Is there any data to support using naloxegol (Movantik) over alvimopan (Entereg) and/or methylnatrexone (Relistor)?

Comment by InpharmD Researcher

Based on the current evidence, naloxegol does not appear to be superior to alvimopan or methylnaltrexone for opioid-induced constipation (OIC). Results from meta-analyses suggest that methylnaltrexone trends towards greater improvement of OIC compared to naloxegol, although included studies were placebo-based and indirectly compared. Direct comparisons between naloxegol and the other agents also focused on demonstrating non-significant differences to potentially use as an alternative agent.

Background

A 2021 systematic review evaluating the existing studies (N= 26) on peripherally acting μ-opioid receptor antagonists (PAMORAs) compared the relative clinical advantages and disadvantages of different agents in patients with OIC. Compared to placebo, all included medications are more efficacious in reducing OIC. While methylnaltrexone is mostly studied in its subcutaneous formulation (n= 10/14), the oral formulation (n= 3/14) is associated with a more rapid reduction of OIC than naloxegol (n= 4) and placebo. Overall, the tolerability is consistent across different agents, and the gastrointestinal tract (GI) effects with flatulence and diarrhea are mainly seen at high dosages. Given the heterogeneity of the included studies and the lack of head-to-head studies, a quantitative meta-analysis was not performed. The authors concluded that further studies have to be undertaken to establish a definitive conclusion regarding cost-effectiveness, safety, and effect on pain scores, as the existing results are inconclusive. [1]

A 2018 network meta-analysis compared available treatments for OIC, including methylnaltrexone, naloxegol, and naldemedine. A total of 16 studies (N= 4,048) were analyzed for differences in rescue-free bowel movements (RFBM) among treatments. Patients receiving subcutaneous methylnaltrexone were found to have the highest odds of observing significant improvement in RFBM compared to placebo (odds ratio [OR] 7.02; 95% confidence interval [CI] 4.26 to 11.57). Oral methylnaltrexone (OR 3.04; 95% CI 1.96 to 4.73), naldemedine (OR 5.77; 95% CI 2.54 to 13.11), and naloxegol (OR 1.66; 95% CI 1.26 to 2.19) also led to significant odds of observing improvement in RFBM. In mixed treatment comparisons, naloxegol had reduced odds of improvements in RFBM compared to oral (OR 0.5; 95% CI 0.3 to 0.9) and subcutaneous methylnaltrexone (OR 0.2; 95% CI 0.1 to 0.4), and naldemedine (OR 0.3; 95% CI 0.1 to 0.7). Additionally, oral methylnaltrexone had reduced odds of improvement in RFBM compared to subcutaneous methylnaltrexone (OR 0.4; 95% CI 0.2 to 0.8). [2]

A 2018 systematic review and meta-analysis evaluated the efficacy and safety of pharmacologic interventions for OIC in patients receiving chronic opioid therapy. The review included 27 studies, consisting of 5,390 patients treated with active pharmacologic agents—such as peripherally acting μ-opioid receptor antagonists: methylnaltrexone, naloxegol, naloxone, alvimopan, naldemedine, and axelopran), lubiprostone, and prucalopride—and 3,491 patients who received placebo. Treatments were analyzed using random-effects models, with the pooled relative risk (RR) for lack of therapeutic response to pharmacologic therapy being 0.70 (95% CI, 0.64–0.75), corresponding to a number needed to treat (NNT) of 5 (95% CI, 4–7). Among FDA-approved therapies, the RR remained similar at 0.69 (95% CI, 0.62–0.77). Methylnaltrexone exhibited the lowest individual NNT at 3.4, followed by naloxone (4), naldemedine (5), naloxegol (7), and lubiprostone (15), indicating varying degrees of clinical benefit. Efficacy appeared to improve in cohorts with higher baseline opioid use and in populations refractory to laxatives, as revealed through meta-regression and subgroup sensitivity analyses. notably, the meta-analysis only included placebo-controlled studies for naloxegol, limiting direct comparison between other agents. [3]

References:

[1] Rekatsina M, Paladini A, Drewes AM, et al. Efficacy and Safety of Peripherally Acting μ-Opioid Receptor Antagonist (PAMORAs) for the Management of Patients With Opioid-Induced Constipation: A Systematic Review. Cureus. 2021;13(7):e16201. Published 2021 Jul 5. doi:10.7759/cureus.16201
[2] Sridharan K, Sivaramakrishnan G. Drugs for Treating Opioid-Induced Constipation: A Mixed Treatment Comparison Network Meta-analysis of Randomized Controlled Clinical Trials [published correction appears in J Pain Symptom Manage. 2018 Mar;55(3):e11]. J Pain Symptom Manage. 2018;55(2):468-479.e1. doi:10.1016/j.jpainsymman.2017.08.022
[3] Nee J, Zakari M, Sugarman MA, et al. Efficacy of Treatments for Opioid-Induced Constipation: Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2018;16(10):1569-1584.e2. doi:10.1016/j.cgh.2018.01.021
Literature Review

A search of the published medical literature revealed 6 studies investigating the researchable question:

Is there any data to support using naloxegol (Movantik) over alvimopan (Entereg) and/or methylnatrexone (Relistor)?

Level of evidence

A - Multiple high-quality studies with consistent results  Read more→


Please see Tables 1-6 for your response.

 

 

Alvimopan

Methylnaltrexone

Naloxegol oxalate

Route & Dosage Form

PO Cap, 12 mg

SubQ Inj Soln; 12 mg/3 mL vial, 8 mg/0.4 mg or 12 mg/0.6 mL pre-filled syringe

PO Tab, 12.5 or 25 mg

AHFS Therapeutic Class

56:18.04 Opioid Antagonists

56:18.04 Opioid Antagonists

56:18.04 Opioid Antagonists

Sub-class

Opioid antagonists

Opioid antagonists

Opioid antagonists

Brand Name

Entereg (discontinued; generic only)

Relistor®

Movantik®

Manufacturer

Various generics

Salix Pharmaceuticals

Valinor Pharma

Initial US approval date

2008

2008

2014

Labeled indication(s)

To accelerate the time to upper and lower GI recovery following surgeries that include partial bowel resection with primary anastomosis

Opioid-induced constipation (adult) in chronic non-cancer pain;

Opioid-induced constipation (adult): with advanced illness or pain caused by active cancer: who require opioid dosage escalation for palliative care

Opioid-induced constipation (adult): with chronic non-cancer pain: in pts who do not require frequent (e.g., weekly) opioid dosage escalation

Mechanism of Action

Selective competitive μ-opioid receptor antagonist with high affinity, resulting in peripheral effects of opioids on GI motility and secretion by binding to GI tract μ-opioid receptors

Selective peripherally-acting mu-opioid antagonist in tissues such as GI tract but does not cross the blood-brain-barrier, thereby decreasing constipating effects of opioids without impacting analgesic effects in CNS

Peripherally-acting mu-opioid receptor antagonist in tissues such as the GI tract, ultimately resulting in reduced constipating effects of opioids

Adult Dose & Frequency

0.5-5 hrs before surgery: 12 mg, followed by 12 mg BID starting the day after surgery until discharge (max: 7 days, 15 doses of alvimopan capsules)

<38 kg: 0.15 mg/kg

38-61 kg: 8 mg (0.4 mL)

62-114 kg: 12 mg (0.6 mL)

>114 kg: 0.15 mg/kg

(Calculate inj volume for pts <38 kg or >114 kg by multiplying pt weight in kg by 0.0075, then rounding up the volume to the nearest 0.1 mL)

25 mg once daily in the morning (if poorly tolerated: may reduce dose to 12.5 mg once daily)

Special Populations

Renal (No labeled guidance for dose adjustment, except as noted)

Mild to severe impairment: No dosage adjustment required, monitor closely for AEs (e.g., diarrhea, gastrointestinal pain, cramping) that could indicate high alvimopan or ‘metabolite’ concentrations, and alvimopan should be discontinued if adverse reactions occur);

End-stage renal disease: Use not recommended

CrCl <60 ml/min:

Opioid-induced constipation with chronic noncancer pain: 6 mg SubQ/day

Opioid-induced constipation in adults with advanced illness or pain caused by active cancer who require opioid dosage escalation for palliative care (in pts <38 kg or >114 kg: Calculate the inj volume for these pts by multiplying the pt weight in kg by 0.00375 and then rounding up the volume to the nearest 0.1 mL):

