logo

ENTEREG® (alvimopan) capsule

DESCRIPTION CLINICAL PHARMACOLOGY INDICATIONS AND USAGE
CONTRAINDICATIONS PRECAUTIONS ADVERSE REACTIONS
DOSAGE AND ADMINISTRATION HOW SUPPLIED WARNINGS
PRESCRIBING HIGHLIGHTS:  Please see package insert for additional information and possible updates to ensure safe and effective use of this medication. The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material. Please read the disclaimer carefully BEFORE accessing or using this site. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.  
  < Constipation SECTIONled  
[ Disclaimer ] <<Back [ New drug index ]

WARNINGS  top of page

WARNING: FOR SHORT-TERM HOSPITAL USE ONLY
ENTEREG is available only for short-term (15 doses) use in hospitalized patients. Only hospitals that have registered in and met all of the requirements for the ENTEREG Access Support and Education (E.A.S.E.) program may use ENTEREG. [see Warnings and Precautions]

(DESCRIPTION) top of page

Initial U.S. Approval: 2008
DESCRIPTION
ENTEREG Capsules contain alvimopan, a peripherally-acting µ-opioid receptor (PAM-OR) antagonist. Chemically, alvimopan is the single stereoisomer [[2(S)-[[4(R)-(3-hydroxyphenyl)-3(R),4-dimethyl-1-piperidinyl]methyl]-1-oxo-3-phenylpropyl]amino]acetic acid dihydrate.

Alvimopan is a white to light beige powder with a molecular weight of 460.6, and the empirical formula is C25H32N2O4•2H2O. It has a solubility of <0.1 mg/mL in water or buffered solutions between pH 3.0 and 9.0, 1 to 5 mg/mL in buffered solutions at pH 1.2, and 10 to 25 mg/mL in aqueous 0.1 N sodium hydroxide. At physiological pH, alvimopan is zwitterionic, a property that contributes to its low solubility.

ENTEREG Capsules for oral administration contain 12 mg of alvimopan on an anhydrous basis suspended in the inactive ingredient polyethylene glycol.

CLINICAL PHARMACOLOGY: top of page

CLINICAL PHARMACOLOGY
Mechanism of Action
Alvimopan is a selective antagonist of the cloned human µ-opioid receptor with a Ki of 0.4 nM (0.2 ng/mL) and no measurable opioid-agonist effects in standard pharmacologic assays. The dissociation of [3H]-alvimopan from the human µ-opioid receptor is slower than that of other opioid ligands, consistent with its higher affinity for the receptor. At concentrations of 1 to 10 µM, alvimopan demonstrated no activity at any of over 70 non-opioid receptors, enzymes, and ion channels.

Postoperative ileus is the impairment of gastrointestinal motility after intra-abdominal surgery or other non-abdominal surgeries. Postoperative ileus affects all segments of the gastrointestinal tract and may last from 5 to 6 days, or even longer. This may potentially delay gastrointestinal recovery and hospital discharge until its resolution. It is characterized by abdominal distention and bloating, nausea, vomiting, pain, accumulation of gas and fluids in the bowel, and delayed passage of flatus and defecation. Postoperative ileus is the result of a multifactorial process that includes inhibitory sympathetic input, release of hormones, neurotransmitters, and other mediators (e.g., endogenous opioids). A component of postoperative ileus also results from an inflammatory reaction and the effects of opioid analgesics. Morphine and other µ-opioid receptor agonists are universally used for the treatment of acute postsurgical pain; however, they are known to have an inhibitory effect on gastrointestinal motility and may prolong the duration of postoperative ileus.

Following oral administration, alvimopan antagonizes the peripheral effects of opioids on gastrointestinal motility and secretion by competitively binding to gastrointestinal tract µ-opioid receptors. The antagonism produced by alvimopan at opioid receptors is evident in isolated guinea pig ileum preparations where alvimopan competitively antagonizes the effects of morphine on contractility. Alvimopan achieves this selective gastrointestinal opioid antagonism without reversing the central analgesic effects of µ-opioid agonists.

