Alvimopan for postoperative ileus following abdominal surgery: a systematic review.

BACKGROUND: Postoperative ileus (POI) is a common complication following abdominal surgery, often leading to extended hospital stays and a higher risk of post-operative complications, leading to poorer patient outcomes. Alvimopan, a peripherally acting µ-opioid receptor antagonist, has been shown to aid in the recovery of normal bowel function after surgery. While its benefits are well-established in open abdominal surgeries, its efficacy in laparoscopic procedures had not been conclusively determined. However, recent clinical trials involving laparoscopic surgeries have since been conducted. This review aims to reassess the efficacy of Alvimopan by incorporating findings from these new studies, potentially providing further insight into its clinical benefits. METHODS: A comprehensive search of PubMed, Google Scholar, EMBASE, and the Cochrane Library was conducted. Studies were included based on the PICO framework, focusing on Alvimopan's impact on postoperative gastrointestinal recovery. Primary outcomes were time to gastrointestinal function recovery (GI-3) and hospital stay duration. RESULTS: Ten studies met the inclusion criteria, with seven focusing on the use of Alvimopan in open abdominal surgeries and three in laparoscopic procedures. Collectively, these studies involved 18,822 patients undergoing various types of abdominal Administration of Alvimopan 6 mg accelerated gastrointestinal function recovery by an average of 14 h (Hazard ratio: 1.62, p = 0.002) and reduced hospital stays by 5.2 h (Hazard ratio: 1.52, p = 0.04) compared to placebo. Similarly, Alvimopan 12 mg reduced GI-3 recovery time by 13.5 h (Hazard ratio: 1.58, p = 0.02) and hospital stay duration by 6.2 h (Hazard ratio: 1.46, p = 0.018). CONCLUSION: Alvimopan shows promise in reducing POI and hospital stay durations following abdominal surgeries. The incorporation of the recent studies in laparoscopic abdominal procedures further supports these findings. Integrating Alvimopan into perioperative care protocols may enhance patient outcomes and help lower healthcare costs.

Effect of Alvimopan on Postoperative Ileus and Length of Hospital Stay in Patients Undergoing Bowel Resection: A Systematic Review and Meta-Analysis.

AIMS: The aim is to investigate the effect of alvimopan on postoperative ileus and length of hospital stay in patients undergoing bowel resection. METHODS: The PRISMA statement standards were followed to conduct a systematic review and meta-analysis. The available literature was searched to identify all studies comparing alvimopan with no alvimopan in patients undergoing bowel resection. Postoperative ileus and length of hospital stay were the primary outcomes, and time to first bowel motion was the secondary outcome. Random-effects modeling was applied for analyses. RESULTS: Analysis of 94 833 patients from 26 studies showed that alvimopan was associated with lower risk of postoperative ileus (OR: .57, 95% CI .48 to .67, P <.00001; high GRADE certainty), shorter length of hospital stay (MD: -1.08 day, 95% CI -1.36 to -.81, P < .00001; moderate GRADE certainty), and shorter time to first bowel motion (MD: -.43 day, 95% CI -.58 to -.28, P < .00001; moderate GRADE certainty). Separate analyses of randomized controlled trials and observational studies showed similar findings. Subgroup analyses suggested consistent findings in patients undergoing elective bowel resection, emergency bowel resection, and open surgery; however, alvimopan did not improve the outcomes in patients undergoing minimally invasive surgery. CONCLUSION: Robust evidence supports the routine use of alvimopan in patients undergoing open bowel resection as indicated by lower risk of postoperative ileus and shorter length of hospital stay. We support incorporation of alvimopan into enhanced recovery after surgery programs for the procedures involving open bowel resection. The role of alvimopan in minimally invasive bowel resection needs more research.

Alvimopan is associated with favorable outcomes in open and minimally invasive colorectal surgery: a regional database analysis.

