THERAPEUTIC APPLICATION BROMFENAC ......2Shandong University Cheeloo College of Medicine, Jinan,...
Transcript of THERAPEUTIC APPLICATION BROMFENAC ......2Shandong University Cheeloo College of Medicine, Jinan,...
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THERAPEUTIC APPLICATION BROMFENAC, MOXIFLOXACIN
AND MOXI-DEXAMETHASONE IN EYE DISORDERS
1Parvathi M. L.,
2Rachita Kurmi and
3Silpa T. S.
1Mangalore University, Karnataka, India.
2Shandong University Cheeloo College of Medicine, Jinan, China.
3St Teresa's College Ernakulam, M G University, Kerala, India.
*Project Mentored by Bharat Kwatra, Invezion Labs.
Topical bromfenac for post-cataract extraction: A systematic
review and pooled analysis
The purpose of this pooled analysis is to investigate the safety and
efficacy of once daily Bromfenac for ocular inflammation and pain
among patients after cataract extraction (CE). Bromfenac, a promising
ophthalmic non-steroidal anti-inflammatory drug, has been shown to
be a safe and effective treatment for postoperative pain and
inflammation in subjects undergoing CE. Non-steroidal anti-
inflammatory drugs (NSAIDs) inhibit COXs so as to inhibit post-
operative pain and inflammation. It is becoming prevalent to begin NSAIDs dosing anywhere
from 1–2 days before surgery to reduce postoperative inflammation and pain.
Bromfenac, a highly potent inhibitor for both COX-1 and 2 isoforms, belongs to the NSAID
class but exhibits unique characteristics that enhances lipophilicity and facilitates its moving
across the epithelial layers and prolongs the duration of analgesic and anti-inflammatory
effect. These superior therapeutic benefits of Bromfenac have led to its ophthalmic use
especially for the pain and inflammation control after CE. Limiting the ocular exposure to
bromfenac may result in decreased adverse events (AEs), which is important because,
historically, ocular NSAID use has resulted in small numbers of corneal erosions or melts.
STUDY SELECTION- Any randomized controlled trial (RCT), controlled clinical trial
designed with at least two groups that one control group receiving vehicle-controlled
WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES
SJIF Impact Factor 7.632
Volume 9, Issue 11, 580-622 Review Article ISSN 2278 – 4357
*Corresponding Author
Project Mentored by Bharat
Kwatra, Invezion Labs.
Article Received on
26 August 2020,
Revised on 15 Sept. 2020,
Accepted on 05 Oct. 2020
DOI: 10.20959/wjpps202011-17544
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ophthalmic solution, and the other receiving once- daily dosing of any type of topical
Bromfenac ophthalmic solution.
DATA SOURCES AND SEARCHES- The electronic databases screened were MEDLINE,
PsycINFO, Scopus, EMBASE, and The Cochrane Library (issue 9 of 12, September 2014)
from 1990 to September 2014.
OUTCOME MEASUREMENT- Primary efficacy outcomes were the proportion of cleared
ocular inflammation as determined by a summed ocular inflammation score (SOIS) of 0 and
ocular pain free. Postoperative ocular inflammation was measured by SOIS, and ocular pain
was evaluated by the ocular comfort grading assessment (OCGA) reported in the participants‟
diaries. Secondary efficacy outcomes were the drug- related reasons for discontinuation,
including adverse events, lack of efficacy, and receiving other rescue medication. Safety
outcomes were the common adverse events, including ocular inflammation, ocular pain,
foreign body sensation, and systemic adverse events. Pooled analyses of primary efficacy
outcomes.
Postoperative ocular inflammation: All trials reported the proportion of cleared ocular
inflammation as determined by an SOIS score of 0. The pooled analysis revealed that topical
bromfenac improved ocular inflammation within 15 postoperative days compared with
placebo. Postoperative ocular pain: All trials reported that the proportion of ocular pain free
was deter- mined by an OCGA pain score of 0. The pooled analysis revealed that topical
bromfenac attenuated postoperative ocular pain within 15 days compared with
placebo. Pooled analyses of secondary efficacy outcomes.
Drug-related reasons for discontinuation: All trials reported the drug-related reasons for
discontinuation. The pooled analysis revealed that the patients in the topical bromfenac group
experienced less discontinuation because of adverse events. Pooled analyses of safety
outcomes: All studies reported the common adverse events including ocular inflammation,
ocular pain, foreign body sensation, and systemic adverse events in a total of 1690 patients.
The pooled analysis revealed that the patients in the topical bromfenac group experienced
fewer overall adverse events.
The utility of ophthalmic NSAIDs for the control of ocular inflammation, reduction of ocular
pain, as well as prevention and treatment of cystoid macular edema (CME) has been well
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documented in previous studies. Recently, Wang et al. and Sher et al.
reported on the role of
bromfenac in managing ocular pain and discomfort following refractive surgery.
The clinical benefits of bromfenac have been extensively discussed in several comparative
studies including the treatment of external or anterior ocular inflammatory diseases, allergic
conjunctivitis, as well as postoperative inflammation.
Bromfenac was found to be 3.7, 6.5, and 18 times more potent than diclofenac, amfenac,
and
ketorolac, respectively in inhibiting COX-2 activity. Although bromfenac and ketoroloc were
both well tolerated by patients undergoing laser in situ keratomileusis (LASIK), Epi-LASIK,
and laser- assisted subepithelial keratomileusis (LASEK), bromfenac was superior in
controlling postoperative pain. The pooled analysis demonstrated that the number of patients
with SOIS of 0 was significantly increased at postoperative day 3. The current pooled
analysis offers evidence for the safety and efficacy of topical bromfenac in reducing overall
ocular pain and inflammation during the whole postoperative period.
This pooled analysis came to the same that bromfenac is an effective treatment for
postoperative inflammation and pain after CE. However, since the merits of all studied RCTs
in the current analysis were weakened by the unreported demographics, co-morbidities of
study participants, and the potential bias, higher quality and more strictly controlled clinical
trials are required to identify the details of patients‟ outcome assessments, hospital costs, and
length of hospital stay, these possible sources of heterogeneity should be examined in future
clinical trials.
An ex vivo human aqueous humor-concentration comparison of two commercial
bromfenac formulations
Topical nonsteroidal anti-inflammatory drugs (NSAIDs) have been used by cataract surgeons
for routine cases to reduce clinically significant cystoid macular edema (CME) and improve
early visual acuity. Clinically, NSAIDs are used by ophthalmologists in combination with or
instead of corticosteroids. The FDA has approved NSAID products in five indications:
seasonal allergic conjunctivitis, pain associated with cataract surgery, inflammation
associated with cataract surgery, pain associated with corneal refractive surgery, and
inhibition of intraoperative miosis. While not approved by the FDA specifically for this use,
NSAIDs are considered the standard of care by many anterior segment surgeons for
preventing CME associated with cataract surgery. More specifically, DuraSite is a synthetic
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polymer of cross-linked polyacrylic acid that stabilizes small molecules in an aqueous matrix.
Both nonclinical and clinical studies have shown the DuraSite drug- delivery system to be
safe and nontoxic. The increased time that DuraSite remains on the eye allows lower
concentrations of a given drug to be administered over a longer period. This offers
convenience of dosing, reduces the potential of adverse side effects, and may lead to
improved patient compliance.
The purpose of this study was to quantify the concentration of bromfenac in the aqueous
humor utilizing high-performance liquid chromatography mass spectrometry between two
commercial nonsteroidal anti-inflammatory drugs, using aqueous humor concentrations to
characterize pharmacokinetic proportional differences between 0.075% bromfenac
ophthalmic solution in DuraSite (BromSite®) and 0.09% bromfenac ophthalmic solution
(Bromday®
).
NSAIDs are believed to exert therapeutic effects based on in vivo concentrations, and if those
concentrations exceed the IC50 for COX1 and COX2 enzymes, and for what period of time.
NSAIDs are considered time-dependent inhibitors of COX1 and COX2. Therefore,
intraocular NSAID concentrations are expected to correlate with the efficacy of a given
topical ocular therapy.
DuraSite allows longer ocular surface-dwelling time for the bromfenac to absorb and exert its
NSAID therapeutic effects. Si et al described the tissue concentration of DuraSite containing
bromfenac was significantly higher than that of 0.09% bromfenac ophthalmic solution
(Xibrom) in all ocular matrices, excluding the retina.
Bromfenac delivered in DuraSite enhances the ocular bioavailability of bromfenac,
contributing to significantly higher NSAID concentrations in the aqueous humor compared to
bromfenac ophthalmic solution.
Comparative study of the efficacy and safety of bromfenac, nepafenac and diclofenac
sodium for the prevention of cystoid macular edema after phacoemulsification.
CME is the most frequent cause of visual loss after phacoemulsification. CME is normally a
subclinical and self-limited process, but in a small group of patients it turns into a chronic
process with permanent loss of visual acuity.
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The currently available topical non-steroidal anti-inflammatory drugs (NSAIDs) for
prevention and management of non-infectious ocular inflammation and CME in USA and
Europe include bromfenac, indomethacin, diclofenac, flurbiprofen, ketorolac tromethamine
and nepafenac. These drugs have been proven to be a safe and effective alternative to
corticosteroids in the topical prevention and management of CME. Miyake et al found that
diclofenac was more effective in preventing CME than a topical corticosteroid eyedrop,
fluorometholone. Indomethacin, among NSAIDs, has been used to prevent CME after
cataract surgery and has good intraocular bioavailability The aim of this research was to
compare the efficacy, tolerability and safety of bromfenac 0.09%, nepafenac 0.1% or
diclofenac 0.1% for the prophylaxis of the cystoid macular edema (CME) after
phacoemulsification. Macular thickness increases in 27% to 41% of eyes undergoing
phacoemulsification. Many studies assess the action of NSAIDs on the macular volume
regarding post- phacoemulsification CME prevention. Most of them conclude that even
though the little increase of the macular thickness following uncomplicated cataract surgery
is not clinically significant, the use of those drugs would be advisable after such operation to
ensure an excellent final visual acuity. However, there is no evidence about which of the
NSAIDs could be the most effective. Bromfenac is the most effective for the CME
prevention and nepafenac was the least effective. Nepafenac was the most effective and
bromfenac the least in reducing inflammation (through the Tyndall effect).Through patient
reported outcome survey, patients reported-Diclofenac achieved the highest reduction of pain,
and bromfenac, the lowest; Diclofenac reduced the blurred vision and foreign body sensation
the most. No patients using bromfenac reported a sticky eyes sensation. The drug which
caused the most ocular discomfort was diclofenac, and bromfenac was the one which caused
the least. The highest medication adherence was performed by patients in the bromfenac
group, and the lowest, by the diclofenac one. The highest satisfaction was reported by the
group that used nepafenac, and the lowest by the diclofenac group.
