Bromfenac Group Research Articles

TOPICAL BROMFENAC AS AN ADJUNCTIVE TREATMENT WITH INTRAVITREAL RANIBIZUMAB FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION

Intravitreal injection of ranibizumab is highly effective for wet age-related macular degeneration. Its limitation is that most patients require repeated intravitreal injections to achieve and maintain the visual gain. We assessed the effectiveness of adjunctive topical bromfenac, a nonsteroidal antiinflammatory drug, with ranibizumab. Patients with wet age-related macular degeneration with lesions smaller than 2 disk diameters were randomized 2:3 to adjunctive topical bromfenac (n = 16) or sham (n = 22) and a 0.5-mg ranibizumab injection in a double-masked fashion. Subjects were examined monthly, and ranibizumab was injected as needed from baseline. The primary endpoint was the comparison of the number of ranibizumab injections over 6 months. The visual and anatomic responses also were compared. The mean number of ranibizumab injections over 6 months was 2.2 in the bromfenac group and 3.2 in the sham, a difference that reached significance (P = 0.0274). The changes in visual acuity did not differ significantly (P = 0.3141) although the central retinal thickness was tended to decrease more in bromfenac group (P = 0.0604). Multivariate analysis showed that topical bromfenac is significantly associated with fewer ranibizumab injections. Topical bromfenac might reduce the frequency of ranibizumab over 6 months in eyes with relatively small age-related macular degeneration lesions.

Comparison of bromfenac 0.09% QD to nepafenac 0.1% TID after cataract surgery: pilot evaluation of visual acuity, macular volume, and retinal thickness at a single site

PurposeThe purpose of this study was to investigate the clinical outcomes of bromfenac ophthalmic solution 0.09% once daily (QD) and nepafenac 0.1% ophthalmic suspension three times daily following cataract extraction with posterior chamber intraocular lens implantation, specifically looking at any differences in Early Treatment Diabetic Retinopathy Study visual acuities, macular volume, and/or retinal thickness changes.MethodsSubjects were randomly assigned to receive either bromfenac (n = 10) QD or nepafenac (n = 10) three times daily. Dosing began 3 days before cataract surgery, continuing to day 21 postsurgery. In addition to the investigated nonsteroidal antiinflammatory drug regimen, all subjects received antiinfective intraoperative and postoperative standard of care. Subjects were followed at 1 day and 1, 3, and 6 weeks postoperatively. Study visit assessments included best-corrected visual acuity, biomicroscopy, summed ocular inflammation score (anterior chamber cells and flare grading), intraocular pressure measurement, adverse event recording, and concomitant medication review. Optical coherence tomography was performed at 1, 3, and 6 weeks.ResultsBoth treatment groups had similar baseline measurements. Outcomes for mean letters read (P = 0.318), mean change in macular volume (P = 0.665), and retinal thickness (P = 0.552) were not statistically different between the groups from baseline through week six, although independently only the bromfenac group demonstrated a statistically significant improvement in letters gained from baseline to week six (P = 0.040). In the same time period, mean macular volume and retinal thickening worsened in the nepafenac group, demonstrating a statistically significant increase (P = 0.006) at week six for macular volume when compared to baseline. One subject in the nepafenac group experienced recurrent inflammation at week six, was unmasked, and then rescued with bromfenac 0.09% QD and difluprednate 0.05% QD.ConclusionBoth bromfenac and nepafenac resulted in positive clinical outcomes of Early Treatment Diabetic Retinopathy Study visual acuities. Postoperative measurements of macular volume and retinal thickness of bromfenac subjects showed a trend toward improved vision, less retinal thickening, and more stable macular volumes overall.

