Alvimopan (Entereg): Peripherally acting mu-opioid receptor antagonist approved to accelerate the time to upper and lower GI recovery after bowel surgery

NME: Alvimopan (Entereg), a peripherally acting mu-opioid receptor antagonist, was approved on May 20, 2008, to accelerate the time to upper and lower GI recovery after partial large or small bowel resection surgery with primary anastomosis.

Alvimopan is a selective antagonist of the human mu-opioid receptor; by competitively binding to gastrointestinal (GI) tract mu-opioid receptors, this agent antagonizes the effects of opioids on GI motility and secretion. This agent was approved on May 20, 2008, to accelerate the time to upper and lower GI recovery after partial large or small bowel resection surgery with primary anastomosis.

Efficacy. The efficacy of alvimopan was assessed in 5 multicenter, randomized, double-blind, parallel-group, placebo-controlled studies. Patients (aged ≥18 y) undergoing partial large or small bowel resection surgery with primary anastomosis or total abdominal hysterectomy under general anesthesia were randomized to receive either alvimopan 12 mg or placebo; the initial dose was administered 30 minutes to 5 hours before the start of surgery, and subsequent doses were administered twice daily beginning on the first day after surgery and thereafter until hospital discharge or for ≤7 days. All patients were scheduled to receive either intravenous (IV) patient-controlled opioid analgesia or bolus parenteral administration of opioids (IV or intramuscular [IM]). The primary end point was time to resolution of postoperative ileus, measured by time to toleration of solid food and time to first bowel movement. In all of the studies, alvimopan accelerated the time to recovery of GI function compared with placebo, with mean treatment differences for time to GI recovery ranging from 10.7 hours to 26.1 hours and HRs ranging from 1.299 to 1.625 across the 5 studies.

Safety. Alvimopan is available only to hospitals that have enrolled in the Entereg Access Support and Education (EASE) program; this program requires that hospital staff receive educational materials about the need to limit treatment with alvimopan to short-term (≤15 doses), inpatient use and mandates that alvimopan is not to be dispensed to patients after hospital discharge. More myocardial infarctions (MIs) were reported in patients taking alvimopan 0.5 mg twice daily versus those taking placebo in a 12-month study; this increased frequency of MIs was not observed in other trials of alvimopan. Patients who were recently exposed to opioids may be more sensitive to the effects of mu-opioid receptor antagonists, which could result in abdominal pain, nausea, vomiting, and diarrhea. Alvimopan is not recommended for use in patients with severe hepatic impairment or with end-stage renal disease. This agent is also not recommended in patients undergoing surgery for correction of a complete bowel obstruction. The most common adverse events associated with alvimopan treatment include constipation, hypokalemia, flatulence, dyspepsia, anemia, urinary retention, and back pain.