Article Date: 6/1/2005

combination therapies
A New Therapeutic Approval: Zylet
In the first part of this series, OM profiles two anti-infective/anti-inflammatory combinations, Zylet and TobraDex.

For the first time in more than 15 years, a new combination drop is available to clinicians. Zylet (Bausch & Lomb) is a combination of tobramycin and loteprednol. This portion of the article will review the research on this new therapeutic agent and the research behind loteprednol.

Zylet combines tobramycin and loteprednol.

TobraDex is one of the most prescribed medications in optometry and the main difference in this new drug is the substitution of dexamethasone for loteprednol etabonate 0.5%. Loteprednol etabonate is a chloromethyl ester in the 17 beta-position modification of prednisolone; research suggests that ester molecules are metabolized quicker once inside the eye, preventing receptor attachment and potential complications. Studies have shown that ketone steroids such as dexamethasone or prednisolone may be more likely to raise intraocular pressures (IOPs). A study involving children under 10 years of age showed that those receiving 0.1% dexamethasone six times per day for up to four weeks had a significantly higher IOP and significantly quicker responses (89% of high responders reached their peak within 8 days). Ketone-based steroids have also been shown to cause IOP rises after PRK and LASIK and the IOP elevation might induce an episode of diffuse lamellar keratitis. Other complications doctors have documented include posterior subcapsular cataract formation and secondary infections. This becomes significant in chronic conditions such as dry eye, blepharitis, meibomitis and keratoconjunctivitis sicca.

Loteprednol safety

In one study evaluating 0.2% loteprednol etabonate, 397 patients were followed long-term, including 159 patients who used the drop continuously for more than 12 months. They were evaluated for IOP rise, cataract formation and other possible topical steroid-induced adverse events. There were no adverse events, including no significant pressure rise, no cataract formation and no secondary infections. In fact, with more than 4 million scripts of loteprednol prescribed there has been no reported case of cataract formation to date. Elevated IOP, although not noted with 0.2% in the Ilyas study, can occur with 0.5% loteprednol and therefore we should continue to take IOP measurements in all patients using corticosteroids including Zylet. However, the difference with loteprednol etabonate is a lower incidence of steroid response and less of an IOP rise in those that do respond. A study by Bartlett compared the use of loteprednol in known steroid responders and found that the IOP elevation in the loteprednol group after 42 days was 21.5mm HG, versus 27.1mm HG in the prednisolone group.

Tobramycin's effectiveness

While the safety of the steroid component is one aspect of the drug, tobramycin still plays a role as an effective antibiotic in both gram-positive and gram-negative organisms. This would make it an effective medication in contact lens-related sterile keratitis or peripheral infiltrates for example. The gram negative coverage would play a more significant role in terms of organisms often associated with contact lens wear. Conditions such as contact lens-induced sterile infiltrates, as well as chronic conditions such as meibomitis and blepharitis, may benefit from this new medication. These are some of the most common conditions encountered by practicing optometrists.

When new therapeutics become available to the practicing clinician, it's important to look into the research and understand what we are prescribing and when to best utilize these new medications. Zylet will make a great addition to the therapeutic formulary based on its application and safety in contact lens-related and chronic conditions.

Dr. Karpecki is Director of Research at Moyes Eye Center in Kansas City and was a principal investigator in the research on Zylet. Dr. Karpecki is a paid consultant to Bausch & Lomb but holds no financial interest in any products mentioned in this article.

Optometric Management, Issue: June 2005