Eluxadoline
mu-opioid receptor agonist / delta-opioid receptor antagonist (also kappa agonist)
Also sold as Viberzi, Truberzi.
Findings for this medication
Research about this medication, graded for how strongly each finding can be attributed to it. Nothing here describes your own levels.
Eluxadoline has almost no classical depletion machinery. It is poorly absorbed (peak plasma levels of about 2 to 4 ng/mL after a 100 mg dose, 82.2% of a radiolabeled dose recovered in feces, under 1% in urine), cytochrome P450 and UGT pathways have minimal involvement in its metabolism, and the label as retrieved contains no statement about vitamins, minerals, iron, the microbiome, mitochondria or oxidative stress [1]. Its one transporter story runs from the body to the drug, not the reverse: eluxadoline is an in vitro substrate of OATP1B1, OAT3, BSEP and MRP2, and a ciclosporin study showed OATP1B1 hepatic uptake is a major determinant of its exposure [1][3]. Red and orange tiers are empty.
mu-opioid receptor agonist / delta-opioid receptor antagonist (also kappa agonist) · ATC A07DA06 (WHO ATC/DDD Index [2]) · also sold as Viberzi (Truberzi outside the US) · reviewed 2026-10-04. This describes research about the medication. It does not say anything about your own levels or health.
How to read the evidence grades
These colours describe how strongly a finding can be attributed to the medication in the research. They are not a severity score and they say nothing about your own health.
Grades describe how strongly a finding can be attributed to Eluxadoline in the research — not how common it is, how serious it would be, and not anything about you personally.
- Red — Severe
- Two or more independent Tier A sources, this drug in the cohort, the nutrient directly measured, consistent direction, clinically meaningful magnitude, a named mechanism, no substantial contradicting Tier A evidence.
- Orange — Moderate
- At least one Tier A source with this drug in the cohort showing a real but bounded deficit: an exposure window, a subgroup, low frequency, or a functional rather than circulating deficit.
- Yellow — Low
- Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction.
- Not graded — disclosed evidence gap
- Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result.Source definition: Not gradeable under the rules above because nothing has been measured. Published as a documented gap, never as reassurance that there is no effect.
What the research found
Pancreatitis, sphincter of Oddi spasm and hepatic enzyme rise: the drug's own toxicity, not a nutrient deficiency
Yellow — LowSee study details
Eluxadoline carries a labeled risk of pancreatitis and sphincter of Oddi spasm, highest without a gallbladder or with heavy alcohol use. This is an adverse drug effect. It is not a depletion, excess or retention of any nutrient, and no nutrient was measured in any source.
Full detail and limits
Pancreatitis, sphincter of Oddi spasm and hepatic enzyme rise: the drug's own toxicity, not a nutrient deficiency
Yellow — LowWhat the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow
Limits on what this shows
- Null findings: Pooled trial safety found general tolerability comparable to placebo for most adverse events [7]. No eluxadoline-named study measured a nutrient after pancreatitis. A 2018 letter titled as questioning whether eluxadoline-associated pancreatitis is "myth or reality" (PMID 30588698) was seen only as a PubMed listing title and was not opened.
- At-risk subgroups: People without a gallbladder, with a history of pancreatitis, with alcohol use above 3 drinks per day, with hepatic impairment (exposure 4-fold to 16-fold higher), with severe renal impairment, and on OATP1B1 inhibitors such as ciclosporin (AUC 4.4-fold) [1][3]. Dose-reduction to 75 mg twice daily is the label response for several of these.
Direction
None. This is neither depletion, excess, retention nor reverse. It is a context flag placed in the yellow tier because it has no nutrient attribution; the grade says nothing about the seriousness of the toxicity, which is a labeled contraindication-level risk.
Regulatory status
Label (as relayed through a summarizing fetch, version 28, July 2024): pancreatitis with or without sphincter of Oddi spasm has been reported at 75 mg and 100 mg, including hospitalizations and fatal cases, "primarily in patients without a gallbladder." Contraindications include no gallbladder, history of pancreatitis, structural pancreatic disease, excessive alcohol use and severe hepatic impairment. Sphincter of Oddi spasm incidence 0.2% (75 mg) and 0.8% (100 mg), mostly in the first week. Increased ALT 3% (100 mg) and 2% (75 mg) versus 1% placebo; increased AST 2% or less; lipase elevation tied to the pancreatitis and spasm events and resolving on discontinuation. Risk is higher above 3 alcoholic drinks per day [1][12].
