Comparison of the safety and efficacy of loteprednol 0.5%/tobramycin 0.3% withdexamethasone 0.1%/tobramycin0.3% in the treatment of blepharokeratoconjunctivitis

ABSTRACT

Objective: This study compared the safety and efficacy of loteprednol etabonate 0.5%/tobramycin 0.3% (LE/T; Zylet) with dexamethasone 0.1%/tobramycin 0.3% (DM/T; Tobradex) in the treatment of ocular inflammation associated with blepharokeratoconjunctivitis.

Research design and methods: This was a multicenter, randomized, investigator-masked, parallel-group study. Subjects with clinically diagnosed blepharokeratoconjunctivitis in at least one eye were randomized to LE/T (n?=?138) or DM/T (n?=?138) administered four times per day, for 14 days. The primary efficacy endpoint was the change from baseline to Day 15 (± 1?day) in the signs and symptoms composite score using a non-inferiority metric to compare LE/T to DM/T. Safety endpoints included visual acuity (VA), biomicroscopy, intraocular pressure (IOP) assessments, and adverse events.

Results: At Day 15, the mean (SD) change from baseline in the signs and symptoms composite score was ?15.2 (7.3) for LE/T-treated subjects and ?15.6 (7.7) for DM/T-treated subjects. The upper bound of the 90% confidence interval for the difference in change from baseline was less than the non-inferiority margin not only at Day 15 but also at Day 7 and Day 3 for both the intent-to-treat and per protocol populations. Subjects treated with DM/T experienced a significant increase in IOP versus those treated with LE/T at Day 7, Day 15, and overall (mean [SD] of 0.6 [2.3] vs, ?0.1 [2.2], p?=?0.03, 1.0 [3.0] vs. ?0.1 [2.4], p?=?0.01, and 2.3 [2.3] vs. 1.6 [1.7], p?=?0.02, respectively).

Conclusions: LE/T satisfied the condition of non-inferiority to DM/T in decreasing the signs and symptoms of ocular inflammation associated with blepharokeratoconjunctivitis. Subjects treated with DM/T experienced more of an increase in IOP.

Limitation: Although the single-masked design of this study could be considered a limitation, care was taken to ensure that the investigator was masked.     

A multicenter,randomized, parallel-group,clinical trial comparing the safety and efficacy of loteprednol etabonate 0.5%/tobramycin 0.3% with dexamethasone 0.1%/tobramycin 0.3% in the treatment of Chinese patients with blepharokeratoconjunctivitis

Abstract

Objective:

To compare the efficacy and safety of loteprednol etabonate 0.5%/tobramycin 0.3% (LE/T) and dexamethasone 0.1%/tobramycin 0.3% (DM/T) ophthalmic suspensions in a Chinese population with ocular inflammation associated with blepharokeratoconjunctivitis (BKC).     

Evaluation of clinical efficacy and safety of tobramycin/dexamethasone ophthalmic suspension 0.3%/0.05% compared to azithromycin ophthalmic solution 1% in the treatment of moderate to severe acute blepharitis/blepharoconjunctivitis

Abstract

Objective:

To evaluate the clinical efficacy and safety of tobramycin/dexamethasone (TobraDex ST^*; ‘ST’) ophthalmic suspension 0.3%/0.05% compared to azithromycin (Azasite^?) ophthalmic solution (1%) in the treatment of moderate to severe blepharitis/blepharoconjunctivitis.     

Ciprofloxacin 0.3%/dexamethasone 0.1% topical drops for the management of otic infections

The American Academy of Otolaryngology – Head and Neck Surgery has recommended that, where possible, infections of the external auditory canal and middle ear be treated with topical preparations. The advantages of topical therapy include i) excellent efficacy; ii) decreased risk of systemic side effects; iii) less likelihood of selecting for resistant strains of microorganisms; and iv) lack of potential for ototoxicity. One advantage of topical therapy arises as a consequence of a very high concentration of antibiotic in topical preparations reaching the site of infection. Ciprofloxacin 0.3%/dexamethasone 0.1% (Ciprodex^®) is the only ototopical drop approved for use in both the middle ear and external auditory canal that combines a fluoroquinolone with a steroid. At 0.3% (3000 mcg/ml), the ciprofloxacin concentration of Ciprodex exceeds the MIC of virtually all relevant organisms by a very considerable margin. The clinical efficacy of ciprofloxacin/dexamethasone suspension has been demonstrated in several large prospective clinical trials. It has been consistently equal to or superior to comparator drugs. The authors believe that the use of topical ciprofloxacin/dexamethasone will increase as the advantages of fluoroquinolone/steroid combination therapy become more widely recognized.     

