Azithromycin Ophthalmic Solution

Dosage Forms And Strengths

2.5 mL of a 1% sterile topical ophthalmic solution.

AzaSite is a sterile aqueous topical ophthalmic formulation of 1% azithromycin.

NDC 31357-040-25: 2.5 mL in 5 mL bottle containing a total of 25 mg of azithromycin in a white, round, low-density polyethylene (LDPE) bottle, with a clear LDPE dropper tip, and a tan colored high density polyethylene (HDPE) eyedropper cap. A white tamper evident over-cap is provided.

NDC 31357-040-03: 2.5 mL in 4 mL bottle containing a total of 25 mg of azithromycin in a white, round, low-density polyethylene (LDPE) bottle, with a clear LDPE dropper tip, and a tan colored high density polyethylene (HDPE) eyedropper cap. A white tamper evident over-cap is provided.

Storage And Handling

Store unopened bottle under refrigeration at 2°C to 8°C (36°F to 46°F). Once the bottle is opened, store at 2°C to 25°C (36°F to 77°F) for up to 14 days. Discard after the 14 days.

Manufactured for: Inspire Pharmaceuticals, Inc., a subsidiary of MERCK & CO., INC., Whitehouse Station, NJ 08889, USA. Manufactured by: Catalent Pharma Solutions, LLC, Woodstock, IL 60098. Revised: Oct 2012

No information provided.

Mechanism Of Action

Azithromycin is a macrolide antibiotic [see Microbiology].

Pharmacokinetics

The plasma concentration of azithromycin following ocular administration of AzaSite (azithromycin ophthalmic solution) in humans is unknown. Based on the proposed dose of one drop to each eye (total dose of 100 mcL or 1 mg) and exposure information from systemic administration, the systemic concentration of azithromycin following ocular administration is estimated to be below quantifiable limits ( ≤ 10 ng/mL) at steady-state in humans, assuming 100% systemic availability.

Microbiology

Azithromycin acts by binding to the 50S ribosomal subunit of susceptible microorganisms and interfering with microbial protein synthesis.

Azithromycin has been shown to be active against most isolates of the following microorganisms, both in vitro and clinically in conjunctival infections [see INDICATIONS AND USAGE].

CDC coryneform group G*

Haemophilus influenzae
Staphylococcus aureus
Streptococcus mitis group
Streptococcus pneumoniae

*Efficacy for this organism was studied in fewer than 10 infections.

The following in vitro data are also available, but their clinical significance in ophthalmic infections is unknown. The safety and effectiveness of AzaSite in treating ophthalmological infections due to these microorganisms have not been established.

The following microorganisms are considered susceptible when evaluated using systemic breakpoints. However, a correlation between the in vitro systemic breakpoint and ophthalmological efficacy has not been established. This list of microorganisms is provided as an aid only in assessing the potential treatment of conjunctival infections. Azithromycin exhibits in vitro minimal inhibitory concentrations (MICs) of equal or less (systemic susceptible breakpoint) against most ( ≥ 90%) of isolates of the following ocular pathogens:

Chlamydia pneumoniae
Chlamydia trachomatis
Legionella pneumophila
Moraxella catarrhalis
Mycoplasma hominis
Mycoplasma pneumoniae
Neisseria gonorrhoeae
Peptostreptococcus species
Streptococci (Groups C, F, G)
Streptococcus pyogenes
Streptococcus agalactiae
Ureaplasma urealyticum
Viridans group streptococci

Animal Toxicology And/Or Pharmacology

Phospholipidosis (intracellular phospholipid accumulation) has been observed in some tissues of mice, rats, and dogs given multiple systemic doses of azithromycin. Cytoplasmic microvacuolation, which is likely a manifestation of phospholipidosis, has been observed in the corneas of rabbits given multiple ocular doses of AzaSite. This effect was reversible upon cessation of AzaSite treatment. The significance of this toxicological finding for animals and for humans is unknown.

Clinical Studies

In a randomized, vehicle-controlled, double-blind, multicenter clinical study in which patients were dosed twice daily for the first two days, then once daily on days 3, 4, and 5, AzaSite solution was superior to vehicle on days 6-7 in patients who had a confirmed clinical diagnosis of bacterial conjunctivitis. Clinical resolution was achieved in 63% (82/130) of patients treated with AzaSite versus 50% (74/149) of patients treated with vehicle. The p-value for the comparison was 0.03 and the 95% confidence interval around the 13% (63%-50%) difference was 2% to 25%. The microbiological success rate for the eradication of the baseline pathogens was approximately 88% compared to 66% of patients treated with vehicle (p < 0.001, confidence interval around the 22% difference was 13% to 31%). Microbiologic eradication does not always correlate with clinical outcome in anti-infective trials.

No information provided. Please refer to the WARNINGS AND PRECAUTIONS section.

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

Side effects that you should report to your doctor or health care professional as soon as possible:

• allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
• changes in vision
• eye irritation, pain

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):

• bad taste in mouth
• burning, stinging, irritation when drops used
• congested nose
• dry eyes
• teary eyes