<38 kg: 0.075 mg/kg

38-61 kg: 4 mg (0.2 mL)

62-114 kg: 6 mg (0.3 mL)

>114 kg: 0.075 mg/kg

Mild impairment: No dosage adjustment required;

Moderate to severe or end-stage renal disease: lower starting dose to 12.5 mg once daily

Hepatic (No labeled guidance for dose adjustment, except as noted)

Mild to moderate impairment: No dosage adjustment required, monitor closely for AEs (e.g., diarrhea, gastrointestinal pain, cramping) that could indicate high alvimopan or ‘metabolite’ concentrations, and alvimopan should be discontinued if adverse reactions occur);

Severe impairment: Use not recommended (increased risk of serious AEs); See Warnings

Mild/moderate impairment: no dosage adjustment required;

Severe hepatic impairment (in pts <38 kg or >114 kg: Calculate the inj volume for these pts by multiplying the pt weight in kg by 0.00375 and then rounding up the volume to the nearest 0.1 mL):

<38 kg: 0.075 mg/kg

38-61 kg: 4 mg (0.2 mL)

62-114 kg: 6 mg (0.3 mL)

>114 kg: 0.075 mg/kg

Mild to moderate impairment: No dosage adjustment required;

Severe impairment: Avoid

Fertility (Inadequate clinical data to assess risk, except as noted)

-

-

-

Pregnancy (Inadequate clinical data to assess risk, except as noted)

-

Use during pregnancy may precipitate fetal opioid withdrawal due to the immature fetal blood-brain barrier

Use during pregnancy may precipitate fetal opioid withdrawal

Lactation (Inadequate clinical data to assess risk, except as noted)

-

Breastfeeding not recommended because of potential serious AEs in the breastfed infant, including opioid withdrawal

Not recommended

Geriatric (No labeled guidance for dose adjustment, except as noted)

No dosage adjustment required

No dosage adjustment required;

Higher incidence of diarrhea in elderly pts: Caution

No dosage adjustment required

Pediatric

Safety & efficacy unestablished

Safety & efficacy unestablished

Safety & efficacy unestablished

Administration Instructions

Take ± food

Administer SubQ inj in upper arm, abdomen, or thigh; rotate Inj sites;

Be close to toilet facilities after administration

Give 1 hr before the 1st meal of the day or 2 hrs after;

If unable to swallow Tab whole, Tab can be crushed to a powder, mixed with water and dosed PO or via a nasogastric tube

Storage and Stability (USP Controlled room temperature, except where specified)

°C

-

-

-

°F

-

-

-

Protect from

-

Light

-

Post-modification stability

-

Vials: once drawn into syringe for administration: ≤24 hrs

-

Pharmacodynamics

Given as 12 mg BID reduced the delay in small & large bowel transit induced by codeine 30 mg given 4 times per day. The same exploratory study found that concomitant alvimopan did not reduce the gastric emptying delay induced by codeine

-

Antagonism of GI mu-opioid receptors reduces opioid-induced delayed GI transit time

Pharmacokinetics

Onset of action

-

-

-

Tmax (hrs, except as noted)

-

0.25-0.5 hrs

<2 hrs

Volume of distribution, Liters

30 ± 10

1.1 L/kg

968-2,140

Protein binding, %

80-94

11-15

4.2

Metabolism

p-glycoprotein

Conversion to methyl-6-naltrexol isomers (5% of total) and methylnaltrexone sulfate (1% of total) appear to be the primary pathways of metabolism

Major: CYP3A; minor: p-glycoprotein

Excretion

-

At 168 hrs: Urine (54%); Feces (17%)

16% urine; 68% feces

T1/2

10-17 hrs

15 hrs

6-11 hrs

Drug Interactions

Strong p-glycoprotein inhibitors (e.g., verapamil, cyclosporine, amiodarone, itraconazole, quinine, spironolactone, quinidine, diltiazem, bepridil): Caution;

Therapeutic doses of opioids for >7 consecutive days immediately before taking alvimopan Cap: CI

Opioid antagonists: avoid (potential for additive effects & increased risk of opioid withdrawal)

Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin): CI (severe increase in naloxegol levels)

Moderate CYP3A4 inhibitors (e.g., diltiazem, erythromycin, verapamil): Increased naloxegol concentrations; avoid concomitant use (if unavoidable, reduce dosage to 12.5 mg once daily and monitor for AEs)

Strong CYP3A4 inducers (e.g., rifampin): Decreased concentrations of naloxegol; concomitant use is not recommended

Other opioid antagonists: Potential for additive effects & increased risk of opioid withdrawal: Avoid

Drugs that alter gastric pH (e.g., antacids, proton-pump inhibitors): Caution

Contraindications, Warning/Precautions, Medication Safety

Contraindications (other than product component hypersensitivity)

-

GI obstruction;

At risk of recurrent obstruction

Known or suspected GI obstruction or at risk of recurrent obstruction

Boxed Warning

WARNING: POTENTIAL RISK OF MYOCARDIAL INFARCTION WITH LONG-TERM USE: FOR SHORT-TERM HOSPITAL USE ONLY
There was a greater incidence of myocardial infarction in alvimopan-treated patients compared to placebo-treated patients in a 12-month clinical trial, although a causal relationship has not been established. In short-term trials with alvimopan, no increased risk of myocardial infarction was observed.

Because of the potential risk of myocardial infarction with long-term use, alvimopan is available only through a restricted program for short-term use (15 doses) under a Risk Evaluation and Mitigation Strategy (REMS) called the Alvimopan REMS Program.

-

-

Warning/Precautions

Potential Risk of Myocardial Infarction with Long-Term Use;

Alvimopan REMS Program;

GI-Related AEs in Opioid-Tolerant Pts;

Risk of Serious Adverse Reactions in Patients with Severe Hepatic Impairment;

End-Stage Renal Disease;

Risk of Serious AEs in pts with Complete GI Obstruction;

Risk of Serious AEs in Pancreatic and Gastric Anastomoses

GI perforation;

Severe or persistent diarrhea;

Opioid withdrawal

Opioid withdrawal;

GI perforation;

Severe abdominal pain and/or diarrhea

Adverse Events

>10%

-

Abdominal pain

Abdominal pain

1-9 %

In pts undergoing surgeries that include bowel resection: dyspepsia

Flatulence, nausea, dizziness, diarrhea, hyperhidrosis, hot flush, tremor, chills, rhinorrhea, muscle spasms, anxiety, abdominal distension, headache

Diarrhea; nausea; flatulence; vomiting; headache; hyperhidrosis

Trace or Frequency not defined

-

Gastrointestinal perforation, cramping, vomiting;

Diaphoresis, flushing, malaise, pain, opioid withdrawal

Hypersensitivity reactions (angioedema, rash, & urticaria);

GI disorders: GI perforation

REMS product

Alvimopan Shared System REMS (FDA last updated 6/12/23):
Healthcare settings https://www.alvimopanrems.com/

No

No

 

References:

Alvimopan (oral capsule). Package insert. Hikma; 2022.
Relistor® (methylnaltrexone). Package insert. Salix Pharmaceuticals Inc; 2024.
Movantik® (naloxegol oxalate) (oral tablet). Package insert. Valinor Pharma; 2024.

Comparison Of Alvimopan Versus Naloxegol For Enhancing Postoperative Recovery Following Radical Cystectomy For Bladder Cancer

Design

Single center retrospective review

N= 86

Objective

To compare return of bowel function, rates of ileus, and length of stay (LOS) following radical cystectomy (RC) during a transition from alvimopan to naloxegol 

Study Groups

Alvimopan (n= 52)

Naloxegol (n= 34)

Inclusion Criteria

Patients undergoing RC (open and robotic) and urinary diversion who received either alvimopan or naloxegol

Exclusion Criteria

 Not specified

Methods

Standard practice at this cancer center transitioned from use of alvimopan to naloxegol, with no other changes to the enhanced recovery after surgery (ERAS) pathways. The use of bivariate comparisons, negative binomial and logistic regression were used to compare return of bowel function, rates of ileus and LOS following RC.

