Implementation of a Clinical Problem-Solving Course for Students Challenged by Early Pharmacy Curriculum.

OBJECTIVE: This study evaluates the impact of offering a clinical decision-making and problem-solving course to students academically challenged in early required clinical and pharmaceutical calculation courses on improving their ability to identify and solve drug-related problems. METHODS: Faculty designed a course with a main objective for students with grades of C or lower in any of the 5 required first-year courses to gain plentiful practice with a systematic approach to identifying and solving drug therapy problems. Students' performance on course-embedded assessments mapped to problem-solver subdomain, a pre-Advanced Pharmacy Practice Experience (APPE) competency on the ability to identify drug-related problems, and performance on Pharmacy Curriculum Outcomes Assessment were compared to a control group of students from 2 previous cohorts who did not take the course but had a subpar academic performance. Pearson chi-square test and independent samples t test were utilized for categorical and continuous data, respectively. RESULTS: The clinical decision-making and problem-solving course significantly improved student performance on pre-APPE competency to identify drug-related problems (first-attempt pass rate of 96% vs 30% when compared to a historic cohort), but not on Pharmacy Curriculum Outcomes Assessment. Student performance on case-based questions mapped to problem-solver subdomain exceeded internally set standard by 13.72% points. CONCLUSION: Students demonstrated learning problem-solving and clinical decision-making, which improved their performance on course-embedded assessments and pre-APPE competency in identifying drug-related problems.

Impostor Phenomenon in Pharmacy Students as It Relates to Professional Identity Formation.

This commentary describes the relationship between impostor phenomenon and professional identity formation and draws attention to validation theory in supporting student development. Student-level challenges are highlighted, and roles faculty members could play in actively encouraging professional identity formation and helping overcome impostor feelings are discussed.

A Program to Prepare Clinical Pharmacy Faculty Members to Use Entrustable Professional Activities in Experiential Education.

Objective. To describe the design and evaluation of a program implemented to ready clinical faculty members to use entrustable professional activities (EPAs) for teaching and assessment in experiential education. Methods. The school adopted a set of EPAs for faculty members to implement in advanced pharmacy practice experiences (APPEs), and then delivered a two-session faculty development program to ensure faculty members' readiness to implement the EPAs. To determine the success of the faculty development program, qualitative analysis of the moderated discussion held during the program was conducted, post-program and follow-up surveys were administered, and the results of the pilot implementation of EPAs were analyzed. Results. Eleven faculty members participated in the development program, and 10 of them completed the pilot implementation of EPAs and the follow-up survey after completing three APPE blocks. All faculty members responded that the program prepared them to apply what they learned about EPAs to their practice setting in both the post-program and follow-up surveys. In the follow-up survey, 80% of faculty members reported that they were confident in correctly applying what they learned from the program to the EPA pilot, and 100% answered a hypothetical application question correctly. Forty students participated in the pilot implementation of EPAs. Of these, 95% were directly observed by faculty members before making an entrustment decision, and 100% received feedback on their performance. Conclusion. The faculty development program was effective in preparing faculty members to implement the EPA framework in experiential teaching and use the entrustment rubric.

Manuscript Referencing Errors and Their Impact on Shaping Current Evidence.

It is imperative that articles published in reputable peer-reviewed journals provide balanced, fair, objective, and accurate references. However, studies on the accuracy of references in various scientific disciplines demonstrate an error rate of 25%-54%. These errors can range from minor errors in citation accuracy to major errors that alter the original content and meaning of the material referenced. This article discusses importance of citation accuracy, reviews principles of good citation practices, and offers recommendations aimed to decrease citation error rates.

Eluxadoline in the treatment of diarrhea-predominant irritable bowel syndrome.

Eluxadoline is a novel drug approved for the management of diarrhea predominant irritable bowel syndrome (IBS-D). It has unique pharmacology and works on three different opioid receptors. Several Phase II and III clinical trials have demonstrated eluxadoline's efficacy in reducing symptoms related to IBS-D. Clinical trial results and postmarketing reports show a risk of pancreatitis in patients without a gallbladder or those abusing alcohol. This review article will include information on clinical trial results related to IBS-D management as well as eluxadoline's limitations.

Update on the Management of Diarrhea-Predominant Irritable Bowel Syndrome: Focus on Rifaximin and Eluxadoline.

