Rx Pharmaceuticals
Zylet®: Loteprednol Etabonate - Favorable Safety Profile
The retrometabolic drug design process used to create loteprednol etabonate
was intended to provide clinicians with a potent ophthalmic corticosteriod that
had a significantly improved margin of safety.13 As demonstrated
in subsequent pharmacologic and clinical studies, this objective has
indeed been realized with loteprednol etabonate. The loteprednol etabonate
compound has had an impressive track record since its first commercial
availability as an ophthalmic product in the US in 1998.
Some of the clinical evidence that confirms this unique and desired drug
metabolic process can be found in a bioavailability study of normal volunteers
which established that plasma levels of loteprednol etabonate and its primary
inactive metabolite (cortienic acid etabonate), were below the limit of
quantitation (1 ng/mL) at all sampling times.3 These results were
obtained following the ocular administration of one drop in each eye of 0.5%
loteprednol etabonate ophthalmic suspension 8 times daily for 2 days or 4 times
daily for 42 days. Also, no evidence of Hypothalamus-Pituitary-Adrenal (HPA)
axis suppression were found after six weeks of therapy.18
Additionally, the safety of loteprednol etabonate 0.5% has been assessed in 20 clinical trials involving a total of 2210 patients. In a summation of controlled, randomized clinical trials of subjects treated for 28 days or longer with loteprednol etabonate, the incidence of significant elevation of intraocular pressure (>10 mm Hg) was 15/901, compared with 11/164 in prednisolone acetate treated patients.3 Of the 15 loteprednol etabonate treated patients described as having elevated intraocular pressure, 11 were from the GPC studies with protocols that allowed concurrent contact lens use. Contact lenses have the potential to act as a reservoir. Thus, the study findings suggest that while the reported incidence of clinically significant intraocular pressure elevations with loteprednol etabonate 0.5% is extremely low in any case, it may be even lower in a population that does not wear contact lenses during treatment.2
Figure 9. Incidence of
clinically significant elevations in intraocular pressure (>= 10 mm Hg) in
patients undergoing long-term treatment with loteprednol etabonate, placebo, or
prednisolone acetate.
Adapted from Novack GD et al. J Glaucoma. 1998:7:266-269, with
permission.7
In a study designed to compare the potential of loteprednol etabonate 0.5% suspension and prednisolone acetate 1.0% suspension to raise intraocular pressure in a population of known steroid responders, the intraocular pressure response to loteprednol etabonate 0.5% was significantly less than that to prednisolone acetate 1.0%. As shown below, over the 42-day period, mean intraocular pressure elevation over baseline was 4.1 mm Hg in the loteprednol etabonate 0.5% group, compared with 9.0 mm Hg in the prednisolone acetate 1.0% group.4
Adapted from Bartlett JD et al. J Ocul Pharmacol. 1993;157-1654
