AZASITE

1 INDICATIONS AND USAGE AzaSite ® is indicated for the treatment of bacterial conjunctivitis caused by susceptible isolates of the following microorganisms: CDC coryneform group G Efficacy for this organism was studied in fewer than 10 infections. Haemophilus influenzae Staphylococcus aureus Streptococcus mitis group Streptococcus pneumoniae AzaSite is a macrolide antimicrobial indicated for the treatment of bacterial conjunctivitis caused by susceptible isolates of the following microorganisms: CDC coryneform group G, Haemophilus influenzae, Staphylococcus aureus, Streptococcus mitis group, and Streptococcus pneumoniae. ( 1 )

2 DOSAGE AND ADMINISTRATION The recommended dosage regimen for the treatment of bacterial conjunctivitis is: Instill 1 drop in the affected eye(s) twice daily, eight to twelve hours apart for the first two days and then instill 1 drop in the affected eye(s) once daily for the next five days. Instill 1 drop in the affected eye(s) twice daily, eight to twelve hours apart for the first two days and then instill 1 drop in the affected eye(s) once daily for the next five days. ( 2 ) 2.1 Recommended Dosage The recommended dosage for the treatment of bacterial conjunctivitis is: Instill 1 drop in the affected eye(s) twice daily, eight to twelve hours apart for the first two days and then instill 1 drop in the affected eye(s) once daily for the next five days. 2.2 Administration Instructions Wash hands prior to using AzaSite. Invert the closed bottle (upside down) and shake once before each use. Remove the tan cap with the bottle still in the inverted position. Tilt head back, and with bottle inverted, gently squeeze bottle to instill one drop into the affected eye(s). Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by AzaSite (azithromycin ophthalmic solution) or other antibacterial drugs in the future.

4 CONTRAINDICATIONS Azasite is contraindicated in patients with hypersensitivity to any component of this product. Hypersensitivity ( 4 )

5 WARNINGS AND PRECAUTIONS For topical ophthalmic use only. ( 5.1 ) Anaphylaxis and hypersensitivity have been reported with systemic use of azithromycin. ( 5.2 ) Growth of resistant organisms may occur with prolonged use. ( 5.3 ) Patients should not wear contact lenses if they have signs or symptoms of bacterial conjunctivitis. ( 5.4 ) 5.1 Topical Ophthalmic Use Only NOT FOR INJECTION. AzaSite is indicated for topical ophthalmic use only, and should not be administered systemically, injected subconjunctivally, or introduced directly into the anterior chamber of the eye. 5.2 Anaphylaxis and Hypersensitivity with Systemic Use of Azithromycin In patients receiving systemically administered azithromycin, serious allergic reactions, including angioedema, anaphylaxis, and dermatologic reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported rarely in patients on azithromycin therapy. Although rare, fatalities have been reported. The potential for anaphylaxis or other hypersensitivity reactions should be considered based on known hypersensitivity to azithromycin when administered systemically. 5.3 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 super-infection 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. 5.4 Contamination of the Applicator Tip Avoid contaminating the applicator tip by not allowing it to touch the eye, fingers or other sources. 5.5 Avoidance of Contact Lenses Patients should be advised not to wear contact lenses if they have signs or symptoms of bacterial conjunctivitis.

6 ADVERSE REACTIONS Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in one clinical trial of a drug cannot be directly compared with the rates in the clinical trials of the same or another drug and may not reflect the rates observed in practice. The data described below reflect exposure to AzaSite in 698 patients. The population was between 1 and 87 years old with clinical signs and symptoms of bacterial conjunctivitis. The most frequently reported ocular adverse reaction reported in patients receiving AzaSite was eye irritation. This reaction occurred in approximately 1 to 2% of patients. Other adverse reactions associated with the use of AzaSite were reported in less than 1% of patients and included ocular reactions (blurred vision, burning, stinging and irritation upon instillation, contact dermatitis, corneal erosion, dry eye, eye pain, itching, ocular discharge, punctate keratitis, visual acuity reduction) and non-ocular reactions (dysgeusia, facial swelling, hives, nasal congestion, periocular swelling, rash, sinusitis, urticaria). Most common adverse reaction reported in patients was eye irritation (1 to 2% of patients). ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Thea Pharma Inc. at 1-833-838-4028 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

8.1 Pregnancy Risk Summary Available data from published literature and postmarketing experience over several decades with azithromycin use in pregnant women have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes ( see Data ). Developmental toxicity studies with azithromycin in rats, mice, and rabbits showed no drug-induced fetal malformations at doses up to 200 mg/kg/day. The doses used in these studies were orders of magnitude in excess of the clinical exposure that would be possible following topical ocular administration of azithromycin. ( see Data ). The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Human Data Available data from published observational studies, case series, and case reports over several decades do not suggest an increased risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes with oral or topical ophthalmic azithromycin use in pregnant women. Limitations of these data include the lack of randomization and inability to control for confounders such as underlying maternal disease and maternal use of concomitant medications. Animal Data Azithromycin administered during the period of organogenesis did not cause fetal malformations in rats and mice at oral doses up to 200 mg/kg/day (moderately maternally toxic). Assuming 100% absorption from topical ocular exposure, this dose is hundreds of times daily dose that can be achieved with topical ophthalmic administration. In rabbits administered azithromycin at oral doses of 10, 20, and 40 mg/kg/day during organogenesis, reduced maternal body weight and food consumption were observed in all groups; no evidence of fetotoxicity or teratogenicity was observed at these doses, the highest of which is estimated to be at least 100 times topical ophthalmic dose assuming 100% absorption from ocular exposure. In a pre- and postnatal development study, azithromycin was administered orally to pregnant rats from day 6 of pregnancy until weaning at doses of 50 or 200 mg/kg/day. Maternal toxicity (reduced food consumption and body weight gain; increased stress at parturition) was observed at the higher dose. Effects in the offspring were noted at 200 mg/kg/day during the postnatal development period (decreased viability, delayed developmental landmarks). These effects were not observed in a pre- and postnatal rat study when up to 200 mg/kg/day of azithromycin was given orally beginning on day 15 of pregnancy until weaning. Assuming 100% absorption from topical ocular exposure, this dose is hundreds of times daily dose that can be achieved with topical ophthalmic administration.