Alvimopan is a peripherally acting mu-opioid receptor (PAM-OR) antagonist that has been studied for the treatment of opioid-induced bowel dysfunction. Alvimopan counteracts the effects of opioids on gastrointestinal motility and secretion. The drug is available as a capsule to take by mouth and has been evaluated in opioid-induced constipation.
Ahmedzai, S.H., & Boland, J. (2010, April). Constipation in people prescribed opioids. Clinical Evidence, 2407.
To answer the following questions: What are the effects of oral laxatives, rectal preparations, and opioid antagonists for constipation in people prescribed opioids?
Databases searched were MEDLINE, Embase, Cochrane Central Register of Controlled Trials and Library, NHS Centre for Reviews and Dissemination (CRD), Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment, TRIP, and the National Institute for Health and Clinical Excellence (NICE) up to August 2009. Alerts from the U.S. Food and Drug Administration and the U.K. Medicines and Healthcare Products Regulatory Agency were included to identify any adverse effects.
Search keyword were constipation and opioids, Lactulose, macrogols, senna, bisacodyl, co-danthrusate/co-danthramer, docusate, ispaghula husk, liquid paraffin, magnesium salts, methylcellulose, arachis oil enema, glycerol suppository, phosphate enema, sodium citrate enema, and opioid antagonists.
Studies were included in the review if they
The GRADE System was used to evaluate study quality. Full information is available online with a subscription.
The final sample comprised 23 systematic reviews, RCTs, or observational studies. This was an update of a previous review that added 1 systematic review and 5 RCTs, with no change in overall recommendations provided.
Nurses should be aware of potential implications related to the use of opioid antagonists in controlling constipation for opioid interactions and changes in pain control. In addition, nurses should routinely assess for pain relief, as well as symptoms of constipation, in this patient population.
Becker, G., Galandi, D., & Blum, H.E. (2007). Peripherally acting opioid antagonists in the treatment of opiate-related constipation: A systematic review. Journal of Pain and Symptom Management, 34, 547-565.
To evaluate evidence on the effectiveness of the peripherally acting mu-receptor antagonists alvimopan and methylnaltrexone in the management of opioid-induced constipation.
Databases searched were Ovid MEDLINE, Biological Abstracts, BIOSIS Previews, CINAHL, Evidence-Based Medicine Reviews (EBMR) (Cochrane Database of Systematic Reviews, ACP [American College of Physicians] Journal Club, Database of Abstracts of Reviews of Effectiveness [DARE], and the Cochrane Central Register of Controlled Trials [1966-May 2005]), PubMed (1996-May 2005), CancerLit (1963-June 2005), and Embase (1980-May 2002). A hand search also was conducted on bibliographies of books about palliative care. From that hand search, reference citations concerning constipation were identified to find additional clinical trials to include in the review.
Search keywords were constipation, intestinal obstruction, opioid bowel dysfunction, opioid related constipation, opioid-related disorders, peripherally acting opioid antagonist, opioid antagonist, opioid mu receptors, narcotic antagonists/naltrexone, methylnaltrexone, and alvimopan.
Studies were included in the review if
Studies were excluded if they had a small sample size (fewer than 10 participants) or used the Rome Diagnostic Criteria to define constipation.
Ten studies were appropriate for this review. However, four of the 10 had two or three parts performed in different populations or using different dosing regimens. The differing parts were treated as different studies and assessed individually, yielding 15 studies (10 randomized controlled trials and five phase II studies addressing dose and toxicity).
This systematic review looked mainly at the efficacy of using the peripherally acting opioid antagonists methylnaltrexone (nine studies) and alvimopan (six studies) in managing opioid-induced constipation. Internal validity of the studies was high, indicating methylnaltrexone and alvimopan may be effective in relieving opioid-induced constipation. However, most study participants were healthy volunteers or members of methadone programs.
Taguchi, A., Sharma, N., Saleem, R.M., Sessler, D.I., Carpenter, R.L., Seyedsadr, M., & Kurz, A. (2001). Selective postoperative inhibition of gastrointestinal opioid receptors. New England Journal of Medicine, 345, 935–940.
To evaluate the effects of alvimopan on postoperative gastrointestinal (GI) function and length of hospitalization.
Alvimopan is an investigational opioid antagonist with limited oral absorption that does not readily cross the blood-brain barrier and, therefore, acts on the peripheral opioid receptors in the GI tract without affecting analgesia in patients taking opioids. Doses used in the study were 1 mg and 6 mg by mouth. On the day of surgery, patients were randomly assigned in equal proportions to one of three arms using computer-generated randomization stratified according to type of surgery. The three arms were 1 mg of alvimopan, 6 mg of alvimopan, or an identical appearing placebo. Patients took the drug or placebo two hours before surgery and then twice daily postoperatively until the first bowel movement, until discharge from the hospital, or for a maximum of seven days. Patients were seen twice daily by the research team, from 6 am to 8 am and then from 4 pm to 6 pm. At each visit, patients were asked about time of first passage of flatus and first bowel movement. Oral intake was measured until patients could tolerate regular meals. Subjects were considered ready for discharge if they had adequate oral intake to discontinue IV fluids, GI function had returned (defined as passage of flatus), they were afebrile, and they were free of major complications.
This was a randomized, placebo-controlled study.
The 6-mg dose of alvimopan improved all major outcomes, with or without correction for the type of surgery. Analgesic efficacy of opioids was not affected by the study drug, and no adverse events occurred.
Webster, L., Jansen, J.P., Peppin, J., Lasko, B., Irving, G., Morlion, B., . . . Carter, E. (2008). Alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist for the treatment of opioid-induced bowel dysfunction: Results from a randomized, double-blind, placebo-controlled, dose-finding study in subjects taking opioids for chronic non-cancer pain. Pain, 137, 428–440.
To assess the effectiveness and safety of alvimopan, a peripherally acting mu-opioid receptor antagonist, in patients with noncancer pain and opioid-induced bowel dysfunction.
Patients were randomized to one of four groups: oral alvimopan 0.5 mg twice daily (n = 130), oral alvimopan 1 mg daily (n = 133), oral alvimopan 1 mg twice daily (n = 130), or placebo capsules (n = 129).
Patients were instructed to discontinue laxative use. Rescue laxative medication (bisacodyl 10-30 mg) could be taken if the patient experienced discomfort with no bowel movement (BM) for four consecutive days. An interactive voice response system via touch-tone telephone was used for number of BMs, associated symptoms, rescue laxative use, opioid consumption, and pain intensity.
This was a phase IIb, randomized, double-blind, placebo-controlled, parallel-group study.
Oral alvimopan increases the frequency of SBMs and improves symptoms in adults on opioid pain regimens.
Oral alvimopan may be effective for the treatment of opioid-induced constipation in patients taking opioids for chronic pain and may improve opioid-induced bowel dysfunction symptoms. Use of alvimopan does not appear to compromise analgesia or induce opioid abstinence. Additional study is necessary to look at efficacy with an oncology population and determine long-term efficacy, as well as an optimal dosing regimen.