Combined use of corticosteroids with topical NSAIDs could reduce the latter‟s damaging
effect on the cornea. Topical NSAIDs may have harmful effects on the cornea, like
superficial punctate keratopathy, infiltrates, or corneal melting. In this study no corneal
adverse events were detected. The show that bromfenac 0.09% obtains a greater reduction of
the retinal thickness values, both at post- phacoemulsification 3-week and 2-month OCT
measurements. Patient‟s subjective satisfaction was highest with bromfenac 0.09%.
Regarding safety, no important adverse effect with any of the three drugs during the follow
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up period were recorded. Still it cannot be concluded which of the three drugs should be
preferentially used after cataract surgery, although it was found, bromfenac 0.09% was most
effective to reduce foveal thickness.
Anterior Chamber Inflammation After Cataract Surgery: A Randomized Clinical Trial
Comparing Bromfenac 0.09% to Dexamethasone 0.1%
Recently, ophthalmic non-steroidal anti-inflammatory drugs (NSAIDs) have received
attention as possible adjuvants to or substitutes for topical steroids after
phacoemulsification.[3]
Several advantages of NSAIDs over steroids have been claimed: they
do not induce changes in intraocular pressure (IOP); they may have a favorable
pharmacologic profile (fewer administrations); they may be more effective than steroids at re-
establishing the blood-ocular barrier after surgery; they can prevent pseudophakic cystoid
macular edema
The purpose of this study was to compare the anti-inflammatory effects of bromfenac 0.09%,
the most recently introduced ocular NSAID, to dexamethasone 0.1% as monotherapy for
2weeks. Postoperative inflammation was precisely evaluated by laser flare photometer with
close follow-up visits. Special attention was used to include a homogeneous population of
patients affected by senile cataract but with no other ocular comorbidities.
Phacoemulsification with IOL implantation was uncomplicated in all patients, with a similar
mean duration of surgery in both groups (13.89 ± 2.98 vs. 14.03 ± 2.95 min). Inflammation in
the anterior chamber in the two treatment groups described as time-to-event curves. The
event was defined as postoperative flare equal or inferior to the preoperative flare value. The
difference between the two treatments was not statistically significant at all time points.
As expected, in both treatment groups laser flare significantly increased the day after surgery
and decreased after starting the treatment. There was no statistically significant difference
between dexamethasone and bromfenac in terms of mean laser flare at all time points.
this clinical trial showed that bromfenac 0.09% was as effective as dexamethasone 0.1% in
reducing anterior chamber inflammation after cataract surgery.
One strength of the present study was the exact quantification of intraocular inflammation at
several time points after cataract surgery. One limit of the study was the absence of a
treatment group based on the combination of bromfenac and dexamethasone.
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This study presented new information on postoperative inflammation after uncomplicated
phacoemulsification. Not all the patients returned to their preoperative laser flare values 1
month after cataract surgery, suggesting that a 2-week treatment may be inadequate for some
patients. This long- lasting inflammation might explain the occurrence of pseudophakic
macular edema several weeks after uneventful cataract surgery in eyes that might have had
prolonged subclinical inflammation but appeared unremarkable at slit-lamp examination.
This clinical trial shed more light onto the controversy between ophthalmic NSAIDs and
steroids in the attempt to clarify their effect as monotherapy on anterior chamber
inflammation after routine cataract surgery. It indicates that modern tools to objectively
assess ocular inflammation should be included in future studies evaluating anti-inflammatory
treatments for ocular diseases.
Effect on Gel Formation Time of Adding Topical Ophthalmic Medications to ReSure
Sealant, an In Situ Hydrogel.
Although sutures to close cataract surgery incisions have been used and recommended for
imperfect wounds,12 infections have occurred despite sutures, and sutures may have even
been the nidus of the postoperative infections, even years after an uneventful surgery.
Various groups have reported on possible sealants, with one recently completing the rigorous
US Food and Drug Administration premarket approval (PMA) process to earn approval with
an indication to seal post cataract.
The pivotal study showed that the sealant is superior to suture in terms of fewer adverse
events and superior to preventing wound leaks (95.9% for sealant vs. 65.9% for sutures).
The purpose of this article was to describe the pharmacokinetics of gel formation of the
sealant, when used on label and when used off label by mixing with various standard topical
ophthalmic medications. In this experimental laboratory study, the commercial product,
ReSure Sealant, was used as per the product insert. Two drops of diluent were mixed with the
polymer and time to gel formation was measured. Following this, various commercial
antibiotic, nonsteroidal anti-inflammatory drug and steroid drops were used in substitution of
one of the drops of the diluent. Combinations of 2 medications were also tested. Each
condition was performed in triplicate and the mean gel time was calculated.
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ReSure Sealant is an in situ forming hydrogel that creates a temporary, soft, and lubricious
sealant to prevent fluid egress following cataract or IOL placement surgery. ReSure hydrogel
persists for approximately 1–3 days (up to 7 days in some cases), or until re-epithelialization
occurs. The cross- linked hydrogel is approximately 89% water at application. The hydrogel
is polyethylene glycol (PEG) based; PEG is commonly used in pharmaceutical, cosmetic, and
ophthalmic applications.
A novel way to possibly reduce the risk of microbes traversing incisions postoperatively, and
potentially reduce the rate of postoperative infections in cataract surgery, is sealing the entire
wound with a hydrogel. ReSure Sealant is a new FDA approved commercial polymer
hydrogel, which has been found to be superior to 10-0 nylon sutures in terms of sealing a
cataract surgery incision.
The data show that when the sealant was mixed with the fluoroquinolones MOX, OFX, GAT,
or CIP, it resulted in un- acceptably long mean gel times of 105 s or longer.
The steroids LOT, DEX, and PRED also produced prolonged mean gel times from 83 s to
>120 s. The NSAID KET caused an increase in the gel time to 49 s, but the NSAID BROM
caused no increase, possibly even reducing the gel time (from 19 s to 13 s). What was more
remarkable was that when BROM was added to the fluoroquinolones MOX, GAT, or OFX,
the time to gel formation was substantially reduced compared with fluoroquinolones alone.
We hypothesize that elements of the BROM‟s formulation, such as elevated pH and the
presence of the amine group, caused the significant reduction of gel time even when added to
medications that alone increased the time to gel formation.
We tested BROM, KET, and NEP since these are the NSAIDs that are the most prescribed in
the United States. BROM improved not only the gel time when used alone but also more
surprisingly, decreased the time to gel formation when added to fluoroquinolone antibiotics
MOX, GAT, and OFX, producing gel times that would not substantially delay surgery.
The sealant, when mixed with a steroid, had a significantly increased gel time such that it
would not be practical to be considered in clinical practice. We did not mix the BROM with
the steroids DEX, PRED, and LOT in this study. This may be the focus of future studies.
Certain medications, specifically bromfenac, may not substantially alter time to gel formation
of ReSure Sealant when added to the hydrogel. In fact, bromfenac added to moxifloxacin,
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ofloxacin, or gatifloxacin reduced gel formation time to acceptable levels. All other
medications and combinations of medications added to ReSure Sealant produced
unacceptably long gel times to be used routinely. Clinical studies may be considered based on
these to assess the safety and efficacy of this strategy.
Topical Treatment With Bromfenac Reduces Retinal Gliosis and Inflammation After
Optic Nerve Crush
Although corticosteroids have a stronger anti-inflammatory effect than NSAIDs, they also
have various side effects and may trigger neuronal apoptosis and axonal loss. Therefore,
NSAID treatment is preferred, and these compounds are being extensively studied in patients
and animal models to assess their toxicity, pharmacokinetics, neuroprotective properties, and
anti-inflammatory and anti-edema effects, among others.
Kida et al. showed that compared to nepafenac and diclofenac, bromfenac concentration after
topical application on rabbit eyes was continuously higher in the retinochoroidal tissues.
Thus, bromfenac may have a better therapeutic effect than these two other NSAIDs in
retinochoroidal inflammatory diseases.
Regarding the therapeutic effect of bromfenac eye drops in animal models, it has been shown
that they reduce retinal edema triggered by lipopolysaccharide systemic injection in rats and
rabbits and prevent reactivation of herpes virus 1 in infected mice.
Thus, in this study the investigation is about the effect of topical bromfenac on retinal
degeneration, gliosis, and release of PGE2 in the rat retina after ONC.
Retinal Thickness
The retinal thickness decreased gradually, reaching statistical significance for both groups at
day 5 in the periphery, and closer to the optic disc in the bromfenac-treated group. Seven
days after the injury, the retina was significantly thinner in both groups and at both distances.
Interestingly, comparing both groups, the retina was thinner at day 7 in the bromfenac-treated
animals, reaching this difference statistical significance at 600 μm from the optic disc.
At 1200 μm from the optic disc, the thickness of RNFL significantly decreased by day 5 in
the bromfenac-treated group and at day 7 in both groups. At this latter time point, the RNFL
was significantly thinner in the treated versus untreated group. At 600 μm from the optic disc,
there were not significant changes in either group compared to baseline. However, 7 days
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after the lesion, the RNFL thickness was significantly reduced in the bromfenac-treated
retinas compared to untreated ones.
Bromfenac Treatment Does Not Accelerate Retinal Degeneration
Bromfenac treatment did not alter the number of Brn3a+RGCs, either in intact or in ONC-
injured retinas. Regarding CRALBP1(Muller cells), compared to intact retinas, its expression
declined after ONC but was maintained in ONC-treated samples. In intact but treated retinas,
CRABLP levels declined as well, although to a lesser extent than after ONC.
Retinal Gliosis
Optic nerve crush triggers a strong glial activation, which, at 7 days, almost reverted with
bromfenac treatment, as observed by immuno- detection and Western blotting. In retinal
extracts from intact animals treated during 7 days with bromfenac, Western blotting analysis
showed that GFAP and vimentin are upregulated compared to intact retinas, but their levels
are still lower than those found in ONC + bromfenac retinas.
Cyclooxygenases and Prostaglandin E2
Bromfenac mechanism of action is due to its ability to block prostaglandin synthesis by
inhibiting COX1 and COX2. Interestingly, in the ONC + bromfenac group, PGE2 levels were
reduced almost to the values found in intact retinas. Although recent work indicates that
bromfenac is more selective for COX2. Expression of COX2 is inducible in response to
injury and the release of cytokines and proinflammatory molecules, both of which occur in
the retina after ONC.
Interestingly, in spite of the increase of macroglial markers in intact + bromfenac retinas
compared to intact ones, the concentration of PGE2 was similar in both groups, suggesting
that perhaps the cytokines / inflammatory mediators that activate COX are released by
microglial cells.
The main findings of this work are that topical instillation of bromfenac (0.09%) reduces
retinal thickness, retinal gliosis, and the release of PGE2 after a complete intra-orbital ONC,
a drastic injury to the retina that in acute and massive RGC death. Importantly, bromfenac
treatment does not affect the number of RGCs in intact retinas or accelerate ONC- induced
degeneration. In fact, current experiments indicate that bromfenac treatment increases RGC
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survival after ONC, although this protection is not immediate but is delayed to 9 days onward
(Rovere G, Nadal-Nicol as FM, Vidal-Sanz M, Agudo-Barriuso, M. unpublished data, 2016).
