Effect Of Alvimopan Research Articles

Efficacy of Naldemedine on Intestinal Hypomotility and Adhesions in Rodent Models of Postoperative Ileus.

Postoperative ileus (POI) often decreases patients' QOL because of prolonged hospitalization and readmission. Alvimopan, a peripheral μ-opioid receptor antagonist, is currently the only therapeutic drug for POI. The aim of this study was to examine the efficacy of naldemedine (a peripheral μ-opioid receptor antagonist with a non-competitive pharmacological profile different from that of alvimopan) on postoperative intestinal hypomotility and adhesion in rodent models, and compare it with the effects of alvimopan. Oral administration of naldemedine (0.3 mg/kg) and alvimopan (3 mg/kg) significantly inhibited the decrease in intestinal motility induced by mechanical irritation in mice (p < 0.01, for both). Naldemedine (1 mg/kg) significantly shortened the adhesion length in chemical-induced postoperative adhesion model rats (p < 0.05). Alvimopan (3 mg/kg) also significantly reduced the adhesion ratio (p < 0.01). These findings suggest that naldemedine is effective for postoperative intestinal hypomotility and adhesions in rodents (i.e., as for alvimopan). Thus, naldemedine may be a useful option for the treatment of POI.

Effect of alvimopan on gastrointestinal recovery and length of hospital stay after retroperitoneal lymph node dissection for testicular cancer.

Alvimopan use has reduced the length of hospital stay in patients undergoing major abdominal surgeries and radical cystectomy. Retroperitoneal lymph node dissection for testicular cancer may be associated with delayed gastrointestinal recovery prolonging hospital length of stay. We evaluate whether alvimopan is associated with enhanced gastrointestinal recovery and shorter hospital length of stay in men undergoing retroperitoneal lymph node dissection for testicular cancer. From 2010 to 2016, 29 patients underwent open, transperitoneal bilateral template retroperitoneal lymph node dissection. Data for patients who received alvimopan were prospectively collected and compared to a historical cohort of patients who did not receive alvimopan. Primary outcome measures were length of stay and recovery of gastrointestinal function. Descriptive statistics were reported. Time-to-event outcomes were evaluated using cumulative incidence curves and log rank test. Factors associated with length of stay were analyzed for correlation using multiple linear regression. Of 29 men undergoing retroperitoneal lymph node dissection, eight received alvimopan and 21 did not. The two cohorts were well matched, with no significant differences. In the alvimopan cohort compared with those who did not receive alvimopan median time to return of flatus was 2 versus 4 days (p=0.0002), and median time to first bowel movement was 2.5 versus 5 days (p=0.046), respectively. Median length of stay in the alvimopan cohort was 4 days versus 6 days in those who did not receive alvimopan (p=0.074). In adjusted analyses, receipt of alvimopan did not influence length of stay. Alvimopan may facilitate gastrointestinal recovery after retroperitoneal lymph node dissection for testicular cancer. Whether this translates into reduced length of stay needs to be determined by randomized controlled trials using larger cohorts. 3b.

Effect of alvimopan on gastrointestinal recovery and length of hospitalization after retroperitoneal lymph node dissection for testicular cancer.

424 Background: Alvimopan use in enhanced recovery programs has reduced the hospital LOS in patients undergoing major abdominal surgeries. Retroperitoneal lymph node dissection (RPLND) for testicular cancer may be associated with delayed GI recovery prolonging hospital LOS. In this study, we evaluate whether alvimopan is associated with enhanced GI recovery and shorter hospital LOS in men undergoing RPLND for testicular cancer. Methods: From 2010 to 2016, 29 patients underwent RPLND by a single surgeon (23 post-chemotherapy). All patients underwent bilateral template dissection. Data for patients who received alvimopan was prospectively collected and compared to a historical cohort of patients who did not receive alvimopan. Primary outcomes measured were hospital LOS and recovery of GI function. Mann-Whitney Wilcoxon and Chi square tests were used to determine statistical significance between the two groups. Results: Of 29 men who underwent RPLND, 8 received alvimopan and 21 did not. There were no differences in preoperative or operative variables between the groups (Table). Median hospital LOS for men receiving alvimopan was 4 days compared to 6 days for those who did not (p=0.074). The median time to return of flatus in men receiving alvimopan was 2 days compared to 4 days for those who did not (p=0.0023). The median time to first bowel movement (BM) in men receiving alvimopan was 2.5 days compared to 4 days for those who did not (p=0.0028). Conclusions: Alvimopan significantly reduced the median time to return of flatus and to first BM after RPLND. Furthermore, there was a trend towards shorter hospital LOS in those receiving alvimopan. [Table: see text]

Effect of alvimopan on return of bowel function after robot-assisted radical cystectomy.