Duration

 Procedure completed betwen November 2019 and July 2021

Outcome Measures

Return of bowel function, rates of ileus, LOS, cost difference

Baseline Characteristics

  

Alvimopan (n= 52)

Naloxegol (n= 34)

  

Age, years

68 (61-74)

 67 (60-75)  

Male

 39 (75%) 24 (71%)  

Caucasian

 48 (92%) 31 (91%)   

Procedure type

Open

Robotic

 

9 (17%)

43 (83%)

 

6 (18%)

28 (82%) 

  

Urinary diversion

Ileal conduit

Neobladder

 

42 (81%)

10 (19%)

 

30 (88%)

4 (12%)

  

Results

Endpoint

Alvimopan (n= 52)

Naloxegol (n= 34)

p-Value

Return of bowel function, days

 3 days  2 days  0.09 

Rates of ileus

 13% 24% 0.26

Length of stay, days

 6 6  NS

The mean cost difference between alvimopan and naloxegol was -$328.22 per day in favor of naloxegol, equivalent to a reduction of $1,969.32 over a six-day hospital stay.

Adverse Events

 N/A

Study Author Conclusions

In patients undergoing RC, there were no significant differences in postoperative recovery based on the use of alvimopan versus naloxegol. Substitution of naloxegol for alvimopan may allow for significant cost savings without compromising outcomes.

InpharmD Researcher Critique

This study was only accessible in an abridged format, thus all details were not able to be evaluated. While this was a single-center, retrospective review limited to an urban academic center in Seattle, WA, medication costs may be similar to other parts of the country. 

 

References:

Kirk P, Wang A, Raskolnikov D, et al. Mp39-09 comparison of alvimopan versus naloxegol for enhancing postoperative recovery following radical cystectomy for bladder cancer. Journal of Urology. 2022;207(Supplement 5):e668. doi:10.1097/JU.0000000000002599.09

A comparison of naloxegol versus alvimopan at the time of cystectomy and urinary diversion
Design

Retrospective review

N= 715
Objective To compare the perioperative outcomes of patients undergoing cystectomy with urinary diversion who receive the mu-opioid antagonist alvimopan versus naloxegol
Study Groups

Naloxegol (n= 57)

Alvimopan (n= 278)

Control (no mu-opioid antagonist; n= 380)
Inclusion Criteria All patients who underwent cystectomy with urinary diversion for any indication
Exclusion Criteria Patients who used chronic opioids and those with significant cardiac events within the prior year of surgery
Methods

Patient data were compiled via retrospective review of electronic health records.

Alvimopan was administered before surgery and continued until return of bowel function. Naloxegol was introduced in 2018 as a cost-effective alternative. Data on perioperative outcomes such as hospital LOS, return of bowel function, and postoperative complications were collected
Duration Treated between 01/01/2007 to 06/01/2020
Outcome Measures

Primary: Return of bowel function, hospital length of stay (LOS)

Secondary: Incidence of postoperative ileus, need for nasogastric tube, hospital readmission
Baseline Characteristics Characteristic Alvimopan (n = 278) Naloxegol (n = 57) p-Value  
Age, years (IQR) 72.0 (65.0 to 77.0) 73.0 (65.0 to 77.0) 0.71  
Female 68 (24.5%) 10 (17.5%) 0.26  
BMI, kg/m2 (IQR) 27.7 (24.2 to 31.3) 26.9 (24.1 to 30.1) 0.23  
White 263 (94.6%) 52 (92.9%) 0.61  
Charlson Comorbidity Index (IQR) 4.0 (3.0 to 5.0) 5.0 (3.5 to 6.0) < 0.001  

Eastern Cooperative Oncology Group status

Grade 1

Grade 2

Grade 3-5

 

123 (44.7%)

122 (44.4%)

30 (10.9%)

 

33 (58.9%)

16 (28.6%)

7 (12.5%)

 

