Dosing and uses of Eluxadoline (Viberzi)
Adult dosage forms and strengths
tablet: Controlled substance schedule pending DEA review
- 75mg
- 100mg
Irritable Bowel Syndrome
Indicated for diarrhea-predominant irritable bowel syndrome (IBS-D) in adult men and women
100 mg PO BID with food
Discontinue in patients who develop severe constipation lasting >4 days
Dosage modifications
Decrease dose to 75 mg PO BID in patients who
- do not have a gallbladder
- are unable to tolerate the 100-mg dose
- are receiving concomitant OATP1B1 inhibitors
- have mild-to-moderate hepatic impairment
Hepatic impairment
- Mild-to-moderate (Child-Pugh A or B): Decrease dose to 75 mg PO BID; monitor for impaired mental or physical abilities needed to perform potentially hazardous activities
- Severe (Child-Pugh C): Contraindicated
Pediatric dosage forms and strengths
Safety and efficacy not established
Eluxadoline (Viberzi) adverse (side) effects
1-10%
Constipation (7-8%)
Nausea (7-8%)
Abdominal pain (6-7%)
URT infection (3-5%)
Vomiting (4%)
Nasopharyngitis (3-4%)
Abdominal distention (3%)
Bronchitis (3%)
Dizziness (3%)
Flatulence (3%)
Rash (3%)
Increased ALT (2-3%)
Fatigue (2-3%)
Viral gastroenteritis (1-3%)
≤2%
- Gastrointestinal: GERD
- General disorders: Feeling drunk
- Investigations: Increased AST
- Nervous system: Sedation, somnolence
- Psychiatric disorders: Euphoric mood
- Respiratory: Asthma, bronchospasm, respiratory failure, wheezing
<1%
Severe constipation
Warnings
Contraindications
Known or suspected biliary duct obstruction or sphincter of Oddi disease or dysfunction; increased risk for sphincter of Oddi spasm
Alcoholism, alcohol abuse, alcohol addiction, or in patients who drink >3 alcoholic beverages/day; increased risk of pancreatitis
History of pancreatitis, pancreatic duct obstruction, or structural diseases of the pancreas; increased risk of acute pancreatitis
Severe hepatic impairment (Child-Pugh C); risk of significantly increased eluxadoline plasma concentrations
History of chronic or severe constipation or sequelae from constipation, or known mechanical GI obstruction; increased risk of bowel obstruction
Cautions
Eluxadoline is a mu opioid receptor agonist; because of this mechanism of action, the potential for increased risk of sphincter of Oddi spasm exists, resulting in pancreatitis or hepatic enzyme elevation associated with acute abdominal pain (see Contraindications)
Increased risk of pancreatitis not associated with sphincter of Oddi spasm reported; most cases were associated with excessive alcohol use
Monitor patients without a gallbladder for new or worsening abdominal pain, with or without nausea and vomiting, or acute biliary pain with liver or pancreatic enzyme elevations; discontinue therapy and seek medical attention if symptoms develop
Drug interaction overview
- OATP1B1 inhibitors may increase systemic exposure to eluxadoline
- Strong CYP inhibitors may increase systemic exposure to eluxadoline
- Risk of constipation increased when coadministered with other drugs that cause constipation
- Eluxadoline may increase systemic exposure of coadministered OATP1B1 and BCRP substrates
- Eluxadoline may increase systemic exposure of coadministered CYP3A substrates with a narrow therapeutic index
Pregnancy and lactation
Pregnancy
No studies in pregnant women
Animal reproduction studies
- Oral and SC administration of eluxadoline to rats and rabbits during organogenesis at doses approximately 51 and 115 times the human exposure after a single oral dose of 100 mg, respectively, demonstrated no teratogenic effects. In a prenatal and postnatal development study in rats
- No adverse effects were observed in offspring with oral administration of eluxadoline at doses approximately 10 times the human exposure
Lactation
Unknown if distributed in human breast milk
Secreted in rat milk
Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Eluxadoline (Viberzi)
Mechanism of action
Mu opioid receptor agonist; it also is a delta opioid receptor antagonist and a kappa opioid receptor agonist
The multiple opioid activity is designed to treat the symptoms of IBS-D while reducing the incidence of constipation that can occur with unopposed mu opioid receptor agonists
Absorption
Peak plasma time: 1.5 hr (with food); 2 hr (fasting)
Peak plasma concentration: 2-4 ng/mL (decreased by 50% with high-fat meal)
AUC: 12-22 ng•hr/mL (decreased by 60% with high-fat meal)
Distribution
Protein bound: 81%
Metabolism
Not clearly established; eluxadoline may decrease elimination of CYP3A, OATP1B1, and BCRP substrates
OATP1B1 inhibitors and strong CYP inhibitors may decrease elimination of eluxadoline
Evidence exists that glucuronidation can occur to form an acyl glucuronide metabolite
Elimination
Half-life: 3-7-6 hr
Excretion: 82.2% feces; <1% urine
Administration
Instructions
Take with food
If a dose is missed, take the next dose at the regular time; do not take 2 doses at the same time to make up for a missed dose
Discontinue with severe constipation that lasts >4 days
Storage
Store at controlled room temperature (20-25°C [68-77°F]); excursions permitted to 15-30°C (59-86°F)
