ENTEREG®

(alvimopan) capsules 12 mg, for oral use

Efficacy

Postoperative ACP and surgery types in ENTEREG clinical studies

A standardized multimodal postoperative accelerated care pathway (ACP) was utilized in both the placebo and ENTEREG study arms in the phase 3 and 4 clinical trials.

Postoperative care in the ENTEREG clinical trials included the following techniques for both ENTEREG and the placebo:

  • Early ambulation: Day after surgery
  • Early nasogastric tube removal: Before the first postoperative dose 
  • Early diet advancement: For bowel resection patients, liquids were offered on postoperative day (POD) 1 and solids by POD 2. For radical cystectomy patients, liquids were offered by POD 3 and solids by POD 4.

ENTEREG in clinical studies

The most common indications for surgery in the ENTEREG clinical studies were:

  • Colon or rectal cancer/malignancy
  • Bladder cancer
  • Diverticular disease

Lower gastrointestinal tract1

Diagram of the Lower Gastrointestinal Tract

The efficacy of ENTEREG in the management of postoperative ileus was evaluated in 5 multicenter, randomized, double-blind, parallel-group, placebo-controlled studies in patients 18 years of age or older who underwent partial large or small bowel resection surgery with primary anastomosis for colorectal or small bowel disease, and 1 study in patients undergoing radical cystectomy. The following surgical procedures were included in the ENTEREG clinical trials2:

  • Large bowel resections 
    • Partial colectomy 
    • Sigmoid colectomy 
    • Right or left colectomy 
  • Small bowel resections 
  • Radical cystectomy

Guidelines for Perioperative Care in Elective Colonic Surgery: Enhanced Recovery After Surgery (ERAS) Society Recommendations (2013)3

Among other perioperative care measures, the guidelines recommended the use of ENTEREG for POI in patients undergoing open colonic resection and receiving postoperative opioid analgesia.

The guidelines present a consensus view by the ERAS Society, the European Society for Clinical Nutrition and Metabolism, and the International Association for Surgical Metabolism and Nutrition on perioperative care in colonic surgery.

Indication

ENTEREG is indicated to accelerate the time to upper and lower gastrointestinal recovery following surgeries that include partial bowel resection with primary anastomosis.

Selected Safety Information

WARNING: POTENTIAL RISK OF MYOCARDIAL INFARCTION WITH LONG-TERM USE: FOR SHORT-TERM HOSPITAL USE ONLY

  • Increased incidence of myocardial infarction was seen in a clinical trial of patients taking alvimopan for long-term use. No increased risk was observed in short-term trials.
  • Because of the potential risk of myocardial infarction, ENTEREG is available only through a restricted program for short-term use (15 doses) called the ENTEREG Access Support and Education (E.A.S.E.) Program.

Contraindications

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

Warnings and Precautions

There were more reports of myocardial infarctions in patients treated with alvimopan 0.5 mg twice daily compared with placebo-treated patients in a 12-month study of patients treated with opioids for chronic pain. In this study, the majority of myocardial infarctions occurred between 1 and 4 months after initiation of treatment. This imbalance has not been observed in other studies of alvimopan, including studies of patients undergoing bowel resection surgery who received alvimopan 12 mg twice daily for up to 7 days. A causal relationship with alvimopan has not been established.

E.A.S.E. Program for ENTEREG: ENTEREG is available only to hospitals that enroll in the E.A.S.E. ENTEREG REMS Program. To enroll in the E.A.S.E. Program, the hospital must acknowledge that:

  • Hospital staff who prescribe, dispense, or administer ENTEREG have been provided the educational materials on the need to limit use of ENTEREG to short-term, inpatient use
  • Patients will not receive more than 15 doses of ENTEREG
  • ENTEREG will not be dispensed to patients after they have been discharged from the hospital

ENTEREG should be administered with caution to patients receiving more than 3 doses of an opioid within the week prior to surgery. These patients may be more sensitive to ENTEREG and may experience GI side effects (eg, abdominal pain, nausea and vomiting, diarrhea).

ENTEREG is not recommended for use in patients with severe hepatic impairment, end-stage renal disease, complete gastrointestinal obstruction, or pancreatic or gastric anastomosis, or in patients who have had surgery for correction of complete bowel obstruction.

Adverse Reactions

The most common adverse reaction (incidence ≥1.5%) occurring with a higher frequency than placebo among ENTEREG-treated patients undergoing surgeries that included a bowel resection was dyspepsia (ENTEREG, 1.5%; placebo, 0.8%).

Before prescribing ENTEREG, please read the accompanying Prescribing Information, including the Boxed Warning about potential risk of myocardial infarction with long-term use.

References

1. The digestive system. In: Tortora GJ, Derrickson BH, eds. Principles of Anatomy and Physiology. 13th ed. Hoboken, NJ: John Wiley & Sons, Inc.; 2012:967-1018. 

2. Data available on request from Merck & Co., Inc., Professional Services-DAP, WP1- 27, PO Box 4, West Point, PA 19486-0004. Please specify information package ANES-1166198-0000.

3. Gustafsson UO, Scott MJ, Schwenk W, et al. Guidelines for perioperative care in elective colonic surgery: Enhanced Recovery After Surgery (ERAS®) Society recommendations. World J Surg. 2013;37(2):259-284.

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