BACKGROUND: Alvimopan is a µ-opioid receptor antagonist associated with shorter time to gastrointestinal recovery in patients having open colorectal surgery. Data demonstrating the benefit of perioperative alvimopan for the minimally invasive surgical approach are inconsistent. The aim of this study is to determine colorectal surgery groups that benefit from perioperative alvimopan. METHODS: This is a retrospective cohort analysis of colorectal surgery patients who had, and patients who did not have, perioperative alvimopan in the Michigan Surgical Quality Collaborative regional risk-adjusted database from 2018 through 2021. Main outcome measures were postoperative length of hospital stay, time to return of bowel function, and postoperative ileus. RESULTS: There were 10,010 patients (30.3% open, 40.5% laparoscopic, 12.7% hand-assist laparoscopic, 43.5% robotic) who met inclusion criteria-4919 received alvimopan in the perioperative period and 5091 did not. When compared to those not receiving alvimopan, unadjusted outcomes showed that the alvimopan group had significantly shorter postoperative length of stay (4.75 days vs 5.5 days, p < 0.001), shorter time to return of bowel function (1.61 days vs 2.01 days, p < 0.001) and less postoperative ileus (5.45% vs 7.94%, p < 0.001). After adjustment, regression models confirmed that alvimopan was associated with an 9.6% reduction in hospital length of stay (p < 0.001), a 14.9% shorter time to return of bowel function (p < 0.001), and a 42.1% reduction in postoperative ileus (p < 0.001). Subgroup analysis showed significant benefit of alvimopan for all three outcomes in patients having the minimally invasive approach. CONCLUSIONS: Alvimopan is associated with shorter hospital length of stay, shorter time to return of bowel function, and decreased postoperative ileus when administered to patients undergoing colorectal surgery. Benefit is not limited to the open approach and includes minimally invasive laparoscopic and robotic colorectal procedures.

An update on the use of pharmacotherapy for opioid-induced bowel dysfunction.

INTRODUCTION: With the growing rate of aging and the incidence of chronic diseases, there has been an upsurge in opioid prescription and abuse worldwide. This has been associated with increased reports of opioid-related adverse events, particularly opioid-induced bowel dysfunction (OIBD), calling for a rational clinical management strategy. AREAS COVERED: Through searching PubMed, Scopus, Cochrane Library, and Web of Science, English literature was gathered as of 1 January 2017. Furthermore, the USFDA, EMA, TGA, Clinicaltrials.Gov, WHO-ICTRP databases, and the latest guidelines were reviewed to extract ongoing clinical studies and provide an evidence-based expert opinion with detailed information on efficacy, safety, approval status, and pharmacokinetics of the currently used medications. EXPERT OPINION: Despite the significant burden of OIBD, the clinical development of agents lags behind disease progress. Although in most places, management of opioid-induced constipation (OIC) is initiated by lifestyle modifications followed by laxatives, opioid antagonists, and secretagogue agents, there are still major conflicts among global guidelines. The fundamental reason is the lack of head-to-head clinical trials providing inter- and intragroup comparisons between PAMORAs, laxatives, and secretagogue agents. These investigations must be accompanied by further valid biopharmaceutical and economic evaluations, paving the way for rational clinical judgment in each context.

Association between use of ERAS protocols and complications after radical cystectomy.

PURPOSE: Implementation of enhanced recovery protocols in cystectomy patients has significantly changed the perioperative course of this major operation. This paper summarizes evidence based interventions to enhance the postoperative course of radical cystectomy. METHODS: A comprehensive search of PubMed and Embase databases was performed and also the results of our institutional enhanced recovery protocol were discussed. RESULTS: One of the major advantages of such changes is the reduced rate of postoperative gastrointestinal (GI) complications especially postoperative ileus which could be contributed to several components of these protocols. However, Alvimopan is the only component which its use is supported by level I evidence. Although there are some evidence suggesting the decreased rate of urinary tract infection with the use of prophylactic antibiotics and wound complications by the use of negative wound pressure devices, their clear benefit is yet to be shown. Although robotic approach has proven advantages in intraoperative blood loss and postoperative blood transfusion rate, surgical team's experience and dedicated infrastructure seem to be more influential in optimized outcome than just the surgical approach. CONCLUSION: current evidence suggests that such protocols have not only reached the goal of maintaining complication rate while decreasing length of hospital stay, but it might have caused a decrease in the rate of low-grade complications, especially GI complications.

Alvimopan for the reduction of postoperative ileus after long posterior spinal fusion: placebo-controlled double-blind randomized trial.