INDICATIONS AND USAGE  top of page

INDICATIONS AND USAGE
ENTEREG is indicated to accelerate the time to upper and lower gastrointestinal recovery following partial large or small bowel resection surgery with primary anastomosis.

USE IN SPECIFIC POPULATIONS
Hepatic impairment: Patients with mild-to-moderate hepatic impairment do not require dosage adjustment, but they should be monitored for adverse effects. ENTEREG is not recommended for patients with severe hepatic impairment.

Renal impairment: Alvimopan has not been studied in patients with end stage renal disease. ENTEREG is not recommended for use in these patients. Dosage adjustment is not required in patients with mild to severe renal impairment but they should be monitored for adverse effects.

CONTRAINDICATIONS top of page

CONTRAINDICATIONS
ENTEREG is contraindicated in patients who have taken therapeutic doses of opioids for more than 7 consecutive days immediately prior to taking ENTEREG.

PRECAUTIONS top of page

WARNINGS AND PRECAUTIONS
  • A higher number of myocardial infarctions was reported in patients treated with alvimopan 0.5 mg twice daily compared with placebo in a 12-month study in patients treated with opioids for chronic pain, although a causal relationship has not been established.
  • Patients recently exposed to opioids are expected to be more sensitive to the effects of ENTEREG and therefore may experience abdominal pain, nausea and vomiting, and diarrhea.
  • Not recommended in patients with severe hepatic impairment.
  • Not recommended in patients with end stage renal disease.

ADVERSE REACTIONS top of page

ADVERSE REACTIONS
Most common adverse reactions (incidence >/=3% and >/=1% placebo) in patients undergoing bowel resection were anemia, dyspepsia, hypokalemia, back pain, and urinary retention.

To report SUSPECTED ADVERSE REACTIONS, contact Adolor Corporation at 1-866-4ADOLOR (1-866-423-6567) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DOSAGE AND ADMINISTRATION  top of page

DOSAGE AND ADMINISTRATION

Usual Dosage in Adults
For hospital use only. The recommended adult dosage of ENTEREG is 12 mg administered 30 minutes to 5 hours prior to surgery followed by 12 mg twice daily beginning the day after surgery for a maximum of 7 days or until discharge. Patients should not receive more than 15 doses of ENTEREG.

Special Populations
Geriatric Use: No dosage adjustment is necessary in elderly patients.

Hepatic Impairment: No dosage adjustment is necessary in patients with mild-to-moderate hepatic impairment (Child-Pugh Class A and B). ENTEREG is not recommended for use in patients with severe hepatic impairment (Child-Pugh Class C) [see Use in Specific Populations  and Clinical Pharmacology - package insert].

Renal Impairment: No dosage adjustment is necessary in patients with mild-to-severe renal impairment, but they should be monitored for adverse effects. ENTEREG is not recommended for use in patients with end-stage renal disease [see Use in Specific Populations  and Clinical Pharmacology - package insert].

Race: No dosage adjustment is necessary in Black, Hispanic and Japanese patients,
however, due to observed 2-fold greater ENTEREG plasma concentrations in healthy male
Japanese subjects, Japanese patients should be monitored for possible adverse effects.[see Use in Specific Populations  and Clinical Pharmacology - package insert].

HOW SUPPLIED top of page

DOSAGE FORMS AND STRENGTHS
12 mg blue, hard gelatin capsules with “ADL2698” printed on both the body and the cap of the capsule.

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature.]

REFERENCE

Package Insert data: 
Manufactured for Adolor Corporation
Exton, PA 19341-1127

Distributed by GlaxoSmithKline
Research Triangle Park, NC 27709

US Patent Nos. 5,250,542; 5,434,171; 6,469,030
©2008, Adolor Corporation. All rights reserved.


18 PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
GlaxoSmithKline Adolor
NDC 11227-010-30 12 mg UNIT DOSE PACK

ENTEREG®
(alvimopan) capsules
12 mg
HOSPITAL USE ONLY Rx only
more Career Center image description
Medical Calculators - A thru Z
Lab Values - A thru Z