Tolerability and safety of 0.1% diclofenac plus 0.3% tobramycin fixed-dose ophthalmic solution: a randomized, comparative, controlled study in healthy volunteers.

The purpose of this double-blind, observer-masked, randomized, crossover trial was to compare the tolerability and safety of a fixed-dose ophthalmic solution of 0.3% tobramycin plus 0.1% diclofenac versus Tobrex (tobramycin sulfate ophth) and Voltaren (diclofenac sodium). Control treatments included a saline solution and a control solution of 0.3% tobramycin prepared by Alcon Cusí. Ten healthy volunteers received three consecutive instillations of 1 drop of a given ophthalmic solution at 08:00, 11:00 and 14:00 h to the same eye; after a washout period of 18 h, the next ophthalmic solution was tested according to a randomized sequence. Occurrence, intensity, and duration of ocular irritation and conjunctival hyperemia at baseline and after the three instillations were recorded. Slit lamp biomicroscopy examination, measurement of intraocular pressure (IOP) changes, visual acuity, and examination of the fundus of the eye were performed after each third instillation by an ophthalmologist. Side effect incidence and patient and investigator opinions were also recorded. Results showed that Voltaren instillation induced statistically significant ocular irritation (p = 0.0077); the remaining ophthalmic solutions tested caused no ocular irritation (Physiological Saline Braun, p = 0.9808; Tobrex, p = 0.8826; control 0.3% tobramycin solution, p = 0.8327; and 0.1% diclofenac plus 0.3% tobramycin, p = 0.5399). None of the ophthalmic solutions tested caused severe conjunctival hyperemia. Analysis of the sum of conjunctival parameters of both eyes for all ophthalmic solutions studied showed no statistically significant differences (p = 0.4688). Moderate superficial punctate keratitis was observed after instillation of Voltaren and of 0.1% diclofenac plus 0.3% tobramycin (1 subject each) that spontaneously resolved within 2 days. Slit lamp biomicroscopy, visual acuity and IOP values showed no statistically significant changes. No systemic side effects related to the study treatments were recorded. In conclusion, the ophthalmic solution containing 0.1% diclofenac plus 0.3% tobramycin was well tolerated under the study conditions. Its tolerability was equivalent to that of Braun physiological saline, Tobrex and a control 0.3% tobramycin solution and was better than that of Voltaren.     

Sun protection strength of a hydroquinone 4%/retinol 0.3% preparation containing sunscreens

BACKGROUND: Dyschromias are common and significantly impact patients' quality of life. Formulas containing hydroquinone 4% are effective in these conditions. Since exposure to ultraviolet radiation (UVR) can worsen disease and complicate treatment, the incorporation of sunscreens can avert this problem. METHODS: We tested the sun protection factor of a hydroquinone formulation (Lustra-Ultra, TaroPharma, Hawthorne, NY) containing avobenzone 3%, and octinoxate 7.5% according to the FDA Sunscreen Monograph on 20 volunteer subjects. We also determined the UVR absorbance spectrum of the preparation. RESULTS: The mean sun protection factor (SPF) of 21.7 satisfied labeling requirements for SPF 20. The formulation exhibited strongest photoprotection near the wavelengths of peak sun burning effectiveness in the UVB region and maintains significant UVR absorbance through the entire UVA region. CONCLUSIONS: Avobenzone 3% and octinoxate 7.5% provide broad spectrum UV protection. Incorporating these sunscreens into a hydroquinone preparation simplifies the treatment regimen while providing significant photoprotection for patients being treated for dyschromia.     

Ciprofloxacin 0.3% + dexamethasone 0.1% for the treatment for otitis media

Introduction: Ciprofloxacin 0.3% with dexamethasone 0.1% (ciprofloxacin/dexamethasone) is an ototopical preparation for acute otitis externa, otorrhea with tympanostomy tubes, and is frequently used to treat chronic suppurative otitis media (CSOM). The advantage of topical therapy is the ability to deliver higher concentration of antibiotics to the treatment site when compared with oral or parenteral antibiotics. The delivery of a high concentration of antibiotics significantly decreases treatment failure and makes the development of resistant organisms unlikely. Previous ototopical preparations contained antibiotics such as aminoglycosides that are known to be ototoxic making treatment of otic infections without an intact tympanic membrane difficulty.