0.09

0.09

0.09

  
History of diabetes mellitus 36 (12.9%) 6 (10.5%) 0.62  
Prior abdominal surgical history 178 (64.3%) 36 (64.3%) > 0.99  
Prior abdominal radiation therapy 33 (12.2%) 3 (13.6%) 0.84  
Results Outcome Alvimopan (n = 278) Naloxegol (n = 57) Odds ratio (95% CI) p-Value
Return of bowel function, days (IQR) 3.0 (2.0 to 3.0) 2.0 (2.0 to 3.0) 0.86 (0.70 to 1.06) 0.15
Hospital LOS, days (IQR) 6.0 (5.0 to 7.0) 6.0 (5.0 to 7.0) 1.37 (1.17 to 1.61) < 0.001
Postoperative ileus 13.3% 21.1% 1.60 (0.48 to 5.31) 0.44
Readmission 61 (21.9%) 17 (29.8%) 1.22 (0.54 to 2.74) 0.63
Nasogastric tube use 18 (6.5%) 7 (12.5%) - 0.12

Postoperative ileus was more common in the control group (21.6%) vs. either alvimopan or naloxegol group.  

CI, confidence interval
Adverse Events The incidence of nasogastric tube use and postoperative ileus was most common in the control group compared to the naloxegol and alvimopan cohorts. Cardiac complications were rare and did not differ between the cohorts.
Study Author Conclusions Naloxegol expedites the return of bowel function to the same degree as alvimopan in cystectomy patients. Given the lower cost of naloxegol, this agent may be a preferable alternative to alvimopan.
Critique The study's retrospective, non-randomized nature limits its ability to establish causality. Variations in perioperative protocols and surgeon preferences may have influenced outcomes. Despite these limitations, the study provides a robust comparison of naloxegol and alvimopan, supporting the use of naloxegol due to its cost-effectiveness.

 

References:

Faraj KS, Bunn W, Durant AM, Mauler D, Chang YH, Tyson MD. A comparison of naloxegol versus alvimopan at the time of cystectomy and urinary diversion. Can J Urol. 2022;29(4):11209-11215.

Naloxegol versus Alvimopan for Enhancing Postoperative Recovery following Radical Cystectomy for Bladder Cancer
Design

Retrospective, single-institution study

N= 117
Objective To compare the effects of naloxegol and alvimopan on postoperative recovery following radical cystectomy, focusing on outcomes such as length of stay and ileus rates, and to evaluate cost savings associated with naloxegol
Study Groups

Alvimopan (n= 59)

Naloxegol (n= 58)
Inclusion Criteria Patients undergoing radical cystectomy for bladder cancer at a single institution, managed with a standardized enhanced recovery after surgery (ERAS) protocol
Exclusion Criteria Death prior to hospital discharge, receipt of both naloxegol and alvimopan, aborted cystectomy due to unresectable disease
Methods A retrospective review of patients undergoing radical cystectomy over a 20-month period was conducted. The transition from alvimopan to naloxegol within the ERAS pathway was assessed. Bivariate comparisons and multivariable models were used to evaluate outcomes. A cost analysis was performed based on the wholesale acquisition cost.
Duration November 2019 to July 2021
Outcome Measures

Postoperative length of stay, time to return of bowel function, rates of ileus, cost savings associated with naloxegol
Baseline Characteristics Characteristic Alvimopan (n= 59) Naloxegol (n= 58)
Age, years  67 (60-74) 68 (60-74)
Male sex 75% 76%
White race 93% 93%
BMI, kg/m2 (IQR) 28 (25-32) 28 (26-33)
Neoadjuvant chemotherapy 26 50
Diabetes mellitus 17 24
Inflammatory bowel disease 3 0
Length of surgery, min 533 492

Urinary diversion

Ileal conduit

Neobladder

 

80

20

 

88

12
There were no significant differences in characteristics between the 2 treatment groups.
Results Outcome Alvimopan (n= 59) Naloxegol (n= 58) p-value
Length of stay, days 6 6 0.3
Time to flatus, days 2 2 0.2
Post-operative ileus rate 14% 17% 0.6
Complication rate 27% 35% 0.3
30-day readmission 17% 17% 0.9
Multivariable adjusted predicted outcomes based on medication used
Outcome Alvimopan (95% CI) Naloxegol (95% CI)  
Length of stay, days 6.9 (6.0-7.8) 7.4 (6.4-8.3)  
Postop ileus probability 0.1 (0.03-0.2) 0.2 (0.06-0.3)  
The wholesale acquisition cost (WAC) of naloxegol was $11.30 per dose, compared to $177.75 for alvimopan. Considering dose scheduling, this results in a daily cost difference of $344.20. For the median hospital length of stay (6 days) in this cohort, naloxegol provides a cost savings of $2,065.20 per patient.
Adverse Events No medication-related adverse effects were observed in either group. 
Study Author Conclusions Substitution of naloxegol for alvimopan in an ERAS pathway for radical cystectomy patients resulted in significant cost savings without compromising postoperative recovery outcomes
Critique The study's retrospective design and single-institution setting limit generalizability. The use of naloxegol was off-label, and future prospective, randomized studies are needed to confirm findings and assess equivalence more rigorously. 