OBJECTIVE: The aim of this study was to evaluate the efficacy of alvimopan administration after posterior spinal fusion (PSF) in adult spine surgery patients who are taking opioid agents. METHODS: In this placebo-controlled, double-blind randomized trial, PSF patients were randomized in blocks to placebo or study drug. Primary and secondary outcome measures were return to normal bowel function, including time to passage of flatus and stool, time to tolerance of oral nutrition, and time to hospital discharge. Patients were included regardless of chronic opioid consumption status. RESULTS: Thirty-one patients provided consent for participation, and 26 patients (13 per group) completed the study. There were no differences between groups with respect to time to flatus, time to bowel movement, time to oral nutrition tolerance, and time to discharge. Calculated effect sizes favored placebo for all interventions. CONCLUSIONS: Alvimopan did not hasten return to bowel function for any primary or secondary outcome measures when compared with placebo for patients undergoing PSF. There were no adverse events related to alvimopan, including for patients with chronic opioid consumption. While underpowered to determine a statistical difference, it is unlikely that a clinically relevant effect exists.

Alvimopan retains efficacy in patients undergoing colorectal surgery within an established ERAS program.

BACKGROUND: Post-operative ileus and delayed return of gastrointestinal function are complications seen frequently in patients undergoing colorectal surgery. Many enhanced recovery after surgery protocols include alvimopan to inhibit the effects of opiates in the gastrointestinal tract and lidocaine to augment analgesics. Limited data exist regarding alvimopan's efficacy in opiate-sparing regimens. METHODS: This single-center, retrospective cohort analysis was conducted in a randomly selected population of adult patients undergoing colorectal resection between February 2018 and October 2019. Patients meeting inclusion criteria were divided into four groups dependent upon whether or not they received alvimopan (A or a) and/or lidocaine (L or l). The primary endpoint in this study was median time to first bowel movement or discharge, whichever came first. Our secondary endpoint was length of stay. RESULTS: Of the 430 patients evaluated, a total of 192 patients were included in the final evaluation in the following groups: AL (n = 93), Al (n = 34), aL (n = 44), and al (n = 21). A significant difference was found among the groups for the primary outcome of median time to bowel movement or discharge (p = 0.001). Three subsequent pair-wise comparisons resulted in a significant difference in the primary outcome: group AL 39.4 h vs. group aL 54.0 h (p = 0.003), group AL 39.4 h vs. group al 55.4 h (p = 0.001), and group Al 44.9 h vs. group al 55.4 h (p = 0.01). Length of stay was significantly reduced by 1.8 days in groups AL and Al compared to group aL (p < 0.001). CONCLUSION: Treatment with alvimopan resulted in a significant improvement in time to GI recovery and decreased length of stay in an established ERAS program. While lidocaine's reduction in opiates was minimal, the group receiving both alvimopan and lidocaine had the greatest reduction in time to GI recovery and length of stay.

Deciphering the molecular basis of the kappa opioid receptor selectivity: A Molecular Dynamics study.

Selective antagonists for the kappa opioid receptor (KOP) have the potential to treat opiate and alcohol addiction, as well as depression and other CNS disorders. Over the years, the development of KOP-selective antagonists yielded very few successful compounds. Recently, N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines have emerged as a novel class of pure opioid receptor antagonists, including the marketed Mu opioid receptor (MOP) peripheral antagonist Alvimopan and the potent KOP antagonist JDTic. However, the selectivity determinants of this class of compounds towards the opioid receptor subtypes are still vague and understudied. In this work, we have performed Molecular Dynamics (MD) simulation to gain insights into the differential binding of this class of compounds into KOP, as exemplified by Alvimopan and JDTic. Our study indicated that the selectivity largely depends on ligands interaction with the selectivity pocket formed by Val108, Thr111, and Val118, supported by two additional polar and hydrophobic contacts with Asp138 and Trp287, respectively. Our results also demonstrate, for the first time, that non-morphinan ligands can still adopt the "message-address model" for KOP efficacy and selectivity by binding to Glu297.

Alvimopan as part of the Enhanced Recovery After Surgery protocol following radical cystectomy is associated with decreased hospital stay.