Areas covered: A literature search of PubMed was performed as the basis for a literature-based discussion on the clinical efficacy of ciprofloxacin/dexamethasone compared to oral antibiotics and ototopical therapy without a steroid component. The potential ototoxicity of ototopical therapies is discussed, including evidence demonstrating the lack of ototoxicity of fluoroquinolone and dexamethasone containing drops.

Expert opinion: Because multiple studies have demonstrated that fluoroquinolones are not ototoxic, fluoroquinolone ototopical drops should be a first-line treatment for otorrhea without an intact membrane. The addition of dexamethasone 0.1% to ciprofloxacin 0.3% has been shown to decrease granulation tissue, improve clinical cure and achieve greater rates of bacterial eradication when compared to ciprofloxacin 0.3% alone.     

A comparison of the fourth-generation fluoroquinolones gatifloxacin 0.3% and moxifloxacin 0.5% in terms of ocular tolerability

SUMMARY

Purpose: To compare the ocular tolerability of the commercially available ophthalmic solutions of the fourth-generation fluoroquinolones, gatifloxacin 0.3% (Zymart, Allergan, Inc., Irvine, CA) with benzalkonium chloride (BAK) and moxifloxacin 0.5% (Vigamoxt) without BAK.

Methods: A baseline evaluation was conducted on 30 healthy volunteers for conjunctival hyperemia, conjunctival vascularity, pupil size, and anterior chamber (AC) cell and flare. Pupils were measured under scotopic conditions with a Colvard pupillometer. Conjunctival hyperemia and vascularity, and AC reaction were measured on a Likert-like scale of 0-3. Subjects then received drops in both eyes from masked bottles of gatifloxacin ophthalmic solution 0.3% with BAK (in one eye determined randomly) and moxifloxacin ophthalmic solution 0.5% without BAK (in the contralateral eye) in a double-masked fashion. Subjects graded pain and ocular irritation in each eye on a scale of 1-10 after 5min with their eyes closed. The examination was then repeated.

Results: The average age of this study population was 34.4years. The groups of eyes receiving moxifloxacin 0.5% demonstrated an increase in mean conjunctival hyperemia (0.21 [range: 0-1] at baseline to 1.52 [range: 0-3] at 5min.)

that was significantly greater (p?=?0.0005) compared with that of the group receiving gatifloxacin 0.3% (0.22 [range: 0-1] at baseline to 0.45 [range: 0-2] at 5min). The group receiving moxifloxacin 0.5% showed an increase in conjunctival vascularity (0.55 [range: 0-1] at baseline to 1.61 [range: 0.5-3] at 5?min.) that was significantly greater (p?=?0.0005) compared with that of the group receiving gatifloxacin 0.3% (0.52 [range: 0-1] at baseline to 0.68 [range: 0-2] at 5?min.). Significantly less pain (1.2 vs. 3.2, p?=?0.001) and irritation (0.64 vs. 3.42, p?=?0.001) occurred with gatifloxacin 0.3% than with moxifloxacin 0.5%. Pupil size was significantly reduced (5.65mm-5.05mm) in eyes receiving moxifloxacin 0.5% (p?=?0.004) and no significant change occurred in pupil size (5.60mm-5.65mm) in eyes that received gatifloxacin 0.3% (p?=?0.878). No AC reaction was noted with either medication.

Conclusions: The group of eyes receiving gatifloxacin 0.3% with BAK demonstrated greater ocular tolerability in comparison to the group receiving moxifloxacin 0.5% without BAK. Moxifloxacin-induced pupillary miosis may be due to prostaglandin release in the anterior chamber. A limitation of this study is the relatively young age of the study population.     

A comparison of the fourth-generation fluoroquinolones gatifloxacin 0.3% and moxifloxacin 0.5% in terms of ocular tolerability

