5-[[[(2S)-2-Amino-3-[4-(aminocarbonyl)-2,6-dimethylphenyl]-1-oxopropyl][(1S)-1-(5-phenyl-1H-imidazol-2-yl)ethyl]amino]methyl]-2-methoxybenzoic acid

569.662

569.65

45TPJ4MBQ1

9725

DTXSID70235589

A07|A - Alimentary tract and metabolism

165

4.35

1.3±0.1 g/cm3

834.2±65.0 °C at 760 mmHg

458.3±34.3 °C

1.640

|Warning|H361 (100%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]|P201, P202, P281, P308+P313, P405, and P501|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

The most common adverse reactions (>5%) are constipation, nausea and abdominal pain.

In preregistration clinical trials, serum aminotransferase elevations were uncommon during eluxadoline therapy and in pooled analyses ALT elevations above 3 times the upper limit of normal occurred in 2% to 3% of eluxadoline- vs 1% of placebo-treated subjects. More detailed analysis found rare instances of marked ALT and AST elevations with eluxadoline therapy, not seen with placebo treatment. These more marked elevations were sometimes accompanied by abdominal pain and signs of sphincter of Oddi spasm (as can occur with opioid therapy) or pancreatitis. The abnormalities also arose largely in patients without a gallbladder or with a history of pancreatitis or hepato-biliary disease. Subsequent to the approval of eluxadoline and its more widescale use, over a hundred reports of pancreatitis (including 2 deaths) were reported to the Food and Drug Administration and eluxadoline was given a “black box” warning regarding its use in persons without a gallbladder. The clinical features of these reactions have not been well described, but they typically arise within the first few weeks of treatment with severe abdominal pain and vomiting sometimes accompanied by marked ALT and AST elevations with or without increases in amylase and lipase. Jaundice is rare and the liver test abnormalities are most likely due to partial bile duct obstruction. There have been no reports of severe acute hepatitis or acute liver failure attributed to eluxadoline therapy.

81%

For the treatment of irritable bowel syndrome with diarrhea (IBS-D).|FDA Label|Truberzi is indicated in adults for the treatment of irritable bowel syndrome with diarrhoea (IBS D).|Treatment of diarrhoea-predominant irritable bowel Syndrome

Eluxadoline is a mixed opioid receptor agonist (mu) and antagonist (delta) that is used to treat diarrhea-predominant irritable bowel disease. Eluxadoline is associated with a low rate of serum aminotransferase elevations that appear to be due to isolated instances of sphincter of Oddi spasm and/or pancreatitis that occurs most frequently in persons without a gallbladder.

Gastrointestinal Agents

Drugs used for their effects on the gastrointestinal system, as to control gastric acidity, regulate gastrointestinal motility and water flow, and improve digestion. (See all compounds classified as Gastrointestinal Agents.)

The oral absorption of eluxadoline is poor - estimated to be 1.02%, this could be attributed to poor in vitro GI permeability, and its zwitterionic nature leading to a negatively charged molecule across the GI pH range.|82% excreted in feces, <1% excreted in urine.

The metabolism of eluxadoline is currently unclear, however evidence suggests limited glucoronidation forms an acyl glucuronide metabolite that is then excreted into urine.

The mean plasma elimination half-life ranged from 3.7 hours to 6 hours.

Eluxadoline is a mu-opioid receptor agonis, kappa opioid receptor agonist and a delta opioid receptor antagonist. Eluxadoline is used for diarrhea predominant IBS because it reduces intestinal contractility and normalizes stress-induced acceleration of upper GI transit. Antagonistic activity at the delta receptor minimizes the constipating effect usually seen by mu-opioid receptor agonists alone. Because of it's limited systemic bioavailability, there may be less side effects associated with the use of eluxadoline in comparison with other therapies used to treat diarrhea predominant IBS.

eluxadoline

Eluxadoline|VIBERZI|9725|Schedule IV - Substances in the DEA Schedule IV have a low potential for abuse relative to substances in Schedule III.|No

Human drugs -> Truberzi -> EMA Drug Category|Antidiarrheals, intestinal antiinflammatory / antiinfective agents -> Human pharmacotherapeutic group|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients