New Drug of the day : Alvimopan

New Pharmacological Drug Classes Introduced in 2008 

Alvimopan : is a peripherally acting μ-opioid receptor antagonist indicated to accelerate gastrointestinal tract recovery following bowel surgery. Use of the drug beyond 7 days is not recommended because of adverse findings related to cardiovascular events and cancer rates .

Alvimopan is a zwitterion with a relatively high molecular weight (461 Da) and low lipophilicity; these physical characteristics hinder penetration of the drug into the central nervous system and account for the predominantly peripheral action.

On average, post-operative patients receiving alvimopan recover GI function 17 hours earlier than patients given placebo. While a faster recovery logically translates to a reduction in the length of hospitalization due to postoperative ileus, the clinical and economic significance of the improved outcome remains unproven.

During pre-marketing clinical trials, the most common adverse reactions among bowel resection patients receiving alvimopan were anemia, dyspepsia, hypokalemia, back pain, and urinary retention. Vigorous gastrointestinal side effects (including abdominal pain, nausea, vomiting, and diarrhea) can be expected when opioid-tolerant patients are given alvimopan, so patients who have taken opioids for the 7 consecutive days immediately prior to surgery should not be considered candidates for the drug.

The oral bioavailability of alvimopan is low (~6%). 

An active metabolite is formed in the gut by intestinal microflora. Since both the parent and metabolite are p-glycoprotein substrates, clinically significant drug interactions may surface with strong p-glycoprotein inhibitors (e.g., verapamil, cyclosporine, amiodorone, itraconazole, quinine, spironolactone, quinidine, diltiazem, and bepridil). 

Biliary secretion is the primary pathway of elimination for unabsorbed alvimopan and the metabolite formed in the gut is eliminated in the feces and urine as unchanged metabolite, the glucuronide conjugate, and other minor metabolites. 

The half-life of alvimopan and the gut metabolite ranges from 10 to 18 hours. The drug accumulates approximately 10-fold in patients with severe hepatic impairment, thereby precluding administration to this group.