The following Structured Product Label (SPL) was submitted to the FDA by Thea Pharma Inc. for the product Azasite (NDC 82584-307). This document serves as the official prescribing information, containing essential scientific data and clinical materials required for healthcare providers and patients.
This specific version of the label includes detailed information regarding 1 indications and usage, 2 dosage and administration, 3 dosage forms and strengths, 4 contraindications, 5.1 topical ophthalmic use only, 5.2 anaphylaxis and hypersensitivity with systemic use of azithromycin, 5.3 growth of resistant organisms with prolonged use, 5.4 avoidance of contact lenses, and other regulatory disclosures. Use the navigation below to review specific sections of the FDA submission.
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.
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.
2.5 mL of a 1% sterile topical ophthalmic solution.
Hypersensitivity to any component of this product.
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.
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.
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.
Patients should be advised not to wear contact lenses if they have signs or symptoms of bacterial conjunctivitis.
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 1-2% 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).
Pregnancy Category B. Reproduction studies have been performed in rats and mice at doses up to 200 mg/kg/day. The highest dose was associated with moderate maternal toxicity. These doses are estimated to be approximately 5,000 times the maximum human ocular daily dose of 2 mg. In the animal studies, no evidence of harm to the fetus due to azithromycin was found. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, azithromycin should be used during pregnancy only if clearly needed.
It is not known whether azithromycin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when azithromycin is administered to a nursing woman.
The safety and effectiveness of AzaSite solution in pediatric patients below 1 year of age have not been established. The efficacy of AzaSite in treating bacterial conjunctivitis in pediatric patients one year or older has been demonstrated in controlled clinical trials [see Clinical Studies (14)] .
No overall differences in safety or effectiveness have been observed between elderly and younger patients.
AzaSite (azithromycin ophthalmic solution) is a 1% sterile aqueous topical ophthalmic solution of azithromycin formulated in DuraSite ® (polycarbophil, edetate disodium, sodium chloride). AzaSite is an off-white, viscous liquid with an osmolality of approximately 290 mOsm/kg.
Preservative: 0.003% benzalkonium chloride. Inactives: mannitol, citric acid, sodium citrate, poloxamer 407, polycarbophil, edetate disodium (EDTA), sodium chloride, water for injection, and sodium hydroxide to adjust pH to 6.3.
Azithromycin is a macrolide antibiotic with a 15-membered ring. Its chemical name is (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribohexopyranosyl)oxy]-2-ethyl-3,4,10-trihydroxy-3,5,6,8,10,12,14-heptamethyl-11-[[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyl]oxy]-1-oxa-6-aza-cyclopentadecan-15-one, and the structural formula is:
Chemical Structure (Azasite 01)
Azithromycin has a molecular weight of 749, and its empirical formula is C 38H 72N 2O 12.
Manufactured for:
Thea Pharma Inc.
Lexington, MA 02420
U.S. Patent No.: 7,758,553
AzaSite is a registered trademark of
Sun Pharma
© 2022. Thea Pharma Inc.
All rights reserved
Rev. 05/22
N10270C2USA/0522A
Azithromycin is a macrolide antibiotic [see Clinical Pharmacology (12.4)] .
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.
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 (1)] .
CDC coryneform group G
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
Long-term studies in animals have not been performed to evaluate carcinogenic potential. Azithromycin has shown no mutagenic potential in standard laboratory tests: mouse lymphoma assay, human lymphocyte clastogenic assay, and mouse bone marrow clastogenic assay. No evidence of impaired fertility due to azithromycin was found in mice or rats that received oral doses of up to 200 mg/kg/day.
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.
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.
AzaSite is a sterile aqueous topical ophthalmic formulation of 1% azithromycin.
NDC 82584-307-03: 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 82584-307-04: 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° to 8°C (36° to 46°F). Once the bottle is opened, store at 2° to 25°C (36° to 77°F) for up to 14 days. Discard after the 14 days.
See FDA-Approved Patient Labeling ( Patient Information).
Patients should be advised to avoid contaminating the applicator tip by allowing it to touch the eye, fingers or other sources.
Patients should be directed to discontinue use and contact a physician if any signs of an allergic reaction occur.
Patients should be told that although it is common to feel better early in the course of the therapy, the medication should be taken exactly as directed. 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.
Patients should be advised not to wear contact lenses if they have signs or symptoms of bacterial conjunctivitis.
Patients should be advised to thoroughly wash hands prior to using AzaSite.
Patients should be advised to invert the closed bottle (upside down) and shake once before each use. Remove cap with 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).
AzaSite
® (A-zuh-site)
(azithromycin ophthalmic solution) 1%
Read this Patient Information before you start using AzaSite ® and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or treatment.
