Maisha Kelly Freeman

Future of bisphosphonates and denosumab for men with advanced prostate cancer.

Prostate cancer is the most common cancer occurring in American men of all races. It is also the second leading cause of cancer death among men in the USA. Bone metastasis is a frequent occurrence in men with advanced prostate cancer, with skeletal-related events being a common complication and having negative consequences, leading to severe pain, increased health care costs, increased risk of death, and decreased quality of life for patients. Bone loss can also result from antiandrogen therapy, which can further contribute to skeletal-related events. Treatment with antiresorptive agents bisphosphonates, and the newly approved denosumab, a receptor activator of nuclear factor kappa-B ligand (RANK-L) inhibitor, has been shown to reduce the risk of skeletal-related complications and prevent treatment-induced bone loss in patients with advanced prostate cancer. This review discusses the role of antiresorptive agents bisphosphonates and RANK-L inhibitor in the current treatment of advanced prostate cancer by examining the primary literature and also focuses on the likely role of the bisphosphonates in the treatment of advanced prostate cancer in the future.

A Survey of Drug Information Resources in Alabama Pharmacy Facilities

The primary purpose of this study was to evaluate the availability and usage of drug information (DI) resources in Alabama pharmacy facilities licensed by the Alabama State Board of Pharmacy. A survey consisting of questions regarding accessible DI resources and their usage was mailed to 1,430 pharmacy facilities, of which 604 (42%) were returned. The survey also consisted of other questions concerning personal data/digital assistant (PDA) usage, computer resources, types of DI questions answered, and other DI-related questions. Drug Facts and Comparisons was the most available and used resource for all pharmacy types; the PDR (Physicians Desk Reference) and OTC (over-the-counter) references were second and third, respectively. PDA usage was relatively low (19.5%) among all pharmacies, but hospital/mental health pharmacies had the highest usage (32.4%). The primary drug questions answered by pharmacists for all pharmacy types concerned drug interaction, adverse reactions, and OTC questions.

Tablet splitting: a review of weight and content uniformity.

OBJECTIVEnTo describe the product integrity and ethical/ legal issues associated with tablet splitting.nnnDATA SOURCESnPubMed (1966-June 2011), International Pharmaceutical Abstract (1975-June 2011), and bibliographic searches were conducted.nnnSTUDY SELECTIONnAll studies that evaluated the weight/dose variations (N = 13) of split tablets were included.nnnDATA EXTRACTIONnThe American Pharmacists Association guidelines, recommendations from the Food and Drug Administration, and clinical studies evaluating product integrity of split tablets were used to provide an overview of issues related to this practice. Legal considerations from various sources were also included.nnnDATA SYNTHESISnThe practice of tablet splitting is increasing and is associated with variations in drug distributions related to the tablet-splitting technique and other causes. The first part of this two-part series will evaluate the product integrity and practice-related issues associated with tablet splitting.nnnCONCLUSIONnThe majority of the studies associated with tablet splitting reveal large fluctuations in weight/dosage, but few studies evaluate variability with narrow therapeutic index medications. Therefore, the clinical impact of these variations is not globally applicable across medication classes. Although tablet splitting has the potential to save patients and health care organizations a significant amount of money, appropriateness of tablet splitting should be determined for individual medications and individual patients. Assessments should include an evaluation of patient understanding and physical abilities for tablet splitting.

Tablet splitting: a review of the clinical and economic outcomes and patient acceptance. Second of a 2-part series. Part 1 was published in May 2012 (Consult Pharm 2012;27:239-53).

OBJECTIVEnTo describe the clinical outcomes, patient acceptance, and economic effect associated with tablet splitting.nnnDATA SOURCESnPubMed (1966-June 2011) and International Pharmaceutical Abstract (1975-June 2011) searches were conducted using tablet splitting as the search terms.nnnSTUDY SELECTIONnAll studies that evaluated the clinical outcome (n = 4), patient acceptance (n = 5), and economic effects (n = 8) of tablet splitting were included.nnnDATA EXTRACTIONnThe American Pharmacists Association guidelines, recommendations from the Food and Drug Administration, and clinical trial data were evaluated.nnnDATA SYNTHESISnThe majority of trials conducted evaluating clinical outcomes associated with tablet splitting were evaluated in patients receiving statins and antihypertensives. Clinical outcomes associated with risperidone were assessed. No adverse clinical outcomes were observed with therapy. Most studies evaluating the economic effects of tablet splitting have revealed a cost savings associated with this process; however, many studies were subject to limitations. The first part of this two-part series reviewed the weight and content uniformity in tablet splitting.nnnCONCLUSIONnTablet splitting does not seem to significantly affect clinical outcomes related to management of hypertension, cholesterol, or psychiatric disorders, nor influence overall patient adherence.