Population evidence
Pooled phase 2 and 3 safety analysis (2,776 patients, 12 to 52 weeks): 10 suspected sphincter of Oddi spasm events (0.5%), typically acute abdominal pain with raised pancreatic and liver enzymes, 8 at the higher dose and resolving after stopping; 5 independently adjudicated pancreatitis cases unrelated to sphincter dysfunction, 3 associated with heavy alcohol use (abstract level) [7]. FDA adverse event reports May 2015 to February 2017: 119 pancreatitis cases, 1 death, 75 hospitalizations; of 67 with gallbladder status recorded, 12 had a gallbladder and 55 did not; alcohol status recorded in 37, of whom 31 showed no misuse and 6 did; median onset 1 day, up to 56 days (abstract via a reconstructed OpenAlex record) [4]. A comparative adverse-event database analysis of 597 eluxadoline reports found pancreatitis in 16.4% versus 0.2 to 0.5% for loperamide, diphenoxylate, oxycodone and rifaximin (relayed from a PubMed listing summary; abstract not independently read) [5]. After the April 2017 contraindication for people without a gallbladder, pancreatitis fell from 14.4% to 8.9% of one manufacturer's adverse event reports (274 of 2,191 overall; 97.5% stopped the drug, 87.1% improved or recovered) [6]. These are spontaneous reports and cannot give incidence.
Mechanism
Present for the toxicity itself: the label names sphincter of Oddi spasm as the pathway to pancreatitis and hepatic enzyme elevation [1]. No nutrient mechanism is claimed. Whether pancreatitis could lead to downstream malabsorption was not studied for eluxadoline in any source read and is not asserted.
Counter-evidence held on record
Counter-evidence and confounding Alcohol use and absent gallbladder are competing explanations for pancreatitis in any single case. Reporting-ratio comparisons across drugs in spontaneous report databases are inflated by stimulated reporting after label warnings. In the FDA report series, cases in people without a gallbladder occurred at the lower recommended dose, so the risk is not explained by dose alone [4]. Framing caution This is a drug safety flag, not a nutrient deficiency claim. Do not present pancreatitis, sphincter of Oddi spasm, constipation or a raised ALT as a vitamin or mineral problem, and do not recommend any supplement from this entry. New severe upper abdominal pain on this drug needs prompt medical evaluation.
The five body-system areas
Each finding is counted once, in a single area. Where a study is mentioned in a second area it is context only.
Mitochondrial Burden
Each finding below is counted once, in this area only.
Mitochondrial burden
Not graded — disclosed evidence gapSee study details
No eluxadoline-named study of mitochondrial structure, electron transport or biogenesis was retrieved.
Full detail and limits
Mitochondrial burden
Not graded — disclosed evidence gapWhat the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded
Limits on what this shows
- Why no grade: Dual condition met on what was opened: no Tier B or C source was read that supports a yellow grade, and no circulating claim of eluxadoline mitochondrial damage was found. Repair pass: the rat colitis study [14] measured tissue MDA, glutathione and catalase, which are redox markers and not mitochondrial structure, respiration or membrane potential, so it is not used here (see Overlap map). Mitochondrial-specific phrasings (HepG2 mitochondrial toxicity, oxidative phosphorylation, membrane potential) were refused by the exhausted search budget. Mixed result: a clean zero on the PubMed listings that returned, plus a remaining tooling limit. Treat as a genuine gap with a tooling caveat. Not a finding of safety.
What was searched
PubMed listing "eluxadoline AND (mitochondria OR mitochondrial OR oxidative stress OR antioxidant)": one record, a 2019 diabetic diarrhea review (PMID 31541370), title only, not opened and not about mitochondrial function. "eluxadoline AND (ATP OR respiration OR membrane potential OR cytotoxicity)": one record, the OATP1B1/OAT3/MRP2 pharmacokinetic paper [3], which has no mitochondrial content. Label: no mitochondrial statement relayed [1].
Class material not borrowed
Sibling dossiers in this series record constipation-model mouse abstracts for loperamide and diphenoxylate. I did not open those sources, and the tissue effects in such models cannot be separated from the induced constipated state, so nothing was carried to eluxadoline. If those sources are opened and pass a cohort check, a yellow CLASS EXTRAPOLATION could become supportable; this is a reviewer judgment call.
Oxidative Stress
Each finding below is counted once, in this area only.
Oxidative stress: reverse direction, lower colonic lipid peroxidation in a rat colitis model, not a human or nutrient finding
Yellow — LowSee study details
In one animal study with eluxadoline itself in the cohort, oral eluxadoline pretreatment was followed by lower colonic malondialdehyde and higher glutathione and catalase than untreated acetic acid colitis. The shift tracked reduced mucosal injury, so it is a disease-model result and not evidence of an antioxidant effect or of any redox depletion in people.
