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Label Changes for:

Entereg (alvimopan) Capsules

October 2013

Changes have been made to the BOXED WARNING, WARNINGS, PRECAUTIONS and ADVERSE REACTIONS sections of the safety label.

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)  

 

October 2013

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 Entereg, no increased risk of myocardial infarction was observed.
  • Because of the potential risk of myocardial infarction with long-term use, Entereg is available only through a restricted program for short-term use (15 doses) under a Risk Evaluation and Mitigation Strategy (REMS) called the Entereg Access Support and Education (E.A.S.E.) Program.

WARNINGS AND PRECAUTIONS

Potential Risk of Myocardial Infarction with Long-term Use
  • 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 non-cancer pain (alvimopan 0.5 mg, n = 538; placebo, n = 267). 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 Entereg in patients treated with opioids for chronic pain, nor in patients treated within the surgical setting, including patients undergoing surgeries that included bowel resection who received Entereg 12 mg twice daily for up to 7 days (the indicated dose and patient population; Entereg 12 mg, n = 1,142; placebo, n = 1,120). A causal relationship with alvimopan with long-term use has not been established.
  • Entereg is available only through a program under a REMS that restricts use to enrolled hospitals
E.A.S.E. ENTEREG REMS Program
  • Entereg is available only through a program called the Entereg  Access Support and Education (E.A.S.E.) ENTEREG REMS Program that restricts use to enrolled hospitals because of the potential risk of myocardial infarction with long-term use of Entereg.
  • Notable requirements of the E.A.S.E. Program include the following: Entereg  is available only for short-term (15 doses) use in hospitalized patients. Only hospitals that have enrolled in and met all of the requirements for the E.A.S.E. program may use Entereg.
Gastrointestinal-Related Adverse Reactions in Opioid-Tolerant Patients
  • Patients recently exposed to opioids are expected to be more sensitive to the effects of µ-opioid receptor antagonists, such as Entereg. Since Entereg acts peripherally, clinical signs and symptoms of increased sensitivity would be related to the gastrointestinal tract (e.g., abdominal pain, nausea and vomiting, diarrhea). Patients…
Risk of Serious Adverse Reactions in Patients with Severe Hepatic Impairment
  • Patients with severe hepatic impairment may be at higher risk of serious adverse reactions (including dose-related serious adverse reactions) because up to 10-fold higher plasma levels of drug have been observed in such patients compared with patients with normal hepatic function. Therefore, the use of ENTEREG is not recommended in this population.
Risk of Serious Adverse Reactions in Patients with Complete Gastrointestinal Obstruction
  • No studies have been conducted in patients with complete gastrointestinal obstruction or in patients who have surgery for correction of complete bowel obstruction. Entereg is not recommended for use in these patients.
Risk of Serious Adverse Reactions in Pancreatic and Gastric Anastomoses
  • Entereg has not been studied in patients having pancreatic or gastric anastomosis. Therefore, Entereg is not recommended for use in these patients.

ADVERSE REACTIONS

Clinical Trials Experience
  • The data described below reflect exposure to ENTEREG 12 mg in 1,793 patients in 10 placebo-controlled studies. The population was 19 to 97 years old, 64% were female, and 84% were Caucasian;…
  • Data Updated

 

November 2009

USE IN SPECIFIC POPULATIONS

Race
  • No dosage adjustment is necessary in Black, Hispanic and Japanese patients. However, the exposure of ENTEREG in Japanese male healthy volunteers was approximately 2-fold greater than in Caucasian subjects. Japanese patients should be closely monitored for possible adverse effects (e.g., diarrhea, gastrointestinal pain, cramping) that could indicate high drug or ‘metabolite’ levels, and ENTEREG should be discontinued if adverse events occur.

 

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