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Eluxadoline

Pronunciation

(el ux AD oh leen)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Viberzi: 75 mg, 100 mg

Brand Names: U.S.

  • Viberzi

Pharmacologic Category

  • Gastrointestinal Agent, Miscellaneous

Pharmacology

Eluxadoline is a mixed mu-opioid receptor agonist, delta opioid receptor antagonist, and kappa opioid receptor agonist which acts locally to reduce abdominal pain and diarrhea in patients with IBS-D without constipating side effects.

Metabolism

Not clearly established; there is evidence that glucuronidation can occur to form an acyl glucuronide metabolite

Excretion

Feces (82.2% ); urine (<1%)

Time to Peak

1.5 hours (range: 1 to 8 hours) under fed conditions; 2 hours (range: 0.5 to 6 hours) under fasting conditions

Half-Life Elimination

3.7 to 6 hours

Protein Binding

81%

Special Populations: Hepatic Function Impairment

Mean eluxadoline plasma exposure was 6-fold, 4-fold, and 16-fold higher in mild, moderate, and severe hepatically impaired subjects (Child Pugh Class A, B, C), respectively.

Use: Labeled Indications

Irritable bowel syndrome with diarrhea: Treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults

Contraindications

Known or suspected biliary duct obstruction or sphincter of Oddi disease or dysfunction; history of pancreatitis or structural diseases of the pancreas, including known or suspected pancreatic duct obstruction; alcoholism, alcohol abuse, or alcohol addiction, or in patients who drink more than 3 alcoholic beverages per day; severe hepatic impairment (Child-Pugh class C); history of chronic or severe constipation or sequelae from constipation, or known or suspected mechanical gastrointestinal obstruction

Dosing: Adult

Irritable bowel syndrome with diarrhea: Oral:

Patients with a gallbladder: 100 mg twice daily; may decrease to 75 mg twice daily in patients unable to tolerate the 100 mg dose.

Patients without a gallbladder: 75 mg twice daily.

Dosage adjustment for concomitant therapy: Coadministration of OATP1B1 inhibitors (eg, cyclosporine, gemfibrozil, atazanavir, lopinavir, ritonavir, saquinavir, tipranavir, rifampin, eltrombopag): 75 mg twice daily.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment

Mild (Child-Pugh class A) to moderate (Child-Pugh class B) impairment: 75 mg twice daily.

Severe impairment (Child-Pugh class C): Use is contraindicated.

Dosing: Adjustment for Toxicity

Severe constipation: Discontinue use in patients who develop severe constipation lasting >4 days.

Sphincter of Oddi spasms: Discontinue use in patients with symptoms of sphincter of Oddi spasm (eg, acute worsening of epigastric- or biliary-type abdominal pain, increased pancreatic enzymes, or increased hepatic transaminases). Permanently discontinue use in patients who develop biliary duct obstruction or sphincter of Oddi spasm.

Administration

Oral: Administer with food.

Dietary Considerations

Take with food

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Drug Interactions

Alcohol (Ethyl): May enhance the adverse/toxic effect of Eluxadoline. Specifically, alcohol use may increase the risk of pancreatitis. Avoid combination

Alosetron: May enhance the constipating effect of Eluxadoline. Avoid combination

Analgesics (Opioid): May enhance the constipating effect of Eluxadoline. Avoid combination

Anticholinergic Agents: May enhance the constipating effect of Eluxadoline. Avoid combination

Antihepaciviral Combination Products: May increase the serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily if combined with antihepaciviral combination products. Monitor patients for increased eluxadoline effects/toxicities. Consider therapy modification

Atazanavir: May increase the serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily if combined with atazanavir and monitor patients for increased eluxadoline effects/toxicities. Consider therapy modification

CycloSPORINE (Systemic): May increase the serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily if combined with cyclosporine and monitor patients for increased eluxadoline effects/toxicities. Consider therapy modification

Eltrombopag: May increase the serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily if combined with eltrombopag and monitor patients for increased eluxadoline effects/toxicities. Consider therapy modification

Gemfibrozil: May increase the serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily if combined with gemfibrozil and monitor patients for increased eluxadoline effects/toxicities. Consider therapy modification

Loperamide: May enhance the constipating effect of Eluxadoline. Monitor therapy

Lopinavir: May increase the serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily if combined with lopinavir and monitor patients for increased eluxadoline effects/toxicities. Consider therapy modification

RifAMPin: May increase the serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily if combined with rifampin and monitor patients for increased eluxadoline effects/toxicities. Consider therapy modification

Ritonavir: May increase the serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily if combined with ritonavir and monitor patients for increased eluxadoline effects/toxicities. Consider therapy modification