PURPOSE: To compare the ocular tolerability of the commercially available ophthalmic solutions of the fourth-generation fluoroquinolones, gatifloxacin 0.3% (Zymar, Allergan, Inc., Irvine, CA) with benzalkonium chloride (BAK) and moxifloxacin 0.5% (Vigamox) without BAK. METHODS: A baseline evaluation was conducted on 30 healthy volunteers for conjunctival hyperemia, conjunctival vascularity, pupil size, and anterior chamber (AC) cell and flare. Pupils were measured under scotopic conditions with a Colvard pupillometer. Conjunctival hyperemia and vascularity, and AC reaction were measured on a Likert-like scale of 0-3. Subjects then received drops in both eyes from masked bottles of gatifloxacin ophthalmic solution 0.3% with BAK (in one eye determined randomly) and moxifloxacin ophthalmic solution 0.5% without BAK (in the contralateral eye) in a double-masked fashion. Subjects graded pain and ocular irritation in each eye on a scale of 1-10 after 5 min with their eyes closed. The examination was then repeated. RESULTS: The average age of this study population was 34.4 years. The groups of eyes receiving moxifloxacin 0.5% demonstrated an increase in mean conjunctival hyperemia (0.21 [range: 0-1] at baseline to 1.52 [range: 0-3] at 5 min.) that was significantly greater (p = 0.0005) compared with that of the group receiving gatifloxacin 0.3% (0.22 [range: 0-1] at baseline to 0.45 [range: 0-2] at 5 min). The group receiving moxifloxacin 0.5% showed an increase in conjunctival vascularity (0.55 [range: 0-1] at baseline to 1.61 [range: 0.5-3] at 5 min.) that was significantly greater (p = 0.0005) compared with that of the group receiving gatifloxacin 0.3% (0.52 [range: 0-1] at baseline to 0.68 [range: 0-2] at 5 min.). Significantly less pain (1.2 vs. 3.2, p = 0.001) and irritation (0.64 vs. 3.42, p = 0.001) occurred with gatifloxacin 0.3% than with moxifloxacin 0.5%. Pupil size was significantly reduced (5.65 mm-5.05 mm) in eyes receiving moxifloxacin 0.5% (p = 0.004) and no significant change occurred in pupil size (5.60 mm-5.65 mm) in eyes that received gatifloxacin 0.3% (p = 0.878). No AC reaction was noted with either medication. CONCLUSIONS: The group of eyes receiving gatifloxacin 0.3% with BAK demonstrated greater ocular tolerability in comparison to the group receiving moxifloxacin 0.5% without BAK. Moxifloxacin-induced pupillary miosis may be due to prostaglandin release in the anterior chamber. A limitation of this study is the relatively young age of the study population.     

Tolerability comparison of adapalene gel, 0.3% versus tazarotene cream, 0.05% in subjects with healthy skin

BACKGROUND: Topical retinoids, including adapalene and tazarotene, are a primary treatment choice for patients with acne. Adapalene is currently marketed in a 0.1% concentration in gel and cream formulation. A new gel containing a higher concentration (0.3%) of adapalene has been developed. In clinical studies, adapalene 0.1% concentration has proven to be better tolerated than other retinoids in skin treatment. However, the tolerability of adapalene gel 0.3% has yet to be compared to other topical retinoids. PURPOSE: The purpose of this study was to compare the local cutaneous tolerability of adapalene gel 0.3% once daily versus tazarotene cream 0.05% once daily. METHODS: Subjects reported to the investigative site each day Monday through Friday, cleansed the faced and then applied adapalene 0.3% gel to one side of the face and tazarotene 0.05% cream to the other in the presence of study personnel. For the weekends, subjects were instructed to apply the treatment at home according to the same procedure. Tolerability was assessed during each weekday visit. The study lasted for 3 weeks. RESULTS: Tolerability results for adapalene 0.3% gel and tazarotene 0.05% cream were statistically similar throughout the study. Investigator-assessed overall tolerability was in favor of adapalene at days 19 and 22 (P=.043). A cosmetic acceptability survey also showed results were better for adapalene 0.3% gel. CONCLUSION: Adapalene gel 0.3% is very well-tolerated with good cosmetic acceptability.     

微生物比浊法测定妥布霉素、硫酸妥布霉素注射液及妥布霉素滴眼液的效价

目的：建立妥布霉素、硫酸妥布霉素注射液及妥布霉素滴眼液效价的微生物比浊法。方法：分别采用微生物比浊法和管碟法对妥布霉素、硫酸妥布霉素注射液及妥布霉素滴眼液的含量进行测定和比较研究。结果：妥布霉素效价测定的线性范围为0.4~1.0 U/ml;R2=0.991 3,硫酸妥布霉素注射液平均回收率为100.2%,RSD为2.6%（n=9）;妥布霉素滴眼液平均回收率为99.6%,RSD为1.5%（n=9）。结论：微生物比浊法具有简便、精确、快速的特点,可应用于产品的控制。     

The ocular penetration of levofloxacin 1.5% and gatifloxacin 0.3% ophthalmic solutions in subjects undergoing corneal transplant surgery

ABSTRACT

Objective: To compare corneal tissue and aqueous humor concentrations of levofloxacin 1.5% and gatifloxacin 0.3% ophthalmic solutions after topical dosing.

