Alvimopan is indicated in people to avoid postoperative ileus following partial large or small bowel resection with primary anastomosis. Alvimopan accelerates the gastrointestinal recovery period as defined by time to first bowel movement or flatus.[6]
The most common side effects associated with alvimopan are:[2]
Adverse Effect
Frequency (%) with placebo
Frequency (%) with alvimopan
Dyspepsia
4.6
7.0
Hypokalemia
8.5
9.5
Back Pain
1.7
3.3
Delayed Micturition
2.1
3.2
Contraindications
Alvimopan is absolutely contraindicated in patients who have taken therapeutic doses of opioids for more than seven consecutive days immediately prior to when alvimopan would be initiated because individuals with recent exposure to opioids are expected to be more sensitive to the effects of μ-opioid receptor antagonists. The peripheral site of action of alvimopan suggests that such a heightened sensitivity would precipitate gastrointestinal effects beyond dyspepsia.[6]
Alvimopan is a competitiveantagonist of the μ-opioid receptors (MOR) in the gastrointestinal tract, with a Ki of 0.2 ng/mL. Activation of these receptors by endogenous or exogenous agonists reduces gastrointestinal motility, and alvimopan blocks this effect. Like most other peripherally-selective MOR antagonists, such as naloxegel and methylnaltrexone, alvimopan is selective for peripheral receptors because is effluxed by P-glycoprotein, which reduces its ability to cross the blood-brain barrier and affect the central nervous system.[9][6]
Pharmacokinetics
Absorption
Peak plasma concentration (Cmax) of alvimopan is reached approximately 2 hours after oral dosing, while the Cmax for metabolite occurs 36 hours after an oral dose. Alvimopan's high affinity for the peripheral μ-receptor results in an absolute bioavailability less than 7%.[6]
Distribution
80% to 90% of systemically available alvimopan is bound to plasma protein. At steady state, the volume of distribution is approximately 30 liters.[6]
Metabolism
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.[6]
Elimination
Alvimopan undergoes 35% renal excretion and greater than 50% biliary excretion. Drug metabolized by intestinal flora is excreted in the feces. Alvimopan's half-life of elimination is 10 to 17 hours, while that of the gut metabolite is 10 to 18 hours.[6]
Dosing and administration
Alvimopan is required by the FDA to participate in Risk Evaluation and Mitigation Strategy (REMS) to ensure safe use. Alvimopan is only approved for short term use of no more than 15 doses. It is available on an inpatient basis at institutions approved by and registered with the Entereg Access Support and Education (E.A.S.E.) program. A person should receive no more than 15 doses.[6]
^Sharma A, Jamal MM (July 2013). "Opioid induced bowel disease: a twenty-first century physicians' dilemma. Considering pathophysiology and treatment strategies". Current Gastroenterology Reports. 15 (7): 334. doi:10.1007/s11894-013-0334-4. PMID23836088. S2CID32265790.
^ abcdefghiAlvimopan Product Label as approved by the FDA on May 20, 2008.
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