Besides reducing gliosis, bromfenac abolishes the release of PGE2, which in turn may
effectively reduce the retinal edema, since prostaglandins in the eye disrupt the blood–ocular
barrier, increase vasodilation, and facilitate leukocyte migration causing edema and
inflammation.
If this hypothesis is sustained, it would be of interest to instill NSAIDs in patients with retinal
edema when diagnosed by in vivo measurement of the retina.
Topical administration of bromfenac is an efficient and non-invasive treatment to control the
retinal gliosis and release of proinflammatory mediators that follow a massive insult to the
RGC population.
Management of ocular inflammation and pain following cataract surgery: focus on
Bromfenac ophthalmic solution
Studies have shown that bromfenac ophthalmic solution 0.09% has equivalent efficacy to the
other topical NSAIDs in reducing postsurgical inflammation and controlling pain. The unique
chemical structure of bromfenac makes it both a potent inhibitor of the COX-2 enzyme and a
highly lipophilic molecule that rapidly penetrates to produce early and sustained drug levels
in all ocular tissues. Bromfenac ophthalmic solution 0.09% is a versatile agent and is
effective when used as either monotherapy or as an adjunct therapy to steroids.
Classification of NSAIDs
Topical NSAIDs are classified into six groups based on their chemical composition: indoles,
phenylacetic acids, phenylalkanoic acids, salicylates, fenamates, and pyrazolones.
Introduction to Bromfenac
Bromfenac sodium ophthalmic solution 0.1% was first approved in May 2000 as Bronuck®
(Senju Pharmaceutical Company, Ltd., Osaka, Japan) and is presently approved by the
Ministry of Health in Japan for the clinical indications of the treatment of postoperative
inflammation, blepharitis, conjunctivitis and scleritis. The recommended dosage of
bromfenac ophthalmic solution 0.09% is one drop in the affected eye(s) twice daily beginning
24 hours after cataract surgery and continuing through the first 2 weeks of the postoperative
period.
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Pharmacology of bromfenac-Chemistry
Bromfenac sodium is designated chemically as sodium 2-amino-3-(4-bromobenzoyl)
phenylacetate sesquihydrate, with an empirical formula of C15H11BrNNaO.11⁄2 H2 0.
Structure of bromfenac is identical to amfenac, with the key exception of a bromine atom at
the C4 position.
Pharmacodynamics of bromfenac vs nepafenac/amfenac vs ketorolac
Walters et al researched the in vivo pharmacokinetics and in vitro pharmacodynamics of
nepafenac, amfenac, ketorolac, and bromfenac. Seventy-five patients participated in this
study and Walters et al determined that nepafenac showed significantly greater ocular
bioavailability and greater potent COX-1 inhibition than any other drug tested and amfenac
demonstrated greater potency and COX-2 inhibition than ketorolac or bromfenac.
COX inhibition of bromfenac vs ketorolac -Another study analysing NSAID COX
inhibitory activities compared the COX inhibitory activity and ocular anti- inflammatory
effects of ketorolac and bromfenac. The authors reported that ketorolac inhibited COX-1
more strongly than bromfenac while bromfenac had greater COX-2 inhibitory activity than
ketorolac.
Bromfenac vs diclofenac ophthalmic solution-Several subsequent clinical studies have
compared the efficacy of bromfenac ophthalmic solution with diclofenac ophthalmic solution
in reducing inflammation after cataract surgery.
Safety and tolerability of bromfenac ophthalmic solution-Subjects in clinical trials of
long-term treatment with the oral bromfenac were found to have an increased incidence of
liver enzyme elevations. While there were no cases of serious liver injury, the FDA
prescribing information for oral bromfenac was subsequently amended to include a re-
emphasized “black box” warning limiting use to no more than 10 days.
Adverse effects of bromfenac-The most common adverse events reported with bromfenac
included abnormal sensation in the eye, conjunctival hyperemia, eye irritation (including
burning/stinging), eye pain, eye pruritis, eye redness, headache, and iritis. No deaths have
been reported with bromfenac 0.09% ophthalmic solution. The rapid onset of bromfenac in
the treatment of postsurgical inflammation diminishes ocular irritation, including burning and
stinging. Reports of serious and no serious adverse effects have been low since drug approval
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and there have been no reports of liver toxicity according to the post- marketing safety
surveillance data available.
Bromfenac vs ketorolac vs diclofenac for the treatment of acute pseudophakia CME-
Rho et al presented of a study comparing bromfenac ophthalmic solution with diclofenac and
ketorolac for the treatment of acute pseudophakia CME. there was a trend toward
significance for the bromfenac group. Rho concluded that twice-daily bromfenac was
statistically as effective as diclofenac or ketorolac dosed 4 times daily.
Bromfenac for the treatment of allergic conjunctivitis-Bromfenac ophthalmic solution
was compared with the ophthalmic mast cell stabilizer pemirolast potassium for the treatment
of seasonal allergic conjunctivitis in a clinical study by Miyake Kashima et al. Both drugs
improved 4 of 5 objective signs but there was no significant difference between the drugs in
objective efficacy. Neither drug significantly improved subjective symptoms after this brief
treatment period nor was there any difference between them in the subjects‟ assessment.
Bromfenac for the treatment of anterior uveitis-Usui and Masude reported on the
evaluation of twice-daily bromfenac ophthalmic solution for the treatment of anterior uveitis
over both 2-week and 12-week treatment courses. The investigators concluded that
bromfenac seemed to reduce inflammation associated with anterior uveitis with minimal side
effects, potentially providing a safer alternative to long- term treatment with ophthalmic
steroids.
In multiple comparative trials, bromfenac ophthalmic solution 0.09% has been shown to
provide safe and effective relief of perioperative inflammation and pain following cataract
surgery. Clinically, these pharmacokinetic features are manifested in a rapid reduction of
postsurgical inflammation and pain with bid dosing. Further clinical investigations will
explore the expanding use of bromfenac in a variety of other clinical settings, including, but
not limited to, the management of ocular inflammation and pain following cataract surgery.
Prophylactic non-steroidal anti-inflammatory drugs for the prevention of macular
oedema after cataract surgery
Macular oedema (MO) is the accumulation of extracellular fluid in the central retina (the
macula). It may occur after cataract surgery and may give rise to poor visual outcome, with
reduced visual acuity and distortion of the central vision. MO is often self-limiting with
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spontaneous resolution, but a small proportion of people with chronic persistent MO may be
difficult to treat. Chronic oedema may lead to the formation of cystic spaces in the retina
termed 'cystoid macular oedema' (CMO). Non-steroidal anti-inflammatory drugs (NSAIDs)
are commonly used in cataract surgery and may reduce the chances of developing MO.
The aim is to answer the question: is there evidence to support the prophylactic use of topical
NSAIDs either in addition to, or instead of, topical steroids postoperatively to reduce the
incidence of macular oedema (MO) and associated visual morbidity.
Randomised controlled trials (RCTs) were included in which adult participants had
undergone surgery for age-related cataract. Participants irrespective of their baseline risk of
MO were included, in particular included people with diabetes and uveitis were included.
Trials of preoperative and/or postoperative topical NSAIDs in conjunction with postoperative
topical steroids were also taken into consideration. The comparator was postoperative topical
steroids alone. A secondary comparison was preoperative and/or postoperative topical
NSAIDs alone versus postoperative topical steroids alone.
The review authors found 34 relevant studies. These studies were conducted in all parts of the
world including the Americas, Europe, the Eastern Mediterranean region and South-East
Asia. Most (28) of these studies compared NSAIDs combined with steroids against steroids
alone. Some of the studies (6) compared NSAIDs with steroids alone. A variety of NSAIDs
were used, including ketorolac, diclofenac, nepafenac, indomethacin, bromfenac, pranopfen
and flurbiprofen. People taking part in these trials were followed up from between one and 12
months. Most studies only followed up to two months or less. Six studies were funded by
industry; seven studies were funded from non-industry sources and the rest of the studies did
not report the source of funding.
There was low-certainty evidence that NSAIDs reduce the chance of poor vision due to
macular oedema three months after cataract surgery.
Only one study reported on poor vision due to macular oedema at 12 months and we judged
this to have very low-certainty of evidence.
Using NSAIDs was associated with a reduced risk of macular oedema but the review authors
judged this to be low-certainty.
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Inconsistent were seen for some measurements of macular oedema, such as the thickness of
the tissue at the back of the eye (central retinal thickness) at three months after surgery. This
measurement was not reported by any studies at 12 months after surgery.
Similarly, inconsistent were seen for vision measurement (visual acuity) but most studies
found small differences between people given NSAIDs and people not given NSAIDs.
Only one study reported quality of life, and this suggested little impact of NSAIDs on quality
of life. Adverse events mainly consisted of a burning or stinging sensation.
Using topical NSAIDs may reduce the risk of developing macular oedema after cataract
surgery, although it is possible that current estimates as to the size of this reduction are
exaggerated. It is unclear the extent to which this reduction has an impact on the visual
function and quality of life of patients.
There is little evidence to suggest any important effect on vision after surgery. The value of
adding topical NSAIDs to steroids, or using them as an alternative to topical steroids, with a
view to reducing the risk of poor visual outcome after cataract surgery is therefore uncertain.
Future trials should address the remaining clinical uncertainty of whether prophylactic topical
NSAIDs are of benefit, particularly with respect to longer-term follow-up (at least to 12
months), and should be large enough to detect reduction in the risk of the outcome of most
interest to patients, which is chronic macular oedema leading to visual loss.
24-Hour Evaluation of the Ocular Distribution of 14C-Labeled Bromfenac Following
Topical Instillation into the Eyes of New Zealand White Rabbits
The octanol/water (O/W) partition coefficient (Clog P) and the quantitative structure-activity
relationship (QSAR) of a drug is another factor that influences its penetration properties and,
consequently, its potency. Clog P estimates the water solubility and the level of lipophilicity
of a compound (a key determinant of the pharmacokinetics parameter).
It is commonly used in drug-design studies, since this property is related to drug absorption,
bioavailability, metabolism, and toxicity. The higher the value, the better the penetration,
with a 1.0-unit difference in the coefficient representing a tenfold difference in penetration.
Ruiz et al.6 reported that the Clog P of bromfenac (2.23) is higher than other NSAIDs, such
as amfenac (1.23) and ketorolac (1.88). This difference in Clog P explains the higher
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lipophilicity of bromfenac that provides a more rapid saturation of the epithelium and a
minimal lag time before the drug crosses the cornea and, thus, the fast analgesic action.
The aim of this preclinical investigation was to evaluate the penetration of 14C-bromfenac
following a single ocular instillation in New Zealand White (NZW) rabbit eyes.