Diarrhea-predominant irritable bowel syndrome (IBS-D) is one of the most common diagnoses made by gastroenterologists. Current pharmacologic treatments for IBS-D include fiber supplements, antidiarrheal over-the-counter medications, probiotics, antispasmodics, antidepressants, and a 5-hydroxytryptophan 3 receptor antagonist. All of these options have limited efficacy in managing IBS-D. Rifaximin, a nonabsorbable antibiotic, has been evaluated in patients with IBS-D. In two randomized, double-blind, placebo-controlled phase III trials evaluating rifaximin 550 mg by mouth 3 times/day for 14 days, the primary efficacy end point was achieved by 9% more patients randomized to the rifaximin group compared with placebo (40.7% vs 31.7%, p<0.001, number needed to treat ~11). The primary efficacy end point was defined as the proportion of patients having adequate relief of global IBS symptoms for at least 2 of the 4 weeks during the primary follow-up period (weeks 3-6). In the phase III trial examining the efficacy and safety of repeated courses of rifaximin in patients who responded to the initial 2-week course, rifaximin given for up to two additional courses provided a statistically significant incremental benefit (33% vs 25%, p=0.02). Eluxadoline is a gut-targeting µ and κ opioid receptor agonist and a δ opioid receptor antagonist. The dual mechanism of eluxadoline may explain the antidiarrheal and abdominal pain-modulating properties and lack of profound constipation. In two identically designed randomized, double-blind, placebo-controlled phase III studies, 10.3% more patients in an eluxadoline 100 mg by mouth twice/day group met the primary efficacy end point during the follow-up 1-12 week period compared with placebo (p<0.001). The primary efficacy end point was a composite response, defined as improvement in worst abdominal pain and stool consistency at the same time on most (50% or more) days during the follow-up period. This review evaluates evidence for the use of rifaximin and eluxadoline in patients with IBS-D. Rifaximin provides an additional modality for the management of IBS-D patients; it has mild to moderate efficacy similar to other currently available treatment options. Rifaximin is relatively safe, lacks significant drug-drug interactions, and can be used for up to two additional retreatment courses. This may make rifaximin a possible initial or second-line treatment option. Eluxadoline can also offer relief to patients with IBS-D. While effective, because of several limitations, including drug-drug interactions and drug disease contraindications, as well as current lack of clinical experience, it may be tried as a second- or third-line agent.

Thinking Clinically from the Beginning: Early Introduction of the Pharmacists' Patient Care Process.

Objective. To describe a student-centered teaching method used to introduce a pharmacist patient care process (PPCP) during the first year of a doctor of pharmacy (PharmD) program. Design. In the fall of 2014, a cohort of students (n=85) began an integrated pharmacotherapy (IPT) course sequence in the first semester of pharmacy school. The first course in this sequence laid the foundation for the delivery of care, focusing on the individual components of a PPCP. Faculty member used a variety of teaching methods in the course to introduce medication history taking, identification of drug-related problems, identifying components of a patient case, and learning/beginning to write subjective, objective, assessment, plan (SOAP) notes. Students' SOAP notes submissions and performance on multiple-choice examinations were evaluated to demonstrate evidence of learning. Students also completed online course evaluations. Assessment. Course-imbedded assessments were designed to measure student learning related to individual School of Pharmacy outcomes and course learning objectives. The mean individual student score on exam questions related to the PPCP topics was 83.7%±18.8%. The majority of students (86%-88%) rated their progress on achieving course learning objectives as "substantial" or "exceptional." Students also enrolled in the introductory pharmacy practice experience (IPPE) in a community setting after completing the first IPT. The students performed significantly better than a historic cohort in identifying actual and potential drug therapy problems. Conclusion. The described teaching methods, when introduced in early curricular stages, are effective in building a foundation for learning PPCP.

Use of Non-Vitamin K Antagonist Oral Anticoagulants in Special Patient Populations with Nonvalvular Atrial Fibrillation: A Review of the Literature and Application to Clinical Practice.

