AzaSite® (azithromycin ophthalmic solution) 1%
AzaSite combines the antibiotic properties of azithromycin with the DuraSite® drug delivery technology.
Azithromycin is a broad spectrum antibiotic that is widely used to treat bacterial infections. Azithromycin differs from other antibiotics in that it remains in body tissues for extended periods, and allows for less frequent dosing. This, combined with its established safety profile in infants, children, adults, and geriatric patients, makes azithromycin an excellent candidate for treating a wide variety of bacterial infections.1 Among its many applications, azithromycin has been used to treat bacterial infections of the throat, ears and skin, tonsillitis, laryngitis, bronchitis, pneumonia, sinusitis, and certain sexually transmitted diseases. However, it was not until the development of AzaSite by InSite Vision that azithromycin was made available for the topical treatment of eye infections.
The number one selling antibiotic in the world
Azithromycin was discovered in 1980 by researchers at Pliva (a Croatian pharmaceutical company) and patented in 1981. In 1986, Pliva and Pfizer entered into a licensing agreement that gave Pfizer exclusive rights for the sale of azithromycin in the United States and parts of Europe. In 1991, Pfizer introduced azithromycin under the brand name Zithromax®, which went on to become the number-one selling antibiotic in the world.
A new treatment for eye infections
Until the introduction of InSite Vision’s new AzaSite formulation, azithromycin had been available only as an oral suspension, tablet, or intravenous injection. The use of azithromycin for the topical treatment of eye infections had been limited by a number of formulation challenges, specifically the instability in aqueous solutions and heat instability.
While other industry leaders were unable to overcome these formulation challenges, InSite Vision saw azithromycin as an excellent candidate for ophthalmic applications. In 2001, InSite Vision began using their DuraSite drug delivery technology to create a formulation that enabled the use of azithromycin for the topical treatment of ocular infections, particularly bacterial conjunctivitis. This formulation with DuraSite led to the development of AzaSite.
The compound advantage
DuraSite is a polymer of cross-linked polyacrylic acid that has been shown to be non-toxic and biocompatible.2 In testing, it was demonstrated that in the aqueous environment of the eye, the size of DuraSite particles increases, resulting in an increased viscosity. When DuraSite was combined with therapeutic dosage levels of azithromycin, the drug remained stable in aqueous solution over a pH range consistent with that of the eye surface. Further research revealed that DuraSite, in combination with the biological properties of azithromycin, was capable maintaining therapeutic levels of a drug in the ocular environment for at least 24 hours. From a pharmacological perspective, this combination offered important therapeutic advantages, including:
- Longer drug residence time
- Improved bacterial resistance
- Less frequent dosing
- Improved patient compliance
Making the vision real
Based on these findings, InSite Vision initiated development of the azithromycin/DuraSite drug delivery technology platform. The company proposed an azithromycin/DuraSite formulation—later named AzaSite—with a dosing regimen that required a minimum of 60-75% fewer doses than conventional anti-infective eye drops. In 2003, these studies led to the first patent on the class of drugs called azalides formulated with DuraSite.
In 2006, InSite Vision submitted a new drug application (NDA) for AzaSite to the U.S. Food and Drug Administration (FDA). In April 2007, the FDA approved the AzaSite NDA (azithromycin ophthalmic solution) 1% for the treatment of bacterial conjunctivitis, and AzaSite became a reality. Looking forward, additional products such as AzaSite Plus (currently in clinical trials), and AzaSite Xtra will benefit directly from DuraSite technology.
Looking beyond AzaSite: Additional Applications
DuraSite is more than a vehicle for the delivery of azithromycin to the eye. Many conventional topical medications that last only a short time and require frequent dosing of a highly concentrated burst of drug to sustain therapeutic levels could benefit from the DuraSite drug delivery technology. The demonstrated “compound advantage” of DuraSite technology has the potential to provide a wide variety of proven drugs like azithromycin.
Potentially, the DuraSite drug delivery system can be customized to deliver small molecule and protein drug candidates to the ear, nose, throat, skin (epidermis), and other sites. The unique properties of DuraSite may allow these drugs to be gradually released over a longer period of time. Increased residence time made possible by DuraSite could permit lower concentrations of a drug to be administered over a longer period of time, thereby minimizing the inconvenience of frequent dosing, reducing potential adverse side effects, and improving patient compliance.
Topical medications such as eye drops delivered with DuraSite drug delivery technology offer a compelling contrast to conventional approaches.
- Zucker J. Macrolides and ketolides: azithromycin, clarithromycin, telithromycin. Infect. Dis Clin, N. Amer. 2005; 18:621-649,
- Final Assessment Report of the Safety of Carbomers -934, -934P, -940, -941, and –962. J Amer College Toxicol. 1982;1(2):109-141. Br. J. Ophthalmol 2003, 87:436-440.