indication

Used to accelerate the time to upper and lower gastrointestinal recovery following partial large or small bowel resection surgery with primary anastomosis. Also investigated for use in the treatment of pain (acute or chronic).

mechanism of action

Alvimopan competitively binds to mu-opioid receptor in the gastrointestinal tract. Unlike methylnaltrexone (another peripherally acting mu-receptor antagonist) that bears a quaternary amine, alvimopan owes its selectivity for peripheral receptors to its kinetics. Alvimopan binds to peripheral mu-receptors with a Ki of 0.2 ng/mL and dissociates slower than most other ligands.

biotransformation

Alvimopan undergoes no significant hepatic metabolism, but is metabolized by intestinal flora. Gut metabolism produces an active metabolite with no clinically significant contribution to drug effect.

absorption

Alvimopan's high affinity for the peripheral mu-receptor results in an absolute oral bioavailability of less than 7%.

half life

10 to 17 hours (gut metabolite: 10 to 18 hours)

route of elimination

Biliary secretion was considered the primary pathway for alvimopan elimination. Unabsorbed drug and unchanged alvimopan resulting from biliary excretion were then hydrolyzed to its ‘metabolite’ by gut microflora.

drug interactions

Buprenorphine: Opioids like buprenorphine may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Consider therapy modification.

Butorphanol: Opioid analgesics such as butorphanol may enhance the adverse/toxic effect of alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. According to alvimopan prescribing information, alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Monitor for increased alvimopan adverse effects in patients using opioids prior to alvimopan.