XTORO

1 INDICATIONS AND USAGE XTORO® is indicated for the treatment of acute otitis externa (AOE) with or without an otowick, caused by susceptible strains of Pseudomonas aeruginosa and Staphylococcus aureus in patients age 1 year and older. XTORO® is a quinolone antimicrobial indicated for the treatment of acute otitis externa (AOE) caused by susceptible strains of Pseudomonas aeruginosa and Staphylococcus aureus . ( 1 )

2 DOSAGE AND ADMINISTRATION Instill four drops into the affected ear(s) twice daily for seven days. For patients requiring use of an otowick, the initial dose can be doubled (to 8 drops), followed by 4 drops instilled into the affected ear twice daily for seven days. Important administration instructions include: Warm the suspension by holding the bottle in the hand for one or two minutes prior to dosing in order to avoid dizziness which may result from the instillation of a cold suspension. Shake bottle well before use. Lie with the affected ear upward, instill the drops, and maintain the position for 60 seconds to facilitate penetration of the drops into the ear canal. Repeat if necessary for the opposite ear. Instill four drops in the affected ear(s) twice daily for seven days. For patients requiring use of an otowick, the initial dose can be doubled (to 8 drops), followed by 4 drops instilled into the affected ear twice daily for seven days. ( 2 )

5 WARNINGS AND PRECAUTIONS Prolonged use of this product may lead to overgrowth of nonsusceptible organisms. Discontinue use if this occurs. ( 5.1 ) Allergic reactions may occur in patients with a history of hypersensitivity to finafloxacin, to other quinolones, or to any of the components in this medication. Discontinue use if this occurs. ( 5.2 ) 5.1 Growth of Resistant Organisms with Prolonged Use As with other antibacterial preparations, prolonged use of XTORO may lead to overgrowth of nonsusceptible organisms, including yeast and fungi. If this occurs, discontinue use and institute alternative therapy. 5.2 Allergic Reactions Allergic reactions to XTORO may occur in patients with a history of hypersensitivity to finafloxacin, to other quinolones, or to any of the components in this medication. If this occurs, discontinue use and institute alternative therapy. 5.1 Growth of Resistant Organisms with Prolonged Use As with other antibacterial preparations, prolonged use of XTORO may lead to overgrowth of nonsusceptible organisms, including yeast and fungi. If this occurs, discontinue use and institute alternative therapy. 5.2 Allergic Reactions Allergic reactions to XTORO may occur in patients with a history of hypersensitivity to finafloxacin, to other quinolones, or to any of the components in this medication. If this occurs, discontinue use and institute alternative therapy.

4 CONTRAINDICATIONS None. None. ( 4 )

8.1 Pregnancy Risk Summary There are no adequate or well-controlled studies with XTORO in pregnant women. Finafloxacin was shown to be teratogenic in rabbits and rats following oral administration. Neural tube defects and skeletal anomalies in both species, and limb anomalies in rabbits, were observed at exposures estimated to be at least 1300 times the maximum human systemic exposure following topical otic administration of 0.3% finafloxacin. Because animal studies are not always predictive of human responses, XTORO should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Data Animal Data In rabbit embryofetal studies, maternal toxicity was not observed at oral doses up to 9 mg/kg/day (estimated 8000 times the maximum human systemic exposure [0.234 ng/mL] following topical otic administration with 0.3% finafloxacin). Fetal toxicity was observed at the lowest dose tested, 1 mg/kg/day (estimated 1300 times the maximum human systemic exposure following topical otic administration with 0.3% finafloxacin), and included exencephaly, enlarged fontanel, spina bifida, phocomelia, paw hyperflexure, missing lumbar vertebra, missing lumbar arch, and sternebra fusion. In a rat embryofetal study, no adverse maternal toxicity was observed at oral doses up to 100 mg/kg/day (estimated 60,000 times the maximum human systemic exposure following topical otic administration with 0.3% finafloxacin). The developmental no observed adverse effect level (NOAEL) was 30 mg/kg (estimated 22,000 times the maximum human systemic exposure following topical otic administration with 0.3% finafloxacin). Exencephaly was observed in one fetus at 100 mg/kg. At 500 mg/kg, additional developmental toxicities were observed including increased preimplantation loss, decreased fetal weight, decreased placental weight, increased incidence of non-ossified sternebrae, and delayed ossifications in the sternebrae, xiphisternum, sacral arches and metacarpals.

6 ADVERSE REACTIONS The most common adverse reactions occurring in 1% of patients with XTORO were ear pruritus and nausea. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Fonseca Biosciences, LLC at 1-877-436-6732 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 the 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. A total of 618 patients were treated with XTORO in two Phase 3 clinical trials. The most frequently reported adverse reactions of those exposed to XTORO occurring at an incidence of 1% included ear pruritus and nausea.