OBJECTIVE: To study the effect of alvimopan and the Enhanced Recovery After Surgery protocol on length of hospital stay in patients undergoing radical cystectomy. METHODS: Our retrospective study involved 296 consecutive patients undergoing radical cystectomy for bladder cancer at our institution from 2010 through 2018. Patients were grouped according to three stages of the Enhanced Recovery After Surgery protocol implementation: (i) pre-Enhanced Recovery After Surgery (group A; n = 146); (ii) pre-alvimopan Enhanced Recovery After Surgery (group B; n = 102); and (iii) Enhanced Recovery After Surgery plus alvimopan (group C; n = 48). The primary outcome was the length of hospital stay. Secondary outcomes were time to first bowel movement, time to tolerate a regular diet, the incidence of postoperative ileus, postoperative complications and 30-day readmission rate. RESULTS: Group C showed a significantly shorter median length of hospital stay (7 days, P = 0.003), shorter gastrointestinal recovery time (4 days, P = 0.018) and a lower rate of postoperative ileus (14.6%, P = 0.005). The reduction in length of hospital stay, gastrointestinal recovery time and a lower rate of postoperative ileus was significant after controlling for other confounders on multivariable regression analysis. With the open approach, group C showed a significantly shorter length of hospital stay and gastrointestinal recovery time (P = 0.005, P = 0.001, respectively); however, in robotic cohorts, no significant differences were observed. There was no difference among groups in the 30-day readmission rate or postoperative complications. CONCLUSIONS: Patients undergoing radical cystectomy and managed by an Enhanced Recovery After Surgery protocol experience a significantly shorter length of hospital stay when receiving alvimopan as part of the protocol. Patients seem to derive the optimum benefits of alvimopan when it is used with an open approach; however, these benefits become less obvious with the robotic approach.

Outcomes of Alvimopan Use in Laparoscopic Intra-abdominal Surgery: A Retrospective Review.

Background: Postoperative ileus is a transient cessation of bowel motility, occurring after bowel resection, characterized by abdominal distension and pain, nausea, vomiting, and an accumulation of gas/fluids in the bowel. It is associated with a greater incidence of postoperative morbidity and increased length of stay or readmission. Alvimopan, a novel peripheral mu receptor antagonist, is indicated for preventing postoperative ileus in patients undergoing intra-abdominal surgery or bowel resection. The objective of this study was to assess the impact of alvimopan use in laparoscopic abdominal surgeries. Objective: To assess alvimopan use's impact in laparoscopic abdominal surgeries. Methods: A retrospective chart review was conducted of 84 patients who underwent laparoscopic procedures that received alvimopan (September 1, 2018 to October 31, 2018) and compared to patients that did not receive alvimopan (May 1, 2018 to June 30, 2018, due to a national shortage of the medication). The primary outcome was the rate of postoperative ileus. Secondary outcomes included rate of 30-day readmission, length of stay (LOS), postoperative opioid and laxative use, time to initiation of oral diet, and return of bowel function (ROBF) as demonstrated by recorded bowel movement. Results: There was no statistical difference observed in primary outcome of postoperative ileus between alvimopan and no alvimopan groups (2.7% vs 4.3%, p=1). Secondary outcomes such as length of stay (5.4 days vs 5.4 days, p=0.49), length of postoperative stay (5 vs 4.9, p=0.44), days to oral diet (0.9 vs 0.4, p=0.16), time to BM (1.8 vs 2.2, p=0.32), and 30-day readmission were also similar between the two groups. Conclusion: The similar outcome profiles in all primary and secondary outcomes do not support the use of alvimopan in the setting of laparoscopic intra-abdominal surgery.

Efficacy and safety of alvimopan use in benign urinary tract reconstruction.

