Loteprednol Etabonate Ophthalmic Gel Research Articles

Dose Uniformity of Loteprednol Etabonate (Submicron) Ophthalmic Gel 0.38% Compared with Prednisolone Acetate Ophthalmic Suspension 1.

IntroductionLoteprednol etabonate (submicron) ophthalmic gel 0.38% (LE SM gel 0.38%) is a corticosteroid formulation designed to retain the nonsettling characteristics of loteprednol etabonate ophthalmic gel 0.5%, but with reduced drug particle size to improve ocular penetration, allowing for reduced dosing frequency. This study compared the dose uniformity of LE SM gel 0.38% with branded and generic prednisolone acetate (PA) 1% suspensions under simulated in-use dosing conditions.MethodsDrug concentrations in drops of LE SM gel 0.38% and PA 1% suspensions, expressed from bottles that were shaken or not shaken, were determined during 2 weeks of simulated on-label dosing (LE SM gel 0.38%: three times daily; PA suspensions: four times daily). Sedimentation of drug particles was assessed for each product using dispersion analysis.ResultsThe mean (SD) percent declared drug concentration of LE SM gel 0.38% over 2 weeks was 103.2% (1.3%) when the drug was dispensed from shaken bottles and 103.3% (1.5%) when dispensed from unshaken bottles. However, for branded and generic PA suspensions, mean (SD) percent declared concentrations were 102.2% (1.4%) and 98.3% (2.9%), respectively, when dispensed from shaken bottles; and 89.2% (18.6%) and 78.3% (13.5%), respectively, when dispensed from unshaken bottles. Dispersion analysis showed that drug particles in LE SM gel 0.38% remained fully suspended under accelerated sedimentation conditions, whereas both branded and generic PA suspension drug particles settled out of suspension.ConclusionsLE SM gel 0.38% delivered the drug consistently at the declared concentration over the entire 2 weeks of simulated in-use dosing conditions, regardless of whether the drug was dispensed from shaken or unshaken bottles. However, both branded and generic PA suspensions required the bottle to be shaken to provide a consistent drug concentration.

Loteprednol Etabonate for the Treatment of Dry Eye Disease.

Dry eye disease (DED) is a common ocular condition that can impair vision and may adversely impact quality of life. Due to the inflammatory nature of this disorder, topical corticosteroids are an effective treatment option, particularly for moderate-to-severe DED when first-line treatments, such as ocular lubricants, are insufficient. Loteprednol etabonate (LE) is a retrometabolically designed corticosteroid with a low propensity to cause corticosteroid-related adverse effects, such as elevated intraocular pressure (IOP). This review was conducted to provide an assessment of published studies on the use of LE for treatment of inflammation associated with DED. Twelve prospective and 2 retrospective studies evaluating LE ophthalmic suspension 0.5% and 2 prospective studies evaluating LE ophthalmic gel 0.5% were identified. LE given as monotherapy or with artificial tears (AT) improved signs of DED, especially among patients with a more pronounced inflammatory component, and also improved DED symptoms compared to baseline and/or control. Treatment with LE before cyclosporine A (CsA) therapy reduced stinging upon CsA initiation and provided more rapid relief of DED signs and symptoms than CsA plus AT alone. In patients with meibomian gland dysfunction, LE alone, or in addition to eyelid scrubs/warm compresses, reduced clinical signs and symptoms, and tear proinflammatory cytokine levels. Overall, LE was safe and well tolerated, with minimal effects on IOP. While larger and longer-term studies are warranted, these data support the use of LE as a safe and effective treatment option for DED.

Loteprednol Etabonate (Submicron) Ophthalmic Gel 0.38%: A Review in Post-Operative Inflammation and Pain Following Ocular Surgery.

Loteprednol etabonate ophthalmic gel 0.38% (Lotemax® SM; hereafter referred to as loteprednol etabonate gel 0.38%) is a topical ophthalmic corticosteroid approved in the USA for the treatment of post-operative inflammation and pain following ocular surgery. This formulation provides improved drug delivery compared with loteprednol etabonate micronized gel 0.5%, with a smaller drug particle size (in the submicron range) to improve dissolution and penetration into ocular tissues, meaning less loteprednol etabonate is required to exert therapeutic effect. In two multicentre, randomized phase III trials, significantly more loteprednol etabonate gel 0.38% than vehicle recipients displayed complete resolution of ocular inflammation and ocular pain at day 8 post cataract surgery. Complete resolution of pain was seen as early as post-operative day 3. Treatment-related ocular adverse events in the loteprednol etabonate gel 0.38% group occurred in < 1% of subjects and included one incidence each of photophobia, cystoid macular oedema, eyelid oedema and instillation site pain. Treatment with loteprednol etabonate gel 0.38% had no meaningful impact on intraocular pressure (IOP) or visual acuity. Thus, loteprednol etabonate gel 0.38% extends the treatment options available in resolving post-operative inflammation and pain in patients who have undergone ocular surgery.