Atrial fibrillation is a commonly encountered arrhythmia associated with increased risk for thromboembolic events. Anticoagulation is necessary to decrease the risk of ischemic stroke. Traditionally, warfarin has been the only oral pharmacotherapeutic option for long-term anticoagulation in patients with nonvalvular atrial fibrillation (NVAF). Recently, non-vitamin K antagonist oral anticoagulants (NOAC), including dabigatran, rivaroxaban, apixaban, and edoxaban, have become available as alternatives for warfarin in the prevention of stroke in patients with NVAF. Recently published atrial fibrillation guidelines contain new recommendations for risk stratification tools in determining the need for anticoagulant therapy and incorporate NOAC pharmacotherapy options for stroke prevention in patients with NVAF. NOACs offer several advantages over warfarin, including the elimination of routine laboratory monitoring, fewer drug and food interactions, and rapid therapeutic onset and offset. However, the lack of antidote in the case of serious bleeding and lack of data for long-term use in patient populations at risk for bleeding is problematic. Older adults are at high risk for thromboembolic and bleeding events as a result of anticoagulation and require special consideration when selecting anticoagulant therapy. The risk of drug accumulation and bleeding is concerning in the presence of renal impairment. The objective of this review is to provide the clinician with an update on the use of NOACs for NVAF, focusing on older adults and patients with renal impairment in light of recently published atrial fibrillation guidelines. Available data on using NOACs in coronary artery stenting, cardioversion, and ablation are also reviewed.

A quantitative professionalism policy in a community pharmacy introductory pharmacy practice experience.

OBJECTIVE: To determine whether implementing a quantitative professionalism policy would lead to improved behaviors in an introductory pharmacy practice experience (IPPE) and to evaluate students' attitudes about professionalism expectations in the IPPE. DESIGN: A policy using quantitative parameters for assessing unprofessional behaviors was developed and implemented in the community pharmacy IPPE after discrepancies were identified in the way professional expectations were assessed. ASSESSMENT: The quantitative professionalism policy reduced the number of assignments submitted post deadline (p<0.05). There was no change in students' attitudes towards professional behaviors after the implementation of the policy. CONCLUSION: The quantitative professionalism policy was effective in changing some of the students' professional behaviors in an IPPE.

Student preferences regarding teaching methods in a drug-induced diseases and clinical toxicology course.

OBJECTIVES: To determine which teaching method in a drug-induced diseases and clinical toxicology course was preferred by students and whether their preference correlated with their learning of drug-induced diseases. DESIGN: Three teaching methods incorporating active-learning exercises were implemented. A survey instrument was developed to analyze students' perceptions of the active-learning methods used and how they compared to the traditional teaching method (lecture). Examination performance was then correlated to students' perceptions of various teaching methods. ASSESSMENT: The majority of the 107 students who responded to the survey found traditional lecture significantly more helpful than active-learning methods (p=0.01 for all comparisons). None of the 3 active-learning methods were preferred over the others. No significant correlations were found between students' survey responses and examination performance. CONCLUSIONS: Students preferred traditional lecture to other instructional methods. Learning was not influenced by the teaching method or by preference for a teaching method.

Rifaximin: new therapeutic indication and future directions.

BACKGROUND: Rifaximin is a nonabsorbable oral antibiotic that acts locally in the gastrointestinal tract with minimal systemic adverse effects. Rifaximin received new labeling for reduction in the risk of the recurrence of overt hepatic encephalopathy (HE) in patients with advanced liver disease in March of 2010. OBJECTIVE: This article reviews the pharmacology, pharmacokinetics, and pharmacodynamics of rifaximin. The efficacy and safety of rifaximin in reducing the risk of the recurrence of overt HE in patients with advanced liver disease, the new US Food and Drug Administration-approved indication, is the focus of this review. Emerging data on the use of rifaximin in irritable bowel syndrome (IBS) and Clostridium difficile infection (CDI) are also evaluated. METHODS: MEDLINE and International Pharmaceutical Abstracts from 1983 to January 31, 2011, were searched using the key terms rifaximin, L/105, secondary hepatic encephalopathy, irritable bowel syndrome, and Clostridium difficile. Ongoing trials were identified using the clinicaltrials.gov Web site. Abstracts from the annual meetings of the American College of Gastroenterology and Digestive Disease Week from 2004 to 2010 and references from relevant articles were reviewed. Only trials examining use of rifaximin in secondary prophylaxis of HE were included. Studies on the efficacy and safety of rifaximin in the treatment of acute episodes of HE have been recently summarized elsewhere and are not reviewed here. RESULTS: Literature search identified one trial on rifaximin use in secondary prevention of HE, six trials in patients with IBS, and six small studies and case reports in patients with CDI. In a trial of 299 patients, use of rifaximin 550 mg by mouth twice daily for 6 months for prevention of recurrent HE was associated with significantly fewer breakthrough HE episodes compared with placebo (rifaximin 22%, placebo 46%; P < 0.001), with a hazard ratio of 0.42 (95% CI, 0.28-0.64). The rifaximin group also had fewer hospitalizations involving HE compared with placebo (rifaximin 13.6%, placebo 22.6%; P = 0.01), with a hazard ratio of 0.50 (95% CI, 0.29-0.87). Rifaximin improved IBS symptom management in ∼9% more patients than placebo in 2 prospective, randomized, double-blind, placebo-controlled trials of 1260 patients (in the rifaximin group, 40.8% patients reported IBS symptom improvement compared with 31.7% in the placebo group; P < 0.001). The efficacy of rifaximin has been reported for the treatment of refractory or recurrent CDI in small studies, case series, and a case report. Optimal dosing, duration, and role of rifaximin for CDI management is unclear. In clinical trials of rifaximin for prevention of recurrent HE and for nonconstipated IBS, its safety profile was comparable to placebo. In the trial of rifaximin for prevention of recurrent HE, the most common adverse events occurring in 10% to 15% of patients were ascites, dizziness, fatigue, and peripheral edema. Most common adverse effects in IBS trials included abdominal pain, diarrhea, bad taste, headache, and upper respiratory tract infection, occurring in <10% of patients. CONCLUSIONS: Rifaximin can be an effective option for reduction in the risk of the recurrence of HE in patients with advanced liver disease. Studies suggest that rifaximin provides relief of global symptoms of diarrhea-predominant IBS and bloating. Use of rifaximin in CDI requires further study.