Dronedarone: an alternative to amiodarone?

OBJECTIVEnTo review the safety and efficacy of the newly approved, mixed-activity antiarrhythmic dronedarone (classes I-IV) versus its parent compound comparator, amiodarone (class III, with mixed activity).nnnDATA SOURCESnA MEDLINE/PUBMED (January 1966 to March 2010) and International Pharmaceutical Abstract (January 1975 to March 2010) search of English language papers in addition to a bibliographic search of retrieved papers.nnnSTUDY SELECTIONnAll human studies of dronedarone, alone or in combination with amiodarone, were reviewed.nnnDATA SYNTHESISnApproved in July 2009, dronedarone is a new antiarrhythmic agent indicated to reduce the risk of hospitalization for cardiac events in patients with paroxysmal or persistent atrial fibrillation or atrial flutter. Dronedarone has been viewed as a potential therapeutic alternative for amiodarone because of a lower risk for pulmonary, thyroid, and dermatologic adverse effects. Compared with amiodarone, dronedarone has poor bioavailability and a shorter terminal disposition half-life, which dictates a twice-daily dosing regimen. Furthermore, dronedarone failed to demonstrate superiority over amiodarone with respect to recurrence of atrial fibrillation in a comparative efficacy analysis. Dronedarone therapy is more costly and increases overall tablet burden. No dosage adjustments are required with dronedarone for renal impairment. Use of dronedarone is contraindicated in the presence of severe hepatic impairment. No serious organ-related toxicities (i.e., thyroid and pulmonary system) have been reported with use of dronedarone.nnnCONCLUSIONnDronedarone as a niche drug may be a reasonable theoretical alternative for patients who cannot tolerate amiodarone or have underlying comorbidities that contraindicate amiodarone use (e.g., pulmonary, thyroid disease). However, dronedarone has not been studied in the vast majority of indications and patient populations in which amiodarone has been studied.

Preapproval and postapproval availability of published comparative efficacy research on biological agents

PURPOSEnPreapproval and postapproval availability of published comparative efficacy studies on biological agents approved between 2000 and 2010 was investigated.nnnMETHODSnApproval packages published on the Food and Drug Administration (FDA) website were examined for all biological agents approved between 2000 and 2010 to determine if comparative efficacy studies were available at the time of FDA approval. The availability of comparative efficacy studies published subsequent to approval was determined by searching PubMed for randomized, active-controlled experimental or observational study designs that measured efficacy as the primary endpoint and were relevant to the original FDA-approved indication.nnnRESULTSnFrom 2000 to 2010, 107 biological agents were approved by FDA. Of the biological agents with alternative treatments, 54.6% had comparative efficacy data available at the time of approval. Although standard-reviewed biological agents were more likely to have comparative efficacy trials included in the FDA approval packages than priority-reviewed biological agents, statistically significant differences are unlikely. Subsequent to approval, 58.1% of biological agents had at least one published comparative efficacy trial, representing a 3.5% absolute increase in the availability of comparative efficacy studies since the time of approval. Vaccines and biological agents in the hematologic diseases, oncology, and miscellaneous diseases classes had fewer published postapproval comparative efficacy studies per agent compared with the overall group of biological agents.nnnCONCLUSIONnNearly half of all biological agents approved for marketing between 2000 and 2010 lacked publicly accessible, active-controlled efficacy studies at the time of drug approval; a slightly greater proportion of biological agents had comparative efficacy data published subsequent to their approval.

Level of Evidence Associated with FDA Safety Communications with Drug Labeling Changes: 2010-2014

Purpose: Approximately 800,000 safety reports are submitted to the FDA annually, however, only significant issues generate drug safety communications (DSC). The purpose of this study was to determine the type of clinical evidence used to warrant a change in drug labeling for drugs with DSC between January 1, 2010 and December 31, 2014. Methods: Selected data was obtained from the FDA website. The primary endpoint of the study was the frequency of the types of clinical evidence used in FDA communications, as reported through the FDA DSC. Results were evaluated via descriptive statistics, and chi-squared for nominal data. Results: A total of 2521 drug safety labeling changes were identified and 99 (3.9%) of safety communications met the inclusion criteria. The majority of the labeling changes were associated with single agents (83.8%). The three most frequently reported labeling changes were warnings (68.7%), precautions (58.6%), and patient package insert/medication guide (23.2%). Case reports resulted in the greatest number of documented literature types (n = 791), followed by randomized controlled trials (n = 76), and case control/cohort studies (n = 74). Significantly more evidence for DSCs were classified as Level of Evidence B (LOE B, 68.6%), compared to LOE A (17.1%), and LOE C (14.1%) (p = 0.007). Conclusions: The majority of drug labeling change initiators was associated with LOE equivalent to B. Practitioners should evaluate data associated with labeling changes to determine how to interpret the information for their patients. nConflict of Interest nWe declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the manuscript, including grants (pending or received), employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents and royalties. nxa0 nType:xa0Original Research