Real world use of loteprednol etabonate ophthalmic gel 0.5% in cases representative of comorbid pathologies responding to minimally invasive glaucoma surgery.

PurposeWith the increasing use of minimally invasive surgical techniques for intraocular pressure (IOP) lowering in glaucoma patients, there is a need to examine best practices regarding the postoperative management of these patients. Corticosteroids, though effective in controlling postoperative ocular pain and inflammation, present distinct challenges in glaucoma surgery patients, as their use can be associated with IOP elevation. Loteprednol etabonate (LE) is an ocular corticosteroid designed to have an improved safety profile relative to other corticosteroids.MethodsWe report here a representative selection of cases in which patients were successfully treated with LE ophthalmic gel 0.5% (LE gel) following a variety of minimally invasive glaucoma surgery (MIGS) procedures. Cases included patients undergoing various procedures including a Trabectome combined with cataract surgery; micro-stent surgery (iStent) combined with cataract surgery; supraciliary CyPass Micro-Stent placement combined with cataract surgery; Kahook Dual Blade goniotomy; and ab interno canaloplasty using the iTrack catheter.ObservationsIn all cases, use of LE gel during the postoperative period appeared effective and safe in reducing inflammation and controlling pain. No adverse events or IOP elevations were noted, even in those patients continuing use of LE gel past the postoperative period for longer than six months with documented follow-up. In two cases, patients with elevated IOP using either prednisolone or difluprednate postoperatively were switched to LE gel, with a subsequent reduction in IOP.ConclusionsThis selection of cases involving patients undergoing MIGS suggests that LE gel may be an effective and safe option for treating postoperative inflammation and pain following such procedures with minimal to no effect on IOP or other negative sequalae.

Submicron loteprednol etabonate ophthalmic gel 0.38% for the treatment of inflammation and pain after cataract surgery

To assess the safety and efficacy of a 0.38% submicron formulation of loteprednol etabonate (LE) gel for the treatment of postoperative inflammation and pain after cataract surgery. Forty-five United States ophthalmology practices. Double-masked vehicle-controlled randomized parallel group study. Patients 18years of age or older with anterior chamber cells grade 2 or higher on day 1 after uncomplicated cataract surgery were randomized to 14days of treatment with LE gel 2 times a day, LE gel 3 times a day, or vehicle. Hierarchical primary endpoints were the proportion of patients with resolution of anterior chamber cells and grade 0 (no) pain at postoperative day 8. Safety outcomes included adverse events, intraocular pressure (IOP), biomicroscopy, visual acuity, ophthalmoscopy, and tolerability (drop comfort and ocular symptoms). The intent-to-treat population included 514 patients. Significantly more patients in the LE gel 2 times a day and 3 times a day groups compared with the vehicle group had complete resolution of anterior chamber cells (26.9% and 28.7% versus 9.3%) and reported grade 0 pain (73.7% and 73.1% versus 47.7%) on day 8 (P<.001 vs vehicle for all). The safety findings were unremarkable, with 1 patient experiencing an IOP increase of 10 mm Hg or higher while on LE gel. More than 75% of patients in each group reported no drop discomfort. In this study, submicron loteprednol etabonate gel 0.38% appeared safe andeffective in the treatment of postoperative inflammation andpain whether instilled 2 times or 3 times a day.

Dose Uniformity of Topical Corticosteroids: A Simulated Trial of Fluorometholone Acetate 0.1% and Loteprednol Etabonate Gel 0.5.

The purpose of the study was to determine the concentrations of Flarex® and Lotemax® when shaken and not shaken. Many patients fail to shake or inappropriately shake suspensions of corticosteroids before instillation as directed. This study was designed to help determine what concentration of corticosteroid these patients are receiving. In addition, independent confirmation of loteprednol etabonate ophthalmic gel dose uniformity was determined and compared as a possible alternative. Drug concentrations of shaken versus unshaken Flarex and Lotemax were determined over a 20-day simulated tapered course in our institutional laboratory. Collected samples were analyzed by reversed-phase high-performance liquid chromatography with photodiode array detection at 240 nm. Flarex had a mean concentration of 93.7% of the declared concentration when shaken and 7.25% when not shaken. The difference between these groups was statistically significant (P = 0.0001). Lotemax had a mean concentration of 96.74% of the declared concentration when shaken and a mean concentration of 98.97% when not shaken. The difference between these groups was not statistically significant (P = 0.194). Flarex maintains dose uniformity when shaken. When not shaken, it has poor dose uniformity. Lotemax was consistent whether shaken or not in our study and can be considered to eliminate the variability of poor patient compliance with shaking. The manufacturers of both drugs recommend shaking before application.