Full detail and limits
Oxidative stress: reverse direction, lower colonic lipid peroxidation in a rat colitis model, not a human or nutrient finding
Yellow — LowWhat the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow
Limits on what this shows
- Null findings: No healthy-animal eluxadoline-only group exists, so there is no measurement of the drug's effect on redox state in uninjured tissue, either protective or harmful. No human redox-marker measurement for eluxadoline was found. The paper does not report mitochondrial function, microbiome, hematologic or iron outcomes.
- At-risk subgroups: None defined. Animal data only.
Direction
Reverse direction (apparently protective) inside an injury model. Not a depletion, excess or retention of any nutrient, and no antioxidant nutrient was measured as a nutrient.
Regulatory status
No oxidative-stress statement in the label as relayed [1]. The FDA summary review as relayed contained a negative genotoxicity battery (Ames, chromosome aberration in human lymphocytes, mouse lymphoma, rat micronucleus) and no redox findings [17]; the EMA assessment report excerpt relayed repeat-dose monkey toxicology with no adverse clinical pathology findings and no redox findings [16].
Population evidence
Anwer et al. 2020 [14], Wistar albino rats (180 to 200 g), n=6 per group, five groups: sham (saline only), acetic acid control (5% v/v, 1.0 mL intrarectal), free eluxadoline 10 mg/kg, eluxadoline-loaded solid lipid nanoparticles (F2) 10 mg/kg, and prednisolone 2 mg/kg; 6 days of oral pretreatment before colitis induction. Colon tissue, sham versus acetic acid: MDA 3.39 +/- 0.16 versus 13.76 +/- 1.21 nmol/mg protein (p<0.001); total glutathione 16.78 +/- 0.56 versus 4.54 +/- 0.36 nmol/mg protein; catalase 25.22 +/- 1.08 versus 11.03 +/- 1.02 U/mg protein. As relayed from the text: "Pre-treatment with ELX and F2 caused a significant reduction in MDA level as compared to the AA group," and "ELX, F2, and prednisolone pretreatments consistently elevated the colonic anti-oxidant activity compared to the AA group." Separate numeric values for the free-drug group were not given in the text read and the figures were not seen; for the nanoformulation, catalase was 22.49 +/- 1.01 and, for prednisolone, glutathione 14.21 +/- 0.88 and catalase 23.17 +/- 2.15. Ulcer index: acetic acid 38.57 +/- 2.86, free eluxadoline 26.57 +/- 1.25 (p<0.01), F2 23.28 +/- 0.61. The dispersion statistic (SD or SEM) was not stated in the text read.
Mechanism
Not established. The antioxidant markers moved together with the ulcer index and also moved with prednisolone, so the simplest reading is that less tissue injury produced less lipid peroxidation, not a direct antioxidant action of eluxadoline. No radical-scavenging, mitochondrial or Nrf2-type assay was run.
Cohort test
Eluxadoline was in the cohort (free drug and nanoformulation), so this is not a class extrapolation. Limits that cap it at yellow: formulation-development paper, n=6 per group, single laboratory, acetic acid colitis (a model of colitis, not of IBS-D), no eluxadoline-only healthy arm, MPO and SOD not measured, and read through a summarizing fetch of the open-access full text. Tier B (in vivo animal study with this medication).
Counter-evidence held on record
Counter-evidence and confounding The positive control prednisolone produced a similar redox shift, consistent with injury and inflammation reduction as the common cause. The model is an induced chemical colitis, so tissue redox markers rise with the disease itself; the drug-versus-disease effect on redox state cannot be separated without a healthy drug-only arm. Eluxadoline's intended pharmacologic effect is gut motility and pain modulation, not redox modulation (Hard Rule 2). Because the same oxidative signal underlies no other entry, it is not double counted (see Overlap map). Framing caution This is a rat disease-model observation, not evidence that eluxadoline is an antioxidant or that it changes oxidative stress in people. It supports no antioxidant or other supplement recommendation.
Copper and Iron Balance
Copper and iron are assessed separately. Nothing here is counted twice.
Copper
Not graded — disclosed evidence gapSee study details
No eluxadoline-named copper, ceruloplasmin or copper-chelation data were retrieved.
