Loteprednol etabonate ophthalmic suspension 0.5 %: efficacy and safety for postoperative anti-inflammatory use

Michael Amon, Massimo Busin, Michael Amon, Massimo Busin

Abstract

Topical corticosteroids are routinely used as postoperative ocular anti-inflammatory drugs; however, adverse effects such as increased intraocular pressure (IOP) are observed with their use. While older corticosteroids such as dexamethasone and prednisolone acetate offer good anti-inflammatory efficacy, clinically significant increases in IOP (≥10 mmHg) are often associated with their use. Loteprednol etabonate, a novel C-20 ester-based corticosteroid, was retrometabolically designed to offer potent anti-inflammatory efficacy but with decreased impact on IOP. After exerting its therapeutic effects on the site of action, loteprednol etabonate is rapidly converted to inactive metabolites, resulting in fewer adverse effects. Randomized controlled studies have demonstrated the clinical efficacy and safety of loteprednol etabonate ophthalmic suspension 0.5 % for the treatment of postoperative inflammation in post-cataract patients with few patients, if any, exhibiting clinically significant increases (≥10 mmHg) in IOP. Furthermore, safety studies demonstrated a minimal effect of loteprednol etabonate on IOP with long-term use or in steroid responders with a much lower propensity to increase IOP relative to prednisolone acetate or dexamethasone. The anti-inflammatory treatment effect of loteprednol etabonate appears to be similar to that of rimexolone and difluprednate with less impact on IOP compared to difluprednate, although confirmatory comparative studies are needed. The available clinical data suggest that loteprednol etabonate is an efficacious and safe corticosteroid for the treatment of postoperative inflammation.

Figures

Fig. 1
Fig. 1
Loteprednol etabonate (I) and its inactive metabolites, Δ1 cortienic acid etabonate (II) and Δ1 cortienic acid (III)
Fig. 2
Fig. 2
Structures of loteprednol etabonate (a), rimexolone (b) and difluprednate (c)
Fig. 3
Fig. 3
Resolution of cells and flare in clinical studies of loteprednol etabonate 0.5 %, rimexolone 1 %, and difluprednate 0.5 % for postoperative inflammation following uncomplicated cataract surgery. Resolution of cells and flare was defined as ≤5 cells and none-to-trace flare in loteprednol etabonate and rimexolone studies and