A retrospective analysis of the postoperative use of loteprednol etabonate gel 0.5% following laser-assisted in situ keratomileusis or photorefractive keratectomy surgery.

BackgroundWhile loteprednol etabonate ophthalmic gel 0.5% (LE gel) is approved for treatment of postoperative ocular inflammation and pain, there have been no reported studies in patients undergoing laser-assisted in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK).MethodsThis was a retrospective chart review conducted at five refractive surgical centers in the USA. Data were collected from primary LASIK or PRK surgery cases in which LE gel was used postoperatively as the clinician’s routine standard of care and in which patients were followed-up for up to 6 months. Data extracted from charts included patient demographics, surgical details, LE gel dosing regimen, pre- and postsurgical refractive characteristics, intraocular pressure (IOP) measurements, and visual acuity. Primary outcomes included postoperative IOP elevations, adverse events, and early discontinuations.ResultsData were collected on 189 LASIK eyes (96 patients) and 209 PRK eyes (108 patients). Mean (standard deviation [SD]) years of age at surgery was 36.0 (11.7) and 33.9 (11.3) in LASIK and PRK patients. LE gel was prescribed most often four times daily during the first postoperative week, regardless of procedure; the most common treatment duration was 7–14 days in LASIK and ≥30 days in PRK patients. No unusual corneal findings or healing abnormalities were reported. Mean postoperative uncorrected distance visual acuity was 20/24 in LASIK and 20/30 in PRK eyes. Mild/trace corneal haze was reported in 20% of PRK patients; two PRK patients with moderate/severe corneal haze were switched to another corticosteroid. Mean postoperative IOP did not increase over time in either LASIK or PRK eyes (P≥0.331); clinically significant elevations from baseline in IOP (≥10 mmHg) were noted in only three eyes of two PRK patients.ConclusionLE gel appears to have a high level of safety and tolerability when used for the management of postoperative pain and inflammation following LASIK and PRK surgery.

Prolonged Exposure to Loteprednol Etabonate in Human Tear Fluid and Rabbit Ocular Tissues Following Topical Ocular Administration of Lotemax Gel, 0.5%

A new gel formulation containing loteprednol etabonate (LE), a C-20 ester corticosteroid used to treat ocular inflammation, was developed to provide increased retention on the ocular surface for improved drug delivery to intraocular tissues. This investigation evaluated concentrations of LE in tear fluid following topical instillation of LE gel to humans and the ocular and systemic pharmacokinetics of LE following administration to rabbits. LE ophthalmic gel 0.5% was administered as a single topical dose to human volunteers (n=12) and Dutch Belted rabbits (n=40). In the human study, tear sampling was performed at 6, 9, 12, and 24 h after instillation. In the rabbit study, tears and ocular tissues were collected from 5 min through 24 h postdose. Serial blood samples were collected from one cohort of rabbits for plasma analysis. Concentrations of LE were determined by high performance liquid chromatography tandem mass spectrometry. In humans, LE was detected in tears at all the time points assessed with mean concentrations of 114 μg/g at 6 h declining to 2.41 μg/g at 24 h postdose. In rabbits, LE was detected in all ocular tissues within 5 min after dosing. Maximum concentrations of LE were achieved within 0.5 h and were highest in tear fluid (1560 μg/g), followed by bulbar conjunctiva (4.03 μg/g), cornea, (2.18 μg/g), iris/ciliary body (0.162 μg/g), and aqueous humor (0.0138 μg/mL). LE remained measurable in all ocular tissues through 24 h with the exception of aqueous humor. In contrast, plasma levels of LE were low with no detectable levels after 4 h. The gel formulation of LE provided prolonged exposure to LE on the ocular surface, with measurable levels in tears through 24 h in both humans and rabbits, for delivery of LE to anterior segment tissues, as evidenced by sustained levels of LE in rabbit conjunctiva, cornea, and iris/ciliary body.