PURPOSE: To analyze the use of alvimopan, a peripheral mu-opioid receptor antagonist, in expediting gastrointestinal recovery after benign abdominal urinary tract reconstruction. Alvimopan use has been well defined in the management of radical cystectomy and urinary diversion for oncologic indications. It has not been studied in benign abdominal genitourinary reconstruction. METHODS: Patients who underwent urinary reconstruction utilizing harvested bowel segments for benign conditions from 12/2014-7/2019 were retrospectively reviewed. From 5/2018-7/2019 our institution approved the use of perioperative alvimopan in the aforementioned patients (N = 11), who were paired 1:2 with patients from a cohort of alvimopan-eligible patients who did not receive the drug (N = 22). Patients were paired by (1) type of reconstruction and (2) presence of neurogenic bowel-bladder (NBB). RESULTS: Of the 70 patients who underwent urinary reconstruction during the study period, 46 patients (66%) were eligible to receive alvimopan. Length of stay was shorter for the alvimopan group compared to the non-alvimopan group (median 5 days [IQR 4-5 days] vs. 8 days [IQR 6-11 days]; P = 0.002). Time to first bowel movement was shorter for the alvimopan group (median 4 days [IQR 3-4 days] vs. 6 days [IQR 4-7], P = 0.001). No patient treated with alvimopan required a nasogastric (NG) tube for post-operative ileus compared to 7 (32%) patients in the non-treatment group (P = 0.035). Post-operative complications and 30-day readmissions were similar between the two groups. CONCLUSION: The use of perioperative alvimopan in benign abdominal urinary tract reconstruction expedited return of bowel function and decreased length of stay compared to a matched cohort of untreated patients.

Peripherally Acting µ-Opioid Receptor Antagonists in the Management of Postoperative Ileus: a Clinical Review.

Postoperative ileus (POI) and constipation are common secondary effects of opioids and carry significant clinical and economic impacts. µ-Opioid receptors mediate opioid analgesia in the central nervous system (CNS) and gastrointestinal-related effects in the periphery. Peripherally acting µ-opioid receptor antagonists (PAMORAs) block the peripheral effects of opioids in the gastrointestinal tract, while maintaining opioid analgesia in the CNS. While most are not approved for POI or postoperative opioid-induced constipation (OIC), PAMORAs have a potential role in these settings via their selective effects on the µ-opioid receptor. This review will discuss recent clinical trials evaluating the safety and efficacy of PAMORAs, with a focus on alvimopan (Entereg®) and methylnaltrexone (Relistor®) in patients with POI or postoperative OIC. We will characterize potential factors that may have impacted the efficacy observed in phase 3 trials and discuss future directions for the management and treatment of POI.

Improving postoperative quality of care in germ cell tumor patients: Does scheduled alvimopan, acetaminophen, and gabapentin improve short-term clinical outcomes after retroperitoneal lymph node dissection?

INTRODUCTION: To determine the benefits of alvimopan and multimodal pain management strategies in men undergoing retroperitoneal lymph node dissection for testicular cancer. METHODS: A retrospective cohort study was completed in men undergoing retroperitoneal lymph node dissection from January 2017 to May 2018. Patients were placed into the 3-drug, 2-drug, and control cohorts as a result of a prospectively determined protocol during the study period. Men in the 3-drug group were managed using alvimopan 12 mg PO the morning of surgery then BID until bowel movement, gabapentin 300 mg daily, and acetaminophen 1,000 mg q6H. The 2-drug group was managed with the above regimen excluding alvimopan. Controls were treated per our standard perioperative pathway. Primary outcomes were length of stay, IV narcotic consumption, bowel movement during hospitalization, and time to bowel movement and assessed in multivariate models controlling for operative time, concomitant surgery, chemotherapy receipt, and residual mass size. RESULTS: One-hundred and fifty-two consecutive patients underwent RPLND (42 3-drug, 38 2-drug, and 72 controls). Multivariable models indicated that the 3-drug (IRR 0.89, P < 0.0001) and 2-drug group (IRR 0.87, P = 0.0209) had shorter hospital stays than controls. Men in the 3-drug group required less narcotic pain medication than the 2-drug (ß -8.16, P = 0.0405) and the control (ß -8.16, P = 0.0302) group. Men receiving alvimopan (3-drug) were almost 6 times more likely than the 2-drug group (odds ratio 5.94, P < 0.0001) and 4 times more likely than the control group (odds ratio 3.86, P = 0.0017) to have a bowel movement during hospitalization. Men in the 3-drug group had the quickest return of bowel movements. CONCLUSIONS: Multimodal pain management improves length of stay in men undergoing retroperitoneal lymph node dissection for testis cancer. The addition of alvimopan allows for quicker return of bowel movements and reduces overall narcotic requirements.

Alvimopan for the Prevention of Postoperative Ileus in Inflammatory Bowel Disease Patients.