A single 50-μL 14
C-bromfenac ophthalmic solution (20–25μ Ci or 0.09%) was administered
into the right eyes of 14–18 randomly assigned NZW rabbits. At various time points, ocular
tissues were collected and analyzed for 14
C-bromfenac contents. Ocular tissues were
combusted and the amount of radioactivity was determined by liquid scintillation counting
(LSC). Aqueous humor samples were directly transferred to LSC vials.
The first study had 14 NZW rabbits randomized into seven groups of 2 rabbits each. The
second study had 18 NZW rabbits randomized into six groups of 3 rabbits each.
The first study was designed to ensure that enough measurable radiolabelled bromfenac was
available. The second study tested commercial-strength bromfenac ophthalmic solution
0.09%.
The radioactivity present in the conjunctiva of 2 dosed eyes in group G (first study) varied
greatly, indicating a possible contamination. Consequently, the samples were excluded.
Excessive tearing occurred in 1 animal in group E, of the same study, following dosing.
Duplicate aliquots (25 μL) of each sample were analyzed by LSC. The radioactivity present
in each wipe was considered as radioactivity lost during dosing, and actual administered
doses were calculated accordingly.
Peak concentrations of radiolabelled bromfenac were observed in all ocular tissues in the first
study at 2 h, with the exception of the conjunctiva, which showed peak tissue concentration at
1 h, and the lens, which showed peak tissue concentration at 3 h (Table 2).
In the second study, peak concentrations of radiolabelled bromfenac were observed in all
ocular tissues at 1–2 h, with the exception of the lens and vitreous humor (Table 3).
The bromfenac concentrations were highest in the cornea. Similar amounts of radiolabelled
bromfenac were measured in the aqueous humor, iris-ciliary body, choroid, and, to a slightly
lesser degree, the retina. Further, radiolabelled bromfenac was detected in all samples 24 h
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following topical administration in the first and second studies, with the exception of the
vitreous humor.
In addition to potency, another important criterion of topical anti-inflammatory drugs is the
ability to penetrate the tissues to reach their target(s) in a timely manner and appropriate
concentration. Thus, the ability to penetrate ocular tissues is an important determinant of the
safety and efficacy of ophthalmic NSAIDs.
The two animal studies presented in this report demonstrate that a single topical dose of
commercial-strength bromfenac ophthalmic solution 0.09% rapidly, within 2 h, achieved
measurable levels in all ocular tissues and detectable levels were sustained over 24 h.
One unexpected finding revealed that, unlike other ocular tissues, radiolabelled bromfenac
was undetectable in the vitreous humor after 1 h.
Topical bromfenac reduces the frequency of intravitreal bevacizumab in patients with
branch retinal vein occlusion
Branch retinal vein occlusion (BRVO) is the second most frequent major retinal vascular
disease after diabetic retinopathy. Macular oedema (ME) develops in ∼60% of eyes with a
BRVO and is one of the major causes for visual loss in eyes with BRVO.
An earlier study on the natural history of BRVO reported that only 14% of eyes with chronic
ME secondary to BRVO retained a visual acuity (VA) of 20/40 or better, whereas 86% had a
final VA of 20/50 or worse. Topical bromfenac, a non-steroidal anti-inflammatory drug
(NSAID) in combination with anti-VEGF antibody therapy for age-related macular
degeneration, showed a synergistic effect with improved anatomical, functional outcomes and
the need for fewer intravitreal injections.
In this study, the efficacy of topical bromfenac in reducing the number of IVB treatments for
ME secondary to BRVO was investigated to determine the number of injections of IVB
necessary to maintain the morphological resolution of ME and to evaluate the clinical course
of visual function.
Prospective interventional case–control study. 48 eyes of 44 patients with ME-BRVO who
received 1.25 mg/0.05 mL of IVB showed temporary regression of ME. Additional IVB were
given when ME recurred. 24 eyes received topical bromfenac, and the other 24 eyes received
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topical saline as control, four times a day during the clinical course of 48 weeks. The clinical
course of foveal thickness (FT) as measured by optical coherence tomography, logarithm of
the minimum angle of resolution visual acuity (VA), was monitored. The number of IVB was
also recorded.
Initial IVB treatment was performed in all 50 eyes. Two eyes belonging to the „not effective‟
group were identified during the first 3 months. Also, eight of the 48 „effective‟ eyes did not
show a recurrence of ME. Thus, 40 eyes were identified as „effective with recurrence‟ and
were eligible for further case– control study. All 40 of the „effective with recurrence‟ eyes
identified after the initial bevacizumab injection received a second injection. Following the
second injection, 20 eyes had continuous topical bromfenac and the other 20 eyes were
observed as controls. There were no significant differences in gender, age, preclinical period,
initial FT and initial VA between the topical bromfenac group and the control group.
Does topical bromfenac affect „effective with recurrence‟ eyes?
During the clinical course, improvement in VA in the topical bromfenac groups was
−0.447±0.122, which was not significantly different from that in the control group of
−0.437±0.096 (p=0.867).
In this prospective case–control study, compared with IVB mono therapy, adjunctive therapy
with topical bromfenac did not have a significant effect on functional and morphological
resolution, while this combination therapy was found to reduce the number of IVB injections
to maintain FT under 300μm within a 1-year follow-up period.
The frequency of the anti-VEGF drug injections represents an economic burden for patients
and society and is possibly associated with serious complications such as endophthalmitis and
arteriothrombotic events.
In this prospective study, although bromfenac, a topical NSAID, did not augment the
reduction effect by IVB, it did extend its effect to reduce the frequency of IVB over a 1-year
follow-up.
Actually, the duration of topical bromfenac in this study was <1 year because the topical
application was started after the confirmation of recurrence of ME at month 3, thus longer
application may bring more prominent.
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The anti-VEGF drug bevacizumab suppressed hyper-vascular permeability, while a topical
NSAID of bromfenac suppressed inflammatory conditions. Both hyper-vascular permeability
and tissue inflammation worsen tissue oedema; thus, it is not surprising that this combination
therapy has a beneficial effect for ME secondary to BRVO.
Although topical bromfenac during IVB therapy in eyes with ME secondary to BRVO did not
affect the visual prognosis, it had the advantage of reducing the number of injections.
Clinical Trials: Bromfenac
Prolensa (Bromfenac) 0.07% QD vs. Ilevro (Nepafenac) 0.3% QD for Treatment of Ocular
Inflammation Post Cataract Surgery (QD)
ClinicalTrials.gov Identifier: NCT01847638
With an interventional and randomized study design, enrolling 50 participants, the purpose of
this clinical trial was to investigate the clinical outcomes for inflammation, visual acuity and
macular thickness after treatment with Prolensa (bromfenac ophthalmic solution) 0.07% QD
in subjects who have undergone cataract extraction with posterior chamber intraocular lens
implantation.
The safety and efficacy of these two compounds in patients undergoing cataract surgery has
been thoroughly examined in independent studies, however, head-to-head data comparing
postoperative outcomes with the two products are limited.
Primary Outcome Measure-Treatment of Inflammation Associated With Cataract Surgery
[Time Frame: change from baseline to final at post op 42 days +/-7 days]
Secondary Outcome Measure-Visual Acuity [Time Frame: baseline score to final
postoperative visit at 42 days +/-7 days]
Other Outcome Measures-Retinal Thickness [Time Frame: change from baseline to final
postoperative visit at 42 days +/- 7 days]
Both, bromfenac 0.07% ophthalmic solution and nepafenac 0.3% ophthalmic suspension,
showed similar efficacy and tolerability in minimizing post-surgical inflammation and retinal
thickening.
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Positive and similar were observed with regard to [Early Treatment Diabetic Retinopathy
Study]ETDRS visual acuity post-cataract surgery. Comparisons in mean retinal thickness and
mean macular volume were made between the two ophthalmic solutions and the increase was
similar and minute.
Comparison Study of ISV-303 to DuraSite Vehicle in Cataract Surgery Subjects (ISV-303)
ClinicalTrials.gov Identifier: NCT01576952
The following study is A multicenter, double-masked, vehicle-controlled, parallel-group
clinical trial of 268 subjects randomized in a 2:1 ratio to bromfenac 0.075% or vehicle was
conducted. The aim was to evaluate the ocular safety, tolerability, and efficacy of topical
administration of ISV-303 compared with DuraSite Vehicle.
At all time points, there was a significant difference between the bromfenac 0.075%-treated
group and the vehicle-treated group .
At each of the postsurgical time points (Days 1, 8, 15, and 29), proportionally more
bromfenac 0.075%-treated subjects (76.8%, 90.5%, 92.9%, and 85.1%, respectively) had no
pain (a VAS score of 0) comparing to the vehicle-treated subjects (48.2%, 38.8%,42.4%, and
47.1%, respectively), and at each time point, these differences in proportions were
statistically significant (P<0.001).
More subjects in the bromfenac 0.075% group had complete ACF resolution (151/167;
90.4%) compared to those in the vehicle group (54/85; 63.5%). There were no new safety
signals reported.
More subjects in the vehicle group had severe TEAEs compared to those in the bromfenac
0.075% group (7.1% [6/85] vs 1.8% [3/169], respectively).
This study shows that bromfenac 0.075% in DuraSite is safe, well tolerated, and effective at
reducing inflammation and preventing pain associated with cataract surgery and confirms that
bromfenac 0.075% reduced inflammation better than the currently marketed versions of
bromfenac in both once- and twice-daily formulations.
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Efficacy and Safety of Bromfenac Ophthalmic Solution in Cataract Surgery(2008) &
Efficacy Study of Bromfenac Ophthalmic Solution in Patients Undergoing Cataract
Surgery(2009)Information provided by (Responsible Party).
ClinicalTrials.gov Identifier: NCT00704418
ClinicalTrials.gov Identifier: NCT00853970
A total of 455 subjects (455 study eyes: 230 bromfenac, 225 placebo) were enrolled in two
randomized double-masked, placebo-controlled, clinical trials at 64 ophthalmology clinics to
evaluate Efficacy and Safety of Bromfenac Ophthalmic Solution 0.09% in Cataract Surgery.
The mean SOIS for the bromfenac 0.09% group was lower than the placebo group at Days 3,
8, 15, and 22 (P < 0.0001). More bromfenac 0.09% subjects were pain free at Days 1, 3, 8,
and 15 (P < 0.0001).
Bromfenac ophthalmic solution 0.09% dosed once daily is clinically safe and effective for the
treatment of ocular inflammation and the reduction of ocular pain associated with cataract
surgery.
Aqueous Humor Concentration of InSite Vision (ISV) 303 (Bromfenac in DuraSite) to
Bromday Once Daily (QD) Prior to Cataract Surgery.
ClinicalTrials.gov Identifier: NCT01387464
This multi-center, randomized, double-masked, 2-arm, parallel-group, comparative clinical
trial of 60 subjects was done To compare the aqueous humor penetration of two different
formulations of Bromfenac, namely commercial Bromday (0.09%) with Bromfenac in
DuraSite (0.075%).
