LEVOFLOXACIN

1 INDICATIONS AND USAGE Levofloxacin ophthalmic solution is indicated for the treatment of bacterial conjunctivitis caused by susceptible strains of the following organisms: Gram-positive bacteria Corynebacterium species * Staphylococcus aureus Staphylococcus epidermidis Streptococcus pneumonia Streptococcus (Groups C/F) Streptococcus (Group G) Viridans group streptococci* Gram-negative bacteria Acinetobacter lwoffii * Haemophilus influenzae Serratia marcescens* *Efficacy for this organism was studied in fewer than 10 infections Levofloxacin ophthalmic solution is indicated for the treatment of bacterial conjunctivitis caused by susceptible strains of the following organisms: Gram-positive bacteria: Corynebacterium species * Staphylococcus aureus Staphylococcus epidermidis Streptococcus pneumonia Streptococcus (Groups C/F) Streptococcus (Group G) Viridans group streptococci* Gram-negative bacteria: Acinetobacter lwoffii * Haemophilus influenzae Serratia marcescens* *Efficacy for this organism was studied in fewer than 10 infections ( 1 )

2 DOSAGE AND ADMINISTRATION Days 1 and 2 Instill one to two drops in the affected eye(s) every 2 hours while awake, up to 8 times per day. Days 3 through 7 Instill one to two drops in the affected eye(s) every 4 hours while awake, up to 4 times per day. Day s 1 and 2: Instill one to two drops in the affected eye(s) every 2 hours while awake, up to 8 times per day. Day s 3 through 7: Instill one to two drops in the affected eye(s) every 4 hours while awake, up to 4 times per day. ( 2 )

5 WARNINGS AND PRECAUTIONS Hypersensitivity and anaphylaxis have been reported with systemic use of levofloxacin as well as topical use of other fluoroquinolones, including levofloxacin ophthalmic solution. ( 5.1 ) Prolonged use may result in the overgrowth of non- susceptible organisms, including fungi. ( 5.2 ) Patients should not wear contact lenses if they have signs or symptoms of bacterial conjunctivitis. ( 5.3 ) 5.1 Hypersensitivity Reactions In patients receiving systemically administered quinolones, including levofloxacin, serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported, some following the first dose. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema, (including laryngeal, pharyngeal or facial edema), airway obstruction, dyspnea, urticaria and itching. If allergic reaction to levofloxacin occurs, discontinue the drug. Serious acute hypersensitivity reactions may require immediate emergency treatment. Oxygen and airway management should be administered as clinically indicated. 5.2 Growth of Resistant Organisms with Prolonged Use As with other anti-infectives, prolonged use may result in overgrowth of non-susceptible organisms, including fungi. If superinfection occurs, discontinue use and institute alternative therapy. Whenever clinical judgment dictates, the patient should be examined with the aid of magnification, such as slit-lamp biomicroscopy, and where appropriate, fluorescein staining. 5.3 Avoidance of Contact Lens Wear Patients should be advised not to wear contact lenses if they have signs and symptoms of bacterial conjunctivitis.

4 CONTRAINDICATIONS Levofloxacin ophthalmic solution is contraindicated in patients with a history of hypersensitivity to levofloxacin, to other quinolones, or to any of the components in this medication. Levofloxacin ophthalmic solution is contraindicated in patients with a history of hypersensitivity to levofloxacin, to other quinolones, or to any of the components in this medication. ( 4 )

8.1 Pregnancy Teratogenic Effects Levofloxacin at oral doses of 810 mg/kg/day in rats caused decreased fetal body weight and increased fetal mortality. No teratogenic effect was observed when rabbits were dosed orally as high as 50 mg/kg/day, at which systemic exposure was approximately 2,250 times that observed at the maximum recommended human ophthalmic dose, or when dosed intravenously as high as 25 mg/kg/day, at which systemic exposure was approximately 1000 times that observed at the maximum recommended human ophthalmic dose. There are, however, no adequate and well-controlled studies in pregnant women. Levofloxacin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

8.3 Nursing Mothers Levofloxacin has not been measured in human milk. Based upon data from ofloxacin, it can be presumed that levofloxacin is excreted in human milk. Caution should be exercised when levofloxacin ophthalmic solution is administered to a nursing mother.

6 ADVERSE REACTIONS The most frequently reported adverse reactions in the overall study population were transient decreased vision, fever, foreign body sensation, headache, transient ocular burning, ocular pain or discomfort, pharyngitis and photophobia. These reactions occurred in approximately 1-3% of patients. Other reported reactions occurring in less than 1% of patients included allergic reactions, lid edema, ocular dryness, and ocular itching. The most frequently reported adverse reactions in the overall study population were transient decreased vision, fever, foreign body sensation, headache, transient ocular burning, ocular pain or discomfort, pharyngitis and photophobia. These reactions occurred in approximately 1 to 3% of patients. Other reported reactions occurring in less than 1% of patients included allergic reactions, lid edema, ocular dryness, and ocular itching. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Advagen Pharma Ltd, at 866-488-0312 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch