Eluxadoline

Uses

Eluxadoline is used for adults for the treatment of irritable bowel syndrome with diarrhea (IBS-D).
Pediatric Use: Safety and effectiveness in pediatric patients have not been established.
Hepatic Impairment: It is contraused for patients with severe hepatic impairment.

Eluxadoline is also used to associated treatment for these conditions: Diarrhoea Predominant Irritable Bowel Syndrome

How Eluxadoline works

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.

Dosage

Eluxadoline dosage

The recommended dosage in adults is 100 mg twice daily taken with food.

The recommended dosage is 75 mg twice daily taken with food in patients who:

• are unable to tolerate the 100 mg dose.
• are receiving concomitant OATP1B1 inhibitors.
• have mild or moderate hepatic impairment.

Side Effects

Most common adverse reactions are constipation, nausea and
abdominal pain.

Toxicity

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

Precaution

Sphincter of Oddi spasm and Pancreatitis.
Patients who should be monitored closely-

• without a gallbladder
• with new or worsening abdominal pain
• with nausea and vomiting
• with acute biliary pain
• with liver or pancreatic enzyme elevation

Interaction

Oral Contraceptive, Cyclosporine, Probenecid, Rosuvastatin.

Food Interaction

• Avoid excessive or chronic alcohol consumption. The risk of pancreatitis is increased with excess/chronic alcohol consumption.
• Take with food.

[Major] CONTRAINDICATED: Consumption of more than 3 alcoholic beverages per day may increase the risk of acute pancreatitis during treatment with eluxadoline.

Pancreatitis has been reported rarely during clinical trials of eluxadoline, and may or may not be related to sphincter of Oddi spasm.

ADJUST DOSING INTERVAL: High-fat meals may reduce the oral bioavailability of eluxadoline.

In 28 healthy volunteers, administration of a single 100 mg dose of eluxadoline with a high-fat meal (approximately 800 to 1000 total calories, 50% from fat) decreased eluxadoline peak plasma concentration (Cmax) and systemic exposure (AUC) by 50% and 60%, respectively, compared to administration in the fasted state.

There was no significant effect on the time to peak concentration (Tmax).

The clinical relevance of this interaction is unknown.

It should be noted that phase 3 clinical trials were conducted under fed conditions.

MANAGEMENT: Chronic or acute excessive use of alcohol should be avoided during treatment with eluxadoline.

Alcoholism, alcohol abuse, alcohol addiction, and consumption of more than 3 alcoholic beverages per day are considered contraindications to the use of eluxadoline.

The product labeling recommends taking eluxadoline with food.

Patients should be advised to stop taking eluxadoline and seek medical attention if they experience potential symptoms of pancreatitis such as persistent nausea, vomiting, abdominal tenderness, and upper abdominal pain, especially that which is made worse after eating or radiates to the back or shoulders.

Eluxadoline Drug Interaction

Moderate: loperamide, dicyclomine, loperamideUnknown: lactobacillus acidophilus, fluticasone / salmeterol, zolpidem, testosterone, aspirin, lorazepam, moxifloxacin, cyanocobalamin, exenatide, ubiquinone, omega-3 polyunsaturated fatty acids, pregabalin, metoprolol, bifidobacterium infantis / lactobacillus acidophilus, s-adenosylmethionine, multivitamin, lisdexamfetamine

Eluxadoline Disease Interaction

Major: constipation, pancreatitis, hepatic impairment

Elimination Route

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.

Half Life

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

Elimination Route

82% excreted in feces, <1% excreted in urine.

Pregnancy & Breastfeeding use

Pregnancy: Not established.
Lactation: Not established.

Contraindication

Known or suspected biliary duct obstruction, sphincter of oddi disease or dysfunction & pancreatitis.

Storage Condition

Store in a cool & dry place, protect from light. Keep out of the reach of children.

Innovators Monograph

You find simplified version here Eluxadoline