Twice-Daily vs. Once-Daily Dosing with 0.075% Bromfenac in DuraSite: Outcomes from a 14-Day Phase 2 Study
William Trattler, Kamran Hosseini, William Trattler, Kamran Hosseini
Abstract
Introduction: Bromfenac is a well-known topical ophthalmic nonsteroidal anti-inflammatory drug (NSAID) that is commercialized in the USA and other regions of the world. A new formulation, 0.075% bromfenac in DuraSite®, was developed to treat postoperative inflammation and reduce pain in patients who have undergone cataract surgery. We hypothesized that efficacy and safety would be enhanced with twice-daily (BID) dosing compared to once-daily (QD) dosing.
Methods: This was a multicenter, double-masked, comparative study in which 40 and 45 subjects were randomized to groups receiving BID dosing and QD dosing, respectively. Subjects self-instilled the study drug for 14 days postoperative and were followed for an additional 2-week evaluation phase. The primary efficacy endpoint was the proportion of subjects with an anterior chamber cell (ACC) grade of 0 at day 15.
Results: A total of 45 subjects had cleared ACC (grade "0") at day 15, of whom 21 were in the BID group (52.5%) and 24 were in the QD group (53.5%). A secondary analysis found 7/40 (17.5%) subjects in the BID group and 10/45 (22.2%) subjects in the QD group achieved an ACC grade of 0 at day 8. There were more adverse events in the QD group (n = 16) than in the BID group (n = 12).
Conclusion: Similar outcomes were observed for subjects using Bromfenac 0.075% in DuraSite® in the BID and QD dosing regimens for the treatment of post-cataract surgery inflammation.
Trial registration: ClinicalTrials.gov identifier, NCT01190878.
Funding: InSite Vision (now a division of Sun Pharma).
Keywords: Bromfenac; Cataract surgery; Cyclooxygenase inhibitor; DuraSite®; Nonsteroidal anti-inflammatory drugs.
References
- Cho H, Wolf KJ, Wolf EJ. Management of ocular inflammation and pain following cataract surgery: focus on bromfenac ophthalmic solution. Clin Ophthalmol. 2009;3:199–210. doi: 10.2147/OPTH.S4806.
- Waterbury LD, Silliman D, Jolas T. Comparison of cyclooxygenase inhibitory activity and ocular anti-inflammatory effects of ketorolac tromethamine and bromfenac sodium. Curr Med Res Opin. 2006;22(6):1133–1140. doi: 10.1185/030079906X112471.
- Donnenfeld ED, Donnenfeld A. Global experience with Xibrom (bromfenac ophthalmic solution) 0.09%: the first twice-daily ophthalmic nonsteroidal anti-inflammatory drug. Int Ophthalmol Clin. 2006;46(4):21–40. doi: 10.1097/01.iio.0000212134.83513.11.
- Henderson BA, Gayton JL, Chandler SP, et al. Safety and efficacy of bromfenac ophthalmic solution (Bromday) dosed once daily for postoperative ocular inflammation and pain. Ophthalmology. 2011;118(11):2120–2127. doi: 10.1016/j.ophtha.2011.04.035.
- Silverstein SM, Cable MG, Sadri E, et al. Once daily dosing of bromfenac ophthalmic solution 0.09% for postoperative ocular inflammation and pain. Curr Med Res Opin. 2011;27(9):1693–1703. doi: 10.1185/03007995.2011.597663.
- Senju Pharmaceutical Co. Bronuck (package insert). Senju Pharmaceutical Co., Osaka, 2009.
- ISTA Pharmaceuticals. Xibrom (package insert). ISTA Pharmaceuticals, Irvine, 2010.
- ISTA Pharmaceuticals. Bromday (package insert). ISTA Pharmaceuticals, Irvine, 2011.
- Committee for Medicinal Products for Human Use (CHMP). Yellox Assessment Report. Report No.: EMA/431843/2011. European Medicines Agency, London, 2011.
- Bowman LM, Si E, Pang J, et al. Development of a topical polymeric mucoadhesive ocular delivery system for azithromycin. J Ocul Pharmacol Ther. 2009;25(2):133–139. doi: 10.1089/jop.2008.0066.
- InSite Vision. BromSite (prescribing information). InSite Vision, Alameda, 2016.
- Hosseini K, Hutcheson J, Bowman LM. Aqueous humor concentration of Bromfenac 0.09% (Bromday) compared with Bromfenac in DuraSite 0.075% (Bromsite) in cataract patients undergoing phacoemulsification after 3 days dosing. Association for Research in Vision and Ophthalmology. Seattle, 2013.
