Effects of Denosumab After Treatment Discontinuation : A Review of the Literature.

OBJECTIVE: To review and summarize studies on the effects of denosumab on bone mineral density following the discontinuation of therapy. DATA SOURCES: A search of PubMed (1966-July 2017) and International Pharmaceutical Abstracts (1970-July 2017) was conducted using the Medical Subject Headings (MeSH) terms denosumab, osteoporosis, and withholding treatment in combination with free term searches including the words drug holiday, discontinue, discontin*, and drug discontinuation. STUDY SELECTION AND DATA EXTRACTION: An initial review yielded 10 articles. Four articles that addressed the effects of denosumab discontinuation on markers of overall bone health, fracture risk, or bone histology were included in the final review. DATA SYNTHESIS: Denosumab is a monoclonal antibody indicated for the treatment of osteoporosis in men and postmenopausal women. Denosumab has proven beneficial effects on bone remodeling and bone mineral density, and these effects have been noted to be reversed upon treatment discontinuation because of the agent's lack of incorporation into bone matrix. After 12 to 24 months off denosumab therapy, BMD, BTMs levels, as well as histologic and histomorphometric analyses, were reflective of baseline values. The number of studies evaluating the residual skeletal effects of denosumab is limited, and the sample sizes in the articles reviewed were relatively small. CONCLUSION: An evaluation of studies showed that the discontinuation of denosumab results in loss of bone mineral density and a decline to near baseline values within 12 months of discontinuing therapy. Larger extension studies in a more diverse population need to be conducted to extrapolate the data to other patient groups.

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

OBJECTIVE: To evaluate the effects on bone mineral density (BMD), bone turnover markers (BTMs), and fracture incidence following zoledronic acid (ZOL) discontinuation. DATA SOURCES: A 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. STUDY SELECTION AND DATA EXTRACTION: An initial review yielded 87 articles. Six articles, which addressed the skeletal effects of ZOL after discontinuation of treatment, were included in the final review. DATA SYNTHESIS: ZOL 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. CONCLUSION: A 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.

Enzymatic Stability of Alteplase Solution for Injection: Effect of Various Methods of Thawing Frozen Solutions.

Objective: To modify and evaluate an established chromogenic assay protocol for measuring plasminogen activator inhibitor type-1 (PAI-1) activity to measure tissue plasminogen activator (tPA) activity and compare the enzymatic activity of alteplase as a function of the conditions under which it is thawed. Methods: A 50 mg vial of alteplase was reconstituted with sterile water to make a 1 mg/mL stock solution (nominal concentration). Plastic syringes were loaded with 0.5 mL of alteplase stock solution and stored at -20°C. After 8 days, samples were thawed by 3 methods - via body temperature (37°C), room temperature (20°C), or in a refrigerator (2°C). Thaw times were recorded. The thawed solutions, along with a freshly prepared alteplase solution, were assayed using the modified protocol of the Spectrolyse PAI-1 kit to determine residual tPA enzyme activity. Results: Validation of the modified protocol for the Spectrolyse PAI-1 kit used to measure tPA activity produced a linear response with coefficients of determination (R2) of greater than 0.9977 when assayed on 2 separate days, which corresponded to an enzymatic activity accuracy between 98.3% and 108.3%. The average percent residual tPA enzyme activity of samples from each group compared to the freshly prepared solution was 106%, 98.7%, and 91.5% for samples thawed at body temperature, room temperature, and refrigerated, respectively. Conclusion: Modifications to the standard procedure for the Spectrolyse PAI-1 kit allows for accurate determination of tPA activity in aqueous based reconstituted solutions of alteplase. Under thawed conditions, alteplase retained greater than 91% enzyme activity as compared to a freshly prepared control.

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).

OBJECTIVE: To describe the clinical outcomes, patient acceptance, and economic effect associated with tablet splitting. DATA SOURCES: PubMed (1966-June 2011) and International Pharmaceutical Abstract (1975-June 2011) searches were conducted using tablet splitting as the search terms. STUDY SELECTION: All studies that evaluated the clinical outcome (n = 4), patient acceptance (n = 5), and economic effects (n = 8) of tablet splitting were included. DATA EXTRACTION: The American Pharmacists Association guidelines, recommendations from the Food and Drug Administration, and clinical trial data were evaluated. DATA SYNTHESIS: The 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. CONCLUSION: Tablet splitting does not seem to significantly affect clinical outcomes related to management of hypertension, cholesterol, or psychiatric disorders, nor influence overall patient adherence.

