Anne Tucker

Crofelemer for the treatment of secretory diarrhea

Secretory diarrhea is a leading cause of morbidity and mortality worldwide. Crofelemer is a first-in-class antidiarrheal agent that simultaneously targets two distinct channels, the cystic fibrosis conductance regulator and calcium-activated chloride channel, responsible for chloride and fluid secretion in the GI tract. Crofelemer is a novel compound extracted from the stem bark latex of the Croton lechleri tree found in the western Amazonian region of South America. There is little to no systemic absorption of crofelemer when given orally and studies have shown minimal toxicity beyond mild gastrointestinal effects. In studies in diarrheal illness associated with primarily a secretory component, such as cholera, travelers’ diarrhea and acute infectious diarrhea, crofelemer has shown improvements in stool consistency and duration of symptoms. Less clear, but interesting, results have been observed in other diarrheal diseases associated with a mixed pathology, including diarrhea in patients with HIV and diarrhea-predominant irritable bowel syndrome.

Crofelemer for the treatment of chronic diarrhea in patients living with HIV/AIDS

Diarrhea is a common comorbidity present in patients with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) who are treated with highly active antiretroviral therapy. With a multifactorial etiology, this diarrhea often becomes difficult to manage. In addition, some antiretrovirals are associated with chronic diarrhea, which potentially creates an adherence barrier to antiretrovirals and may ultimately affect treatment outcomes and future therapeutic options for HIV. A predominant type of diarrhea that develops in HIV patients has secretory characteristics, including increased secretion of chloride ions and water into the intestinal lumen. One proposed mechanism that may lead to this type of secretory diarrhea is explained by the activation of the cystic fibrosis transmembrane conductance regulator and calcium-activated chloride channels. Crofelemer is a novel antidiarrheal agent that works by inhibiting both of these channels. The efficacy and safety of crofelemer has been evaluated in clinical trials for various types of secretory diarrhea, including cholera-related and acute infectious diarrhea. More recently, crofelemer was approved by the US Food and Drug Administration for the symptomatic relief of noninfectious diarrhea in adult patients with HIV/AIDS on antiretroviral therapy. Results from the ADVENT trial showed that crofelemer reduced symptoms of secretory diarrhea in HIV/AIDS patients. Because crofelemer is not systemically absorbed, this agent is well tolerated by patients, and in clinical trials it has been associated with minimal adverse events. Crofelemer has a unique mechanism of action, which may offer a more reliable treatment option for HIV patients who experience chronic secretory diarrhea from antiretroviral therapy.

Crofelemer, a novel antisecretory agent approved for the treatment of HIV-associated diarrhea.

Secretory diarrhea has a significant impact on morbidity and mortality worldwide and may be a predominant or minor component of pathogenesis in diarrhea of various etiologies. Crofelemer is a first-in-class antidiarrheal medication with unique inhibitory mechanisms at both the cystic fibrosis transmembrane conductance regulator and the calcium-activated chloride channels which are responsible for chloride secretion and subsequent luminal hydration. The efficacy of crofelemer has been investigated in patients with HIV-associated diarrhea, diarrhea of various infectious etiologies, as well as diarrhea-predominant irritable bowel syndrome. Crofelemer was approved by the FDA in December 2012 to treat diarrhea in HIV/AIDS patients on antiretroviral therapy. Crofelemer is not absorbed in the body and well-tolerated in small trials performed to date although long-term safety data is lacking. Crofelemer may be an important addition to the currently available drugs for the management of secretory diarrhea.

Significant Published Articles for Pharmacy Nutrition Support Practice in 2014 and 2015

Purpose To assist the pharmacy clinician engaged in nutrition support in staying current with the most pertinent literature. Methods Several experienced board-certified clinical pharmacists engaged in nutrition support therapy compiled a list of articles published in 2014 and 2015 that they considered to be important to their practice. Only those articles available in print format were considered for potential inclusion. Articles available only in preprint electronic format were not evaluated. The citation list was compiled into a single spreadsheet where the author participants were asked to ascertain whether they considered the paper important to nutrition support pharmacy practice. A culled list of publications was then identified whereby the majority of author participants (at least 5 out of 8) considered the paper to be important. Results A total of 108 articles were identified; 36 of which were considered to be of high importance. An important guideline article published in early 2016, but not ranked, was also included. The top-ranked articles from the primary literature were reviewed. Conclusion It is recommended that the informed pharmacist, who is engaged in nutrition support therapy, be familiar with the majority of these articles.

