Approved May 20, 2008

ALVIMOPAN
(FDA Category 1S)

ENTEREG (Adolor, Inc) is a peripherally acting muopioid receptor antagonist. It antagonizes the peripheral effects of opioids on gastrointestinal motility and secretion but does not reverse the central analgesic effects of mu-opioid agonists.

DOSING INFORMATION: The usual recommended dose is 12 mg orally 30 minutes to 5 hours prior to surgery followed by 12 mg orally twice daily beginning the day after surgery. Alvimopan should be administered for a maximum of 7 days or until hospital discharge. No more than 15 doses of alvimopan should be administered.

PHARMACOKINETICS: Plasma alvimopan concentration peaked 2 hours after oral administration to healthy volunteers. The absolute bioavailability was approximately 6% (range, 1% to 19%). The plasma protein binding of alvimopan and its metabolite (an amide hydrolysis compound) averaged 80% and 94%, respectively. Both alvimopan and its metabolite were bound to albumin and not to alpha-1 acid glycoprotein. An amide hydrolysis compound is present in the systemic circulation and is considered a product exclusively of intestinal flora metabolism. There is no evidence that the liver plays a significant role in metabolism. The mean terminal half-life after multiple oral doses ranged from 10 to 17 hours.

CAUTIONS: Alvimopan is available only for short-term (15 doses) use in hospitalized patients. Only hospitals that have registered in and met all of the requirements for the ENTEREG(R) Access Support and Education (E.A.S.E.) program may use alvimopan. The use of opioids for more than 7 consecutive days immediately prior to taking alvimopan is contraindicated. Not recommended in patients with complete bowel obstruction correction surgery, severe hepatic impairment, and end-stage renal disease. The risk of diarrhea, gastrointestinal pain, cramping is increased in patients with severe renal impairment and mild-to moderate hepatic impairment. Common adverse events include hypokalemia, constipation, flatulence, indigestion, anemia, backache, and urinary retention. Myocardial infarction has been reported.

FDA APPROVED INDICATIONS: Indicated as short-term, in-hospital treatment (maximum 15 doses) to accelerate time to lower and upper gastrointestinal recovery in patients who have undergone partial large or small bowel resection surgery with primary anastomosis.