- Luchs J. Azithromycin in DuraSite for the treatment of blepharitis. Clin Ophthalmol. 2010;4:681–688. doi: 10.2147/OPTH.S6370.
- Malhotra R, Gira J, Berdy GJ, Brusatti R. Safety of besifloxacin ophthalmic suspension 0.6% as a prophylactic antibiotic following routine cataract surgery results of a prospective parallel-group investigator-masked study. Clin Ophthalmol. 2012;6:855–863. doi: 10.2147/OPTH.S29604.
- Protzko E, Bowman L, Abelson M, Shapiro A. Phase 3 safety comparisons for 1.0% azithromycin in polymeric mucoadhesive eye drops versus 0.3% tobramycin eye drops for bacterial conjunctivitis. Invest Ophthalmol Vis Sci. 2007;48(8):3425–3429. doi: 10.1167/iovs.06-1413.
- Shafiee A, Bowman LM, Hou E, Hosseini K. Ocular pharmacokinetics of bimatoprost formulated in DuraSite compared to bimatoprost 0.03% ophthalmic solution in pigmented rabbit eyes. Clin Ophthalmol. 2013;7:1549–5156. doi: 10.2147/OPTH.S48766.
- Singh R, Alpern L, Jaffe GJ, et al. Evaluation of nepafenac in prevention of macular edema following cataract surgery in patients with diabetic retinopathy. Clin Ophthalmol. 2012;6:1259–1269. doi: 10.2147/OPTH.S31902.
- Robin A, Grover DS. Compliance and adherence in glaucoma management. Indian J Ophthalmol. 2011;59(Suppl):S93–S96. doi: 10.4103/0301-4738.73693.
- Tsai T, Robin AL, Smith JP., III An evaluation of how glaucoma patients use topical medications: a pilot study. Trans Am Ophthalmol Soc. 2007;105:29–33.
- Comte L, Vrijens B, Tousset E, et al. Estimation of the comparative therapeutic superiority of QD and BID dosing regimens, based on integrated analysis of dosing history data and pharmacokinetics. J Pharmacokinet Pharmacodyn. 2007;34(4):549–558. doi: 10.1007/s10928-007-9058-0.
- Ruer-Mulard M, Aberer W, Gunstone A, et al. Twice-daily versus once-daily applications of pimecrolimus cream 1% for the prevention of disease relapse in pediatric patients with atopic dermatitis. Pediatr Dermatol. 2009;26(5):551–558. doi: 10.1111/j.1525-1470.2009.00981.x.
- Tsai T, Kroehl M, Smith S, et al. Efficacy and safety of twice- versus once-daily dosing of lisinopril for the treatment of hypertension. In: 50th Midyear meeting of the American Society of Health-System Pharmacists. New Orleans, LA, 2015.
- Eriksson BI, Dahl OE, Buller HR, et al. A new oral direct thrombin inhibitor, dabigatran etexilate, compared with enoxaparin for prevention of thromboembolic events following total hip or knee replacement: the BISTRO II randomized trial. J Thromb Haemost. 2005;3(1):103–111. doi: 10.1111/j.1538-7836.2004.01100.x.
- Lan AJ, Colford JM, Colford JM., Jr The impact of dosing frequency on the efficacy of 10-day penicillin or amoxicillin therapy for streptococcal tonsillopharyngitis: a meta-analysis. Pediatrics. 2000;105(2):E19. doi: 10.1542/peds.105.2.e19.
- Zeng C, Wei J, Li H, et al. Comparison between 200 mg QD and 100 mg BID oral celecoxib in the treatment of knee or hip osteoarthritis. Sci Rep. 2015;5:10593. doi: 10.1038/srep10593.
- de la Pena A, Ma X, Reddy S, et al. Application of PK/PD modeling and simulation to dosing regimen optimization of high-dose human regular U-500 insulin. J Diabetes Sci Technol. 2014;8(4):821–829. doi: 10.1177/1932296814532326.
- Wielders LH, Lambermont VA, Schouten JS, et al. Prevention of cystoid macular edema after cataract surgery in nondiabetic and diabetic patients: a systematic review and meta-analysis. Am J Ophthalmol. 2015;160(5):968–981e33. doi: 10.1016/j.ajo.2015.07.032.
- Elsawy MF, Badawi N, Khairy HA. Prophylactic postoperative ketorolac improves outcomes in diabetic patients assigned for cataract surgery. Clin Ophthalmol. 2013;7:1245–1249. doi: 10.2147/OPTH.S39188.
Source: PubMed