References

    1. El-Harazi SM, Feldman RM. Control of intra-ocular inflammation associated with cataract surgery. Curr Opin Ophthalmol. 2001;12:4–8. doi: 10.1097/00055735-200102000-00002.
    1. The Loteprednol Etabonate Postoperative Inflammation Study Group 2 A double-masked, placebo-controlled evaluation of 0.5 % loteprednol etabonate in the treatment of postoperative inflammation. Ophthalmology. 1998;105:1780–1786. doi: 10.1016/S0161-6420(98)99054-6.
    1. McColgin AZ, Heier JS. Control of intraocular inflammation associated with cataract surgery. Curr Opin Ophthalmol. 2000;11:3–6. doi: 10.1097/00055735-200002000-00002.
    1. Flach AJ. The incidence, pathogenesis and treatment of cystoid macular edema following cataract surgery. Trans Am Ophthalmol Soc. 1998;96:557–634.
    1. Guex-Crosier Y. The pathogenesis and clinical presentation of macular edema in inflammatory diseases. Doc Ophthalmol. 1999;97:297–309. doi: 10.1023/A:1002130005227.
    1. Donnenfeld ED, Holland EJ, Solomon KD, Fiore J, Gobbo A, Prince J, et al. A multicenter randomized controlled fellow eye trial of pulse-dosed difluprednate 0.05 % versus prednisolone acetate 1 % in cataract surgery. Am J Ophthalmol. 2011;152(609–17):e1.
    1. Assil KK, Massry G, Lehmann R, Fox K, Stewart R. Control of ocular inflammation after cataract extraction with rimexolone 1 % ophthalmic suspension. J Cataract Refract Surg. 1997;23:750–757.
    1. Korenfeld MS, Silverstein SM, Cooke DL, Vogel R, Crockett RS. Difluprednate ophthalmic emulsion 0.05 % for postoperative inflammation and pain. J Cataract Refract Surg. 2009;35:26–34. doi: 10.1016/j.jcrs.2008.09.024.
    1. Henderson BA, Gayton JL, Chandler SP, Gow JA, Klier SM, McNamara TR. Safety and efficacy of bromfenac ophthalmic solution (Bromday) dosed once daily for postoperative ocular inflammation and pain. Ophthalmology. 2011;118:2120–2127. doi: 10.1016/j.ophtha.2011.04.035.
    1. McCormack PL. Ketorolac 0.45 % ophthalmic solution. Drugs Aging. 2011;28:583–589. doi: 10.2165/11207450-000000000-00000.
    1. Numaga J. Phase II placebo-controlled study of nepafenac ophthalmic suspension 0.1 % for postoperative inflammation and ocular pain associated with cataract surgery in Japanese patients. J Ophthalmic Inflamm Infect. 2011;1:147–155. doi: 10.1007/s12348-011-0036-8.
    1. Kim SJ, Flach AJ, Jampol LM. Nonsteroidal anti-inflammatory drugs in ophthalmology. Surv Ophthalmol. 2010;55:108–133. doi: 10.1016/j.survophthal.2009.07.005.
    1. Stewart R, Horwitz B, Howes J, Novack GD, Hart K. Double-masked, placebo-controlled evaluation of loteprednol etabonate 0.5 % for postoperative inflammation. Loteprednol Etabonate Post-operative Inflammation Study Group 1. J Cataract Refract Surg. 1998;24:1480–1489.
    1. Pavesio CE, Decory HH. Treatment of ocular inflammatory conditions with loteprednol etabonate. Br J Ophthalmol. 2008;92:455–459. doi: 10.1136/bjo.2007.132621.
    1. Tripathi RC, Parapuram SK, Tripathi BJ, Zhong Y, Chalam KV. Corticosteroids and glaucoma risk. Drugs Aging. 1999;15:439–450. doi: 10.2165/00002512-199915060-00004.
    1. Doughty MJ. Ophthalmic corticosteroids: management of the ocular inflammatory response. Ocular pharmacology & therapeutics. London: Butterworth-Heinemann; 2001. pp. 92–102.
    1. Ilyas H, Slonim CB, Braswell GR, Favetta JR, Schulman M. Long-term safety of loteprednol etabonate 0.2 % in the treatment of seasonal and perennial allergic conjunctivitis. Eye Contact Lens. 2004;30:10–13. doi: 10.1097/01.ICL.0000092071.82938.46.
    1. Loteprednol Etabonate US Uveitis Study Group Controlled evaluation of loteprednol etabonate and prednisolone acetate in the treatment of acute anterior uveitis. Am J Ophthalmol. 1999;127:537–544. doi: 10.1016/S0002-9394(99)00034-3.
    1. Yablonski ME, Burde RM, Kolker AE, Becker B. Cataracts induced by topical dexamethasone in diabetics. Arch Ophthalmol. 1978;96:474–476. doi: 10.1001/archopht.1978.03910050250011.
    1. McGhee CN, Dean S, Danesh-Meyer H. Locally administered ocular corticosteroids: benefits and risks. Drug Saf. 2002;25:33–55. doi: 10.2165/00002018-200225010-00004.
    1. Clark AF. Basic sciences in clinical glaucoma: steroids, ocular hypertension, and glaucoma. J Glaucoma. 1995;4:354–369.
    1. Kersey JP, Broadway DC. Corticosteroid-induced glaucoma: a review of the literature. Eye (Lond.) 2006;20:407–416. doi: 10.1038/sj.eye.6701895.
    1. Jones R, 3rd, Rhee DJ. Corticosteroid-induced ocular hypertension and glaucoma: a brief review and update of the literature. Curr Opin Ophthalmol. 2006;17:163–167.
    1. Cantrill HL, Palmberg PF, Zink HA, Waltman SR, Podos SM, Becker B. Comparison of in vitro potency of corticosteroids with ability to raise intraocular pressure. Am J Ophthalmol. 1975;79:1012–1017.