NSAIDS IN COMBINATION THERAPY FOR THE TREATMENT OF CHRONIC PSEUDOPHAKIC CYSTOID MACULAR EDEMA

The purpose of this study was to evaluate the addition of topical nonsteroidal antiinflammatory drugs (NSAIDs) to intravitreal corticosteroid and antivascular endothelial growth factor injections for the treatment of chronic cystoid macular edema. Thirty-nine patients with chronic pseudophakic cystoid macular edema completed a single-center, randomized, investigator-masked study. All patients were treated with an intravitreal triamcinolone and bevacizumab injection at study entry; the bevacizumab injection was repeated at 1 month. To evaluate the effect of adding an NSAID, patients were randomized to treatment with 1 of 4 topical NSAIDs (diclofenac 0.1%, ketorolac 0.4%, nepafenac 0.1%, and bromfenac 0.09%) or placebo for 16 weeks. At Weeks 12 and 16, both the nepafenac and bromfenac groups showed a significant reduction in retinal thickness compared with that in placebo (nepafenac, P = 0.0048, bromfenac, P = 0.0113). A difference, however, between these 2 NSAID groups was observed in that only the nepafenac group was able to maintain the demonstrated retinal thickness decrease at Weeks 12 and 16. The nepafenac group also experienced a significant improvement in visual acuity at Weeks 12 (P = 0.0084) and 16 (P = 0.0233). The addition of NSAIDs did not produce an increase in mean intraocular pressure over the course of therapy. Although NSAID therapy seems to potentiate the improvements produced by corticosteroids and antivascular endothelial growth factor therapy for chronic pseudophakic cystoid macular edema, only nepafenac- and bromfenac-treated eyes showed reduced retinal thickness at 12 weeks and 16 weeks. Furthermore, nepafenac produced a sustained improvement in visual acuity.

Effect of bromfenac ophthalmic solution on ocular inflammation following cataract surgery

This study compared the post-cataract surgery anti-inflammatory effects of topical treatment with 0.1% bromfenac, 0.1% betamethasone or both on postoperative anterior chamber inflammation and corneal swelling. Seventy-two patients with no eye disease other than cataract were enrolled in a prospective, randomized study to undergo phacoemulsification combined with intraocular lens implantation. After cataract surgery, patients were randomized to treatment with bromfenac, betamethasone or both agents. Twenty-five eyes were assigned to bromfenac, 23 to betamethasone and 24 to the combined treatment group. Inflammatory reactions in the anterior chamber were measured with laser flare photometry preoperatively and at 1 and 3 days, 1 and 2 weeks, and 1 and 2 months postoperatively. Intraocular pressure (IOP) and corneal thickness were measured at the same time-points. Best corrected visual acuity (BCVA) was measured preoperatively and at 2 days, 1 and 2 weeks, and 1 and 2 months postoperatively. Specular microscope endothelial photography of the central region of the cornea was performed preoperatively and at 3 months after surgery. There were no significant differences among the bromfenac, betamethasone and combined treatment groups in BCVA, IOP, aqueous flare or corneal thickness. Cystoid macular oedema was present in one eye treated with betamethasone. There were no significant differences in anti-inflammatory effects among the three treatments. These findings suggest that bromfenac is as effective as betamethasone in minimizing inflammatory reactions after cataract surgery.

Effects of nonsteroidal ophthalmic drops on epithelial healing and pain in patients undergoing bilateral photorefractive keratectomy (PRK)