Evaluation of the role of the critical care pharmacist in identifying and avoiding or minimizing significant drug-drug interactions in medical intensive care patients.

STUDY OBJECTIVE: The aim of the study was to evaluate the impact of prospective review of significant drug-drug interactions (DDIs) occurring in medical intensive care unit (MICU) patients by the critical care pharmacist participating in patient care rounds on improvement of safer and more efficacious medication use. STUDY DESIGN: A prospective consecutive 10-week study was conducted in the MICU, St Luke's/Roosevelt Hospital Center (St Luke's site), New York, NY. This study compared baseline period when clinical pharmacist services were not provided with the period when each patient's profile was reviewed daily during MICU rounds and interactions were minimized. The study examined whether the presence of critical care pharmacist would decrease the number of significant DDIs in the MICU. Impact of decreasing presence of severe DDIs on length of stay (LOS) and discharge status was also evaluated. RESULTS: Having a pharmacist on rounds resulted in statistically significant decrease in number of clinically important interactions requiring therapy modification, rated D-X (Poisson regression B = -1.036; 95% confidence interval, -1.318 to -0.753; P < .01). The coefficient (-1.036) indicates the incidence rate ratio of 0.35, meaning that the presence of clinical pharmacist in MICU rounds decreased DDI rate by 65%. According to the multiple linear regression, lower number of DDIs was associated with shorter LOS (P < .01). Inpatient mortality rate was lower in the intervention group compared with the preintervention group. Number of DDIs was not significantly associated with mortality based on simple regression (P = .45) or multiple regression analysis (P = .09). CONCLUSION: Implementing a DDI screening procedure results in significantly lower number of important DDI in the MICU and shortens LOS.

Certolizumab pegol for the management of Crohn's disease in adults.