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.

Tablet splitting: a review of weight and content uniformity.

OBJECTIVE: To describe the product integrity and ethical/ legal issues associated with tablet splitting. DATA SOURCES: PubMed (1966-June 2011), International Pharmaceutical Abstract (1975-June 2011), and bibliographic searches were conducted. STUDY SELECTION: All studies that evaluated the weight/dose variations (N = 13) of split tablets were included. DATA EXTRACTION: The 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. DATA SYNTHESIS: The 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. CONCLUSION: The 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.

Thienopyridine antiplatelet agents: focus on prasugrel.

OBJECTIVE: To assess the potential role of prasugrel in the management of acute coronary syndrome (ACS) in older adults. DATA SOURCE: PubMed and International Pharmaceutical Abstracts searches (1966 to 2009) were conducted to identify pertinent English-language studies on the use of prasugrel. STUDY SELECTION AND DATA EXTRACTION: All human studies evaluating pharmacokinetic/pharmacodynamic or clinical efficacy of prasugrel were evaluated. DATA SYNTHESIS: Prasugrel is a third-generation thienopyridine antiplatelet agent. Other thienopyridine antiplatelet agents (e.g., clopidogrel, ticlopidine) have been associated with interindividual variability, drug-drug interactions, and unfavorable adverse effect profile. Prasugrel therapy is associated with more profound platelet inhibition and improved cardiovascular (CV) outcomes compared with clopidogrel; however, prasugrel therapy is associated with an increased bleeding risk. Prasugrel should not be used in adults older than 75 years of age, those who have had a recent transient ischemic attack (TIA) or stroke, those who have a low body weight < 60 kg, and those receiving medications or having conditions associated with a bleeding risk unless they are at a high risk for a CV event. CONCLUSION: Prasugrel therapy does not appear to be associated with interindividual variability in platelet aggregation and has superior CV outcomes compared with clopidogrel. No dosage adjustments need to be made for renal or hepatic impairment. Prasugrel shows promise for the treatment of ACS patients with clopidogrel resistance or those who have an increased risk of CV events (e.g., patients with diabetes); head-to-head trials evaluating these uses have not been conducted. Geriatric patients have an increased risk of bleeding with this agent. Additional studies need to be conducted to determine the appropriate population for prasugrel.

Dronedarone: an alternative to amiodarone?

OBJECTIVE: To 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). DATA SOURCES: A 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. STUDY SELECTION: All human studies of dronedarone, alone or in combination with amiodarone, were reviewed. DATA SYNTHESIS: Approved 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. CONCLUSION: Dronedarone 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.

Evaluation of Antidiabetic Injectable Technique: Is There an Association between Accuracy and Health Literacy or Duration of Diabetes?

INTRODUCTION: Effective diabetes pharmacotherapy often involves injectable medications, which if used inappropriately represents a type of unintentional medication nonadherence that leads to poor outcomes. OBJECTIVES: The primary objective of this study was to assess the percent of patients who accurately prepared, administered, stored, and disposed of their injectable diabetes medication. Secondary objectives included comparing the accuracy of injectable use among those with diabetes <5 years vs. ≥ 5 years duration and those with limited vs. proficient health literacy. METHODS: This was a prospective analysis conducted on a convenience sample of patients who received a pilot pharmacist-led, quality improvement service at an urban, ambulatory care clinic. The service components included health literacy screening, using the Rapid Assessment of Adult Literacy in Medicine - Short Form (REALM-SF) tool, evaluation of injectable technique by use of a standardized questionnaire, and provision of medication education. Duration of diabetes was determined by patient self-report. Chi-square and Fisher's exact tests were utilized to assess accuracy of injectable technique in two group comparisons: (1) patients with limited vs. proficient health literacy and (2) patients with diabetes <5 years vs. ≥5 years. RESULTS: Thirty-five patients were included in the analysis. Despite the majority (71.4%) of patients reporting prior education on injectable use, 54.3% reported at least one error in product use. Significant findings noted were that those with limited health literacy had higher rates of accurately using the skin-fold technique and appropriate angle for injection vs. those with proficient health literacy (p<0.05 for both comparisons). Likewise, more patients in the cohort of diabetes duration ≥5 years accurately rotated the injection site vs. those with a duration <5 years (p=0.001). CONCLUSION: Errors in injectable technique were common in this study and spanned across health literacy levels and duration of diabetes. Patients prescribed injectable diabetes medications should be routinely educated on proper technique for use.