The present study, which was designed as a prospective, double-masked, randomized, controlled, single-site study, was conducted to compare the effects of 3 approved ophthalmic nonsteroidal anti-inflammatory drugs-nepafenac ophthalmic suspension 0.1% (Nevanac; Alcon Laboratories, Inc., Fort Worth, Tex), ketorolac tromethamine ophthalmic solution 0.4% (Acular LS; Allergan, Irvine, Calif), and bromfenac 0.09% (Xibromtrade mark; ISTA Pharmaceuticals, Irvine, Calif)-on corneal reepithelialization and postoperative pain control in patients undergoing photorefractive keratectomy. In addition to nonsteroidal anti-inflammatory drugs, each patient received an antibiotic-moxifloxacin hydrochloride ophthalmic solution 0.5% (nepafenac group) or gatifloxacin ophthalmic solution 0.3% (ketorolac and bromfenac groups). All treatments were administered 3 times daily beginning 1 d preoperatively and continuing for 1 wk postoperatively; prednisolone acetate 1.0% was administered concurrently 4 times daily. Bandage contact lenses were replaced at each postoperative visit for corneal staining and epithelial defect grading. Self-evaluation of pain relief was recorded on postoperative days 1 and 3 with the use of a visual analog scale. A total of 29 patients (58 eyes) were enrolled and underwent bilateral custom photorefractive keratectomy. Mean time to reepithelialization was 5.50+/-1.59 d for the nepafenac 0.1% group, 5.62+/-1.23 d for the ketorolac 0.4% group, and 7.25+/-2.53 d for the bromfenac 0.09% group. A significant difference was detected between nepafenac 0.1% and bromfenac 0.09% and between ketorolac 0.4% and bromfenac 0.09% (P<.05). Significant reductions in pain scores were observed with nepafenac 0.1% on day 1 (-1.13) and day 3 (-1.32), ketorolac 0.4% on day 3 (-0.88), and bromfenac 0.09% on day 3 (-0.83). No adverse events were reported. Eyes treated with nepafenac 0.1% or ketorolac 0.4% achieved complete reepithelialization significantly faster than those treated with bromfenac 0.09%. Daily contact lens removal and application of fluorescein may have delayed reepithelialization in the overall population; however, the effect would have been the same in all 3 groups. Pain relief with nepafenac 0.1% was achieved sooner than with ketorolac 0.4% or bromfenac 0.09%.

Bromfenac Ophthalmic Solution 0.09% (Xibrom) for Postoperative Ocular Pain and Inflammation

To evaluate the efficacy and ocular safety of bromfenac ophthalmic solution 0.09% (Xibrom) for the treatment of postoperative inflammation and reduction of ocular pain in subjects who have undergone cataract extraction (CE). Two phase III, multicenter, randomized, double-masked, parallel, placebo-controlled clinical trials were conducted under a common protocol. Data were pooled for analyses. Five hundred twenty-seven subjects were sequentially assigned, according to a computer-generated randomization list (2:1), to bromfenac (n = 356) or a placebo (n = 171). Subjects who underwent cataract surgery without prior antiinflammatory treatment with a postsurgical Summed Ocular Inflammation Score (SOIS) of > or =3 were treated with either bromfenac or the placebo, instilled twice daily for 14 days in the study eye, and observed for an additional 14 days for safety evaluation. Cleared ocular inflammation with a SOIS of 0 (cells< or =5 and absence of flare after 14 days of treatment). Secondary outcomes included time to resolution of ocular inflammation, time to resolution of ocular pain, proportion of subjects with photophobia, and ocular adverse events. Baseline characteristics were comparable between groups for age, gender, and race. The baseline mean SOIS was 3.7 in both groups. A greater proportion of bromfenac (64.0%) than placebo subjects (43.3%) achieved complete clearance of ocular inflammation at study day 15 (P<0.0001). The effect of bromfenac on clearance of ocular inflammation was as early as study day 3 after initiation of treatment, compared with the placebo (8.4% vs. 1.2%, P = 0.0012). The median time to resolution of ocular pain was 2 days (bromfenac) versus 5 days (placebo) (P<0.0001). Numbers of most ocular adverse events were lower for the bromfenac group than for the placebo group. Eye irritation was reported in a lower percentage of subjects for bromfenac (2.5%) versus placebo (4.7%), as were burning and stinging (1.4% vs. 2.5%), and photophobia (2.0% vs. 11.1%). Bromfenac ophthalmic solution 0.09% effectively and rapidly cleared ocular inflammation and reduced ocular pain after CE. There were no serious ocular adverse events, and fewer adverse events were reported for the bromfenac group.