Rosuvastatin: Eluxadoline may increase the serum concentration of Rosuvastatin. Management: Use the lowest effective dose of rosuvastatin if combined with eluxadoline. Consider therapy modification

Saquinavir: May increase the serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily if combined with saquinavir and monitor patients for increased eluxadoline effects/toxicities. Consider therapy modification

Teriflunomide: May increase the serum concentration of OAT3 Substrates. Monitor therapy

Teriflunomide: May increase the serum concentration of OATP1B1/SLCO1B1 Substrates. Monitor therapy

Tipranavir: May increase the serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily if combined with tipranavir and monitor patients for increased eluxadoline effects/toxicities. Consider therapy modification

Adverse Reactions

1% to 10%:

Central nervous system: Dizziness (3%), fatigue (3%), drowsiness (≤2%), euphoria (≤2%), intoxicated feeling (≤2%), sedation (≤2%)

Dermatologic: Skin rash (3%)

Gastrointestinal: Constipation (7% to 8%), nausea (7% to 8%), abdominal pain (6% to 7%), vomiting (4%), spasm of sphincter of Oddi (<1%; 1% to 4% in patients without a gallbladder), abdominal distention (3%), flatulence (3%), viral gastroenteritis (3%), gastroesophageal reflux disease (≤2%)

Hepatic: Increased serum ALT (2% to 3%), increased serum AST (≤2%)

Respiratory: Upper respiratory tract infection (5%), nasopharyngitis (4%), bronchitis (3%), asthma (≤2%), bronchospasm (≤2%), respiratory failure (≤2%), wheezing (≤2%)

<1% (Limited to important or life-threatening): Increased liver enzymes, pancreatitis

Warnings/Precautions

Concerns related to adverse effects:

• Pancreatitis: May cause pancreatitis (not associated with sphincter of Oddi spasm); the majority of cases were associated with excessive alcohol intake and resolved with discontinuation of treatment. Avoid chronic or acute excessive alcohol use during therapy. Monitor for signs and symptoms of pancreatitis; discontinue use if new or worsening abdominal pain that may radiate to the back or shoulder (with or without nausea/vomiting) develops.

• Sphincter of Oddi spasm: May cause sphincter of Oddi spasm resulting in pancreatitis or elevated hepatic enzymes; most often occurs during the first week of treatment and resolves with discontinuation of therapy. Discontinue use if patients experience symptoms of sphincter of Oddi spasm such as acute worsening of epigastric- or biliary-type abdominal pain (eg, right upper quadrant pain) that may radiate to the back or shoulder with or without nausea/vomiting, associated with elevations of pancreatic enzymes or hepatic transaminases). Permanently discontinue use in patients who develop biliary duct obstruction or sphincter of Oddi spasm.

Disease-related concerns:

• Hepatic impairment: Plasma concentrations are increased in patients with hepatic impairment; contraindicated in patients with severe hepatic impairment. Use with caution in patients with mild-to-moderate hepatic impairment; dosage adjustment required; monitor these patients for impaired mental or physical abilities needed to perform potentially hazardous activities (eg, driving a car, operating machinery) and for other eluxadoline-related adverse reactions.

• Patients without a gallbladder: Use with caution in patients without a gallbladder, as they are at an increased risk for sphincter of Oddi spasm. Consider alternative therapy in these patients; if therapy is initiated, use a lower dose and monitor for signs and symptoms of sphincter of Oddi spasm (eg, acute abdominal pain, elevated hepatic enzymes, pancreatitis), especially during the first few weeks of treatment.

Concurrent drug therapy issues:

• CYP metabolism: The cytochrome P450 (CYP) isoenzymes involved in the metabolism of eluxadoline have not been clearly established. Thus, strong inhibitors of CYP isoenzymes have the potential to increase exposure to eluxadoline. Monitor patients for increased eluxadoline effects and toxicities if combined with a strong CYP inhibitor.

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Abuse potential: Current data suggest that eluxadoline has some potential for drug abuse and psychological dependence. Naloxone should be considered in the event of overdose.

Monitoring Parameters

Monitor for new or worsening abdominal pain that may radiate to the back or shoulder, with or without nausea/vomiting and acute biliary pain with hepatic or pancreatic enzyme elevations, especially in patients without a gallbladder during the first few weeks of therapy. Monitor patients with hepatic impairment for impaired mental or physical abilities and other eluxadoline-related adverse reactions.

Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea and constipation. Have patient report immediately to prescriber abdominal pain, constipation (lasting for more than 4 days), or abdominal pain that moves to back or shoulder with or without nausea and vomiting (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating, and advising patients.

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