BACKGROUND: Crohn's disease (CD) is an inflammatory disorder that can affect any portion of the gastrointestinal tract, from the mouth to the rectum. The American Gastroenterological Association recommends that treatment with anti-tumor necrosis factor (TNF)-alpha be considered in patients with moderate to severe CD refractory to concomitant aminosalicylates, corticosteroids, or immunosuppressive treatment, or who have contraindications to or poor tolerance of these agents. Anti-TNF-alpha agents available in the United States for the management of CD are infliximab, adalimumab, and certolizumab pegol. The latter is a recombinant humanized antibody Fab' fragment against TNF-alpha. It is conjugated with a 40-kDa polyethylene glycol molecule to increase the t(1/2) of the treatment to approximately 2 weeks. OBJECTIVE: The objective of this review was to extract and assess all relevant available data on the efficacy and tolerability of certolizumab pegol in the treatment of CD. METHODS: Searches of MEDLINE and International Pharmaceutical Abstracts from 1985 to March 3, 2009, were conducted using the key terms certolizumab pegol, CDP870, and Crohn's disease. Data from all available clinical trials published in English and ongoing trials were included in this review. The reference lists of the identified articles were searched for additional references. Data from abstracts presented at the annual meetings of the American College of Gastroenterology and Digestive Disease Week from 2004 to 2008 were reviewed and included if relevant. RESULTS: A total of 8 studies were included in this review (1474 patients). In Phase II trials, there were no significant differences between certolizumab pegol and inactive vehicle (placebo) in week-4 or week-12 clinical response or remission rates. In the first of 2 Phase III clinical trials, certolizumab pegol was associated with significantly greater rates of response compared with placebo at weeks 6 (37% vs 26%; P = 0.04) and 26 (22% vs 12%; P = 0.05) of induction treatment (data from patients with baseline CRP concentrations > or =10 mg/L). Response was defined as a decrease from baseline in CD activity index > or =100 at week 6 and at both weeks 6 and 26 in patients with baseline C-reactive protein > or =10 mg/L. Remission rates were not significantly different between the 2 groups. In the second Phase III trial, the proportion of patients in whom response was sustained up to 26 weeks was significantly greater with certolizumab pegol compared with placebo (63% vs 36%; P < 0.001). The tolerability profile of certolizumab pegol was similar to those of other anti-TNF-alpha agents and included an increased risk for infections (including opportunistic infections [eg, tuberculosis]) compared with placebo. Infusion and injection-site reactions were infrequent (3%) with certolizumab pegol treatment. The most common adverse events reported with certolizumab pegol treatment included upper respiratory infection (20%), immunogenicity (8%), and urinary tract infection (7%). No new unanticipated adverse events emerged during the 30-month tolerability follow-up. Certolizumab pegol is being assessed in patients with CD refractory to other medications, including other biologic agents. CONCLUSIONS: Based on the findings from the present review, certolizumab pegol had moderate efficacy in the treatment of moderate to severe, active CD. In well-designed Phase III clinical trials, certolizumab pegol was associated with significantly greater response rates compared with placebo at weeks 6 and 26 of induction treatment. In patients who responded to the 6-week induction, certolizumab pegol administered as a monthly subcutaneous injection was effective in maintaining CD response and remission. Findings from studies of certolizumab pegol in refractory CD are awaited.

Panitumumab: human monoclonal antibody against epidermal growth factor receptors for the treatment of metastatic colorectal cancer.

BACKGROUND: Panitumumab, formerly known as ABX-EGF, was the first recombinant human immunoglobulin G2 monoclonal antibody approved by the US Food and Drug Administration for the treatment of patients with epidermal growth factor receptor-expressing metastatic colorectal cancer (mCRC) refractory to fluoropyrimidine-, oxaliplatin-, and/or irinotecan-containing chemotherapeutic regimens. OBJECTIVE: The purpose of this review was to evaluate the pharmacokinetic and pharmacodynamic properties, clinical efficacy, and safety profile of panitumumab in the treatment of metastatic colorectal cancer. METHODS: Computerized searches of MEDLINE and International Pharmaceutical Abstracts from 1985 to August 15, 2007, were performed with the search terms panitumumab, ABX-EGF, EGFr, and colorectal cancer. All available clinical trials and ongoing trials were included in this review. Relevant abstracts presented at the annual meetings of the American Society of Clinical Oncology, American Association for Cancer Research, and Gastrointestinal Cancer Symposium (1999-2007) also were reviewed and included. RESULTS: Preclinical and clinical studies have established a role for panitumumab in mCRC refractory to multiple chemotherapeutic regimens. In a Phase III trial of panitumumab plus best supportive care (BSC) versus BSC alone in patients with refractory mCRC, panitumumab was found to have efficacy in time-related end points, such as progression-free survival. In the panitumumab group, a significant (46%) reduction in tumor progression rate was reported compared with BSC (hazard ratio, 0.54; 95% CI, 0.44-0.66; P < 0.001). At the present time, the use of panitumumab as first-line treatment for mCRC with standard chemotherapy and bevacizumab is not indicated due to increased toxicity with no advantage in efficacy. The efficacy of panitumumab is being evaluated in other solid tumors, such as lung, breast, ovarian, bladder, and head and neck cancers. CONCLUSION: Panitumumab appears to have relatively acceptable tolerability and is now available as an additional option for patients with mCRC refractory to multiple chemotherapeutic regimens.

Admissions to a medical intensive care unit related to adverse drug reactions.

