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 & Education (E.A.S.E.™) Program may use ENTEREG.

See additional Important Safety Information below


Risk Evaluation and Mitigation Strategy (REMS) Program
for ENTEREG

Communication Plan | Implementation System | Timetable for Submission of Assessments | Elements to Help Assure Safe Use

The Food and Drug Administration (FDA) Amendments Act of 2007 gave the FDA authority to require the submission and implementation of a REMS program to ensure that the drug's benefits outweigh its risks. ENTEREG has a REMS, restrictions for use, because there were more reports of myocardial infarctions in patients treated with alvimopan 0.5 mg twice daily compared with placebo-treated patients in a long-term (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.1,2

The four components of the REMS for ENTEREG include a communication plan, implementation system, timetable for submission of assessments, and elements to assure safe use.

Communication Plan

The communication plan consists of an E.A.S.E. Program kit, which includes a program overview, hospital brochure, registration form, and prescribing information brochure.

Click here to learn about and enroll in the E.A.S.E. Program.

Implementation System

The implementation system of the REMS for ENTEREG includes maintaining a database of registered hospitals, distributing the drug through drop-shipment only, and monitoring the use of ENTEREG for inpatient bowel resection surgery only and a maximum of 15 doses per patient.

Timetable for Submission of Assessments

The timetable for submission of assessments for ENTEREG includes quarterly reports submitted to the FDA for the first 18 months post approval, then annually. The report includes, but is not limited to inpatient and outpatient use, summary and analysis of myocardial infarctions reported with the use of ENTEREG, number of doses per patient, and survey of healthcare professionals to measure their awareness and understanding of the REMS for ENTEREG.

Elements to Help Assure Safe Use

The elements to assure safe use of ENTEREG in the REMS is the ENTEREG Access Support and Education (E.A.S.E.) program. This program helps to ensure that ENTEREG is for in-hospital use, will be dispensed only in hospitals that have registered in the E.A.S.E. program, is distributed only to hospitals performing bowel resection surgeries, and is administered no more than 15 doses per patient.

Important Safety Information
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 & Education (E.A.S.E.™) Program may use ENTEREG.

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

  • 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

  • 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, or in patients undergoing surgery for correction of complete bowel obstruction

  • Overall, the incidence of adverse reactions in short-term surgical clinical trials was similar between patients receiving either ENTEREG or placebo. Most common adverse reactions in patients treated with ENTEREG (incidence ≥3% with ENTEREG and at least 1% greater than placebo) undergoing bowel resection were anemia, dyspepsia, hypokalemia, back pain, and urinary retention

  • ENTEREG is available only to hospitals that enroll in the E.A.S.E. 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
Adverse Event Reporting
Healthcare professionals should report all suspected adverse events associated with the use of ENTEREG. Please contact Adolor Corporation at 1.866.4ADOLOR (1.866.423.6567).

Alternatively, this information may be reported to the FDA MedWatch Reporting System by phone at 1.800.FDA.1088 (1.800.332.1088) or by mail using Form 3500 at www.fda.gov/medwatch.

If you have any questions, please contact Adolor Corporation at 1.866.4ADOLOR (1.866.423.6567).


References: 1. Approved Risk Evaluation and Mitigation Strategies (REMS). US Food and Drug Administration Web site. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm111350.htm. Accessed May 24, 2010. 2. NDA 21-775 Entereg® (alvimopan) REMS. October 6, 2008. US Food and Drug Administration Web site. http://www.fda.gov/downloads/Drugs/DrugSafety/Postmarket
DrugSafetyInformationforPatientsandProviders/ucm129511.pdf. Accessed May 21, 2010.