC (59oF to 77oF). After opening, MIEBO can be used until the expiration date on the bottle.

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION Use with Contact Lenses Advise patients that contact lenses should be removed prior to and for at least 30 minutes after administration of MIEBO. Administration InstructionsAdvise patients to instill one drop of MIEBO four times daily into each eye as depicted in the Administration Instructions [see Dosage and Administration (2.2)].Distributed by:Bausch Lomb Americas Inc.Bridgewater, NJ 08807 USAPatented. See https://patents.bausch.com for US patent information.MIEBO is trademark of Bausch Lomb Incorporated or its affiliates.(C) 2023 Bausch Lomb Incorporated or its affiliates.

ADVERSE REACTIONS SECTION.

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 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.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies in animals have not been conducted to evaluate the carcinogenic potential of perfluorohexyloctane.Perfluorohexyloctane was not mutagenic or clastogenic in standard battery of genotoxicity tests, including bacterial mutagenicity assay (Ames assay), an in vitro chromosome aberration assay using human peripheral lymphocytes, and an in vivo bone marrow micronucleus assay in rats.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Perfluorohexyloctane, semifluorinated alkane, contains perfluorinated carbon atoms and hydrogenated carbon atoms. Perfluorohexyloctane forms monolayer at the air-liquid interface of the tear film which can be expected to reduce evaporation. The exact mechanism of action for MIEBO in DED is not known.. 12.3 Pharmacokinetics The pharmacokinetics of perfluorohexyloctane following topical ocular administration of MIEBO has not been quantitatively characterized in humans. single pharmacokinetic (PK) study was conducted that showed low systemic perfluorohexyloctane blood levels after topical ocular administration. Perfluorohexyloctane was not metabolized by human liver microsomes in vitro.

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES In two randomized, multicenter, double-masked, saline-controlled trials (GOBI and MOJAVE), total of 1,217 patients with history of DED and clinical signs of meibomian gland dysfunction were randomized to MIEBO or saline 0.6% (1:1 ratio) to evaluate safety and efficacy after receiving MIEBO four times daily (QID) for 57 days.The mean age of the 614 patients who received MIEBO was 57 years (range, 19-87 years). The majority of patients were female (76%).Effects on Signs of Dry Eye Disease Total corneal fluorescein staining (tCFS) was recorded at each study visit using standardized grading system of 0-3 for each of the five areas on the cornea (inferior, superior, central, nasal, and temporal), totaling maximum tCFS score for each eye of 15. The average baseline tCFS was approximately 6.7 in GOBI and 7.0 in MOJAVE. At Days 15 and 57, statistically significant reduction in tCFS favoring MIEBO was observed in both studies (Figure 1).Effects on Symptoms of Dry Eye Disease Eye dryness score was rated by patients using visual analogue scale (VAS) (0=no discomfort, 100=maximal discomfort) at each study visit. The baseline VAS eye dryness average score was approximately 67 in GOBI and 65 in MOJAVE. At Days 15 and 57, statistically significant reduction in VAS eye dryness score favoring MIEBO was observed in both studies (Figure 2).. Figure 1. Figure 2.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies in animals have not been conducted to evaluate the carcinogenic potential of perfluorohexyloctane.Perfluorohexyloctane was not mutagenic or clastogenic in standard battery of genotoxicity tests, including bacterial mutagenicity assay (Ames assay), an in vitro chromosome aberration assay using human peripheral lymphocytes, and an in vivo bone marrow micronucleus assay in rats.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics The pharmacokinetics of perfluorohexyloctane following topical ocular administration of MIEBO has not been quantitatively characterized in humans. single pharmacokinetic (PK) study was conducted that showed low systemic perfluorohexyloctane blood levels after topical ocular administration. Perfluorohexyloctane was not metabolized by human liver microsomes in vitro.

PREGNANCY SECTION.

8.1 Pregnancy Risk SummaryThere 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 risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects is to 4%, and of miscarriage is 15 to 20%, of clinically recognized pregnancies.DataAnimal Data An embryofetal study was conducted in pregnant rabbits administered perfluorohexyloctane by oral gavage on gestation days 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. 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 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).

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk SummaryThere 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 risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects is to 4%, and of miscarriage is 15 to 20%, of clinically recognized pregnancies.DataAnimal Data An embryofetal study was conducted in pregnant rabbits administered perfluorohexyloctane by oral gavage on gestation days 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. 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 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).. 8.2 Lactation There are no data on the presence of perfluorohexyloctane in human milk, the effects on the breastfed infant, or the effects on milk production. The lack of clinical data during lactation precludes clear determination of the risk of MIEBO to an infant during lactation; however, the developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for MIEBO.. 8.4 Pediatric Use The safety and effectiveness of MIEBO in pediatric patients below the age of 18 years have not been established.. 8.5 Geriatric Use No overall differences in safety and effectiveness have been observed between elderly and younger patients.