PURPOSE: The frequency, severity, and preventability of adverse drug reactions (ADRs) leading to admission in a medical intensive care unit (MICU) were studied. METHODS: A prospective consecutive 19-week observational study was conducted between December 2004 and May 2005 in the department of critical care medicine at a tertiary care teaching hospital. Patients admitted to the MICU because of an ADR were followed prospectively until hospital discharge or death. The causality, severity, and preventability of each ADR were determined. Duration of MICU stay and overall duration of hospital stay were also assessed. RESULTS: A total of 281 patients were admitted to the MICU over the 19-week study period. Of these, 21 (7.5%) admissions were ADR related. Of the 21 ADRs analyzed, 3 (14%) were moderate, 14 (67%) were severe, and 4 (19%) were fatal. A total of 18 ADRs (86%) were deemed preventable. Drug interactions were the cause of 12 ADRs (57%), 100% of which were preventable. Aspirin was the most commonly implicated medication (28.6%). Bleeding was the most common ADR admission diagnosis (gastrointestinal bleeding accounted for 33% of all ADRs). ADR-related admissions resulted in an additional 119 total days of MICU stay and an additional 114 days of medical ward stay. CONCLUSION: The majority of the ADRs for which patients were admitted to an MICU were deemed preventable. Bleeding caused by some combination of nonsteroidal antiinflammatory drugs (NSAIDs), cyclooxygenase-2-selective NSAIDS, aspirin, and clopidogrel was the most common reason for ADR-related MICU admissions.

Thrombotic thrombocytopenic purpura induced by metronidazole vaginal gel.

Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening disorder characterized by microangiopathic hemolytic anemia and thrombocytopenia. Patients with TTP often have an increased reticulocyte count, elevated serum lactate dehydrogenase level, and decreased serum haptoglobin level. Other symptoms include fever, neurologic changes, and renal abnormalities. Thrombotic thrombocytopenic purpura may occur in association with various disorders or conditions, including infections, malignancies, pregnancy, and autoimmune disorders. The disorder may also be drug induced; however, antibiotics are not commonly implicated. A 58-year-old Hispanic woman went to her gynecology clinic and was prescribed metronidazole 0.75% vaginal gel for possible vaginal infection. Three days later, she came to the emergency department with complaints of chest pain and blood in her urine. A complete blood cell count was remarkable for a hemoglobin level of 10.2 g/dl (which decreased to 5.5 g/dl the next day), hematocrit of 29.1% (which decreased to 15.9% the next day), and platelet count of 11 x 10(3)/mm3. Based on these laboratory abnormalities and other clinical findings, the patient was diagnosed with TTP. She was treated with plasmapheresis and corticosteroids and initially responded; however, she relapsed twice, which required increasing the frequency of plasmapheresis, and vincristine and rituximab therapy. The patient's condition resolved, and she experienced no other complications. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship between the metronidazole vaginal gel and the development of TTP. This patient had developed TTP after only one exposure to metronidazole vaginal gel. Clinicians should be aware of this life-threatening adverse reaction to a commonly prescribed drug.

Entecavir: a new nucleoside analogue for the treatment of chronic hepatitis B.

Infection with hepatitis B virus (HBV) is extremely widespread - it infects two billion people out of the six billion world population. It is estimated that between 350 and 400 million people are chronically infected with HBV. Chronic HBV infection leads to development of complications, such as cirrhosis and hepatocellular carcinoma (HCC), which arise in 15-40% of patients. HBV-related liver disease and its complications result in approximately one million deaths each year. The ultimate goals of chronic hepatitis B (CHB) therapy are decreases in the incidence of cirrhosis, end-stage liver disease and HCC. The following six medications are currently approved by the U.S. Food and Drug Administration for the treatment of CHB: interferon (INF)-alpha2b, pegylated INF-alpha2a, lamivudine, adefovir dipivoxil, entecavir and, recently, telbivudine. Interferon therapy has many contraindications and commonly causes multiple intolerable adverse effects. Lamivudine therapy leads to increased development of resistant mutations with each year of use. Entecavir, a new guanosine nucleoside analogue with specific activity against HBV DNA polymerase, represents a third agent within the nucleoside/nucleotide HBV polymerase inhibitor class. It has distinct advantages over lamivudine and adefovir dipivoxil: it has a three-step mechanism of action, is the most potent inhibitor of HBV DNA polymerase, is not associated with any major adverse effects and has a limited potential for resistance. In clinical trials, entecavir was superior to lamivudine in all primary endpoints in both nucleoside-naive and lamivudine-refractory hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. Preliminary data support entecavir efficacy in patients with cirrhosis and HIV/HBV coinfected patients. No resistance occurred after two years of entecavir therapy in nucleoside-naive patients. Up to 9% resistance developed in patients with documented prior lamivudine resistance during 96 weeks of entecavir therapy. Currently, entecavir should be considered a first- or second-line treatment option for the management of HBeAg-positive or -negative nucleoside-naive or lamivudine-refractory CHB patients.

