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Safety and Efficacy of Methylnaltrexone in Shortening the Duration of Postoperative Ileus Following Segmental Colectomy: Results of Two Randomized, Placebo-Controlled Phase 3 Trials

Yu, Chang Sik M.D., Ph.D.1; Chun, Ho-Kyung M.D.2; Stambler, Nancy M.S.3; Carpenito, Jennifer3; Schulman, Seth M.D.4; Tzanis, Evan4; Randazzo, Bruce M.D., Ph.D.4

Diseases of the Colon & Rectum: May 2011 - Volume 54 - Issue 5 - p 570-578
doi: 10.1007/DCR.0b013e3182092bde
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PURPOSE: Postoperative ileus contributes to surgical morbidity and is associated with prolonged hospitalization and increased health care costs. The efficacy and safety of the peripherally acting μ-opioid receptor antagonist methylnaltrexone in shortening the duration of postoperative ileus following segmental colectomy was evaluated.

METHODS: Two identically designed, multicenter, double-blind, parallel-group, placebo-controlled studies randomly assigned patients undergoing segmental colectomy (study 1, N = 515; study 2, N = 533) to receive 12 or 24 mg of methylnaltrexone intravenously or placebo every 6 hours starting within 90 minutes of surgery completion, continuing for up to 10 days or up to 24 hours after gastrointestinal recovery. The primary efficacy end point was the time from the end of surgery to the first bowel movement. Safety was evaluated via standard assessments (ie, adverse events and related withdrawals, physical examinations, laboratory tests, vital signs, electrocardiograms) and assessment of surgical complications.

RESULTS: The primary and secondary efficacy outcomes (time to discharge eligibility, time to hospital discharge, and clinically meaningful events of nausea and vomiting following segmental colectomy) did not differ significantly between patients treated with either a dose of methylnaltrexone or with placebo. Rates of adverse events and serious adverse events were comparable across all treatment groups in both studies. The most commonly observed adverse events were nausea, pyrexia, and vomiting.

CONCLUSIONS: Although the efficacy of methylnaltrexone in reducing the duration of postoperative ileus was not demonstrated in these studies, intravenous methylnaltrexone at doses of 12 mg and 24 mg was safe, in general, and well tolerated in postcolectomy patients. The utility of intravenous methylnaltrexone in treating postoperative ileus remains unproven.

1University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea

2Samsung Medical Center, Seoul, Korea

3Progenics Pharmaceuticals, Tarrytown, New York

4Pfizer Inc, Collegeville, Pennsylvania

Funding/Support: This research was funded by Wyeth Pharmaceuticals, which also provided support for the preparation of this article.

Financial Disclosure: At the time of this study, Seth Schulman, Evan Tzanis, and Bruce Randazzo were employees of Wyeth Pharmaceuticals, which was acquired by Pfizer Inc in October 2009. No author received an honorarium or other form of financial support related to the development of this article.

Chang Sik Yu and Ho-Kyung Chun contributed equally to the research, design, and preparation of this article.

Clinical Trials: http://www.clinicaltrials.gov Registry numbers, NCT00387309 and NCT00401375.

Correspondence: Chang Sik Yu, M.D., Ph.D., Asan Medical Center, Division of Colorectal Surgery, Department of Surgery, 388-1 Pungnap-2 Dong, Songpa-Gu, Seoul 138-736, Korea. E-mail: csyu@amc.seoul.kr

© The ASCRS 2011