BACKGROUND: Postoperative ileus (POI) is a temporary delay of coordinated intestinal peristalsis. Alvimopan, an oral peripherally acting mu-opioid receptor antagonist approved for accelerating gastrointestinal recovery, has never been studied specifically in patients with inflammatory bowel disease (IBD). AIM: To investigate the efficacy of alvimopan in preventing POI among IBD patients. METHODS: A retrospective chart review was conducted on 246 IBD patients undergoing bowel surgery between 2012 and 2017. Data collected included demographics, IBD subtype, length of stay (LOS), postoperative gastrointestinal symptoms, and administration of alvimopan. The primary outcome was POI; secondary gastrointestinal recovery outcomes were: time to first flatus, time to first bowel movement, time to tolerating a liquid diet, time to tolerating solid food, and LOS. RESULTS: When compared with the control group, patients in the alvimopan group had shorter times to tolerating liquids and solids, first flatus, and first bowel movements (p < 0.01). LOS was shorter in the alvimopan group when compared with controls (p < 0.01). The overall incidence of POI was higher in controls than in the alvimopan group (p = 0.07). For laparoscopic surgeries, the incidence of POI was also higher in controls than in the alvimopan group (p < 0.01). On multivariable analysis, alvimopan significantly decreased time to all gastrointestinal recovery endpoints when compared to controls (p < 0.01). CONCLUSIONS: Alvimopan is effective in accelerating time to gastrointestinal recovery and reducing POI in IBD patients. While the benefits of alvimopan have been demonstrated previously, this is the first study of the efficacy of alvimopan in IBD patients.

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

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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. LEVEL OF EVIDENCE: 3b.

Identification and structural characterization of hydrolytic degradation products of alvimopan by LC/QTOF/MS/MS and NMR studies.

Alvimopan (ALV), a peripherally acting mu-opioid receptor (PAM-OR) antagonist used for the treatment of postoperative ileus, was examined for its degradation behaviour under different stress conditions. A total of five degradation products (DP1-DP5) were formed and identified using high-performance liquid chromatography (HPLC) method. Primarily, complete fragmentation pathways of the protonated drug and its degradation products (DP1-DP5) were elucidated by using liquid chromatography-mass spectrometry (LC/MS) and high-resolution mass spectrometry (HRMS) studies. Subsequently, three major degradation products (DP1-DP3) formed under acid hydrolytic stress conditions were isolated by preparative-high performance liquid chromatography (prep-HPLC) and subjected to nuclear magnetic resonance (NMR) experiments (1D and 2D NMR) for further confirmation of their structures. All the spectral data from LC/QTOF/MS/MS and NMR studies were used for the identification and structural characterization of degradation products (DP1-DP5).

Alvimopan usage increasing following radical cystectomy.

PURPOSE: Alvimopan (Entereg), a peripherally acting opioid receptor antagonist, is effective in reducing the rate of postoperative ileus and length of hospital stay in patients undergoing colorectal surgery, and is now approved for use after radical cystectomy (RC). Using data from Vizient (formerly University Health System Consortium), we assessed the utilization of alvimopan and its effect on perioperative factors after RC. METHODS: The Vizient database, contributed to by over 200 US academic hospitals, was evaluated from 2014 to 2016. Patients who had undergone radical cystectomy were included. Alvimopan exposure and postoperative outcomes were collected. RESULTS: 7472 patients underwent cystectomy in the 3 years examined, with 3391 (45.4%) patients receiving alvimopan over this time period. The use of alvimopan increased from 35 to 59%. The receipt of alvimopan was associated with a decrease in perioperative morbidity (10.53% vs 19.23%, p = 0.027). CONCLUSION: This study, the largest to examine the real-world utilization of alvimopan since FDA approval for RC, shows that alvimopan utilization has increased substantially and is associated with reduced perioperative morbidity in patients undergoing cystectomy.

A Retrospective Study of Patients Undergoing Radical Cystectomy and Receiving Peri-Operative Naloxegol or Alvimopan: Comparison of Length of Stay.