Study showed that the mean concentration of bromfenac in the aqueous humor of subjects in
the ISV-303 treatment group was more than twice greater compared to those subjects dosed
with Bromday.
There were no adverse events reported in this study and no safety concerns for either of the 2
treatment groups.
Therapeutic concentrations of bromfenac are very necessary to prevent pain and regulate
inflammation of anterior and the posterior ocular tissues, and this study confirmed superior
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tissue penetration of ISV-303 against the market leader, Bromday, to reduce the pain and
inflammation associated with ocular surgery.
A Comparison of Prostaglandin E2 (PGE2) Inhibition of Acuvail (Ketorolac 0.45%), Xibrom
(Bromfenac 0.09%)and Nevanac (Nepafenac)in Patients Undergoing Phacoemulsification
ClinicalTrials.gov Identifier: NCT01021761
This interventional randomized clinical trial of 126 participants was done to compare the
PGE2 inhibition of three topical NSAIDs - ketorolac 0.45% (Acuvail), bromfenac 0.09%
(Xibrom), and nepafenac 0.1% (Nevanac) in patients undergoing phacoemulsification at peak
dosing levels. Study show that The mean PGE2 values were 224.8 +/-164.87 pg/ml for
ketorolac (n=42), 288.7 +/-226.05 pg/ml for bromfenac (n=42), and 320.4 +/-205.6 pg/ml for
nepafenac (n=42).No adverse events or safety concerns were reported. Difference between
Bromfenac and Nepafenac is not so significantly different, while between Ketorolac and
Nepafenac the difference is quite large being in favour of Ketorolac. Similarly, between
Bromfenac and Ketorolac the difference is statistically visible and in favour of Ketorolac.
This new ketorolac compound achieved the greatest inhibition of PGE2 compared to
nepafenac 0.1% and bromfenac 0.09%. Thus it can be concluded that Ketorolac 0.45% is
more efficient in inhibition of PGE2 and controlling ocular inflammation at the time of
surgery than Bromfenac 0.09% and Nepafenac 0.1%.
A Comparison of Peak Aqueous Penetration of Acuvail (Ketorolac 0.45%), Xibrom
(Bromfenac 0.09%), and Nevanac (Nepafenac 0.1%)in Patients Undergoing
Phacoemulsification.
ClinicalTrials.gov Identifier: NCT01001806
The purpose of this interventional, randomized clinical trial of 126 participants was to
compare the peak to-aqueous penetration of three nonsteroidal anti-inflammatory drugs:
ketorolac tromethamine 0.45%, bromfenac 0.09% and nepafenac 0.1% in patients undergoing
phacoemulsification.
The peak aqueous concentration of ketorolac 0.45% was 10 times the concentration of
bromfenac 0.09%. The mean peak aqueous concentration of ketorolac 0.45% was
688.87 ± 749.6 ng/ml. Bromfenac achieved a mean peak aqueous concentration of
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67.64 ± 62.4 ng/ml. While mean peak aqueous concentrations of nepafenac reached till
447.10 ± 225.7 ng/ml.
The peak concentration of ketorolac was thus statistically significantly greater than
bromfenac and nepafenac as it achieved dramatically greater aqueous concentrations.
Thus ketorolac has high efficacy to treat pain and post-surgery ocular inflammation.
Therapeutic Applications of Moxifloxacin
1) Review of moxifloxacin hydrochloride ophthalmic solution in the treatment of
bacterial eye infections
Moxifloxacin hydrochloride ophthalmic solution 0.5% is the ocular formulation/adaptation of
moxifloxacin. Moxifloxacin is a broad spectrum, 8-methoxy fluoroquinolone is an
antibacterial agent which is concentration dependent with improved anti- infective activity
against bacterial infections. Moxifloxacin hydrochloride ophthalmic solution 0.5 is an
isotonic, preservative free solution used for the treatment of bacterial conjunctivitis, keratitis
and surgical prophylaxis. Modification of the moxifloxacin core molecule inhibit the bacterial
growth by binding to DNA gyrase (topoisomerase II) and topoisomerase IV. DNA gyrase and
topoisomerase IV are essential bacterial enzymes involved in the replication, translation,
repair and recombination of deoxyribonucleic acid. Inhibition of either of these enzymes will
leads to bacteria death. Affinity for both enzymes improves potency and reduces the
probability of selecting resistant bacterial subpopulations. In vitro and clinical studies
indicates that the moxifloxacin treatment is safe in childrens (3 days to 17 years) and adults
(up to age 93). Moxifloxacin was significantly more tolerable in healthy adult and pediatric
eyes. Adverse events including conjunctivitis, keratitis and endophthalmitis have been low
after moxifloxacin treatment. Moxifloxacin hydrochloride ophthalmic solution 0.5% have
moderately high rate of clinical success against common ocular pathogens.
2) An assessment of the tolerability of moxifloxacin 0.5% compared to azithromycin
1.0% in Moxifloxacin
Moxifloxacin 0.5% ophthalmic solution is a broad spectrum which is concentration-
dependent and highly effective against bacterial infections. While azithromycin is
bacteriostatic and time-dependent. Depending on the concentration, azithromycin show high
level of Gram-positive resistance patterns. The purpose of this study was to compare subjects
perceptions of moxifloxacin and azithromycin in healthy adult and pediatric subjects. One
hundred and twenty-five healthy volunteers with normal ocular health were selected for the
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study. It is a single center, single-visit, subject-masked, randomized, active, and placebo-
controlled study. A trained technician instilled one drop of moxifloxacin and azithromycin in
the eyes of healthy adults and pediatric populations. Drops were installed in different time
points (0, 1, 3, 5, and 10 minutes). After instillation, subjects rated comfort, acceptability, and
blurring on 0–10 point analog scales stating their preference of treatment at different time
points. There was a significant preference for moxifloxacin over azithromycin at every time
point (p ≤ 0.0001 and p ≤ 0.0002, respectively) in both pediatric and adult subjects . An
average of 84% of all subjects and 82% of pediatric subjects preferred moxifloxacin over
azithromycin. Moxifloxacin was found to be more comfortable (p < 0.0001), acceptable (p <
0.0001), and resulted in less blurring (p < 0.0001) than azithromycin at every time point.
Some adverse events were also observed during the study. One subject receiving
moxifloxacin experienced 2 ocular adverse events and 18 subjects receiving azithromycin
experienced 25 adverse events. Moxifloxacin resulted in less blurred vision and was more
comfortable and acceptable to subjects than azithromycin. Azithromycin was less tolerable
than moxifloxacin because of the more adverse events.
3) Application of intracameral moxifloxacin to prevent endophthalmitis in cataract
surgery
Endophthalmitis is a serious complication of cataract surgery that can lead to severe visual
loss. It is a rare complication occurring after cataract surgery. In order to prevent
endophthalmitis, several preoperative, perioperative, and postoperative measures were taken.
Moxifloxacin is a fourth - generation fluoroquinolone that affects gram-positive and gram-
negative bacteria. The study was conducted to evaluate the safety and efficacy of
intracameral moxifloxacin immediately after cataract surgery to prevent the risk of
endophthalmitis. A total of 65 patients were selected for the study. All the selected patients
had undergone a care cataract surgery and were retrospectively examined. Immediately after
the cataract surgery, intracameral moxifloxacin was instilled in some patients (moxifloxacin
group), but not in some other patients which is called as the control group. After cataract
surgery, the patients were examined at different time periods and the pre- and postoperative
findings were then compared. Adverse events were observed in both the groups and are
considered to be insignificant. Corneal edema was observed in 2 (6% ) subjects in the
moxifloxacin group (2 mild cases) and in 3 (9% ) subjects in the control group (2 mild cases,
1 moderate case). Anterior chamber cells ( 1 + ) were observed in 4 ( 12% ) subjects in the
moxifloxacin group and in 3 ( 9% ) subjects in the control group. These slight differences in
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corneal edema (P= 0. 623) and anterior chamber cell ( P = 0. 726) were not statistically
significant. Moxifloxacin were found to have an acceptable retinal safety profile. Therefore
the application of intracameral moxifloxacin for prophylaxis of endophthalmitis following
cataract surgery is both safe and effective.
4) Penetration of 0.3% ciprofloxacin, 0.3% ofloxacin, and 0.5% moxifloxacin into the
cornea and aqueous humor of enucleated human eyes
Eyes retrieved for corneal transplantation have a high rate of bacterial contamination that can
lead to graft infections. Therefore it is essential for eye banks to minimize bacterial
contamination. Ciprofloxacin, ofloxacin, and moxifloxacin were different anti- bacterial
agents used for the treatment of bacterial contamination. The study was conducted to quantify
the penetration of ciprofloxacin, ofloxacin, and moxifloxacin into the cornea and aqueous
humor of cadaver eyes. A total of 60 enucleated eyes, not eligible for corneal transplantation
were selected for the study. All the subjects were divided into three groups and immersed in
commercial solutions of 0.3% ciprofloxacin, 0.3% ofloxacin, or 0.5% moxifloxacin for 10
min. Only 1 eye of each donor was used. Whole corneas and samples of aqueous humor were
then harvested and frozen, and drug concentrations analyzed by liquid chromatography
tandem mass spectrometry. The mean corneal concentration of moxifloxacin was found to be
twice as high as ofloxacin, which was twice as high as ciprofloxacin. Moxifloxacin displayed
a mean concentration four times higher than the other antibiotics in the aqueous humor. If
these measurements would hold true in vivo, there will be a decreasing order of bactericidal
efficacy for antibiotics in the cornea should be moxifloxacin, ofloxacin, and ciprofloxacin. In
the aqueous humor, it should be moxifloxacin, ciprofloxacin, and ofloxacin. In either
medium, moxifloxacin should be far more efficient than ciprofloxacin and ofloxacin. The
amount of drug that penetrated the anterior chamber after a 10-min soaking was far below the
safe limit of endothelial toxicity of each preparation (21–23). Therefore, the application of
anti-bacterial drugs are found to be safe and effective especially moxifloxacin.
5) Intraocular penetration of sequentially instilled topical moxifloxacin, gatifloxacin,
and levofloxacin
Fluoroquinolones have been used extensively due to their excellent activity against ocular
pathogens, including both Gram-positive and Gram negative bacteria. The objective of study
was to compare the penetration levels of new fluoroquinolones, including the fourth-
generation fluoroquinolones (moxifloxacin and gatifloxacin) and a third-generation
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fluoroquinolone (levofloxacin) in the cornea, aqueous humor, and conjunctiva after topical
instillation in White rabbits. The rabbits were randomly divided into four treatment groups
for the study and one drop of each topical preparation was instilled in both eyes of each
animal at two-minute intervals. Instillation was repeated every 15 minutes for a total of three
drops of each fluoroquinolone per eye. Sixty (60) minutes after the final instillation, corneal,
aqueous humor, and conjunctival samples of rabbits were collected from each eye. The
sample concentrations of each fluoroquinolone were simultaneously determined by high-
performance liquid chromatography (HPLC). The mean concentration of moxifloxacin was
significantly higher than levofloxacin or gatifloxacin in the cornea (P = 0.0102 and P =
0.0006, respectively), aqueous humor (P = 0.0015 and P < 0.0001, respectively), and
conjunctiva (P = 0.0191 and P = 0.0236) respectively.