Racial disproportionality of students in United States colleges of pharmacy.

OBJECTIVE: To describe the disproportionality of racial and ethnic people of color (i.e., minorities) among the student body in schools and colleges of pharmacy (COPs) compared to county-specific United States Census Bureau data. METHODS: Data were obtained from national databases and published reports from the American Association of Colleges of Pharmacy. In addition, demographic information for enrollees of minority-serving institutions and predominantly white institutions was obtained and racial disproportionality was assessed to determine the degree of concordance between enrollees and the demographics of people within the county that the school was located. Data were evaluated using descriptive statistics. RESULTS: Compared to the general population in counties where COPs are located, Asians are over-represented while all other students of color are underrepresented. The top schools that have a negative disproportionality rate for Black students included Thomas Jefferson University (-40.49), Wayne State University (-40.13), Philadelphia College of Pharmacy (-39.90), and the University of Tennessee (-39.74).The top five schools that have a negative disproportionality rate of Hispanic students included Loma Linda University (-45.67), California Health Sciences (-45.64), the University of Southern California (-43.79), the University of the Pacific California (-37.95), and Texas Southern University (-36.65). The enrollments within most COPs do not reflect the racial and ethnic diversity of the counties in which they are located. CONCLUSIONS: To meet the healthcare needs of an increasingly diverse population, each institution should establish a strategic plan for increasing diversity and evaluating and adopting best practices.

Google Scholar versus PubMed in locating primary literature to answer drug-related questions.

BACKGROUND: Google Scholar linked more visitors to biomedical journal Web sites than did PubMed after the database's initial release; however, its usefulness in locating primary literature articles is unknown. OBJECTIVE: To assess in both databases the availability of primary literature target articles; total number of citations; availability of free, full-text journal articles; and number of primary literature target articles retrieved by year within the first 100 citations of the search results. METHODS: Drug information question reviews published in The Annals of Pharmacotherapy Drug Information Rounds column served as targets to determine the retrieval ability of Google Scholar and PubMed searches. Reviews printed in this column from January 2006 to June 2007 were eligible for study inclusion. Articles were chosen if at least 2 key words of the printed article were included in the PubMed Medical Subject Heading (MeSH) database, and these terms were searched in both databases. RESULTS: Twenty-two of 33 (67%) eligible Drug Information Rounds articles met the inclusion criteria. The median number of primary literature articles used in each of these articles was 6.5 (IQR 4.8, 8.3; mean +/- SD 8 +/- 5.4). No significant differences were found for the mean number of target primary literature articles located within the first 100 citations in Google Scholar and PubMed searches (5.1 +/- 3.9 vs 5.3 +/- 3.3; p = 0.868). Google Scholar searches located more total results than PubMed (2211.6 +/- 3999.5 vs 44.2 +/- 47.4; p = 0.019). The availability of free, full-text journal articles per Drug Information Rounds article was similar between the databases (1.8 +/- 1.7 vs 2.3 +/- 1.7; p = 0.325). More primary literature articles published prior to 2000 were located with Google Scholar searches compared with PubMed (62.8% vs 34.9%; p = 0.017); however, no statistically significant differences between the databases were observed for articles published after 2000 (66.4 vs 77.1; p = 0.074). CONCLUSIONS: No significant differences were identified in the number of target primary literature articles located between databases. PubMed searches yielded fewer total citations than Google Scholar results; however, PubMed appears to be more specific than Google Scholar for locating relevant primary literature articles.

Immuno-Oncology Medicines: Policy Implications and Economic Considerations.