Significant Published Articles for Pharmacy Nutrition Support Practice in 2016

Purpose: To assist the pharmacist engaged in nutrition support therapy in staying current with pertinent literature. Methods: Several clinical pharmacists engaged in nutrition support therapy compiled a list of articles published in 2016 considered important to their clinical practice. The citation list was compiled into a single spreadsheet where the author participants were asked to assess whether the paper was considered important to nutrition support pharmacy practice. A culled list of publications was then identified whereby the majority of author participants (at least 5 out of 8) considered the paper to be important. Guideline and consensus papers from professional organizations, important to practice but not scored, were also included. Results: A total of 103 articles were identified; 10 from the primary literature were voted by the group to be of high importance. An additional 11 organizational guidelines, position, recommendation, or consensus papers were also identified. The top-ranked articles from the primary literature were reviewed. Conclusion: It is recommended that pharmacists, engaged in nutrition support therapy, be familiar with the majority of these articles as it pertains to their practice.

Validation Study of Energy Requirements in Critically Ill, Obese Cancer Patients

BACKGROUND Current guidelines from the American Society for Parenteral and Enteral Nutrition and the Society of Critical Care Medicine (ASPEN/SCCM) regarding caloric requirements and the provision of nutrition support in critically ill, obese adults may not be suitable for similar patients with cancer. We sought to determine whether the current guidelines accurately estimate the energy requirements, as measured by indirect calorimetry (IC), of critically ill, obese cancer patients. MATERIALS AND METHODS This was a retrospective validation study of critically ill, obese cancer patients from March 1, 2007, to July 31, 2010. All patients ≥18 years of age with a body mass index (BMI) ≥30 kg/m(2) who underwent IC were included. We compared the measured energy expenditure (MEE) against the upper limit of the recommended guideline (25 kcal/kg of ideal body weight [IBW]) and MEE between medical and surgical patients in the intensive care unit. RESULTS Thirty-three patients were included in this study. Mean MEE (28.7 ± 5.2 kcal/kg IBW) was significantly higher than 25 kcal/kg IBW (P < .001), and 78% of patients had nutrition requirements greater than the current guideline recommendations. No significant differences in MEE between medical and surgical patients in the ICU were observed. CONCLUSIONS Critically ill, obese cancer patients require more calories than the current guidelines recommend, likely due to malignancy-associated metabolic variations. Our results demonstrate the need for IC studies to determine the energy requirements in these patients and for reassessment of the current recommendations.

Hang Height of Enteral Nutrition Influences the Delivery of Enteral Nutrition.

PURPOSE Adequate enteral nutrition (EN) delivery to critically ill patients is difficult to achieve. Given the large number of unpreventable influences affecting adequate caloric intake, further research on preventable influences of adequate EN administration is warranted. The purpose of this study was to evaluate whether hang height of EN formula, formula viscosity, or flow rate influences pump accuracy and formula delivery. METHODS Formulas of varying viscosities (1.0, 1.5, and 2.0 kcal/mL) were infused at different hang heights (0, 6, 12, and 18 inches) and rates (20, 40, and 80 mL/h). The mean percent difference and the bias between the programmed volume, volume reported, and volume delivered were calculated for the different hang heights, formula compositions, and infusion rates studied. RESULTS For all prespecified hang heights and infusion rates, the volume delivered was less than the programmed volume and volume reported; the mean percent difference increased as the hang height decreased. The volume was overestimated for both the programmed volume (14.4% ± 5.5%) and volume reported (12.9% ± 6.7%) compared with volume delivered. The overestimation bias was significantly influenced by differences in hang height as well as type of formula (P < .0001, each) but not by rate of delivery (P = .4633 for programmed volume and .8411 for volume reported). CONCLUSIONS Measures should be taken in clinical practice to ensure adequate hang height of EN. Appropriate hang height of EN may result in more accurate delivery of nutrition provisions to the critically ill patient and subsequently reduce complications related to underfeeding.