Research design and methods: This was a randomized, observer-masked, parallel-group, multicenter study. Fifty-nine subjects undergoing planned penetrating keratoplasty were randomly assigned to receive either levofloxacin 1.5% or gatifloxacin 0.3% as follows: one drop 15?min prior to surgery and a second drop 10?min before surgery. Corneal button and aqueous humor samples were collected during surgery and immediately stored at –70?°C. Levofloxacin and gatifloxacin concentrations were determined by high-pressure liquid chromatography and mass spectrometry.

Main outcome measures: Corneal tissue and aqueous humor concentrations of levofloxacin and gatifloxacin.

Results: Levofloxacin achieved statistically significantly higher concentrations in both corneal tissue and aqueous humor compared to gatifloxacin in patients undergoing penetrating keratoplasty. In corneal tissue the mean concentration of levofloxacin was 64.8 ± 123.4?µg/g vs. 7.0 ± 9.3?µg/g for gatifloxacin (p < 0.0001). Mean aqueous humor concentration of levofloxacin was 0.976 ± 2.215?µg/mL vs. 0.0523 ± 0.143?µg/mL for gatifloxacin (p = 0.0002).

Conclusions: The high concentrations of levofloxacin achievable in corneal tissue with topical dosing suggest that levofloxacin 1.5% should be a useful agent in the treatment of ocular bacterial infections. However, the corneal concentrations achieved in this study may not be representative of concentrations in patients using less frequent dosing.     

The effect of gatifloxacin 0.3% or moxifloxacin 0.5% on corneal healing,ocular tolerability and toxicity following pterygium surgery

Purpose: To compare the rate of corneal epithelial healing and ocular tolerability following pterygium surgery between gatifloxacin and moxifloxacin.

Methods: In this double masked, prospective, controlled study 40 patients were randomized to receive prophylactic topical gatifloxacin 0.3% or moxifloxacin 0.5% following pterygium surgery. Patients were examined on days 1, 3, 7 and 21 post-operatively or until complete corneal epithelial healing. The primary outcome measure was the area of corneal epithelial defect during the post-operative period. Patients graded post-operative ocular pain, foreign body sensation, tearing, general burning sensation and burning sensation post-antibiotic drops instillation on a scale of 1–5. Conjunctival hyperemia and superficial punctate keratopathy (SPK) were measured on a scale of 0–3.

Results: No significant differences between groups were found in terms of corneal epithelial defect percentage over time (p?=?0.989) and there was no significant difference between groups on each of the post-operative days. No significant differences were noted in terms of post-operative ocular pain, foreign body sensation, tearing, general burning sensation, burning sensation post-antibiotic drops instillation, conjunctival hyperemia and SPK.

Conclusions: Gatifloxacin and moxifloxacin showed equivalent results in terms of corneal epithelial healing and ocular tolerability following pterygium surgery. This study suggests that there was no apparent added epithelial toxicity due to the presence of benzalkonium chloride in the gatifloxacin preparation when compared to moxifloxacin.     

Ocular penetration of moxifloxacin 0.5% and gatifloxacin 0.3% ophthalmic solutions into the aqueous humor following topical administration prior to routine cataract surgery

A prospective, double-masked, randomized, parallel-group study (n = 25) was conducted to examine the ocular penetration of moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3% solution into the aqueous humor following topical administration prior to routine cataract surgery. One drop of antibiotic was instilled every 10 min for four doses beginning 1 h prior to surgery. Preliminary results showed aqueous humor concentrations for moxifloxacin that were significantly greater (p < 0.01) than those for gatifloxacin.     

Ocular penetration of moxifloxacin 0.5% and gatifloxacin 0.3% ophthalmic solutions into the aqueous humor following topical administration prior to routine cataract surgery

ABSTRACT

A prospective, double-masked, randomized, parallel-group study (n = 25) was conducted to examine the ocular penetration of moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3% solution into the aqueous humor following topical administration prior to routine cataract surgery. One drop of antibiotic was instilled every 10?min for four doses beginning 1?h prior to surgery. Preliminary results showed aqueous humor concentrations for moxifloxacin that were significantly greater (?p < 0.01) than those for gatifloxacin.