Significant progress has taken place in the field of cancer immunotherapy in recent years. Cancer immunotherapy, particularly immune checkpoint inhibitors, have shown rather dramatic results and are believed to have completely transformed the field of oncology. However, these transformational therapies are more expensive than previous cancer therapies. As more cancer immunotherapy agents are being developed, with some already being marketed, it is important to consider how economic constraints will shape health policy and value assessment related to these agents. A number of strategies have been suggested to alleviate the price burden and the ensuing concerns about the sustainability of publicly funded healthcare systems. Among these strategies, value-based pricing (VBP) for innovative drugs dominates the headlines in the field of oncology. The specifics of how VBP may be implemented in the United States is still unclear. Nonetheless, policy reform and economic considerations will have to be incorporated into the planning of VBP. The objective of this paper is multifold: (i) to identify the factors affecting the impact of cancer immunotherapy on healthcare cost; (ii) to critically appraise current approaches used to assess the value of novel cancer therapies; (iii) to assess the methodological challenges associated with the economic evaluation of cancer immunotherapy. As the health care system in the U.S transitions toward a value-based model, the need for a formal value assessment framework is warranted in cancer immunotherapy.

Hypothyroid Symptoms in Levothyroxine-Treated Patients.

PURPOSE: Approximately 15% of patients with hypothyroidism are dissatisfied with their treatment due to persistence of residual symptoms associated with hypothyroidism. The purpose of this study was to compare thyroid symptoms using the hypothyroid symptom scale (HSS) in patients receiving stable thyroid therapy for 6 months to patients without hypothyroidism. The HSS was used to identify the percentage of levothyroxine-treated hypothyroid patients with residual or persistent hypothyroid symptoms. METHODS: Patients included in the study had hypothyroidism and were receiving a stable/maintenance dose of levothyroxine sodium therapy, unchanged for at least 6 months. A control group of patients were included if they did not have an active prescription for thyroid hormone therapy. The HSS was administered via phone or face-to-face interactions. Patients were asked to score 10 symptoms over the past month on a scale of 0 to 4 (e.g., 0, absence of, to 4, severe symptoms). Results were analyzed using descriptive and inferential statistics. T-tests and chi-squared analysis were used to assess differences in continuous and categorical variables. RESULTS: A total of 68% of the contacted patients responded to the survey. A total of 302 patients were in the intervention group and 273 were in the control group. The mean total HSS scores between groups were significantly higher in the treatment compared to the control group (13.92 ± 10.91 vs.10.07 ± 7.85; P < 0.001). CONCLUSION: Significantly more patients receiving thyroid hormone therapy experienced residual thyroid symptoms compared to control patients. Attempts should be made to offer alternatives for hypothyroid patients with persistent symptoms.

Modafinil augmentation for residual symptoms of fatigue in patients with a partial response to antidepressants.

OBJECTIVE: To evaluate the literature discussing the use of modafinil in the treatment of residual symptoms of fatigue in patients with depression. DATA SOURCES: PubMed (1966-March 2007) and International Pharmaceutical Abstracts (1970-March 2007) were searched using the key words modafinil and depression. A manual search of the reference section of the articles retrieved was conducted to identify articles not indexed in either of these sources. STUDY SELECTION AND DATA EXTRACTION: All articles published in English were evaluated. Studies were included if modafinil was used to treat patients with residual fatigue from depression and the effects were measured with validated fatigue subscales. DATA SYNTHESIS: One retrospective study, 5 open-label trials, and 2 randomized controlled clinical trials met the inclusion criteria for assessment of residual symptoms of fatigue as assessed by commonly used fatigue subscales after modafinil administration. Although improvement with fatigue has occurred with modafinil therapy, literature regarding the topic is limited by the lack of well-controlled clinical trials. Modafinil does appear to improve residual fatigue with depression as evidenced by open-label trials; however, the efficacy of this agent has not been duplicated in randomized controlled trials. The open-label trials that have been conducted often had no comparator and a small number of patients. In addition, outcome measures used in the studies were not consistent between trials. Modafinil appears to be well tolerated, with the main adverse effects being headache and nausea. CONCLUSIONS: Open-label trials indicate that modafinil may be effective in ameliorating fatigue associated with depression; however, this effect has not been reproduced in randomized, double-blind, placebo-controlled clinical trials. Therefore, the use of modafinil for the treatment of residual fatigue is not recommended due to the lack of reproducible data of its efficacy. Long-term, adequately powered clinical trials should be conducted to determine its place in therapy.

Characteristics of FDA drug recalls: A 30-month analysis.

