Eluxadoline (Viberzi) is a mixed opioid receptor agonist/ antagonist. It is indicated for the treatment of adult patients with diarrhea-predominant irritable bowel syndrome.

Eluxadoline (Viberzi) Uses:

• Irritable bowel syndrome with diarrhea:

  • It is indicated for the treatment of adult patients with irritable bowel syndrome with predominant symptoms of diarrhea (IBSD).

Adult dose:

Eluxadoline (Viberzi) Dose in the treatment of Irritable bowel syndrome with diarrhea:

• 100 mg orally two times a day.
• The dose may be reduced to 75 mg orally two times a day in patients who are intolerant to the 100 mg dose.

• Dosage adjustment for concomitant therapy:

  • Coadministration of OATP1B1 inhibitors such as cyclosporine, gemfibrozil, lopinavir, ritonavir, atazanavir, saquinavir, tipranavir, rifampin, eltrombopag:
    • 75 mg orally two times a day.

Use in Children:

Not indicated

Eluxadoline (Viberzi) Pregnancy Risk Category: N (Not assigned)

• • • • Although data on human pregnancies is limited, adverse events in animal reproduction studies have not been observed.

  Eluxadoline use during breastfeeding:

  • • It is unknown if the drug will be excreted into breastmilk.
    • Manufacturer suggests weighing the risks and benefits of treatment for the mother and drug exposure in infants.

Eluxadoline (Viberzi) Dose in Kidney disease:

The manufacturer has not provided any recommendations regarding adjustment in the dose in patients with renal impairment. 

Eluxadoline (Viberzi) Dose in Liver disease:

• Mild (Child-Pugh class A) to moderate (Child-Pugh class B) impairment:
  • 75 mg orally two times a day.
• Severe impairment (Child-Pugh class C):
  • Avoid in Child-Pugh Class C liver disease.

Side Effects of Eluxadoline (Viberzi):

• Central Nervous System:

  • Dizziness
  • Fatigue
  • Drowsiness
  • Euphoria
  • Intoxicated Feeling
  • Sedation

• Dermatologic:

  • Skin Rash

• Gastrointestinal:

  • Constipation
  • Nausea
  • Abdominal Pain
  • Vomiting
  • Abdominal Distention
  • Flatulence
  • Viral Gastroenteritis
  • Gastroesophageal Reflux Disease

• Hepatic:

  • Increased Serum Alanine Aminotransferase
  • Increased Serum Aspartate Aminotransferase

• Respiratory:

  • Upper Respiratory Tract Infection
  • Nasopharyngitis
  • Bronchitis
  • Asthma
  • Bronchospasm
  • Respiratory Failure
  • Increased Bronchial Secretions

Contraindications to Eluxadoline (Viberzi):

• • • Allergy reactions to any component of the drug or the drug itself
    • Patients who had a cholecystectomy.
    • Patients suffering from biliary obstruction
    • Dysfunction or disease in the sphincter.
    • Patients with a history of pancreatitis and/or structural diseases of the Pancreas (e.g. obstruction of the pancreatic drain)
    • Patients who consume more than 3 alcoholic beverages per day are called an Alcoholic.
    • Severe (Child Pug Class C) hepatic impairment
    • Patients who have suffered from chronic or severe constipation in the past or any sequelae of constipation should be evaluated.
    • A suspected or known mechanical obstruction of the gastrointestinal tract.

Canadian labeling: Additional contraindications not in US labeling

• • • Hepatic impairments of mild (Child–Pugh Class A) or moderate (Child–Pugh class B).
    • Use with potent OATP1B1 inhibitors like cyclosporine.

Warnings and precautions

• • CNS depression:

    • It can lead to CNS depression, which may lead to impairment of physical and mental abilities.
    • Patients who are required to be alert for mental tasks should be cautious about taking the drug, especially those who drive heavy machinery or operate motor vehicles.

  • Constipation

    • It can sometimes cause severe constipation, which may need hospitalization.
    • Patients who suffered severe constipation were reported to have experienced intestinal obstruction, perforation and fecal impaction, which required manual evacuation.
    • Patients with severe constipation, or patients who are taking concomitant medication that can cause constipation, should stop or interrupt their treatment.

  • Hypersensitivity reactions

    • There have been numerous cases of severe drug reactions, including anaphylactic reactions.
    • Any drug reaction must be monitored.
    • If you notice any symptoms or signs of drug reactions, stop taking the treatment immediately.

  • Pancreatitis

    • Hospitalization may be required for pancreatitis.
    • Patients can develop pancreatitis, with or without the concomitant dysfunctions of the sphincter Oddi.
    • Patients who suffer from pancreatitis usually had a cholecystectomy. Patients without a gallbladder are not advised to take the drug.
    • Within a matter of weeks after starting treatment, pancreatitis can develop, which can be fatal and especially severe.
    • Patients are advised not to consume alcohol, especially excessive alcohol, during treatment.
    • Monitor patients for signs and symptoms such as pancreatitis, epigastric pain radiating down the back and nausea/ vomiting.
    • Avoid excessive alcohol consumption during therapy.

  • Spasm of the Sphincter Oddi:

    • The spasm of Oddi's sphincter may occur in the first few weeks after the treatment, or occasionally after one or more doses.
    • Acute abdominal pain may be more prominent in the right hypochondrium or epigastrium. It may radiate to the shoulders or back. It is often associated with nausea or vomiting.
    • Patients might have elevated liver enzymes or pancreatic enzymes.
    • If patients experience spasms of the sphincter or biliary obstruction, they should discontinue treatment.

  • Hepatic impairment

    • It can cause an increase in plasma hepatic enzymes.
    • Patients with severe hepatic impairment should be avoided
    • Patients with mild or moderate hepatic impairment should adjust the dosage and be cautious.

Eluxadoline: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Patients should be monitored for the clinical features of pancreatitis manifesting as abdominal pain that radiates to the back, nausea, and vomiting.
• Observe for epigastric pain or biliary pain caused by spasm of the sphincter of Oddi.
• Monitor liver functions
• Pancreatic functions
• Monitor for physical or mental impairment.

How to administer Eluxadoline (Viberzi)?

It is administered with meals. 

Mechanism of action of Eluxadoline (Viberzi):

It acts as a mixed opioid receptor antagonist/agonist.

It works locally on the following opioid receptors:

• • • An agonist for mu-opioid receptors
    • The antagonist of the delta-opioid receptor,
    • Kappa-opioid receptor antagonist

Patients with IBS-predominant diarrhea will notice a decrease in their symptoms, including diarrhea. This is without causing constipation. Protein binding:

• 81%

Metabolism:

• The metabolic pathways have not been clearly studied.
• Some evidence suggests that glucuronidation to form an acyl glucuronide metabolite may occur.

Half-life elimination:

• 3.7 to 6 hours

Time to peak:

• 1.5 hours (range: 1 to 8 hours) when administered with meals
• 2 hours (range: 0.5 to 6 hours) when administered without meals.

Excretion:

• Feces (82.2%);
• urine (<1%)

International Brand Names of Eluxadoline:

• Viberzi
• Truberzi

Eluxadoline Brand Names in Pakistan:

• No Brands Available in Pakistan.