Lubiprostone: chloride channel activator for chronic constipation.

BACKGROUND: Chronic constipation is a common and costly health problem occurring in approximately 4.5 million Americans. Current management of constipation is suboptimal and requires a stepwise approach using a combination of laxatives to decrease symptoms. OBJECTIVE: The objective of this review was to describe the efficacy and safety of a new therapeutic entity, lubiprostone, recently approved by the US Food and Drug Administration for the treatment of chronic idiopathic constipation. METHODS: Computerized searches of MEDLINE and International Pharmaceutical Abstracts were conducted (1966-July 10, 2006). Search terms utilized were lubiprostone, RU-0211, and chronic constipation. References of selected articles were searched for additional articles or abstracts. All relevant published literature regarding lubiprostone was included in this review. Pertinent abstracts presented at meetings of the American College of Gastroenterology and Digestive Diseases Week were also included. RESULTS: Lubiprostone activates a chloride channel (ie, subtype 2) and increases chloride and fluid secretion into the intestines, resulting in relief of constipation. It is poorly absorbed after oral administration, and its metabolism occurs primarily in the stomach and jejunum. Lubiprostone was evaluated in 6 placebo-controlled, double-blind, randomized Phase II or III clinical trials. Overall, in clinical trials, >1400 patients were exposed to 24 mug of lubiprostone BID for up to 48 weeks. It improved the number of bowel movements, stool consistency, bloating, and global assessment of constipation compared with placebo (P < 0.05). Nausea was the most common adverse effect reported in clinical trials, occurring in 30.9% of patients. However, nausea was dose dependent and decreased when lubiprostone was given with food. CONCLUSIONS: Lubiprostone is the first in its class of chloride channel activators that results in improvement of symptoms of constipation. It has not been compared with other laxatives but, based on the available placebo-controlled studies, its efficacy is superior to placebo and its safety is acceptable. Considering the currently available laxatives, lubiprostone will become an additional option for the treatment of patients with chronic constipation.

A review of entecavir in the treatment of chronic hepatitis B infection.

BACKGROUND: Infection with the hepatitis B virus (HBV) affects two billion people worldwide, and an estimated 400 million people are chronically infected. Currently, FDA-approved regimens for the treatment of chronic HBV include interferon-alpha2b, peginterferon-alpha2a, lamivudine, adefovir dipivoxil, and recently, entecavir. OBJECTIVE: The purpose of this review is to evaluate the pharmacokinetic and pharmacodynamic properties, and the clinical efficacy and safety of entecavir in the treatment of nucleoside-naive and nucleoside-resistant HBeAg-positive and HBeAg-negative chronic hepatitis B (CHB). SEARCH METHODOLOGY: Computerized searches of PubMed and International Pharmaceutical Abstracts from 1985 to July 10, 2005, were performed with the search headings: entecavir, BMS-200475, and chronic hepatitis B. FINDINGS: Entecavir, a new deoxyguanosine analog, represents a third agent within the nucleoside/nucleotide HBV polymerase inhibitor class with distinct advantages over lamivudine and adefovir dipivoxil: it has a three-step mechanism of action, is the most potent inhibitor of HBV DNA polymerase, is not associated with any major adverse effects, and has a limited potential for resistance. In phase II and III clinical trials, entecavir was found to be superior to lamivudine for all primary endpoints evaluated in both nucleoside-naïve and lamivudine-resistant patients. Entecavir was effective in both HBeAg-positive and HBeAg-negative nucleoside-naïve patients. At this time, optimal duration of entecavir therapy is unknown. CONCLUSION: Entecavir represents a new first- or second-line treatment option for patients chronically infected with HBV. Long-term efficacy and safety studies as well as studies of entecavir in combination with interferon products or other nucleoside/nucleotide analogs are eagerly awaited.