6) The efficacy of moxifloxacin in patients with bacterial keratitis
Keratitis is a sociomedical problem of moderately developed countries which in the loss of
vision. The aim of the study was to analyze the efficiency of moxifloxacin in the treatment of
bacterial keratitis. Keratitis is an acute or chronic inflammation of the cornea. Moxifloxacin
is an antibacterial agent that can be used for the local treatment of bacterial keratitis and/or
conjunctivitis. It has an excellent penetration through the cornea and conjunctiva and destroys
pathogens quickly. Moxifloxacin is a highly efficient anti-bacterial drug with low adverse
effects. The study was designed as a prospective, randomized, double-blind, clinical study.
The study included 30 patients with diagnosed keratitis. All the subjects were locally applied
with antibiotic moxifloxacin. 60 patients were placed in control group, with locally applied
artificial tears. After the application of therapies, all participants were subjected to complete
clinical ophthalmologic analysis for a period of 1–15 days. There was a statistically
significant difference between the study group patients who received moxifloxacin and the
control group patients who received arteficial tears. Moxifloxacin had significant therapeutic
effect (total benefit) both in terms of the effective shortening, time of healing (epithelization
corneal defects real fast) and reduction of complications of bacterial keratitis, without
unwanted effects.
7) Kinetics of kill of bacterial conjunctivitis isolates with moxifloxacin, a
fluoroquinolone, compared with the aminoglycosides tobramycin and gentamicin
Conjunctivitis is a common disease caused by many ocular pathogens, but is mainly bacterial
or viral in origin. Bacterial conjunctivitis is particularly common in children, with
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Streptococcus pneumoniae and Haemophilus influenzae being the most common causative
organisms. The purpose of study was to compare the time required in vitro for tobramycin
and gentamicin (aminoglycosides) and moxifloxacin (fourth-generation fluoroquinolone) to
kill S. pneumoniae and H. influenza. Bacterial conjunctivitis isolates of S. pneumoniae and
H. influenza were exposed to 1:1000 dilutions of moxifloxacin 0.5%, tobramycin 0.3%,
gentamicin 0.3%, and water (control). At different time periods, aliquots were collected, cells
were cultured, and viable cell counts were determined using standard microbiological
methods. Kinetics of kill studies with moxifloxacin ophthalmic solution 0.5% support a
greater speed of kill against S. pneumonia and H. influenzae than with the aminoglycosides,
tobramycin ophthalmic solution 0.3% and gentamicin ophthalmic solution 0.3%.
Moxifloxacin can be used as a first-line treatment for bacterial conjunctivitis to minimize
patient symptoms and to limit the contagiousness of the disease.
8) Concentrations of besifloxacin, gatifloxacin and moxifloxacin in human conjunctiva
after topical ocular administration
Bacterial conjunctivitis is normally an acute, self-limiting infection caused by Gram-positive
species and the Gram-negative species. Bacterial conjunctivitis are usually treated with
topical antibiotics for the speed recovery from signs and symptoms associated with the
infection. The study was conducted to evaluate the pharmacokinetic profiles of 3
fluoroquinolones in the conjunctiva of healthy adults. One-hundred eight (108) subjects of at
least 18 years of age without any ocular abnormalities were selected for the study. All
subjects received one drop of besifloxacin (0.6% suspension), gatifloxacin (0.3% solution), or
moxifloxacin (0.5% solution) ophthalmic formulations in one eye prior to conjunctival
biopsy. Samples were collected from all subjects at different time periods (15 minutes, 30
minutes, 2 hours, 6 hours, 12 hours, or 24 hours) after dosing. The maximum mean
concentration (Cmax) occurred at 15 minutes for all three compounds. . The Cmax for
moxifloxacin (10.7 µg/g) was more than double that of gatifloxacin (4.03 µg/g) and
besifloxacin (2.30 µg/g). Concentrations decreased with each subsequent time point.
Besifloxacin had the greatest mean residence time (4.7 hours) in the conjunctival tissue. No
serious adverse effects were occurred in this study. The most commonly reported adverse
events were ocular pain and headache. The three medications provide broad-spectrum
coverage and cause few adverse reactions. They offer excellent therapeutic choices for
treating bacterial conjunctivitis.
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9)Antibacterial efficacy of prophylactic besifloxacin 0.6% and moxifloxacin 0.5% in
patients undergoing cataract surgery
Bacterial endophthalmitis is a vision-threatening complication after cataract surgery. The
most common causes of bacterial endophthalmitis are gram positive organisms. Besifloxacin
is an ophthalmic drug with antibacterial properties. The purpose of this study was to
investigate the ocular bacterial flora in patients who had undergone cataract surgery and to
compare the antibacterial effects of besifloxacin ophthalmic suspension 0.6% and
moxifloxacin ophthalmic solution 0.5% in these patients. This was a prospective,
randomized, laboratory-masked clinical trial. All patients received besifloxacin or
moxifloxacin four times a day for 3 days before cataract surgery in the surgical eye and 1
hour before surgery in the nonsurgical fellow eye. Conjunctival and eyelid swabs were
obtained from both eyes and were processed for bacterial colony counts (in terms of colony-
forming units) and species identification. Fifty-nine patients were selected for the study.
Majority of the samples were found to be gram negative. Besifloxacin reduced the lid CFU
estimate 1 hour following instillation of a single drop (P=0.039) than moxifloxacin.
Besifloxacin was more active in vitro against MRSE. Besifloxacin appeared more effective in
reducing bacterial counts on eyelids of patients undergoing cataract surgery. There were no
adverse events, either ocular or nonocular, reported for any patient in either the besifloxacin
or moxifloxacin treatment groups.
10)Pharmacokinetics and aqueous humor penetration of levofloxacin 1.5% and
moxifloxacin 0.5% in patients undergoing cataract surgery
Microbial keratitis and endophthalmitis can present a substantial risk to vision.
Fluoroquinolone antimicrobial agents, like levofloxacin and moxifloxacin, have in vitro
activity against the bacterial pathogens that threaten the health of the eye. The study was
conducted to compare the pharmacokinetics in aqueous humor of levofloxacin 1.5% and
moxifloxacin 0.5% ophthalmic solutions of patients undergoing cataract surgery. This was a
two-visit, randomized, single-center, single-masked, active-comparator and parallel-group
study. Subjects who had underwent cataract surgery and met the requirements of PK analysis
were selected. Three days prior to cataract surgery, each patient instilled one drop of the
assigned study medication into the operative eye four times daily at different time periods.
Aqueous humor specimen was collected from the eye at the randomized time point and
assayed using liquid chromatography and tandem mass spectrometer. The obtained mean
concentrations were statistically significant at time periods. The mean concentration of
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levofloxacin was 50% higher than moxifloxacin concentrations across all time points. No
treatment-emergent adverse events were reported during the course of the study.
Levofloxacin 1.5% shows a greater potential for bacterial eradication.
Clinical Trials : Moxifloxacin
1)Pharmacokinetic Evaluation of Moxifloxacin in Aqueous Humor Samples Following
Preoperative Antibiotic/Steroid Dosing in Cataract Surgery Patients
ClinicalTrials.gov Identifier: NCT01859702
The purpose of study was to determine the aqueous penetration of Moxifloxacin with
Vigadexa drug preoperatively in cataract patients. 36 subjects were selected for the clinical
trials. This was a phase – 4 clinical trial. The drug selected for the trial was Moxifloxacin
0.5% / Dexamethasone ophthalmic solution (Vigadexa). The health status of volunteers must
be acceptable before intervention. One drop of drug was installed in the study eye 2 days
before the surgery, followed by 1 drop instilled 4 times a day before the day of surgery. On
the day of surgery, 1 drop was instilled 60 minutes prior to the procedure. During the cataract
surgery, 0.15 millimetre sample of an aqueous humour was collected. The concentration of
moxifloxacin was measured using high performance liquid – spectroscopy. The Mean
Aqueous Humor Concentration of Moxifloxacin was found to be 1110.6. Among the 36
subjects, only 31 patients completed the trial. Majority of subjects were females. Only 2
patients were reported with mild adverse events. In fact adverse serious events were not
reported. Therefore Moxifloxacin was found to be safe and effective in cataract patients. This
clinical trial was conducted in Brazil from April 2012 – August 2012.
2) An Evaluation of the Safety and Efficacy of Moxifloxacin Ophthalmic Solution 0.5%
Versus Ofloxacin Ophthalmic Solution 0.3% in the Treatment of Bacterial
Conjunctivitis in Chinese Patients
ClinicalTrials.gov Identifier: NCT01573910
Moxifloxacin and ofloxacin are drugs that can be used against bacterial infections. The study
was conducted to evaluate the efficacy of Moxifloxacin 0.5% relative to Ofloxacin 0.3% in
treatment of bacterial conjunctivitis in Chinese patients. This was a 3 – phase clinical trial.
The trial began from March 2012 to April 2014. The drug selected for the study was
Moxifloxacin 0.5% and Ofloxacin 0.3%. 985 patients were selected for this study. Patients
diagnosed with bacterial conjunctivitis were enrolled for the trials. From the 985 enrolled, 3
participants were exited as screen failures prior to randomization. Majority of the subjects
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were females. Subjects will self-administer 1 drop of study drug into the operative eye 3
times per day (TID) in each eye for 7 days with a test-of-cure (TOC) at Day 9. 489 patients
were instilled with Moxifloxacin 0.5% and only 469 patients completed the experiment. On
the other hand, 493 patients were instilled with Ofloxacin 0.3% and only 469 patients
completed the trials. The investigator rated the ocular signs of bacterial conjunctivitis on a 4 –
point scale, with 0 = normal/absent ; 1 = mild ; 2 = moderate and 3 = severe . The result of
the clinical cure rate is presented as the percentage of participants for which the sum of the
numerical scores for the 2 cardinal ocular signs of bacterial conjunctivitis was 0 at day 9 Toc
/ Exit visit. The result obtained was 85.4% for Moxifloxacin and 81.4% for Ofloxacin.
Microbiological specimen(s) from the affected eye(s) were collected accordingly to protocol
– defined process. Microbiological success rate is presented as the percentage of participants
for which the pre – therapy pathogens at Visit 1 (Day 1) were eradicated at Day 9 Toc / Exit
visit. The percentage obtained was 95.3% for Moxifloxacin and 94.8% for Ofloxacin. Some
patients were reported with mild adverse events.