Alvimopan is a µ-opioid receptor antagonist used in the post-operative period to decrease rates of post-operative ileus (POI) following radical cystectomy (RC) and thereby shorten length of stay (LOS). Naloxegol is a much less expensive drug of the same class that has yet to be studied for prevention of POI in the peri-operative period. The purpose of the current study is to evaluate the differences in LOS and development of POI in patients post-RC who take alvimopan versus those who take naloxegol, with the hope that drug efficacy can be evaluated against the significant difference in cost burden between the two drugs. The study population included all adult patients between 18-89 years of age with bladder cancer undergoing radical cystectomy with urostomy at University of Colorado Hospital. Those patients who received usual post-operative care as well as either alvimopan or naloxegol between September 2011 and December 2017 were selected for analysis. Patients who did not take either medication or were switched from one drug to the other were excluded from the study. A zero-truncated binomial regression analysis was used to analyze differences in length of stay in patients who received alvimopan versus those who received naloxegol. Additionally, the incidence of post-operative ileus was compared between treatment groups. 130 patients who underwent RC and received either alvimopan or naloxegol were included in the study: 75 (58%) received alvimopan and 55 (42%) received naloxegol. Baseline characteristics were similar between treatment groups. There was no significant difference in the length of stay between patients who received alvimopan and patients who received naloxegol after adjusting for age, sex, BMI, length of surgical time, or stage of disease (p = 0.41). There was no significant between the two drugs for development of POI (p = 0.85). Development of POI was significantly associated with a longer LOS (p = 0.007). The analysis showed that naloxegol was comparable to alvimopan when it came to length of hospital stay following RC. Therefore, naloxegol may be offered as a less expensive, effective alternative to alvimopan.

Alvimopan, Regardless of Ileus Risk, Significantly Impacts Ileus, Length of Stay, and Readmission After Intestinal Surgery.

BACKGROUND: Previous analyses evaluating alvimopan included patients at varying risk for ileus after intestinal resection, which may have precluded its widespread adoption. We assess the early and delayed effects of alvimopan in patients stratified by risk for ileus after intestinal and colon resection. METHODS: From the Premier Perspective database, patients with elective small and large bowel resections from 2012 to 2014 were identified. Multivariable analysis identified 14 perioperative risk factors for postoperative ileus. Within low- (0-4 factors), intermediate- (5 factors), and high-risk (6-12 factors) ileus categories, alvimopan and no-alvimopan patients were propensity-score matched for demographics, morbidities, diagnosis, surgery and approach, postoperative complications, surgeon specialty, and hospital features. In-hospital postoperative ileus, length of stay, discharge destination, and ileus-related readmission were compared. RESULTS: Of 52,948 patients, 15,719 (29.7%) received alvimopan. Risk for ileus in low- (18,784), intermediate- (14,370), and high-risk (19,794) categories was 8.9, 13, and 22% (p ≤ .0001) respectively. After matching, alvimopan was associated with significantly reduced in-hospital postoperative ileus in all (low, 6%; intermediate, 9.4%; and high risk, 16.2%) categories. Hospital stay and 30-, 60-, and 90-day postdischarge ileus were also significantly lower with alvimopan. For low-risk patients, alvimopan increased discharge to home, while 90-day emergency readmission was reduced. CONCLUSIONS: Alvimopan, regardless of ileus risk, improves ileus, hospital stay, and ileus-related readmission after intestinal resection and these effects are sustained over the long term. Since fewer than a third of patients currently receive alvimopan, its routine adoption with small and large intestinal resection will significantly impact patients and health systems.

Stereoselective HPLC separation of alvimopan on cellulose-based immobilized polysaccharide as a chiral stationary phase.

Chiral separation by normal phase high performance liquid chromatography is one of the most powerful technique to quantify the chiral purity of the compounds. In this study, a novel, simple, and specific analytical method was proposed to ascertain the chiral purity of alvimopan (ALV). The normal phase HPLC method was developed based on cellulose tris (3,5-dichlorophenylcarbamate) stationary phase. The separation of ALV isomers achieved by using column CHIRALPAK IC (250 × 4.6 mm, 5 µm), mobile phase n-hexane: isopropyl alcohol: ethanol: diethylamine (650:200:150:5 v/v), column oven temperature 30°C, flow rate 1.0 mL min-1 , injection volume was 10 µL, chromatographic response monitored at 273 nm. The developed method was validated as per the ICH guidelines and found precise, accurate, and linear. The advantage of the method is a good separation of ALV isomers within 35 minutes of the analysis time. Therefore, this method is suitable for routine determination of chiral purity of ALV active pharmaceutical ingredient.