 

References:

Kirk PS, Wang A, Raskolnikov D, et al. Naloxegol versus Alvimopan for Enhancing Postoperative Recovery following Radical Cystectomy for Bladder Cancer. Urol Pract. 2022;9(5):364-370. doi:10.1097/UPJ.0000000000000332

Impact of oral naloxegol vs subcutaneous methylnaltrexone in treatment of opioid-induced constipation in the hospital setting
Design

Multicenter retrospective chart review

N=330
Objective To evaluate the efficacy, safety, and cost of oral naloxegol vs subcutaneous methylnaltrexone for opioid-induced constipation (OIC) in the hospital
Study Groups

Methylnaltrexone (n= 220)

Naloxegol (n= 110)
Inclusion Criteria Patients 18 years or older, admitted to the hospital 48 hours after the first PAMORA dose, with an outpatient opioid prescription or received at least 30 morphine milligram equivalents in the 24 hours before the first PAMORA dose
Exclusion Criteria Gastrointestinal obstruction, colitis, NPO order at the time of the first dose, taking a PAMORA as a home medication, received both study agents within a 48-hour period, pregnant or incarcerated
Methods Patients received either oral naloxegol or subcutaneous methylnaltrexone. The primary outcome was a bowel movement within 48 hours of the first dose. Secondary outcomes included bowel movement in 24 hours, time to first bowel movement, antimotility agent use, PAMORA cost per patient, and use of a second PAMORA due to failure of the first agent. Data were extracted from electronic medical records
Duration January 1, 2013, to March 7, 2022
Outcome Measures

Primary: Achievement of a bowel movement within 48 hours of the first dose

Secondary: Bowel movement in 24 hours, time to first bowel movement, antimotility agent use, PAMORA cost per patient, use of a second PAMORA due to failure of the first agent
Baseline Characteristics Characteristic Methylnaltrexone (n= 220) Naloxegol (n= 110) p-Value
Age, years 60 (52-70) 64 (52-73) 0.250
Female, No. (%) 121 (55) 55 (50) 0.391
Weight, kg 80 (66-98) 87 (69-112) 0.039
BMI, kg/m2 28.2 (22.8-32.7) 29.3 (24.3-39.2) 0.029
AST, U/L 22.5 (15-39) 28 (19-51) 0.009
ALT, U/L 17 (11-36) 28 (18-48) <0.001
Preadmission opioid prescription, No. (%) 157 (71.4) 54 (49.1) <0.001
Opioid in 24 hours before PAMORA, MME 45 (12-100) 100 (47-100) <0.001
Laxative given before PAMORA, No. (%) 138 (62.7) 85 (77.3) 0.008
Receiving ≥60 MME, No. (%) 99 (45) 78 (70.9) <0.001
Results Outcome Methylnaltrexone (n= 220) Naloxegol (n= 110) p-Value
Time to bowel movement, hours 24.8 21.8 0.776
Bowel movement in 24 hours, No. (%) 106 (48.2) 60 (54.6) 0.27
Antimotility agent required, No. (%) 1 (0.5) 4 (3.6) 0.044
Switch to another PAMORA, No. (%) 0 (0) 2 (1.8) 0.110
Adverse Events Antimotility agent use was higher with naloxegol, but event rates were low in both groups (4 events for naloxegol vs 1 event for methylnaltrexone)
Study Author Conclusions Oral naloxegol may be an effective, cost-efficient alternative to subcutaneous methylnaltrexone for treatment of OIC in the hospital setting
Critique The study's retrospective design and reliance on accurate documentation may limit its findings. The inclusion of data spanning 11 years could introduce unmeasured differences in clinical practice. The study's real-world nature increases external validity, but potential confounders like provider-specific dosing strategies were not recorded. The study's noninferiority margin was based on clinical opinions, which may affect the robustness of conclusions.
References:

