Loteprednol/tobramycin yields comfort, tolerability

Jun 01, 2009

Loteprednol etabonate 0.5%/tobramycin 0.3% ([LE/T]; Zylet, Bausch & Lomb) was found to be superior to dexamethasone 0.1%/tobramycin 0.3% ([DM/T]; Tobradex, Alcon Laboratories) in a comparison study that tested ocular comfort and tolerability in healthy volunteers. LE/T also has shown to be less likely to cause increases in IOP levels compared with DM/T. LE/T may provide some small advantages, possibly resulting from formulation differences and/or the steroid used, the researchers concluded.

Key Points

Formulation differences between the two drugs, the steroid used, or both may result in "small advantages" of LE/T over DM/T in comfort and tolerability, he and his colleagues suggested, because subjects who were randomly assigned to receive LE/T "were more likely to report better ocular comfort/tolerability ratings relative to baseline artificial tears than subjects receiving DM/T."

The investigators, who reported their findings in Current Medical Research and Opinion (2008;24:2219–2227), compared the "comfort and tolerability profiles of these medications using parameters that the current labels for these drugs suggest are different as well as commonly accepted standard parameters for determining ocular tolerability and comfort." The parameters were pain, stinging and burning, irritation, itchiness, foreign-body sensation, dryness, and light sensitivity.

In a diary, patients used a scale of 0 to 100 to rate the seven comfort and tolerability parameters for each eye; zero indicated "extremely uncomfortable," and 100 indicated "extremely comfortable." The primary study endpoint for each parameter was the mean difference between the average score of each parameter during the final study week and the baseline score that was recorded 5 minutes after artificial tears were instilled during the first visit.

The secondary study endpoints were the between- and within-treatment comparisons of the differences from baseline to each study visit for each parameter, the comparison of differences between treatment groups for the area under the curve for each parameter over the entire study period, and the between- and within-treatment comparisons of mean changes from 5 minutes before instillation to 5 minutes after instillation measured at clinic visits for each of the seven parameters.

A total of 156 subjects received loteprednol, and 150 received dexamethasone; 149 subjects and 136 subjects, respectively, completed the study. No significant differences existed between the groups in age, gender, or race/ethnicity.

"For all seven of the comfort/tolerability parameters, LE/T met the noninferiority conditions compared to DM/T, with all 97.5% lower confidence bounds within –10," the authors wrote. "Additional within-treatment analysis showed significant differences from baseline to the final week of diary assessment for pain favoring LE/T over artificial tears (p < 0.01) and for light sensitivity favoring artificial tears over DM/T (p < 0.01)."

No other statistically significant within-treatment differences were observed, they said.

The researchers also reported small between-treatment differences in the changes from baseline tear ratings to individual study visits that favored LE/T for pain, stinging and burning, irritation, itchiness, foreign-body sensation, and light sensitivity at day 15 (p ≤ 0.04); for pain, stinging and burning, and foreign body sensation at day 22 (p ≤ 0.03), and for dryness and light sensitivity at day 29 (p ≤ 0.05).

IOP elevation

A previously reported study (Holland et al. Cornea. 2008;27:50–55) found that LE/T was significantly less likely to cause increases in the IOP levels compared with DM/T. Three of the patients who received LE/T had increases in IOP that were >10 mm Hg compared with baseline; the DM/T group had 11 such patients, a difference that reached significance (p < 0.03).

"The results . . . demonstrate that LE/T is noninferior to DM/T in comfort/tolerability and may, in fact, provide some, albeit small, advantages in comfort/tolerability over DM/T possibly resulting from formulation differences and/or the steroid utilized," the investigators said.

The findings of this study, paired with the safety findings of the aforementioned study by Holland et al., particularly as related to greater increases in IOP following treatment with DM/T as compared with LE/T, suggest that "ophthalmic practitioners may prefer the comfort/tolerability and safety benefits of LE/T for their patients with ocular inflammatory conditions for whom a corticosteroid is indicated and either superficial bacterial ocular infection or a risk of bacterial infection exists," they concluded.

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