Alvimopan has been shown to improve time to return of bowel function in patients undergoing bowel resection. The objective of this study is to determine if alvimopan has similar benefits for patients undergoing robot-assisted radical cystectomy (RARC). All RARC cases were reviewed from January 2008 to March 2012. All patients during this time were administered alvimopan unless they had been receiving narcotics preoperatively. Patients receiving alvimopan received a preoperative dose of 12 mg perorally and then were dosed twice daily for 7 days or until first bowel movement. Clinicopathologic outcomes were summarized and compared, and functional outcomes of treated patients were compared with outcomes of untreated patients. One hundred seventeen RARCs meeting study criteria were performed. All urinary diversions used an extracorporeal approach. Urinary diversions consisted of 50 Studer neobladders, 22 Indiana pouches, and 45 ileal conduits. Fifty-four patients received alvimopan, and 63 did not. The median time to first bowel movement was 5 days in the alvimopan group and 6 days in the untreated group (P=.03). Median time to solid diet was 6 days in the treated group and 7 days in the untreated group (P=.03). There was a trend toward fewer hospital days in the alvimopan group (alvimopan, 8 days; untreated, 9 days; P=.1). Alvimopan administration appears to reduce the time to return of bowel function and initiation of diet following RARC. This was a trend toward shorter hospitalization in the alvimopan group. Alvimopan should be considered in ongoing research into protocols to aid in shorter convalescence following RARC.

A Meta-analysis of the Effectiveness of the Opioid Receptor Antagonist Alvimopan in Reducing Hospital Length of Stay and Time to GI Recovery in Patients Enrolled in a Standardized Accelerated Recovery Program After Abdominal Surgery

Despite accelerated recovery programs and the widespread uptake of laparoscopic surgery, postoperative ileus remains a significant factor affecting length of stay after abdominal surgery. Alvimopan, an opioid-receptor antagonist, may reduce the incidence of postoperative ileus and expedite hospital discharge. The aim of this study was to perform a meta-analysis to determine the role of alvimopan in accelerating GI recovery and hospital discharge after laparoscopic and open abdominal surgery performed within an accelerated recovery program. Cochrane (1999-2010), Embase (1980-2010), MEDLINE (1980-2010), and International Pharmaceutical Abstracts (1970-2010) were searched for relevant double-blinded, randomized controlled trials. Twelve milligrams of alvimopan and placebo were given to patients enrolled in an accelerated recovery program after abdominal surgery. The primary outcomes measured were the length of stay as defined by the writing of the hospital discharge order and GI-3 and GI-2 GI tract recovery. : Three trials were included that reported on a pooled modified intention-to-treat population of 1388 patients; 685 (49%) patients received alvimopan. On meta-analysis, alvimopan reduced time to the hospital discharge order (HR 1.37 (1.21, 1.62), p < 0.0001), GI-3 recovery (HR 1.42 (1.25, 1.62), p < 0.001), and GI-2 recovery (HR 1.49 (1.32, 1.68), p < 0.0001). The search criteria identified only a small number of trials of alvimopan after abdominal surgery with no randomized trials of alvimopan after laparoscopic surgery. In addition, the use of length of hospital stay as the primary outcome measure may be inappropriate, because it is open to many confounding factors. Finally, adverse events, in particular, adverse cardiovascular events, were not considered. Alvimopan 12 mg can further reduce time to GI recovery and hospital discharge in patients undergoing abdominal surgery within an accelerated recovery program. Investigation into the effect of alvimopan following laparoscopic surgery and additional cost-benefit analyses are required to further define the role of this intervention.