Dabigatran for the prevention of thromboembolic complications in the elderly: a RE-LY-able alternative to warfarin?

On October 19, 2010, the Food and Drug Administration approved dabigatran (Pradaxa) for reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF). The use of warfarin sodium has been considered a mainstay therapy for the prevention of thromboembolic complications secondary to AF. Despite its efficacy among oral antithrombotic agents for the prevention of thromboembolic complications secondary to AF, only about 67% of candidates for warfarin receive appropriate antithrombotic therapy. Dosed twice daily, dabigatran offers recipients the ability to forego regular international normalized ratio coagulation monitoring as well as eliminating dietary restrictions (i.e., vitamin K) associated with warfarin therapy. In a 2011 guideline update, dabigatran has been recognized by the American College of Cardiology and the American Heart Association as a useful alternative to warfarin in patients with AF who are at risk for thromboembolic complications and who are without severe renal or hepatic impairment. The Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) study is the only direct, prospective, comparative clinical trial of dabigatran versus warfarin to date that enrolled subjects for the purpose of examining the ability of dabigatran to prevent stroke and thromboembolic complications associated with nonvalvular AF. Currently, the published literature has not adequately defined which patient populations would be most suitable to treat with dabigatran. While dabigatran has a place in the therapeutic prevention stroke and systemic embolism associated with AF, careful consideration of the risks and benefits of therapy is recommended.

Assessment of Electronic Drug Information Resource Availability in Alabama Pharmacies

The two primary objectives of this study were to identify available electronic drug information (DI) resources in licensed Alabama pharmacies and to identify common electronic resources to teach in the doctor of pharmacy curriculum at the McWhorter School of Pharmacy. A survey consisting of 10 questions was mailed to all licensed medication-dispensing pharmacy practices in Alabama (N = 1,562), of which 699 (44%) were returned for analysis, primarily by community and hospital practices (78.8% and 10.7%, respectively). The survey identified type of pharmacy, demographics, and availability and usage of electronic DI resources. Drug Facts and Comparisons, Internet search engine, the Pharmacists Letter, and Clinical Pharmacology were the most available electronic DI resources (59.5%, 48.6%, 42.3%, and 31%, respectively) among responding pharmacies. Drug Facts and Comparisons was the most common print-based resource; Lexi-Comp and Epocrates were the most utilized handheld DI resources.

Retained Skeletal Effects of Zoledronic Acid Following Discontinuation of Treatment: A Review of the Literature

OBJECTIVEnTo evaluate the effects on bone mineral density (BMD), bone turnover markers (BTMs), and fracture incidence following zoledronic acid (ZOL) discontinuation.nnnDATA SOURCESnA search of PubMed (1966-May 2016) and International Pharmaceutical Abstracts (1970-May 2016) was conducted using the MeSH terms zoledronic acid, osteoporosis, and withholding treatment. Free text searches included drug holiday and drug discontinuation.nnnSTUDY SELECTION AND DATA EXTRACTIONnAn initial review yielded 87 articles. Six articles, which addressed the skeletal effects of ZOL after discontinuation of treatment, were included in the final review.nnnDATA SYNTHESISnZOL is a widely prescribed bisphosphonate agent. Studies have shown that discontinuation of ZOL may have lasting skeletal benefits. However, there is inconsistent evidence regarding the duration of the residual skeletal effects of ZOL after treatment discontinuation, or the continued length of therapy required for the prolonged protective benefits on BMD and BTMs. Sample sizes have been small, and studies were not adequately powered to evaluate fracture incidence.nnnCONCLUSIONnA single ZOL infusion has been shown to decrease BTMs and improve BMD for at least 12 months after infusion. Patients may experience continued benefit beyond this period, but there is concern that this long-term effect may lead to severe bone-turnover suppression, increased bone fragility, and increased risk of fractures. Additional extension studies should be conducted to determine the long-term effects of discontinuing ZOL therapy on bone health as well as the length of preserved bone strength after last administration.