Full detail and limits
Copper
Not graded — disclosed evidence gapWhat the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded
Limits on what this shows
- Why no grade: Dual condition met: no Tier B or C source and no circulating claim. Repair pass: the FDA summary review, clinical pharmacology review and EMA assessment report excerpts relayed no copper statement [16][17][18], and the dedicated PubMed "eluxadoline AND (copper OR ceruloplasmin)" listing was rate limited (429) and not retried. Genuine gap for the queries that ran, with a tooling caveat for the copper-specific listing. Kept independent of Iron (Hard Rule 7).
What was searched
PubMed listing "eluxadoline AND (copper OR zinc OR magnesium OR trace element)": one record, a 2022 SARS-CoV-2 protease docking study (PMID 33847241), title only, unrelated to copper status. Vitamin and malabsorption listing: reviews and guideline titles only. Label: no mineral interaction relayed [1]. Drugs.com food and supplement interaction page: alcohol only [12].
Iron
Not graded — disclosed evidence gapSee study details
No eluxadoline-named ferritin, iron-deficiency or iron-absorption data were retrieved.
Full detail and limits
Iron
Not graded — disclosed evidence gapWhat the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded
Limits on what this shows
- Why no grade: Dual condition met: no Tier B or C source and no circulating claim. Repair pass: "eluxadoline iron" and "eluxadoline hemoglobin" PubMed listings returned 404 again, the combined hematologic and laboratory listing returned 20 records with no iron-specific title, and the FDA and EMA documents opened relayed no iron statement [16][17][18]. A narrative review of the phase 3 program reports no significant trends in hematologic laboratory findings [15]; it does not name ferritin or iron indices and is a null observation, not support for a grade. Tooling-limited in part: iron, ferritin and iron-absorption web queries were refused by the exhausted search budget. Re-check when access is restored.
What was searched
PubMed listing "eluxadoline AND (anemia OR hemoglobin OR iron OR hemolysis OR methemoglobin)": HTTP 404. A narrower "eluxadoline iron" listing was rate limited and not retried. Label: no iron statement relayed [1].
Gut Microbiome Risk
Each finding below is counted once, in this area only.
Gut microbiome risk: CLASS EXTRAPOLATION from loperamide, short course, transit-mediated
Yellow — LowSee study details
No microbiome study names eluxadoline. A loperamide healthy-volunteer study links slowed gut transit to a reversible composition shift, and eluxadoline shares the transit-slowing opioid agonism, so a transit-mediated shift is plausible but unmeasured for this drug.
Full detail and limits
Gut microbiome risk: CLASS EXTRAPOLATION from loperamide, short course, transit-mediated
Yellow — LowWhat the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow
Limits on what this shows
- Null findings: No eluxadoline null result exists because no eluxadoline microbiome measurement was found. The loperamide study did not report a harm outcome such as infection or short-chain fatty acid change in the abstract read.
- At-risk subgroups: None defined. The class source covers healthy adults over 6 days; IBS-D patients, long-term users and people with prior antibiotic exposure were not studied.
Direction
Neutral composition change (not a depletion). Not shown to be harmful in the source.
Regulatory status
No microbiome statement in the label as relayed. The label does record constipation (8% at 100 mg, 7% at 75 mg, 2% placebo) and postmarketing intestinal obstruction, perforation and fecal impaction, which are evidence that the drug slows transit in a share of patients [1].
Population evidence
Eluxadoline-named: none found. PubMed listing queries for eluxadoline with microbiome, microbiota, dysbiosis, bacteria and C. difficile returned review articles and an unrelated small-bowel dysbiosis paper; titles only, none appeared to report eluxadoline microbiome measurements, and none was opened. Class source (Tier C for this drug): Hillman 2025 [8], randomized cross-over in 18 healthy volunteers, loperamide and senna 6 days each at least 16 days apart. Loperamide lengthened whole gut transit and increased bile salt hydrolase genes and species richness; 36 species differed; treatment-induced changes reverted to baseline within 16 days. Abstract level only (OpenAlex reconstruction); doses, effect sizes and taxa were not seen.
Mechanism
Present as a shared pharmacodynamic pathway (classes A and G): slowed transit changes the stool microbiome in the cited study, and eluxadoline slows transit through peripheral mu-opioid agonism. A direct antimicrobial or luminal effect of eluxadoline was not tested in any source; with about 82% of a dose recovered in feces [1], luminal exposure is high, which makes the direct pathway an open question rather than a finding.
Class cohort test
CLASS EXTRAPOLATION. Eluxadoline was NOT in the cohort (loperamide and senna were the only drugs given) [8]. Passes on mechanism only: both drugs are peripheral mu-opioid agonists that slow gut transit, and the study authors attribute the effect to transit time. Limits on the borrowing: eluxadoline is also a delta antagonist and kappa agonist, is given to patients whose baseline transit is accelerated rather than normal, and the study was a 6-day course in healthy adults. Senna arm data are not used. Capped at yellow.