3)Aqueous Absorption and Pharmacokinetics of Besivance Versus VIGAMOX in
Patients Undergoing Phacoemulsification
ClinicalTrials.gov Identifier: NCT01296191
The objective of this study is to compare drug concentrations in aqueous humor following
ocular instillation of Besivance or VIGAMOX in subjects undergoing cataract surgery. This
was a phase 3 clinical trial. The drug used for the study was Moxifloxacin and besifloxacin.
120 healthy adults were selected for the study. Eligible subjects will be randomized to
treatment with Besivance or VIGAMOX. Subjects will self-administer 1 drop of study drug
into the operative eye 4 times a day for 3 days prior to surgery. Subjects will have one final
drop of study medication on the day of surgery. Prior to the cataract surgery, a sample of
aqueous humor will be collected by paracentesis. Concentration of Besivance and
VIGAMOX in the aqueous humor will be measured using standardized high pressure liquid
chromatography and mass spectrometry assays. Pharmacokinetic parameters determined from
the aqueous humor concentration will minimally include the area under the curve and the
maximum concentration. 60 subjects were instilled with VIGAMOX and 57 subjects
completed the trials. On the other hand, 60 subjects were instilled with Besivance and 59
subjects completed the trials. The calculated mean value for Besivance and VIGAMOX is
56.4525 and 443.07 respectively. Adverse events were not reported during the study.
Aqueous absorption of Besivance is greater than VIGAMOX because of unique properties of
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Besivance which promote increased contact time of this antibiotic with the ocular surface.
The study was conducted in US from May 2011to January 2013.
4) Assessment of the Concentrations of Besifloxacin, Moxifloxacin, or Gatifloxacin in
the Aqueous Humor of Subjects
ClinicalTrials.gov Identifier: NCT00824070
The purpose of this study is to assess the concentration of besifloxacin, moxifloxacin, or
gatifloxacin in aqueous humor samples collected following topical instillation of the
associated formulation in subjects undergoing cataract surgery. This was a phase 1 clinical
trial. The drug used for the study was Moxifloxacin ophthalmic solution 0.5% (Vigamox),
Besifloxacin and Gatifloxacin ophthalmic solution 0.3% (Zymar). The trial began from
February 2009 to August 2009. 36 subjects were selected for the clinical trials. Subjects will
instill the study medication in the study eye prior to making an incision for cataract extraction
surgery. An aqueous humor specimen was collected from the study eye for determination of
drug concentration 60 min after study drug instillation. They were obtained by calculating
the Aqueous Humor Drug Concentration. The concentration of Moxifloxacin, Besifloxacin
and Gatifloxacin was 0.1349 (0.5820), 0.6681(0.4980) and 0.1251 (0.07624) respectively.
Adverse events were not reported during the study. The study was conducted in US.
5) Study of AzaSite (Azithromycin) Versus Vigamox in the Conjunctiva of Healthy
Volunteers
ClinicalTrials.gov Identifier: NCT00564447
The study was conducted to evaluate the drug concentrations of AzaSite™ compared to
Vigamox at various time points in conjunctiva tissue of healthy volunteers. This was a phase
4 clinical trial. The drug used for the study was Moxifloxacin and Azithromycin eyedrops.
Moxifloxacin and Azithromycin were used against bacterial infections and eye infections
respectively. 48 healthy participants were selected for the clinical trials. Subjects will instill
the study medication in the study eye as a single drop in a single eye. 48 healthy participants
were divided into 8 different groups of 6 members each. The study medications were instilled
to 8 groups at different time periods (30 min, 2 hours, 12 hours and 24 hours post dose).
Majority of subjects were females. The were obtained by calculating the Conjunctiva
Concentration of Azithromycin and Moxifloxacin. The concentration of Moxifloxacin and
Azithromycin at different time periods (30 min, 2 hours, 12 hours and 24 hours post dose)
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were 1.9 (2.0), 3.8 (9.0), 0.0 (0.0), 0.0 (0.0) and 130.8 (89.1),51.6 (26.0), 67.1 (51.8), 31.9
(20.4) respectively. Some patients were reported with mild adverse events.
Therapeutic Application of Moxi-dexamethasone
1) Efficacy and Tolerability of a Combined Moxifloxacin/Dexamethasone Formulation
for Topical Prophylaxis in Phacoemulsification: An Open-Label
Cataract surgery with intraocular lens (IOL) implantation is the most common ophthalmic
surgical operation. The 0.05 to 0.14% of cataract patients suffer from postoperative
endophthalmitis (POE). Normally ophthalmologists apply topical antibiotic drops to prevent
this. A fixed-combination eye preparation not only helps in cutting costs but also improves
patient compliance due to convenience in dosing and application. The combination
formulation of moxifloxacin 0.5%/dexamethasone 0.1%(vigadexa) is used. Its efficiency and
tolerability in the prevention of postoperative inflammation and infection in predominantly
Asian Patients is studied. With 64 patients 15-day, open-label, and single-arm clinical trial
was conducted at the American Eye Center, Philippines. Adult patients (≥18 years) with a
diagnosis of cataract underwent clear cornea incision phacoemulsification with IOL
implantation. Surgery was performed in only one eye in each patient.no other antimicrobial
drugs should not be taken by the patients. Patients were instructed to instill one drop from a
labeled bottle of moxifloxacin 0.5%/dexamethasone 0.1% (Vigadexa) 4 times a day in the
conjunctival sac of the eye to be operated on beginning from day −1 (1 day before the
surgery) until day 15 (15 days after the surgery).The patients underwent phacoemulsification.
During the screening visit (within 14 days prior to surgery), baseline values of both eyes were
recorded for best-corrected visual acuity (BCVA), and intraocular pressure (IOP) was
measured. Patients were examined for the presence of anterior chamber (AC) cells. Patients
were seen postoperatively on days 1, 3, 8, and 15. At each visit, patients were examined for
signs of infection, inflammation, and ocular pain. An increased inflammatory response was
observed for the first few days after surgery which gradually declined until day 15. The
combination moxifloxacin 0.5%/dexamethasone 1% was as effective in preventing infection
and controlling inflammation postoperatively compared to when its individual components
were administered concurrently. patients did not report any discomfort during or immediately
after its application.
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2) Simultaneous Determination of Moxifloxacin Hydrochloride and Dexamethasone
Sodium Phosphate in Eye Drops by HPLC and Absorbance Correction Method
HPLC , HPTLC, LC-MS , Capillary electrophoresis and UV Spectroscopy method has been
reported for determination of moxifloxacin hydrochloride and dexamethasone sodium
phosphate alone or in combination with other drugs in pharmaceutical formulations and in
human plasma. The aim of this work is to determine both drugs simultaneously by simple,
rapid, and selective HPLC and absorbance correction method which could be used for quality
control and routine analysis. All absorption spectra were recorded with a Shimadzu UV-1700
Pharmaspec, UV-Visible double-beam spectrophotometer with 1 cm quartz cuvettes. The
spectral bandwidth was 0.2 nm. HPLC instrument was equipped with a model series LC-10
AS pump. A Grace smart reversed-phase C18 column was used as the stationary phase. Class
CR10 software was used for data acquisition.Milflox-DM eye drops and Occumox-DM eye
drops were used for analysis. Each eye drops claimed to contain 0.5 % w/v MOXI and 0.1%
w/v DEXP.Calibration graphs for both MOXI and DEXP were obtained by plotting the peak
area against concentration, and the corresponding regression equations were calculated by
HPLC. In absorbance correction method the difference in absorbance between 244.2 nm and
357 nm is due to DEXP and this difference was plotted against DEXP concentration. The
absorbance at 357 nm is due to MOXI only and was plotted against MOXI concentration. The
linearity of the HPLC and absorbance correction methods for the determination of MOXI and
DEXP was evaluated by analyzing a series of different concentrations of each drug. The
developed HPLC and Absorbance correction methods are precise, specific, and accurate.
Statistical analysis proves that the methods are suitable for the analysis of MOXI and DEXP
as a bulk drug and in pharmaceutical formulation without any interference from the
excipients.
Simultaneous determination of dexamethasone and moxifloxacin in pharmaceutical
formulations using stability indicating HPLC method
Moxifloxacin hydrochloride and dexamethasone have been analysed by various techniques
either alone or in combination with other drugs. Attempts were made to develop and validate
simple, precise, and sensitive, isocratic reverse phase stability indicating high performance
liquid chromatographic method for the simultaneous determination of moxifloxacin
hydrochloride and dexamethasone and their stress induced degradation products in
pharmaceutical formulations. Occumox DM and Moxiblu-D eye drops (containing 5 mg per
ml of moxifloxacin and 1 mg per ml of dexamethasone) were used for method applications.
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The HPLC system consisting of Shimadzu LC-20A system is equipped with model LC-20AT
pump,The mobile phase was consisting of methanol and 20 mM phosphate buffer. Flow rate
of the mobile phase was 1.5 mL min1 and all chromatographic experiments were performed
at room Temperature. Due to high carbon content and hydrophobic character of moxifloxacin
hydrochloride and dexamethasone these drugs can be separated through C8 or C18 stationary
phases. The variations in the composition of the mobile phase and dissimilar stationary
phases had substantial influences on peak shape, tailing factor, retention factor, theoretical
plates and resolution.Under the mentioned chromatographic conditions highly symmetrical
and sharp peaks of moxifloxacin hydrochloride and dexamethasone were obtained at
retention times of 3.372, and 6.503 min, respectively.The developed method was validated
by testing its linearity, accuracy, precision, specificity, limits of detection and quantitation. It
is also clear from the chromatograms that both the active ingredient peaks in all the stress
conditions were free from any sort of degradation impurities. All these convince us to
conclude that the method can be successfully used for any sort of stability and validation
studies.
Endophthalmitis following cataract surgery and intracameral antibiotic: Moxifloxacin
resistant Staphylococcus epidermidis
Endophthalmitis is a rare but potentially sight-devastating complication after cataract surgery,
estimated to affect between 0.012% and 0.2% of patients. A 76- year old female with a past
medical history of quiescent birdshot chorioretinitis (BSCR) and rheumatoid arthritis (RA)
was referred for cataract surgery, the patient underwent uneventful clear corneal
phacoemulsification with insertion of a posterior chamber intraocular lens (PCIOL) for the
right eye. Moxifloxacin was injected intracamerally at the end of the case. The patient
reported decreased vision and new onset floaters.Cultures of the vitreous aspirate grew
Staphylococcus epidermidis, resistant to moxifloxacin. The inflammation resolved over two
months. Eight months later, the patient underwent uncomplicated cataract surgery in the left
eye. Intracameral antibiotics were not used, however her systemic immunosuppressive
therapy was held for several weeks perioperatively. One year after the initial surgeries, the
patient had an uncorrected visual acuity of 20/20 in each eye. The use of IC moxifloxacin has
been reported to reduce the rate of acute-onset postoperative endophthalmitis in many series.
However, endophthalmitis may still occur with its use. Adequate concentrations of IC
antibiotics need to be achieved in order to exceed MIC values of the targeted pathogen. Other
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preventive methods (such as strict aseptic measures) remain important in reducing the
incidence of this devasting complication.