What is AzaSite?
AzaSite is a prescription sterile eye drop solution. AzaSite is used to treat bacterial conjunctivitis which is an infection of the eye caused by certain bacteria.
It is not known if AzaSite is safe and effective in children less than 1 year of age.
Information about bacterial conjunctivitis.
Bacterial conjunctivitis is a bacterial infection of the mucous membranes which line the inside of the eyelids. Symptoms may include redness of the eye and discharge. The infection can be spread to other people and to both eyes.
Who should not use AzaSite?
Do not use AzaSite if you are allergic to azithromycin or any of the ingredients in AzaSite. See the end of this Patient Information leaflet for a complete list of the ingredients in AzaSite.
What should I tell my doctor before using AzaSite?
Before you use AzaSite, tell your doctor if you:
Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.
Know the medicines you take. Keep a list of them to show your doctors and pharmacist when you get a new medicine.
How should I use AzaSite?
What should I be aware of while using AzaSite?
Do not wear contact lenses if you have signs or symptoms of bacterial conjunctivitis and until you have finished your prescribed course of treatment. The symptoms of bacterial conjunctivitis may include:
Only your doctor can tell you if you have bacterial conjunctivitis.
Severe allergic reactions have been reported rarely when azithromycin has been taken by mouth.
Increased risk of other infections caused by bacteria or fungi.
What are the possible side effects of AzaSite?
The most common side effect of AzaSite is eye irritation.
Other side effects seen with AzaSite include:
Tell your doctor about any side effect that bothers you or that does not go away.
These are not all of the possible side effects of AzaSite. For more information, ask your doctor or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store AzaSite?
Keep AzaSite and all medicines out of reach of children.
General information about the safe and effective use of AzaSite
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use AzaSite for a condition for which it was not prescribed. Do not give AzaSite to other people, even if they have the same symptoms that you have. It may harm them.
This Patient Information summarizes the most important information about AzaSite. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about AzaSite that is written for health professionals.
For more information, go to www.azasite.com or call 1-833-838-4028.
What are the ingredients in AzaSite?
Active ingredient: azithromycin
Inactive ingredients: 0.003% benzalkonium chloride, mannitol, citric acid, sodium citrate, poloxamer 407, polycarbophil, edetate disodium (EDTA), sodium chloride, water, and sodium hydroxide.
AzaSite
® (A-zuh-site)
(azithromycin ophthalmic solution) 1%
Read this Instructions for Use for AzaSite before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking to your doctor about your medical condition or treatment.
Important:
The checklist below tells you when to use your medicine for each eye that has bacterial conjunctivitis:
| □ □ | Day 1:
| 1 drop in the morning and 1 drop in the evening |
| □ □ | Day 2:
| 1 drop in the morning and 1 drop in the evening |
| □ | Day 3
| 1 drop anytime during the day |
| □ | Day 4
| 1 drop anytime during the day |
| □ | Day 5
| 1 drop anytime during the day |
| □ | Day 6
| 1 drop anytime during the day |
| □ | Day 7
| 1 drop anytime during the day |
This is a total of 9 drops of AzaSite for each infected eye.
| Before using a new bottle of AzaSite: | |
 Figure A (Azasite 02)
|  Figure B (Azasite 03)
|
| Wash your hands each time you use AzaSite. | |
| To use AzaSite: | |
 Figure C (Azasite 04) |  Figure D (Azasite 05) |
| Step 1. Turn the closed bottle upside down. See Figure C | Step 2. Shake your hand firmly. This helps move the medicine into the tip of the bottle. See Figure D |
 Figure E (Azasite 06) |  Figure F (Azasite 07) |
| Step 3. Hold the bottle upside down and take off the tan cap. See Figure E | Step 4. Tilt your head back. Hold the bottle over your eye and gently squeeze the bottle to let 1 drop into each eye that has bacterial conjunctivitis. Put the tan cap back on the bottle and close tightly. See Figure F |
| If a drop does not come out of the bottle, repeat steps one to four. | |
| This Patient Information and Instructions for Use have been approved by the U.S. Food and Drug Administration. | |
Manufactured for:
Thea Pharma Inc.
Lexington, MA 02420
U.S. Patent No.: 7,758,553
AzaSite is a registered trademark of Sun Pharma.
© 2022. Thea Pharma Inc.
All rights reserved
Rev. 05/22
N10270C2USA/0522B
NDC 82584-307-03
AzaSITE
®
(azithromycin ophthalmic solution) 1%
Sterile 2.5 mL
Rx Only
FOR OPHTHALMIC USE ONLY
Principal Display Panel (2.5 mL Bottle Carton)
* Please review the disclaimer below.
