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| Clinical data | |
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| Trade names | Entereg |
| Other names | Alvimopan, Entereg |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a608051 |
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| Routes of administration | Oral |
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| Pharmacokinetic data | |
| Bioavailability | 6% |
| Protein binding | 80% (parent drug), 94% (metabolite) |
| Metabolism | Gut microflora-mediated hydrolysis to active metabolite |
| Eliminationhalf-life | 10-17 hours |
| Excretion | Faeces, urine (35%) |
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| Chemical and physical data | |
| Formula | C25H32N2O4 |
| Molar mass | 424.541 g·mol−1 |
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Alvimopan (trade nameEntereg) is adrug which behaves as aperipherally acting μ-opioid receptor antagonist. With the limited ability to cross theblood–brain barrier and reach theμ-opioid receptors of thecentral nervous system, the clinically undesirable effects of centrally actingopioid antagonists (like reversal of opioid-mediated analgesia) are avoided without affecting the intended blockade of μ-opioid receptors in thegastrointestinal tract.[1][2] It is currently onlyFood and Drug Administration approved for the treatment of postoperativeileus which it received in May 2008.[3][4]
Alvimopan is indicated in people to avoid postoperative ileus following partial large or small bowel resection with primary anastomosis. Alvimopan accelerates the gastrointestinal recovery period as defined by time to first bowel movement or flatus.[5]
There is a potential risk ofmyocardial infarction in patients using alvimopan long-term.[6][7]
The most common side effects associated with alvimopan are:[1]
| Adverse Effect | Frequency (%) with placebo | Frequency (%) with alvimopan |
|---|---|---|
| Dyspepsia | 4.6 | 7.0 |
| Hypokalemia | 8.5 | 9.5 |
| Back Pain | 1.7 | 3.3 |
| Delayed Micturition | 2.1 | 3.2 |
Alvimopan is absolutely contraindicated in patients who have taken therapeutic doses of opioids for more than seven consecutive days immediately prior to when alvimopan would be initiated because individuals with recent exposure to opioids are expected to be more sensitive to the effects of μ-opioid receptor antagonists. The peripheral site of action of alvimopan suggests that such a heightened sensitivity would precipitate gastrointestinal effects beyond dyspepsia.[5]
Alvimopan is not a substrate for thecytochrome P450 enzyme system. Therefore, no interactions are expected with hepatically metabolized drugs. Alvimopan is substrate forP-glycoprotein. Thus, interactions are to be expected with known P-glycoprotein inhibitors such asamiodarone,bepridil,diltiazem,ciclosporin,itraconazole,quinine,quinidine,spironolactone, andverapamil.[5]
Alvimopan is acompetitiveantagonist of theμ-opioid receptors (MOR) in the gastrointestinal tract, with a Ki of 0.2 ng/mL. Activation of these receptors by endogenous or exogenousagonists reduces gastrointestinal motility, and alvimopan blocks this effect. Like most other peripherally-selective MOR antagonists, such asnaloxegol andmethylnaltrexone, alvimopan is selective for peripheral receptors because it is effluxed by P-glycoprotein, which reduces its ability to cross theblood-brain barrier and affect the central nervous system.[8][5]
Peak plasma concentration (Cmax) of alvimopan is reached approximately 2 hours after oral dosing, while the Cmax for metabolite occurs 36 hours after an oral dose. Alvimopan's high affinity for the peripheral μ-receptor results in an absolute bioavailability less than 7%.[5]
80% to 90% of systemically available alvimopan is bound to plasma protein. At steady state, the volume of distribution is approximately 30 liters.[5]
Alvimopan undergoes no significant hepatic metabolism, but is metabolized by intestinal flora. Gut metabolism produces an active metabolite with no clinically significant contribution to drug effect.[5]
Alvimopan undergoes 35% renal excretion and greater than 50% biliary excretion. Drug metabolized by intestinal flora is excreted in the feces. Alvimopan's half-life of elimination is 10 to 17 hours, while that of the gut metabolite is 10 to 18 hours.[5]
Alvimopan is required by the FDA to participate inRisk Evaluation and Mitigation Strategy (REMS) to ensure safe use. Alvimopan is only approved for short term use of no more than 15 doses. It is available on an inpatient basis at institutions approved by and registered with the Entereg Access Support and Education (E.A.S.E.) program. A person should receive no more than 15 doses.[5]