    1. Macri A, Rosa R, Papadia M, Scotto R. Inflammation after modern cataract surgery: a comparison of different therapeutic regimen. Eur J Ophthalmol. doi:10.5301/EJO.2011.7589
    1. Bodor N. Design of novel soft corticosteroids. Curr Probl Dermatol. 1993;21:11–19.
    1. Druzgala P, Hochhaus G, Bodor N. Soft drugs—10. Blanching activity and receptor binding affinity of a new type of glucocorticoid: loteprednol etabonate. J Steroid Biochem Mol Biol. 1991;38:149–154. doi: 10.1016/0960-0760(91)90120-T.
    1. Alberth M, Wu WM, Winwood D, Bodor N. Lipophilicity, solubility and permeability of loteprendnol etabonate: a novel, soft anti-inflammatory steroid. J Biopharm Sci. 1991;2:115–125.
    1. Comstock TL, Usner DW (2010) Effect of loteprednol etabonate ophthalmic suspension 0.5 % on post-operative pain and discomfort [E-abstract]. ASCRS symposium
    1. Stewart RS. Controlled evaluation of fluorometholone acetate and loteprednol etabonate in the treatment of postoperative inflammation following cataract surgery [abstract] IOVS. 2004;45(Suppl 1):U159.
    1. Grigorian RA, Shah A, Guo A (2007) Comparison of loteprednol etabonate 0.5 % (Lotemax) to prednisolone acetate 1 % (Falcon) for inflammation treatment following cataract surgery [abstract]. IOVS
    1. Çoban P, Kocak Altintas AG. Comparison of the effect of loteprednol etabonate and prednisolone acetate on the intraocular pressure in uncomplicated phacoemulsification surgery [abstract] Turk Klin J Ophthalmol. 2010;19:234–238.
    1. Howes J, Novack GD. Failure to detect systemic levels, and effects of loteprednol etabonate and its metabolite, PJ-91, following chronic ocular administration. J Ocul Pharmacol Ther. 1998;14:153–158. doi: 10.1089/jop.1998.14.153.
    1. Holland EJ, Bartlett JD, Paterno MR, Usner DW, Comstock TL. Effects of loteprednol/tobramycin versus dexamethasone/tobramycin on intraocular pressure in healthy volunteers. Cornea. 2008;27:50–55. doi: 10.1097/ICO.0b013e31815873c7.
    1. Novack GD, Howes J, Crockett RS, Sherwood MB. Change in intraocular pressure during long-term use of loteprednol etabonate. J Glaucoma. 1998;7:266–269.
    1. Holland EJ, Djalilian AR, Sanderson JP. Attenuation of ocular hypertension with the use of topical loteprednol etabonate 0.5 % in steroid responders after corneal transplantation. Cornea. 2009;28:1139–1143. doi: 10.1097/ICO.0b013e3181a3c52f.
    1. Bartlett JD, Horwitz B, Laibovitz R, Howes JF. Intraocular pressure response to loteprednol etabonate in known steroid responders. J Ocul Pharmacol. 1993;9:157–165. doi: 10.1089/jop.1993.9.157.
    1. Leibowitz HM, Bartlett JD, Rich R, McQuirter H, Stewart R, Assil K. Intraocular pressure-raising potential of 1.0 % rimexolone in patients responding to corticosteroids. Arch Ophthalmol. 1996;114:933–937. doi: 10.1001/archopht.1996.01100140141005.
    1. Bron A, Denis P, Hoang-Xuan TC, Boureau-Andrieux C, Crozafon P, Hachet E, Medhorn E, Akingbehin A. The effects of rimexolone 1 % in postoperative inflammation after cataract extraction. A double-masked placebo-controlled study. Eur J Ophthalmol. 1998;8:16–21.
    1. Kavuncu S, Horoz H, Ardagil A, Erbil HH. Rimexolone 1 % versus prednisolone acetate in preventing early postoperative inflammation after cataract surgery. Int Ophthalmol. 2008;28:281–285. doi: 10.1007/s10792-007-9131-0.
    1. Yaylali V, Ozbay D, Tatlipinar S, Yildirim C, Ozden S. Efficacy and safety of rimexolone 1 % versus prednisolone acetate 1 % in the control of postoperative inflammation following phacoemulsification cataract surgery. Int Ophthalmol. 2004;25:65–68. doi: 10.1023/B:INTE.0000018551.80409.0a.
    1. Hirneiss C, Neubauer AS, Kampik A, Schonfeld CL. Comparison of prednisolone 1 %, rimexolone 1 % and ketorolac tromethamine 0.5 % after cataract extraction: a prospective, randomized, double-masked study. Graefes Arch Clin Exp Ophthalmol. 2005;243:768–773. doi: 10.1007/s00417-005-1126-9.
    1. Donnenfeld ED. Difluprednate for the prevention of ocular inflammation postsurgery: an update. Clin Ophthalmol. 2011;5:811–816. doi: 10.2147/OPTH.S6541.
    1. Smith S, Lorenz D, Peace J, McLeod K, Crockett RS, Vogel R. Difluprednate ophthalmic emulsion 0.05 % (Durezol) administered two times daily for managing ocular inflammation and pain following cataract surgery. Clin Ophthalmol. 2010;4:983–991. doi: 10.2147/OPTH.S10696.
    1. Cable MM. Intraocular pressure spikes using difluprednate 0.05 % for postoperative cataract inflammation. ARVO (Meeting Abstracts) 2010;2010(51):1981.
    1. Spaeth GL, Monteiro de Barros DS, Fudemberg SJ. Visual loss caused by corticosteroid-induced glaucoma: how to avoid it. Retina. 2009;29:1057–1061. doi: 10.1097/IAE.0b013e3181b32cfd.

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