Pharmacy & Therapeutics - October 2008 - (Page 574)

DRUG FORECAST Alvimopan (Entereg), a Peripherally Acting mu-Opioid Receptor Antagonist For Postoperative Ileus Goldina Ikezuagu Erowele, PharmD INTRODUCTION In 2007, Goldstein et al. sought to determine the economic burden attributed to the management of postoperative ileus (POI) associated with abdominal surgery in the U.S. Their study revealed an annual national hospital cost of $1.46 billion for both the index hospitalization and any readmissions within 30 days.1 POI is one of the expected complications of major abdominal surgery. It can occur with other procedures, including extraperitoneal, gynecological, joint replacement, and cardiovascular surgeries,1,2 and it is the most common cause of delayed hospital discharge after abdominal surgery.2,3 POI is the impairment of gastrointestinal (GI) motility after intra-abdominal surger y or other non-abdominal procedures. It affects all segments of the GI tract and may last from five to six days or even longer, and it has the potential to delay GI recovery and hospital discharge until its resolution. POI is characterized by abdominal distention and bloating, nausea, vomiting, pain, accumulation of gas and fluids in the bowel, and delayed passage of flatus and defecation (Table 1). It is the result of a multifactorial process that includes inhibitory sympathetic input and the release of hormones, neurotransmitters, and other mediators (e.g., endogenous opioids). A component of POI also results from Disclosure: The author has no financial arrangement or commercial or industrial relationships to report in regard to this article. an inflammatory reaction and the effects of opioid analgesics. Morphine and other mu-opioid receptor agonists are universally used for the treatment of acute postsurgical pain; however, they have an inhibitory effect on GI tract motility and may prolong the duration of POI. 1–6 These changes result in decreased motility and inhibition of propulsive motion.3,4 Because opioid receptors are present in the GI tract, when opioids bind to these receptors, they can disrupt normal GI function, which allows for the passage of food through the GI tract. Consequently, POI can cause significant discomfort and pain.2 POI is associated with longer hospital stays and a high utilization of health care resources.1–3 The duration of POI varies among patients and is associated with delayed enteral feeding, resulting in a negative impact on postoperative pain management and an increased risk of other postoperative morbidities.2,3 Despite the consequences of the possible causative factors, the ensuing clinical injury associated with POI is characterized by abdominal distention and a delay in the return to normal bowel function.1,3 partial large-bowel or small-bowel resection with primary anastomosis.3,6,7 It is the first FDA-approved therapy for POI and is available for short-term use in hospitals. The drug is registered under the Entereg Access Support and Education (EASE) program.2 CLINICAL PHARMACOLOGY Alvimopan is a mu-opioid receptor antagonist with a considerably greater binding affinity for mu-opioid receptors than for delta- and kappa-opioid receptors. Following oral administration, the drug antagonizes the peripheral effects of opioids on GI motility and secretion by competitively binding to mu-opioid receptors in the GI tract. By working peripherally, alvimopan effectively antagonizes the GI motility ef fects of an algesics (such as morphine) without reversing central analgesic efficacy. Alvimopan is a white to light beige powder with a molecular weight of 460.6. The empirical formula is C25H32N2O4 • 2 H2O (Figure 1). At physiological pH, alvimopan is zwitterionic, a property that contributes to its low solubility because of the ion’s ability to carry a positive and negative charge at the same time.6,7 INDICATION AND USAGE In May 2008, the U.S. Food and Drug Administration (FDA) approved alvimopan (Entereg, Adolor/ GlaxoSmith Kline), a selective, quaternary, peripherally acting mu-opioid receptor (PAM-OR) antagonist, for accelerating upper and lower GI tract recovery after PHARMACOKINETICS AND PHARMACODYNAMICS In healthy subjects, the plasma concentration of alvimopan peaks approximately two hours after ingestion. The drug’s oral bioavailability is approximately 6% (range, 1%–19%). Because of its Table 1 Clinical Features and Consequences of Postoperative Ileus Nausea Vomiting Inability to eat Bowel distention Patient discomfort Delayed enteral feeding No flatus or bowel movement Cost: more than $1 billion per year Dr. Erowele is a Clinical Pharmacy Specialist at Harris County Hospital District in Houston, Texas. Drug Forecast is a regular column coordinated by Alan Caspi, PhD, PharmD, MBA, President of Caspi & Associates in New York, New York. Data from Wolff BG, Leslie JB, Saclarides TJ, et al. Contemp Sugery 2006(Suppl):1–24.3; Foss JF, Fisher DM, Schmith VD. Clin Pharmacol Ther 2008;83(5):770–776;4 and Alvimopan (Entereg), package insert.6 continued on page 580 574 P&T® • October 2008 • Vol. 33 No. 10

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Pharmacy & Therapeutics - October 2008 Contents Editorial Medication Errors Prescription: Washington New Drugs/Drug News/ New Medical Devices Drug Forecast Medical Management of Parkinson’s Disease Why Is Health Care Regulation So Complex? The Next President’s Prescription for Action on Drugs Trends in Managing Multiple Sclerosis Product Profiler: Sancuso®

Pharmacy & Therapeutics - October 2008

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