285 INCREASED EXPENDITURES ON FOLLOW-UP CARE AFTER DEFINITIVE SURGERY FOR BLADDER CANCER

with a full course of alvimopan were $5712.20 while the mean charge for a hospital day was $10275.30. The mean savings based on LOS were $9803.50 per patient. CONCLUSIONS: Use of alvimopan in the routine perioperative care of our cystectomy and urinary diversion patients has decreased LOS by 1.5 days for a savings of $9803.50 per patient treated. While our results are promising, they may underestimate the effect of alvimopan due to the regimented cystectomy pathway that we practice. This is reflected by our low rate of readmission for ileus, even in the control group. A forthcoming multicenter, placebo-controlled double-blinded study (NCT00708201) should help clarify the role for alvimopan in cystectomy.

The Effect of Alvimopan on Recovery After Laparoscopic Segmental Colectomy

The Effect of Alvimopan on Recovery After Laparoscopic Segmental Colectomy

Effect of alvimopan (ALV) on gastrointestinal (GI) recovery, length of hospital stay (LOS), and postoperative ileus (POI)-related morbidity in patients (PTS) undergoing bowel resection (BR) for colon or rectal cancer (CRC)

4014 Background: POI, an interruption of bowel motility, occurs universally after BR and is exacerbated by exogenous opioid analgesia. ALV, a peripherally acting mu-opioid receptor (PAM-OR) antagonist, accelerated GI recovery after BR in multicenter, randomized phase III efficacy trials. CRC is the most common reason for BR in the US, and in the ALV trials CRC was the primary reason for BR for 723 of 1,409 (51%) PTS. This abstract examines GI recovery, LOS, POI-related morbidity, and safety in only this subset of PTS. Methods: This pooled ad hoc analysis assessed the subset of PTS in phase III ALV trials who underwent BR via laparotomy because of CRC and received ALV 12 mg or placebo (PLA) (N = 723). All PTS were scheduled for postoperative intravenous patient-controlled opioid analgesia and received oral ALV or PLA preoperatively and BID postoperatively until hospital discharge or for = 7 postoperative days. Efficacy endpoints included GI-2 recovery (first bowel movement and tolerance of solid food) and postoperative LOS (calendar day after surgery to hospital discharge order written). Treatment effect on GI-2 recovery was analyzed using Cox proportional hazards models, and magnitude of effect was expressed with Kaplan-Meier means. POI-related morbidity included nasogastric tube insertion or complications of POI resulting in prolonged hospital stay or readmission. Safety was monitored by adverse event reports. Conclusions: ALV significantly accelerated GI recovery, reduced postoperative LOS, and reduced the proportion of PTS with POI-related morbidity compared with PLA in PTS undergoing BR for CRC. ALV was well tolerated with a lower incidence of nausea and vomiting in the ALV group than in the PLA group. [Table: see text] No significant financial relationships to disclose.

Postoperative Ileus-Related Morbidity Profile in Patients Treated with Alvimopan after Bowel Resection

Postoperative ileus (POI), an interruption of coordinated bowel motility after operation, is exacerbated by opioids used to manage pain. Alvimopan, a peripherally acting mu-opioid receptor antagonist, accelerated gastrointestinal (GI) recovery after bowel resection in randomized, double-blind, placebo-controlled, multicenter phase III POI trials. The effect of alvimopan on POI-related morbidity for patients who underwent bowel resection was evaluated in a post-hoc analysis. Incidence of POI-related postoperative morbidity (postoperative nasogastric tube insertion or POI-related prolonged hospital stay or readmission) was analyzed in four North American trials for placebo or alvimopan 12 mg administered 30 minutes or more preoperatively and twice daily postoperatively until hospital discharge (7 or fewer postoperative days). GI-related adverse events and opioid consumption were summarized for each treatment. Estimations of odds ratios of alvimopan to placebo and number needed to treat (NNT) to prevent one patient from experiencing an event of POI-related morbidity were derived from the analysis. Patients receiving alvimopan 12 mg were less likely to experience POI-related morbidity than patients receiving placebo (odds ratio = 0.44, p < 0.001). Fewer patients receiving alvimopan (alvimopan, 7.6%; placebo, 15.8%; NNT = 12) experienced POI-related morbidity. There was a lower incidence of postoperative nasogastric tube insertion, and other GI-related adverse events on postoperative days 3 to 6 in the alvimopan group than the placebo group. Opioid consumption was comparable between groups. Alvimopan 12 mg was associated with reduced POI-related morbidity compared with placebo, without compromising opioid-based analgesia in patients undergoing bowel resection. Relatively low NNTs are clinically meaningful and reinforce the potential benefits of alvimopan for the patient and health care system.

