Version May 2024
Irritable bowel syndrome with diarrhea (alternative agent ):
Note: Safety: Due to risk of serious adverse effects (eg, acute pancreatitis), reserve use for patients with a gallbladder who do not consume >3 alcoholic beverages per day or have a history of alcohol use disorder (AGA [Lembo 2022]). Some experts only use in selected patients with severe IBS-D that is refractory to all other agents (Wald 2022). Patient should be under the care of a clinician experienced with use of eluxadoline.
Oral: Initial: 100 mg twice daily; decrease to 75 mg twice daily in patients who experience intolerance (eg, constipation, nausea) (Barshop 2017; Cash 2021; Lembo 2016). If no improvement in symptoms by 1 month, consider discontinuation (Barshop 2017). Some experts will trial for up to 3 months (Wald 2022).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
eGFR ≥60 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR <60 mL/minute/1.73 m2: 75 mg twice daily.
eGFR <15 mL/minute/1.73 m2 (end-stage renal disease not yet requiring dialysis): 75 mg twice daily.
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.
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.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
1% to 10%:
Dermatologic: Skin rash (3%)
Gastrointestinal: Abdominal distention (3%), abdominal pain (6% to 7%), constipation (7% to 8%), flatulence (3%), gastroesophageal reflux disease (≤2%), nausea (7% to 8%), viral gastroenteritis (3%), vomiting (4%)
Hepatic: Increased serum alanine aminotransferase (2% to 3%), increased serum aspartate aminotransferase (≤2%)
Nervous system: Dizziness (3%), drowsiness (≤2%), euphoria (≤2%), fatigue (3%), intoxicated feeling (≤2%), sedated state (≤2%)
Respiratory: Asthma (≤2%), bronchitis (3%), bronchospasm (≤2%), nasopharyngitis (4%), respiratory failure (≤2%), upper respiratory tract infection (5%), wheezing (≤2%)
<1%: Gastrointestinal: Pancreatitis, spasm of sphincter of Oddi
Postmarketing:
Gastrointestinal: Fecal impaction, intestinal obstruction, intestinal perforation
Hypersensitivity: Hypersensitivity reaction (including anaphylaxis, angioedema, severe hypersensitivity reaction)
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; alcohol use disorder, 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).
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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).
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 1 or 2 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 1 or 2 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.
• Renal impairment: Use with caution in patients with moderate to severe renal impairment; dosage adjustment required.
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Viberzi: 75 mg, 100 mg
No
Tablets (Viberzi Oral)
75 mg (per each): $32.03
100 mg (per each): $32.03
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Viberzi: 75 mg, 100 mg
C-IV
Administer with food.
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206940s007lbl.pdf#page=20, must be dispensed with this medication.
Irritable bowel syndrome with diarrhea: Treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults.
Substrate of BSEP/ABCB11, MRP2, OAT1/3, OATP1B1/1B3 (SLCO1B1/1B3); Inhibits BCRP/ABCG2, OATP1B1/1B3 (SLCO1B1/1B3)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alcohol (Ethyl): May enhance the adverse/toxic effect of Eluxadoline. Specifically, alcohol use may increase the risk of pancreatitis. Risk X: Avoid combination
Alosetron: May enhance the constipating effect of Eluxadoline. Risk X: 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. Risk D: Consider therapy modification
Anticholinergic Agents: May enhance the constipating effect of Eluxadoline. Risk X: Avoid combination
Asciminib: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Asunaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Asunaprevir. Risk X: Avoid combination
Atogepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Atogepant. Management: For episodic migraine, the recommended atogepant dose is 10 mg or 30 mg once daily if given with OATP1B1/1B3 inhibitors. For chronic migraine, the recommended atogepant dose is 30 mg once daily with OATP1B1/1B3 inhibitors. Risk D: Consider therapy modification
Berotralstat: BCRP/ABCG2 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with BCRP inhibitors. Risk D: Consider therapy modification
Brincidofovir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Brincidofovir. Management: Consider alternatives to OATP1B/1B3 inhibitors in patients treated with brincidofovir. If coadministration is required, administer OATP1B1/1B3 inhibitors at least 3 hours after brincidofovir and increase monitoring for brincidofovir adverse reactions. Risk D: 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. Risk D: Consider therapy modification
Elagolix: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix. Risk X: Avoid combination
Elagolix, Estradiol, and Norethindrone: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix, Estradiol, and Norethindrone. Specifically, concentrations of elagolix may be increased. Risk X: Avoid combination
Elbasvir and Grazoprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination
Leniolisib: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Loperamide-Loperamide Oxide: May enhance the constipating effect of Eluxadoline. Risk C: Monitor therapy
Momelotinib: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Momelotinib. Risk C: Monitor therapy
Nirmatrelvir and Ritonavir: May increase the serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily and monitor patients for increased eluxadoline effects/toxicities (eg, impaired mental or physical abilities needed to drive a car or operate machinery, constipation, abdominal pain). Risk D: Consider therapy modification
OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors: May increase the serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily if combined with OATP1B1/1B3 inhibitors and monitor patients for increased eluxadoline effects/toxicities. Risk D: Consider therapy modification
Opioid Agonists: May enhance the constipating effect of Eluxadoline. Risk X: Avoid combination
PAZOPanib: BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
Pretomanid: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Revefenacin: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentrations of the active metabolite(s) of Revefenacin. Risk X: Avoid combination
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. Risk D: Consider therapy modification
Rosuvastatin: BCRP/ABCG2 Inhibitors may increase the serum concentration of Rosuvastatin. Risk C: Monitor therapy
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. Risk D: Consider therapy modification
Talazoparib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Talazoparib. Risk C: Monitor therapy
Taurursodiol: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Taurursodiol. Risk X: Avoid combination
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. Risk D: Consider therapy modification
Topotecan: BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination
Trofinetide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Avoid concurrent use with OATP1B1/1B3 substrates for which small changes in exposure may be associated with serious toxicities. Monitor for evidence of an altered response to any OATP1B1/1B3 substrate if used together with trofinetide. Risk D: Consider therapy modification
Ubrogepant: BCRP/ABCG2 Inhibitors may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and second dose (at least 2 hours later if needed) of 50 mg when used with a BCRP inhibitor. Risk D: Consider therapy modification
Voclosporin: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Voxilaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Voxilaprevir. Risk X: Avoid combination
Zavegepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Zavegepant. Risk X: Avoid combination
Administration with a high fat meal decreased the Cmax by 50% and AUC by 60%; administration under fed conditions decreased the Tmax to 1.5 hours as compared to 2 hours under fasting conditions. Management: Administer with food.
Adverse events have not been observed in animal reproduction studies.
It is not known if eluxadoline is present in breast milk. According to the manufacturer, the decision to breastfeed during therapy should take into account the risk of exposure to the infant and the benefits of treatment to the mother.
Take with food
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 and renal function (at baseline and when clinically indicated); impaired mental or physical abilities; alcohol consumption.
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.
Protein binding: 81%
Metabolism: Not clearly established; there is evidence that glucuronidation can occur to form an acyl glucuronide metabolite
Half-life elimination: 3.7 to 6 hours
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
Excretion: Feces (82.2%); urine (<1%)
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.
Altered kidney function: Mean Cmax and AUC0-t were up to 2.4- to 5.9-fold higher, respectively, in patients with eGFR ≤30 mL/minute/m2.
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