Dose uniformity of loteprednol etabonate ophthalmic gel (0.5%) compared with branded and generic prednisolone acetate ophthalmic suspension (1%)

IntroductionLoteprednol etabonate (LE) ophthalmic gel 0.5% (Lotemax®) is a new polycarbophil-based, nonsettling topical ophthalmic formulation. The formulation is a semisolid gel at rest and a shear thinning fluid when expressed through a dropper tip. The present study was undertaken to determine how the nonsettling character of LE ophthalmic gel affects dose uniformity. Prednisolone acetate ophthalmic suspension 1% (Pred Forte®) and a generic prednisolone acetate suspension 1% were used as comparators.MethodsDrug concentrations of LE ophthalmic gel, Pred Forte, and a generic prednisolone acetate suspension were determined following simulated dosing – consisting of 2 drops, expressed four times daily for 2 weeks, with bottles that were shaken or not shaken immediately prior to expressing the drops. Drug concentrations were determined using a reverse-phase high-performance liquid chromatography (HPLC) method and reported as a percentage of the declared (labeled) concentration. Comparative kinetics of drug particle sedimentation were also determined for each formulation, using dispersion analysis under gravity.ResultsMean drug concentrations in drops of all three formulations were within a few percentage points of the declared concentration when the bottles were shaken for 5 seconds prior to dispensing. Only LE ophthalmic gel showed consistent and on-target concentrations when the bottles were unshaken prior to dispensing, with a mean (standard deviation [SD]) percent declared concentration of 102% (1.92%) over the 2-week dosing regimen. Drug concentrations for the branded and generic prednisolone acetate suspensions following expression from unshaken bottles were highly variable (overall relative SDs of 16.8% and 20.3%, respectively), with mean concentrations for both falling significantly below the declared concentration for drops expressed at the beginning of the 2-week dosing regimen and significantly above the declared concentration for drops expressed near the end of the dosing regimen. Dispersion analysis at 120× g showed no drug particle sedimentation for LE ophthalmic gel over the 24-hour testing period, whereas the prednisolone acetate suspensions settled in less than 6 hours.ConclusionLE ophthalmic gel 0.5% provided consistent dose uniformity at the declared concentration whether or not the bottle was shaken prior to dispensing, whereas Pred Forte® and the generic prednisolone acetate required shaking to provide consistent drug concentrations. LE ophthalmic gel may be beneficial to patients because it eliminates the potential impact on the clinical response of both under- and overdosing.

Tear levels of loteprednol etabonate following instillation of a novel gel formulation

AbstractPurpose A new gel formulation of loteprednol etabonate (LE) has been developed which is non‐settling, provides a pH close to physiological, and a reduced level of benzalkonium chloride. This study sought to examine the levels of LE in tear fluid following a single topical instillation of LE ophthalmic gel 0.5% to healthy volunteers.Methods Single center, open label study. Twelve healthy subjects received LE ophthalmic gel 0.5% in one eye and tear sampling was performed at 6 hours (h), 9 h, 12 h, and 24 h after instillation. LE levels in tears were determined by LC‐MS/MS. Ocular and non‐ocular treatment emergent adverse events (AEs) were recorded.Results 17 subjects were screened and 12 were enrolled. Mean age was 46 years and all but one subject was male. LE was detected in all tear fluid samples at all time points assessed. Mean (SD) LE levels were 114 (116) µg/g at 6 h, 19.7 (18.2) µg/g at 9 h, 26.9 (29.6) µg/g at 12 h and 2.41 (3.36) µg/g at 24 h. No drug‐related AEs were reported.Conclusion LE administered in the gel formulation remains present in tear fluid 24 hours after a single instillation. These results suggest a long residency time of LE on the ocular surface with the gel formulation. No safety concerns were identified. Commercial interest

Loteprednol Etabonate Ophthalmic Gel 0.5 %: A Review of Its Use in Post-Operative Inflammation and Pain Following Ocular Surgery

Loteprednol etabonate ophthalmic gel 0.5% (Lotemax(®)) is approved in the USA for the treatment of post-operative inflammation and pain in patients who have undergone ocular surgery. The new gel formulation of loteprednol etabonate offers some potential advantages over the previously available ophthalmic suspension and ointment formulations of the drug. Because the gel is non-settling, a uniform dose of loteprednol etabonate is delivered without the need to vigorously shake the product. The pH of the gel formulation is close to that of physiological tears and the concentration of preservative is low. In clinical trials, loteprednol etabonate ophthalmic gel 0.5% for 14 days was effective, very well tolerated and safe when used for the treatment of post-operative inflammation and pain following cataract surgery. Relative to vehicle, loteprednol etabonate ophthalmic gel 0.5% effectively reduced postoperative ocular inflammation and ocular pain and had a similar overall tolerability, comfort and safety profile. It is associated with a low risk of inducing clinically significant increases in intraocular pressure. In conclusion, loteprednol etabonate ophthalmic gel 0.5% is an additional formulation option for the short-term treatment of post-operative inflammation and pain in patients who have undergone ocular surgery. It provides uniform dosing of a topical ophthalmic corticosteroid that has been demonstrated to be effective and well-tolerated in the treatment of ocular inflammation.