PURPOSE: The characteristics of drug recalls issued over 30 months by the Food and Drug Administration (FDA) were analyzed. METHODS: All FDA-issued recalls for drugs (prescription and nonprescription, including dietary supplements) and biological products issued from June 20, 2012, to December 31, 2014, were included in this retrospective analysis. Data for all drug recalls were downloaded and sorted by the inclusion criteria from weekly FDA enforcement reports. The following data were analyzed: product type, recall firm, type of recall firm (compounding or noncompounding), country, voluntary or involuntary recall, method of communication of recall, recall number, FDA recall classification (class I, II, or III), product availability (prescription or nonprescription), reason for recall, recall initiation date, and recall report date. RESULTS: A total of 21,120 products were recalled during the 30-month study period. Of these, 3,045 drug products (14.4%) met the inclusion criteria and were analyzed. A total of 348 total manufacturers were associated with recalled drug products. The 5 firms most frequently involved in recalls accounted for 299, 273, 212, 118, and 112 recalls. The most common reasons for recalls were contamination, mislabeling, adverse reaction, defective product, and incorrect potency. There was a significant association between FDA recall classification and the following outcomes: reasons for recall, product availability, type of recall firm, and form of communication. CONCLUSION: An investigation of FDA drug recalls revealed that the five most common recall reasons were contamination, mislabeling, adverse reaction, defective product, and incorrect potency. Compounding firms were associated more frequently with contamination than were noncompounding firms.

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.

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

PURPOSE: Preapproval and postapproval availability of published comparative efficacy studies on biological agents approved between 2000 and 2010 was investigated. METHODS: Approval 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. RESULTS: From 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. CONCLUSION: Nearly 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.

Prazosin for treatment of nightmares related to posttraumatic stress disorder.

PURPOSE: The efficacy of prazosin for the treatment of posttraumatic stress disorder (PTSD)-related nightmares is reviewed. SUMMARY: PTSD is an anxiety disorder that can occur after experiencing or witnessing a life-threatening event, such as military combat, natural disasters, terrorist attacks, serious accidents, or violent personal assaults. The event that induced PTSD is often relived through nightmares or flashbacks. Sleep disturbances affect approximately 70% of patients with PTSD. Several medications have been evaluated for reducing PTSD-related nightmares, with limited success. Prazosin is a centrally and peripherally acting alpha(1)-adrenergic antagonist whose mechanism of action, favorable adverse-effect profile, and low cost make it a promising agent for the treatment of PTSD. To date, two case reports, two chart reviews, three open-label trials, and two placebo-controlled trials have been published documenting the efficacy and safety of prazosin in the treatment of PTSD-related nightmares. Therapy with prazosin resulted in a reduction in nightmares in patients with both combat- and noncombat-related trauma. A therapeutic benefit occurred with prazosin dosages as low as 1 mg daily, and suppression of nightmare symptoms occurred within one week of prazosin initiation. The most frequently reported adverse event was orthostatic hypotension. The variability in the populations studied (e.g., combat, noncombat, recent traumatic experiences) leaves additional unanswered questions that must be addressed in large, randomized, controlled trials. CONCLUSION: Prazosin appears to be a promising and well-tolerated agent for the management of PTSD-related nightmares. Further well-designed trials are warranted to establish its place in the treatment of PTSD.

Preparing students for community pharmacy practice during a drug information advanced practice experience.

OBJECTIVE: To determine whether students completing an advanced pharmacy practice experience (APPE) at an academic-affiliated drug information center received questions similar to those received by pharmacists practicing in community settings. METHODS: Graduates of Samford University McWhorter School of Pharmacy residing in Southeastern states were surveyed via US mail to determine the characteristics of inquiries received from health care providers and the public in community practice. Survey results were compared to inquiries received at Samford University Global Drug Information Center (SUGDIS). RESULTS: The response rate to the survey of graduates was 36% (268 of 738 surveys). Respondents identified nonprescription drugs (65%), adverse drug reactions (62.7%), and drug interactions (62.4%) as the top 3 types of questions answered routinely in community practice, while drug therapy (13.9%), dosing (10.2%), and adverse drug reactions (6.5%) were the 3 types of questions most commonly answered at SUGDIS. The most common resources used to answer questions in the community and SUGDIS were Drug Facts and Comparisons and specialty references, respectively. CONCLUSIONS: Differences were noted in types of questions received, expected speed of response, and reference utilization. As a result, activities were incorporated into the drug information APPE to address the disparities noted in the study.