Comparing the Efficacy of Ophthalmic NSAIDs in Common Indications: A Literature Review to Support Cost-effective Prescribing.

OBJECTIVE: To review the commercially available ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs), identify opportunities for therapeutic substitutions within and outside of their Food and Drug Administration (FDA)-approved indications, and identify clinically superior drugs within the class for specific indications. DATA SOURCE: A PubMed search (1992 through January 2014) was performed on the terms diclofenac, ketorolac, flurbiprofen, bromfenac, and nepafenac. STUDY SELECTION AND DATA EXTRACTION: Clinical trials, meta-analyses, and review articles were evaluated if they were written in English and pertained to human subjects. Studies were excluded if they were in vitro studies, solely evaluated pharmacokinetic or pharmacodynamic properties, did not relate to the topical ophthalmic route, did not evaluate the FDA-approved indications of any available ophthalmic NSAID, or compared a reviewed drug with a nonreviewed drug (without placebo comparison). DATA SYNTHESIS: A total of 67 articles met the criteria for evaluation. Article quality, study design, and dosing of the medications were assessed to determine the clinical applicability of the results. The quality of the article was determined using the Oxford Centre for Evidence-based Medicine Levels of Evidence 1. CONCLUSIONS: Many formulations of the 5 reviewed NSAIDs have been studied across the 4 primary indications. These indications are (1) pain and inflammation associated with cataract surgery, (2) pain associated with corneal refractive surgery, (3) inhibition of intraoperative miosis, and (4) seasonal allergic conjunctivitis. Several studies have directly compared drugs within this class and have identified instances in which certain selections are therapeutically superior or equivalent to another. This information provides practitioners with guidance in selecting an optimal medication.

Ranibizumab: the first vascular endothelial growth factor inhibitor approved for the treatment of diabetic macular edema.

OBJECTIVE: To review the pharmacology, efficacy, and safety data available for ranibizumab and compare the drug to other therapeutic options for diabetic macular edema (DME) to determine its likely role in therapy. DATA SOURCES: A PubMed search was initially used to identify all trials pertaining to the use of ranibizumab for DME. This search was conducted in February 2013 without a time frame for exclusion of older trials (all references included were published between January 1987 and February 2013). Following a review of the references of these articles, additional sources were obtained from PubMed, the manufacturer's website, and clinicaltrials.gov. STUDY SELECTION AND DATA EXTRACTION: Trials conducted in animals and those written in a language other than English were excluded. Abstracts of remaining trials were reviewed for determination of relevance to this review. Preference was given to randomized controlled trials. Additional information sources were obtained from a review of references as deemed necessary by the authors. DATA SYNTHESIS: Six Phase 2 or 3 randomized controlled trials studying the effects of ranibizumab in patients with DME were identified. Within these trials, ranibizumab consistently produced significantly greater gains in mean best corrected visual acuity than focal/grid laser photocoagulation or sham (7.4-12.5 letter improvement with ranibizumab vs 0.5-3 letters following focal/grid laser photocoagulation monotherapy) with a favorable safety and tolerability profile. Ranibizumab was also studied in combination with focal/grid laser photocoagulation, showing no additional gains in vision versus ranibizumab monotherapy. CONCLUSIONS: The identified trials provide support for the safety and efficacy of ranibizumab in the treatment of vision loss due to DME and present a strong case for the shift to first-line treatment with vascular endothelial growth factor inhibitors from focal/grid laser photocoagulation, the standard of care since the Early Treatment Diabetic Retinopathy Study of 1985.

Aflibercept: newly approved for the treatment of macular edema following central retinal vein occlusion.

OBJECTIVE: To review the pharmacology, efficacy, and safety data available for aflibercept and compare the drug to other therapeutic options for treatment of macular edema following central retinal vein occlusion (CRVO) to determine its likely role in therapy. DATA SOURCES: A PubMed search using the terms aflibercept and VEGF trap-eye was conducted to identify initial literature sources. No timeframe was used for exclusion of older trials. All trials referenced were published between January 1995 and December 2012. STUDY SELECTION AND DATA EXTRACTION: Trials pertaining to oncologic use were excluded, as were studies conducted in animals and those written in a language other than English. Abstracts of the remaining trials were evaluated for determination of relevance to this review. Additional information sources were obtained via Internet and PubMed following a review of references. DATA SYNTHESIS: While previous Phase 1, 2, and 3 trials for other indications (age-related macular degeneration and diabetic macular edema) have shown intravitreal injections of aflibercept to be safe and well tolerated in many patients, preliminary results from the ongoing COPERNICUS and GALILEO trials proved the efficacy of this medication in treating macular edema secondary to CRVO. Of the combined 358 patients studied in COPERNICUS and GALILEO, 56% and 60%, respectively, of the patients receiving aflibercept 2 mg monthly achieved at least a 15-letter improvement in best-corrected visual acuity (BCVA) from baseline over 6 months compared with just 12% and 22% in the control group (p < 0.01 for both). Additionally, in COPERNICUS and GALILEO, patients achieved a 21.3- and 14.7-letter improvement, respectively, in BCVA compared with placebo (p < 0.01 for both). CONCLUSIONS: In September 2012, aflibercept became the second vascular endothelial growth factor (VEGF) inhibitor approved for treatment of macular edema secondary to CRVO. While efficacy and safety appear similar to other anti-VEGF treatments, the higher potency, binding affinity, and duration of action make aflibercept an appealing new option.