Latrogenic Cushing’s Syndrome Following Short-Term Intranasal Steroid Use
Development of iatrogenic Cushing‟s syndrome (CS) due to oral steroid use is common.
Some features of CS like increased intraocular pressure, cataract, benign intracranial
hypertension, aseptic necrosis of the femoral head, osteoporosis, and pancreatitis are more
frequently observed after exogenous steroid exposure. CS following use of ocular
administration of steroids (eye drops) has not been reported. A 6-year-old girl was referred to
our endocrinology clinic for evaluation. Her height was 102 cm, weight 18kg, and body mass
index was 17.3kg/m2 found that the child was prescribed combined moxifloxacin-
dexamethasone eye drops (Milflox-DM eye drops, Unimed, India) by her family physician, to
be applied intranasally for epistaxis. She has finished 6 bottles in 3 months. The steroid drop
administration was stopped; hydrocortisone was started in a dose of 15mg/day. When the
patient was evaluated 1 month after the initial diagnosis, it was observed that a significant
decrease in the facial puffiness had occurred. Her use of 2 bottles per month is equivalent to
20 mg of dexamethasone per month which is around 0.7mg of dexamethasone per day, which
is high for a 6-year-old girl. Moxifloxacin does not inhibit or stimulate the hepatic
microsomal P450 system and hence has no effect on steroid metabolism. Since drops were
used instead of nasal spray, it is likely that a significant amount would be swallowed and
absorbed from the gastrointestinal tract, resulting in CS. The purpose of this research article
was to highlight the occurrence of CS even with steroid eye drop preparations, some of which
can contain high concentrations of steroids. Steroids with a high potency, such as
dexamethasone, increase the risk of developing CS.
Efficacy and tolerability of a combined moxifloxacin/dexamethasone formulation for
topical prophylaxis and reduction of inflammation in phacoemulsification: a
comparative, double masked clinical trial
The incidence of acute postoperative endophthalmitis among cataract patients in the
developed world ranges from 0.04% to 0.099%. Most surgeons prescribe topical antibiotics
immediately following surgery and for the next 10–14 days, when microbial colonization is
most likely to occur.
The scientist evaluated the clinical usefulness of a new single-vehicle, fixed-dose
combination antibiotic/ corticosteroid formulation, Vigadexa*, consisting of 0.5%
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moxifloxacin (Vigamox*) and 0.1% dexamethasone (Maxidex*). Phacoemulsification and
intraocular lens (IOL) implantation was performed in 139 patients with cataracts. Each
patient had surgery in only one eye. The first group comprised 64 eyes that received the
combination moxifloxacin/dexamethasone eye drops and a dextran/ methylcellulose placebo
(Lacrima Plus†). The second group comprised 62 eyes that were treated with 0.5%
moxifloxacin and 0.1% dexamethasone eye drops in the conventional manner. Patients were
asked to subjectively rank their eye pain on a five-point scale, from 0 = none to 5 = severe.
Any sign of active ocular inflammation – redness, edema, tearing, or discharge – was
documented, and slit-lamp examination produced information regarding structural changes in
the cornea and conjunctiva. A Goldmann applanation tonometer was used to measure the
intraocular pressure. Physicians rated bacterial infection to be absent in both groups on days
1, 3, 8, and 15. The efficacy of the study medication was assessed by comparing the two
treatment groups for signs of Inflammation, including hyperemia or edema of the lids or
conjunctiva, ocular discharge, structural changes of the cornea, photophobia, and excessive
tearing. With regard to the safety parameters of visual acuity, ocular pain, and intraocular
pressure, eyes that received the combined moxifloxacin/dexamethasone eye drops had
virtually identical to those dosed conventionally with moxifloxacin and dexamethasone from
separate bottles. scientist believe that cataract patients will find the single-vehicle, fixed-dose
moxifloxacin/dexamethasone eye drops easier to use and will enjoy the benefits of single-
bottle drop application.In this study population of cataract patients, the single vehicle, fixed-
dose combination of 0.5% moxifloxacin and 0.1% dexamethasone eye drops was found to be
as well tolerated as, and therapeutically equivalent to, conventional, separate dosing with
0.5% moxifloxacin and 0.1% dexamethasone.
7)Efficacy and tolerability of a fixed-dose moxifloxacin – dexamethasone formulation
for topical prophylaxis in LASIK: a comparative, double-masked clinical trial
Laser-assisted in situ keratomileusis (LASIK) is the most popular operation for refractive
correction. LASIK patients are usually prescribed antibiotic and steroid eye drops for the first
5–14 days after surgery to prevent infection and minimize inflammation, Alcon Laboratories,
Inc. has developed a new antibiotic–steroid formulation consisting of 0.5% moxifloxacin and
0.1% dexamethasone (MFLX/DEX). A total of 64 consecutive patients who presented for
LASIK correction were randomly assigned to receive either the fixed-dose combination of
MFLX/DEX formulation or the separate bottles of moxifloxacin and dexamethasone. Patients
who were receiving a topical prostaglandin for IOP control were instructed to discontinue its
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use at least 4 days prior to surgery and until the study was completed. All surgical candidates
were told to stop wearing contact lenses for at least 2 weeks before the LASIK procedure.All
patients were instructed to apply 1 drop from each bottle in both eyes 4 times a day. Two
days before surgery the baseline values were recorded for visual acuity (VA), IOP, number of
cells in the anterior chamber, clinical impression of inflammation of eyelids and conjunctiva,
ocular pain, burning or itching sensation, and fundus status. These assessments were repeated
on the fi rst day after surgery (Day 1) and thereafter on days 3, 8, and 15. With regard to eye
pain, no statistically significant differences were observed between the MFLX/DEX
combined and the moxifloxacin and dexamethasone separate groups. The present study
evaluated a fixed-dose combination product of moxifloxacin and dexamethasone in patients
undergoing LASIK. From an economical standpoint, the combination product reduces
medication cost since patients only need to purchase a single bottle of medication instead of
two separate bottles. A fixed-dose formulation of moxifloxacin and dexamethasone was
found to be safe and effective in preventing infection and controlling inflammation post-
LASIK
8)Management of traumatic proptosis in a pug: A case study
Proptosis is forward displacement of globe which occur secondary to any blunt trauma to
head . Proptosis typically occurs in dogs following trauma to the face or head. During trauma,
the globe is luxated from the orbit, and eyelid spasms prevent its retraction. Secondary orbital
hemorrhage and swelling displace the globe further from the orbit following corneo-
conjunctival drying and malacia. Only 20-40% of dogs that have the reattachment of the
eyeball regain their vision. A three year old male pug of 10 kg weight was presented with
unilateral traumatic proptosis having recent history of blunt head trauma by hitting head
against the wall .Clinical examination revealed partial prolapse of right eye globe through the
pulpebral fissure with severe periorbital edema, haemorrhage without fracture of skull. Early
presentation for early treatment reduce inflammation and edema. Treatments of proptosis
depend upon the type, duration of trauma and damage to globe. Treatment was started using
triflupromazine at 4mg/kg body weight. The protruded eye ball was cleaned with sterile pads
soaked in normal saline to remove dirt and debrise, followed by intrapalpebral injection of
gentamicine and dexamethasone. Pug was given eye drop of moxifloxacine and
dexamethasone 4times a day for instillation. Animal recovered successfully after 7days of
regular treatment. Therapeutic management was successful with high prognosis for proptosed
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globe. Vision was normal in treated pug as assessed after 15 days of recovery by simple
vision testing using junction box.
9)Safety and Efficacy of Moxifloxacin-Dexamethasone Eyedrops as Treatment for
Bacterial Ocular Infection Associated with Bacterial Blepharitis
Fourth generation fluoroquinolones have a broad spectrum of activity against Gram-positive
bacteria, and are considered appropriate choices for treating an ocular infection caused by an
unknown organism with unknown resistance. A single preparation combining moxifloxacin
plus dexamethasone could reduce treatment burden and improve patient compliance relative
to the independent dosing of an antibiotic and steroid for the treatment of blepharitis. The
purpose of this study was to evaluate the efficacy and safety of a fixed combination of
moxifloxacin 0.5%/dexamethasone 0.1% eye drops in the treatment of bacterial ocular
inflammation and infection (blepharitis) compared with the concomitant administration of
moxifloxacin 0.5% and dexamethasone, 0.1% eye drops from individual bottles. Subjects 18
years and older diagnosed with bacterial blepharitis were recruited from the Ophthalmology
Department from Brazil. The fixed-dose group received a fixed combination of moxifloxacin
0.5%/ dexamethasone 0.1% ophthalmic solution the concomitant group received
moxifloxacin 0.5% ophthalmic solution (bottle A) and dexamethasone 0.1% ophthalmic
solution (bottle B).Intraocular pressure (IOP) was measured in both eyes with a Goldmann
applanation tonometer. A specimen for microbiological analysis was collected using a sterile
disposable collection and transportation system from the affected eye Samples were cultured
onto 5% blood (sheep) agar and chocolate agar as well as into tryptic soy broth (TSB) for 48
hours. All eyes had blepharitis. The treatment groups had similar demographics and baseline
characteristics. This clinical study evaluated the efficacy and safety of a fixed combination of
moxifloxacin 0.5%/dexamethasone 0.1% eye drops in the treatment of bacterial ocular
inflammation and infection compared with concomitant administration of moxifloxacin 0.5%
and dexamethasone, 0.1% eye drops from individual bottles. The fixed-combination
treatment was as effective clinically as moxifloxacin, 0.5% and dexamethasone, 0.1% used
concomitantly in treatment of ocular infection and inflammation associated with bacterial
blepharitis.
This clinical trial was to demonstrate that the combination formulation of
Moxifloxacin/Dexamethasone Eye Drop is effective and safe for the prevention of
postoperative inflammation as a consequence of cataract extraction surgery. This was a phase
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Parvathi Rachita and Silpa. World Journal of Pharmacy and Pharmaceutical Sciences
4 trial. The drug used was Vigadexa (moxifloxacin 0.5% and dexamethasone 0.1%) eye
drops. 64 patients were selected from September 2008 to February 2009 but only 60 of them
completed the trial. Vigadexa was instructed to apply one drop for 6 hours. All patients were
adults. 43 patients were above 64 age group. 37 patients were female and the rest were males.
Anterior chamber inflammation was evaluated based on the number of cells per high-power
field measured using the narrowest slit beam of the lamp (0.5 at a height of 8mm). Anterior
chamber cells was recorded on a 0-4 point scale,0 = Less than 5 cells; 1 = Mild: 5-10 cells; 2
= Moderate:11-20 cells; 3 = Marked: 21-50 cells; 4 = Severe: Greater than 50 cells /
hypopyon. 91.7% patients anterior chamber inflammation rate was scale 0. After surgery for
15 days no ocular pain was observed in 96.7% patients. Serious adverse event wasn‟t
observed in any of the patients. This clinical trial was conducted in America
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