Nero R, Allen B, Hailu K, Noor R, Theiss K. Impact of oral naloxegol vs subcutaneous methylnaltrexone in treatment of opioid-induced constipation in the hospital setting. Am J Health Syst Pharm. 2023;80(Suppl 2):S70-S76. doi:10.1093/ajhp/zxac356

Naloxegol versus Methylnaltrexone for Opioid-Induced Constipation in Critically Ill Patients
Design

Multicenter, retrospective cohort study

N= 161
Objective To evaluate the efficacy of enteral naloxegol (NGL) versus subcutaneous methylnaltrexone (MNTX) for the management of opioid-induced constipation (OIC) in critically ill patients
Study Groups

NGL group (n= 110)

MNTX group (n= 51)
Inclusion Criteria

Adults over the age of 18 admitted to an ICU for at least 48 hours, received a continuous parenteral opioid infusion for at least 4 hours prior to administration of NGL or MNTX, and experienced no bowel movements (BM) within the 48-hour period preceding the initiation of NGL or MNTX
Exclusion Criteria Pregnant, incarcerated, on a strict NPO diet, diagnosed with an ileus or small bowel obstruction, gastric residuals > 500 mL, admitted to an ICU specific for burn patients, history of OIC, previously received an alternative agent for OIC, or received both study drugs
Methods

Retrospective analysis of adult ICU patients who received NGL or MNTX after a parenteral opioid infusion. NGL was administered enterally and MNTX subcutaneously. Data were collected from electronic health records and manual medical record review.
Duration January 1, 2014 to September 1, 2022
Outcome Measures

Primary: Time to first BM from the start of NGL or MNTX therapy

Secondary: Number of BMs 72 hours following administration, ICU LOS, cost-effectiveness, safety outcomes (aspiration with NGL, injection site reaction with MNTX, development of delirium)
Baseline Characteristics Demographic MNTX (n= 51) NGL (n= 110)
Age 57.9 ± 15.7 61.1 ± 15
Sex, male 27 (53%) 65 (59%)
Ethnicity - Caucasian 33 (64.7%) 78 (70.3%)
Ethnicity - African American 15 (29.4%) 18 (16.4%)
Ethnicity - Other 3 (5.8%) 14 (12.7%)
BMI (kg/m2) 34.6 (13.6) 31.3 (12.2)
Results

Primary endpoint

 Noninferiority margin Wald statistic p-Value

Noninferiority test

 0.90 (10%) 1.67 0.047

Secondary endpoints

 MNTX (n= 51) NGL (n= 110) p-Value

BMs in 72 hours

 3.8 (2.4-5.4) 3.9 (2.5-5.4) 0.70

ICU LOS after study drug

 12 (7-25) 14 (8-23) 0.57

Hours to first BM

 18.3 (6.5-37.4) 23.7 (10.9-41.8) --

Percentage with BM within 48 hours

 43 (84.3%) 91 (82.7%) --
Adverse Events

No injection site reactions with MNTX or aspiration events with NGL. In the 72-hour period after initiation, 54.5% of NGL and 58.8% of MNTX patients exhibited at least 1 positive CAM-ICU score (p= 0.61).
Study Author Conclusions

NGL was noninferior to MNTX in time to first BM in ICU patients with OIC. NGL appears to have similar effectiveness to MNTX and was found to have a lower acquisition cost per BM. Randomized controlled trials are needed to confirm these results.
Critique

The study's retrospective design introduces potential confounders, and the reliance on nursing documentation for primary outcome reporting may lead to variance. The lack of a placebo group limits the ability to assess the true efficacy of the treatments. However, the study's multicenter approach and conservative noninferiority margin enhance its generalizability and validity.

 

References:

Tobben D, Carpenter S, Kolar R, et al. Naloxegol versus Methylnaltrexone for Opioid-Induced Constipation in Critically Ill Patients. Ann Pharmacother. 2024;58(7):678-684. doi:10.1177/10600280231205023