A virtual clean room to teach USP 797 regulations for intravenous medications.

OBJECTIVE: To provide a virtual environment for pharmacy students to learn United States Pharmacopeia Chapter 797 (USP 797) requirements, while recognizing the role of pharmacists in the safe use of intravenous (IV) medications. DESIGN: A virtual laboratory was created that included stations for IV medications, product verification, medication safety, and patient cases pertaining to high-alert medications. Pharmacy students used 3-D glasses and a wireless controller to navigate through the session and identify violations of USP 797 regulations. ASSESSMENT: Pre-assessments and post-assessments were administered to students who completed the session in each of the 2 years it was offered. In the first year, 88% of students strongly agreed or agreed that the sessions met their expectation. Following their APPE clerkship, 92% of these students felt the virtual IV room prepared them for the IV clean room experience. In the second year, 88% of students felt the experience enhanced their understanding of clean room procedures. After session completion, 75% of participants perceived medication errors to be more significant. Written examinations also were administered and students' mean scores improved significantly compared to those of students' prior to implementation of the session (89.6% in year 0; 91.2% in year 1; and 96.1% in year 2). CONCLUSION: The immersive virtual environment is a contemporary and effective way to teach USP 797 requirements and enhance the awareness of medication errors.

Interdisciplinary analysis of chemotherapy preparation at a pediatric hospital.

This report represents the results of an interprofessional investigation of the pharmaceutical procedures for hematology and oncology at a pediatric hospital. Pharmacists and industrial engineers identified areas for improvement, including a reduction in the interruption of regular pharmaceutical operations for the expedited preparation of chemotherapy treatments and the development of more robust drug preparation procedures that would ensure medication safety. The establishment of a satellite hematology/oncology pharmacy was also examined. Procedural changes were proposed in an effort to increase the safety and service levels of chemotherapy treatments for patients with hematological and oncological disorders.

Validation study: clarity multistrip urocheck.

OBJECTIVE: To test the interchangeability of a previously untested urine reagent strip, Clarity (RAC Medical), with the gold standard, Multistix (Bayer). DESIGN: Seventy-six urine samples were tested with both the comparator and the gold standard urine reagent strips. Pairs of reagent strips were analyzed in the Clinitek Analyzer, recording the following: leukocytes, nitrite, urobilinogen, protein, pH, blood, specific gravity, ketone, bilirubin, glucose, and color. Data was assessed using statistical comparison of ordinal data (chi-square, Fisher's Exact, kappa, and weighted kappa). This study was approved by the Indiana University-Purdue University at Indianapolis Institutional Review Board. SETTING: The study took place at Wishard Health Services, Indianapolis IN. PATIENTS OR OTHER PARTICIPANTS: All urine tested was obtained from patients of the primary care clinic at Wishard Health Services. INTERVENTIONS: n/a. PRIMARY OUTCOME MEASURE: The ability for both reagent strips to generate (statistically significant) identical readings across all 11 measurements for each sample. RESULT: Kappa values were deemed the best indicator to consistently examine the reproducibility of all 11 measurements of the Clarity versus the Multistix. Ten of eleven measurements were concluded to be non-reproducible by the Clarity strips; nitrite readings achieved a kappa value above 0.85, whereas all other readings achieved kappa values well below the acceptable limits of this investigation (ranging from 0.00 to 0.65). CONCLUSION: There was a lack of statistically significant agreement between the results of both products and therefore it was concluded that both products cannot be used interchangeably.

Prostaglandin analog treatment of glaucoma and ocular hypertension.

OBJECTIVE: To review available data related to the use of prostaglandin analogs (bimatoprost, latanoprost, travoprost, unoprostone) in the management of ocular hypertension and open-angle glaucoma. DATA SOURCES: Primary and review articles were identified from a MEDLINE search (1966-May 2001) and requested information from product manufacturers. STUDY SELECTION AND DATA EXTRACTION: All available information, including that published in articles and abstracts, which was deemed relevant was included in this review. Limited data have been published to date. DATA SYNTHESIS: The prostaglandin analogs appear to be effective, well-tolerated agents for the reduction of intraocular pressure (IOP) in patients with primary open-angle glaucoma and ocular hypertension. This drug class offers an alternative for patients who do not achieve control with another topical antiglaucoma agent or for those with a contraindication to first-line therapy with beta-adrenergic antagonists. Based on preliminary clinical data, bimatoprost, latanoprost, and travoprost appear to be at least as effective as timolol, while the effectiveness of unoprostone is similar or slightly less. Prostaglandin analogs may be used in conjunction with other antiglaucoma medications, although further studies must establish the optimal combination. Whether clinical experience will yield outcomes in favor of one of the prostaglandin analogs remains to be determined. Patients should be educated on adverse events associated with prostaglandin analogs, particularly the potential for changes in the pigmentation of the iris and eyelashes. CONCLUSIONS: Bimatoprost, latanoprost, and travoprost appear to be equivalent to the current standard of therapy in the topical treatment of elevated IOP. Further clinical data published in article versus abstract format is required to better assess potential differences among these 3 agents.