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MICHAEL D. KRAFT, PHARM.D., is Clinical Assistant Professor, University of Michigan, College of Pharmacy, and Clinical Coordinator and Clinical Pharmacist, University of Michigan Health System, 1500 East Medical Center Drive, Ann Arbor, MI 48109 (mdkraft{at}umich.edu).

Purpose. Characteristics of the ideal drug therapy for postoperative ileus (POI); the pharmacology, efficacy, and safety of currently available nonselective opioid antagonists and the new peripherally selective opioid antagonists methylnaltrexone and alvimopan for the treatment of POI; and formulary considerations associated with the introduction of these new POI drug therapies are discussed. Summary. The ideal drug therapy for treating POI would selectively antagonize the inhibitory effects on the gastrointestinal (GI) tract of all of the potential factors implicated in the pathophysiology of POI (neurogenic, inflammatory, hormonal, and pharmacologic mediators). The most promising target to date is inhibition of the adverse GI effects of endogenous and exogenous opioids. Selective inhibition of the µ-opioid receptors in the GI tract, without reversing centrally mediated opioid-induced analgesia, may be beneficial in reducing POI. The nonselective opioid antagonists naloxone and nalmefene have not been studied for POI, and they cross the blood–brain barrier. Therefore, they are not appropriate for preventing or treating POI. The peripherally selective opioid antagonist methylnaltrexone shortens the duration of POI and the hospital length of stay (LOS). Alvimopan, a more extensively studied peripherally selective opioid antagonist, has been shown to reduce the duration of POI, frequency of postoperative nausea and vomiting, and hospital LOS. Both methylnaltrexone and alvimopan also appear effective for treating opioid-induced constipation. Preliminary results of a long-term study of alvimopan safety have revealed some potential concerns, and the significance of the adverse effects must be understood before the most appropriate role of alvimopan in patient care can be determined. Restricting the prescribing of new POI drug therapies to certain types of patients, surgeries, and prescribers; incorporating these therapies into preoperative and postoperative policies, procedures, and protocols; and the potential cost savings from reducing hospital LOS are among the considerations in adding these agents to health-system formularies. Conclusion. Peripherally selective opioid receptor antagonists are promising new drug therapies that can reduce the clinical and economic burden of POI. Index terms: Alvimopan; Blood brain barrier; Drugs, body distribution; Economics; Formularies; Hospitals; Ileus; Mechanism of action; Methylnaltrexone; Nalmefene; Naloxone; Opiate antagonists; Opiates; Pharmacokinetics; Postoperative complications; Postoperative nausea and vomiting; Protocols; Toxicity