A dose-ranging study of bromfenac sodium in oral surgery pain

Objective. The purpose of this study was to evaluate the analgesic efficacy and safety of five graded doses of bromfenac sodium in patients experiencing moderate to severe pain after the surgical removal of impacted third molar teeth. Study Design. The study employed a randomized, double-blind, single-dose, 8-hour, inpatient evaluation period. The treatment groups included placebo ( n = 21) and bromfenac ( n = 102) at dosage strengths of 5 mg ( n = 21), 25 mg ( n = 20), 50 mg ( n = 20), 100 mg ( n = 20), and 200 mg ( n = 21). Patients ingested a dose of study medication when their postsurgical pain reached a moderate or severe intensity. Pain intensity and pain relief were rated at 15, 30, 60, 90, and 120 minutes and then hourly for the remaining 6 hours. Efficacy and safety variables were analyzed by means of analysis of variance and chi-squared tests where appropriate. Results. At all doses, bromfenac exhibited statistical superiority ( p < 0.05) to placebo, with all but the 5-mg dose being significantly more efficacious for every summary analgesic measure (3- and 8-hour sum pain intensity difference and sum pain analog intensity difference, total pain relief, peak effects, sum of pain half gone, and global evaluation). Peak analgesic effects did not increase beyond those provided by the 25-mg dose of bromfenac, although both the 100- and 200-mg bromfenac doses provided a more rapid onset and a longer duration of analgesia than either the 25- or 50-mg dosage strengths. The most common side effects reported were headache, nausea, dizziness, and drowsiness; the incidence in the bromfenac group was no different from that in the placebo group. Conclusions. Bromfenac is a safe and efficacious analgesic, with a threshold dose of 5 mg and a positive dose-response up to 25 mg for peak effects and 100 mg for total analgesic activity.

Bromfenac, a Non-Opioid Analgesic, Compared with Tramadol and Placebo for the Management of Postoperative Pain

Bromfenac, a new non-opioid analgesic agent, in single oral doses of 25 and 50mg was compared with tramadol 100mg and placebo in the treatment of 130 outpatients with moderate or severe pain after oral surgery. Patients rated their pain intensity and pain relief for up to 8 hours after medication. Bromfenac at 25 and 50mg doses was superior to tramadol 100mg and placebo. Pain relief was significantly (p < 0.05) higher than that with tramadol 100mg and placebo 30 minutes after dose administration, and the difference remained significant for 6 to 8 hours. Patients who received bromfenac reported more favourable global responses to therapy than did those who received tramadol 100mg or placebo. The responses to tramadol 100mg were not distinguishable from placebo for any of the efficacy variables. Adverse events were infrequent but significantly (p < 0.05) more patients in the tramadol group than in the bromfenac 50mg group reported events: 7 patients in the tramadol group vs 1 patient in the bromfenac group. Four patients in the tramadol group reported digestive adverse events (dyspepsia, nausea, vomiting) compared with no patients in either of the bromfenac treatment groups (p < 0.05). The results indicate that a single oral dose of bromfenac 25 or 50mg is more efficacious and better tolerated than tramadol 100mg.

Bromfenac sodium, acetaminophen/oxycodone, ibuprofen, and placebo for relief postoperative pain

The objective of this double-masked, parallel-group, multicenter, inpatient study was to compare bromfenac with an acetaminophen/oxycodone combination and ibuprofen in patients who had pain due to abdominal gynecologic surgery. In the 8-hour, single-dose phase, 238 patients received single oral doses of bromfenac (50 or 100 mg), acetaminophen 650 mg/oxycodone 10 mg, ibuprofen 400 mg, or placebo. In the multiple-dose phase, 204 patients received bromfenac, acetaminophen/oxycodone, or ibuprofen for up to 5 days. In the single-dose phase, both bromfenac doses produced peak analgesic responses equivalent to acetaminophen/oxycodone, but the responses to bromfenac were longer lasting. Bromfenac produced significantly better overall (8-hour) analgesic summed scores than acetaminophen/oxycodone. Ibuprofen was less efficacious than the other analgesics. The remedication rate was lower in both bromfenac groups than in the other treatment groups. The acetaminophen/oxycodone group reported more somnolence and vomiting. Single doses of bromfenac provided analgesia at least equivalent to that of the acetaminophen/oxycodone combination, with a longer duration of action. Both doses of bromfenac and acetaminophen/oxycodone were superior to ibuprofen in this study.