Alvimopan (2 brand names, 1 dosage form, 1 route)
Available dosage forms: CAPSULE.
Routes of administration: ORAL.
Brand Names
- ALVIMOPAN
- ENTEREG
Boxed Warning
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 [see Warnings and Precautions (5.1)]. 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 [see Warnings and Precautions (5.1, 5.2)].
Indications and Usage
Alvimopan capsules are indicated to accelerate the time to upper and lower gastrointestinal recovery following surgeries that include partial bowel resection with primary anastomosis.
Dosage and Administration
For hospital use only. The recommended adult dosage of alvimopan capsules is 12 mg administered 30 minutes to 5 hours prior to surgery followed by 12 mg twice daily beginning the day after surgery until discharge for a maximum of 7 days. Patients should not receive more than 15 doses of alvimopan capsules. Alvimopan capsules can be taken with or without food [see Clinical Pharmacology (12.3)].
Contraindications
Alvimopan capsules are contraindicated in patients who have taken therapeutic doses of opioids for more than 7 consecutive days immediately prior to taking alvimopan capsules [see Warnings and Precautions (5.3)].
Adverse Reactions
The following clinically significant adverse reactions are described elsewhere in the labeling: Potential Risk of Myocardial Infarction with Long-Term Use [see Warnings and Precautions (5.1)] Gastrointestinal-Related Adverse Reactions in Opioid-Tolerant Patients [see Warnings and Precautions (5.3)] Risk of Serious Adverse Reactions in Patients with Severe Hepatic Impairment [see Warnings and Precautions (5.4)] Risk of Serious Adverse Reactions in Patients with Complete Gastrointestinal Obstruction [see Warnings and Precautions (5.6)] Risk of Serious Adverse Reactions in Pancreatic and Gastric Anastomoses [see Warnings and Precautions (5.7)]
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 and 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 in which alvimopan competitively antagonizes the effects of morphine on contractility. Alvimopan achieves this selective gas