Company:

Adolor and GlaxoSmithKline

Opioid antagonist (peripheral)

Alvimopan 12mg; caps.

To accelerate the time to upper and lower gastrointestinal recovery after partial large or small bowel resection surgery with primary anastomosis.

Postoperative ileus, the impairment of normal GI motility following surgery, has several contributing factors, including the use of morphine and other mu-opioid receptor agonists, inhibitory sympathetic input, the release of endogenous opioids, as well as an inflammatory component. Following surgery, abdominal pain, distention, bloating, nausea, vomiting, and gas and fluid accumulation in the GI tract may delay recovery and can last ≥6 days, possibly resulting in longer hospital stays. Alvimopan is a peripherally-acting mu-opioid receptor blocker that antagonizes the effects of opioids on GI motility and secretion without affecting the analgesic effects of mu-opioid agonists such as morphine.

Five placebo-controlled trials were conducted to evaluate the efficacy of alvimopan in the management of postoperative ileus. Patients ≥18yrs old undergoing partial large or small bowel resection with anastomosis or total abdominal hysterectomy under general anesthesia were randomly assigned to receive alvimopan or placebo. In these 5 studies, 1096 patients were randomized to receive alvimopan, and 1081 patients were given placebo. Intrathecal and epidural opioids were prohibited, but there was no limitation placed on the type of general anesthesia used. An accelerated post-op care plan was used: early NG tube removal, early ambulation, and early diet advancement as tolerated.

The primary endpoint was time to resolution of postoperative ileus (a composite measure of upper and lower GI recovery). For those undergoing bowel resection, the use of alvimopan was associated with a shortened time to recovery of GI function (a composite of tolerance of solid food and first bowel movement) and time to discharge order written, compared to placebo. The mean differences in hours for the composite measure for each of the five studies were 19.8, 26.1, 14.0, 13.2, and 10.7. The use of alvimopan was not associated with a reversal of opioid analgesia.

In a 12-month study in patients being treated with opioids for chronic pain, the use of alvimopan was associated with an increase in reports of MI, compared to placebo; a causal relationship has not been established.

12mg orally 30min to 5 hours before surgery, then 12mg twice daily starting on 1st post-op day for up to 7 days or until hospital discharge (max 15 doses).

Not recommended.

Opioid use, at therapeutic doses, for >7 consecutive days prior.

For hospital use only. Severe hepatic impairment or end stage renal disease: not recommended. Mild-to-severe renal dysfunction or mild-to-moderate hepatic impairment (monitor; discontinue if adverse reactions occur). Recent (within 1 week) use of more than 3 doses of opioids. Pregnancy (Cat.B). Nursing mothers.

Dyspepsia, constipation, flatulence, back pain, urinary retention.

Available only to hospitals that enroll in Entereg Access and Support Program (EASE). For more information, and to enroll, call (866)-4ADOLOR.

Caps—30

6/26/08