The selective mu opioid receptor antagonist, alvimopan, improves delayed GI transit of postoperative ileus in rats

Postoperative ileus (POI) is often exacerbated by opioid analgesic use during and following surgery, since mu opioid receptor activation results in a further delay of gastrointestinal (GI) transit. The effects of alvimopan, a novel, selective, and peripherally acting mu opioid receptor antagonist, and the reference compound methylnaltrexone, upon POI were investigated in rats. Under isoflurane anesthesia, POI was induced by laparotomy with intestinal manipulation. Immediately after the surgery, the rats received 51Cr by gavage. Three hours after the surgery, the rats were sacrificed and GI transit was estimated using the geometric center (GC) of 51Cr. Alvimopan (0.1–3 mg/kg) or methylnaltrexone (100 mg/kg) were administered by gavage either before or after the surgery, with or without morphine administration (1 mg/kg). GI transit was delayed by intestinal manipulation (GC = 2.92 ± 0.17). Alvimopan (1 and 3 mg/kg) significantly reversed this delayed GI transit when administered 45 min prior to surgery. However, the effects of alvimopan were less pronounced when administered following surgery. Morphine administration further delayed GI transit induced by intestinal manipulation (GC = 1.97 ± 0.11). Under these conditions, alvimopan (1 and 3 mg/kg) also significantly improved delayed GI transit when administered before surgery. Methylnaltrexone was inactive under all experimental conditions. These data suggest that mu opioid receptors play a role in the pathogenesis of POI, and that the clinical benefit reported to be afforded by alvimopan may be in part mediated via inhibition of an endogenous opioid release as well as blockade of the unwanted GI actions of analgesic agents.

(945): Effect of alvimopan, a peripheral opioid receptor antagonist, on health-related quality of life (HRQOL) in patients who develop gastrointestinal adverse events (GIAEs) while taking opioids for persistent-non-cancer pain

(945): Effect of alvimopan, a peripheral opioid receptor antagonist, on health-related quality of life (HRQOL) in patients who develop gastrointestinal adverse events (GIAEs) while taking opioids for persistent-non-cancer pain

Effect of Alvimopan and Codeine on Gastrointestinal Transit: A Randomized Controlled Study

background & aims: Opiate bowel dysfunction is a significant clinical problem. Our aim was to evaluate the ability of a peripheral mu-opioid antagonist, alvimopan, to reverse the effect of codeine on gastric, small-bowel, and colonic transit time in healthy volunteers. Seventy-four healthy participants (43 women) were randomized in a double-blind, placebo-controlled manner to 1 of 4 groups: alvimopan 12 mg twice daily in the presence and absence of codeine sulfate 30 mg 4 times/day, or codeine or placebo alone. Gastric emptying, small-bowel, and colonic transit were measured by scintigraphy using a 99m-labeled technetium egg meal and 111-labeled indium charcoal delivered to the proximal colon via a delayed-release capsule. The primary end points for colonic transit were geometric center of the colonic counts at 24 hours and time for 50% ascending colon emptying. Analysis of covariance was used to assess the significance of the primary and secondary end points. Codeine delayed gastric, small-bowel, proximal, and overall colonic transit (P < .05). Alvimopan reversed codeine's effect on small bowel and colon (ascending colon and overall colonic transit). Alvimopan also accelerated overall colonic transit compared with placebo. Thus, the mean colonic geometric center at 24 hours was 2.33 with placebo/placebo, 3.25 with alvimopan/placebo (P < .05), 1.5 with placebo/codeine (P < .05), and 2.63 with alvimopan/codeine. Alvimopan did not reverse codeine's delay of gastric emptying. Alvimopan reverses codeine's inhibitory effect on small-bowel and colon transit and has potential for treatment of opiate bowel dysfunction. Alvimopan alone accelerates colonic transit, suggesting that mu-opiate mechanisms participate in the physiologic control of colonic transit.