Eluxadoline

Dosage Forms

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

Tablet, Oral:

Viberzi: 75 mg, 100 mg

Pharmacology

Mechanism of Action

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.

Pharmacokinetics/Pharmacodynamics

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%

Use in Specific Populations

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

Hypersensitivity to eluxadoline or any component of the formulation; patients without a gallbladder; 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 >3 alcoholic beverages per day; severe hepatic impairment (Child-Pugh class C); history of chronic or severe constipation or sequelae from constipation; mechanical gastrointestinal obstruction (known or suspected).

Canadian labeling: Additional contraindications (not in US labeling): Mild and moderate hepatic impairment (Child-Pugh class A and B); concomitant use with potent OATP1B1 inhibitors (eg, cyclosporine).

Dosage and Administration

Dosing: Adult

Irritable bowel syndrome with diarrhea: Oral: 100 mg twice daily; may decrease to 75 mg twice daily in patients unable to tolerate the 100 mg dose

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: Adjustment for Toxicity

Constipation: Discontinue use in patients who develop severe constipation.

Pancreatitis or sphincter of Oddi spasms: Discontinue use in patients with symptoms of pancreatitis or sphincter of Oddi spasm; permanently discontinue use in patients who develop biliary duct obstruction or sphincter of Oddi spasm.

Administration

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

Alpelisib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Alpelisib. Management: Avoid coadministration of BCRP/ABCG2 inhibitors and alpelisib due to the potential for increased alpelisib concentrations and toxicities. If coadministration cannot be avoided, closely monitor for increased alpelisib adverse reactions. Consider therapy modification

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

Asunaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Asunaprevir. Avoid combination

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

Cladribine: BCRP/ABCG2 Inhibitors may increase the serum concentration of Cladribine. Management: Avoid concomitant use of BCRP inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider dose reduction of the BCRP inhibitor and separation in the timing of administration. 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

Elagolix: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix. Avoid combination

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

Grazoprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Grazoprevir. Avoid combination

Loperamide-Loperamide Oxide: 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

Nitisinone: May increase the serum concentration of OAT1/3 Substrates. Monitor therapy

Opioid Agonists: May enhance the constipating effect of Eluxadoline. Avoid combination

PAZOPanib: BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination

Pretomanid: May increase the serum concentration of OAT1/3 Substrates. Monitor therapy

Revefenacin: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentrations of the active metabolite(s) of Revefenacin. Avoid combination

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

Talazoparib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Talazoparib. Monitor therapy

Teriflunomide: May increase the serum concentration of OAT1/3 Substrates. Monitor therapy

Teriflunomide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) 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

Tolvaptan: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. Consider therapy modification

Tolvaptan: May increase the serum concentration of OAT1/3 Substrates. Management: Patients being treated with the Jynarque brand of tolvaptan should avoid concomitant use of OAT1/3 substrates. Concentrations and effects of the OAT1/3 substrate would be expected to increase with any combined use. Consider therapy modification

Topotecan: BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan. Avoid combination

Ubrogepant: BCRP/ABCG2 Inhibitors may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and second dose (if needed) of 50 mg when used with a BCRP inhibitor. Consider therapy modification

Voxilaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Voxilaprevir. Avoid combination

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%), abdominal distention (3%), flatulence (3%), viral gastroenteritis (3%), gastroesophageal reflux disease (≤2%)

Hepatic: Increased serum alanine aminotransferase (2% to 3%), increased serum aspartate aminotransferase (≤2%)

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

<1%, postmarketing, and/or case reports: Anaphylaxis, angioedema, chest pain, chest tightness, dyspnea, fecal impaction, hypersensitivity reaction, intestinal obstruction, intestinal perforation, pancreatitis, pharyngeal edema, spasm of sphincter of Oddi

Warnings/Precautions

Concerns related to adverse effects:

• Constipation: Constipation, sometimes requiring hospitalization, has been reported; severe cases with intestinal obstruction, intestinal perforation, and fecal impaction requiring intervention may also occur. Discontinue use immediately if severe constipation occurs; avoid concomitant use with drugs that may cause constipation.
• Hypersensitivity reactions: Severe hypersensitivity reactions, including anaphylaxis, have been reported during postmarketing surveillance. Some reactions occurred following the first or second dose. Discontinue immediately in patients who develop signs or symptoms of a hypersensitivity reaction.
• Pancreatitis: May cause pancreatitis, with or without sphincter of Oddi spasm, including serious cases (some fatal) requiring hospitalization. Primarily occurs in patients without a gallbladder (use is contraindicated). Most reported serious pancreatitis cases occurred within a week of starting treatment; some developed after one or two doses. 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 reported serious cases occurred during the first week of treatment, while some developed symptoms after one or two doses. 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.

Concurrent drug therapy issues:

• 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 signs/symptoms of pancreatitis (new or worsening abdominal pain that may radiate to the back, with or without nausea/vomiting) or sphincter of Oddi spasm (eg, acute epigastric or biliary pain with hepatic or pancreatic enzyme elevations); hepatic impairment; impaired mental or physical abilities.

Pregnancy

Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies.

Patient Education

What is this drug used for?

• It is used to treat irritable bowel syndrome.

Frequently reported side effects of this drug

• Common cold symptoms
• Nausea

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Pancreatitis like severe abdominal pain, severe back pain, severe nausea, or vomiting.
• Abdominal pain
• Constipation
• Abdominal pain that moves to back or shoulder with or without nausea and vomiting
• Signs of a significant reaction like 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. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.