Counter-evidence held on record
Counter-evidence and confounding Confounding by indication is presumed for any patient study, because the underlying diarrheal disorder may itself differ in microbiome (Hard Rule 6). A transit-driven shift is a consequence of the drug's intended antipropulsive effect, not a toxic action. The same Hillman source supports the loperamide dossier at a higher grade because loperamide was in its cohort; that does not transfer to eluxadoline. Framing caution This is a monitoring-level class flag, not a finding of dysbiosis from eluxadoline. Do not recommend probiotics or any supplement from this entry.
Oxygen and ATP Output
Oxygen delivery and ATP production are assessed separately. Nothing here is counted twice.
Oxygen delivery/utilization
Not graded — disclosed evidence gapSee study details
No evidence was found that eluxadoline changes hemoglobin, red-cell mass or tissue oxygen delivery.
Full detail and limits
Oxygen delivery/utilization
Not graded — disclosed evidence gapWhat the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded
Limits on what this shows
- Why no grade: Dual condition met: no Tier B or C source supporting an effect and no circulating claim. Null observations recorded in the repair pass, none of which is a grade: Barshop and Staller 2017 [15], a narrative review, states of the phase 3 trials (IBS-3001 to 52 weeks, IBS-3002 to 26 weeks) that "there were no significant trends observed in hematologic, metabolic, or renal laboratory findings in eluxadoline treatment groups" (secondhand, no values; the primary trial laboratory tables were not opened because the NEJM full text returned 403); the EMA assessment report excerpt relays that 13-week cynomolgus monkey studies up to 200 mg/kg/day, and a 2-week intravenous study up to 20 mg/kg/day, showed no adverse effects on clinical pathology or haematology [16]. Tooling-limited in part (hematologic and methemoglobin or hemolysis web queries refused by the exhausted budget; PubMed hemoglobin listings 404). Kept independent of ATP production (Hard Rule 7).
What was searched
PubMed listings for eluxadoline with hemoglobin (twice), anemia, and the combined hematologic terms all returned HTTP 404, consistent with no records but unconfirmed. Label adverse-reaction and lab-abnormality sections relayed no hematologic events [1]; the Drugs.com side-effect page listed none [13]. Postmarketing label events relayed were hypersensitivity reactions only (anaphylaxis, angioedema, dyspnea, throat tightness, chest tightness) [1], which are not oxygen-carrying measures.
Hard Rule 2 note
Opioid-related respiratory effects are a toxicity matter, not an oxygen-delivery deficiency. Eluxadoline is minimally absorbed and a human study found low central effect [10], and no respiratory or hypoxia finding for the therapeutic dose was retrieved.
ATP production
Not graded — disclosed evidence gapSee study details
No eluxadoline-named data on mitochondrial ATP synthesis or cellular energy output were retrieved.
Full detail and limits
ATP production
Not graded — disclosed evidence gapWhat the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded
Limits on what this shows
- Why no grade: Dual condition met: no Tier B or C source and no circulating claim. Repair pass: the FDA and EMA documents opened relayed no energy-metabolism statement [16][17][18]. Genuine gap with a tooling caveat: the "oxidative phosphorylation", "membrane potential" and "ATP depletion" web queries were refused by the exhausted search budget. Kept independent of Mitochondrial burden and Oxygen delivery/utilization (Hard Rule 7).
What was searched
PubMed listing with ATP, respiration, membrane potential and cytotoxicity terms: only the transporter pharmacokinetic paper [3], which concerns ATP-binding cassette transporter handling (MRP2, BSEP), not cellular ATP production. That match is a term overlap and is not evidence for this entry. Label: no energy-metabolism statement relayed [1].
Claims checked and not supported
These circulate online for this medication. They are listed here only so they can be answered, never as findings, and they are not graded.
A claim with no supporting evidence is not necessarily disproven. Where evidence actually argues against a claim, that is stated below.
None found
Where it comes from: Consumer drug-nutrient depletion pages were checked: the Antidote Research drug and nutrient-depletion pages for eluxadoline returned 404, and the Drugs.com Viberzi food-interaction and side-effect pages list alcohol and the take-with-food instruction only [12][13]. Open web search for other claim sources was unavailable.
Why it fails: There is no claim to rebut, so no white entry is printed. This is a limited result: the check covered two consumer sites, not the whole consumer literature. A conflation a reader might make (pancreatitis or raised liver enzymes read as a nutrient problem) is handled in the toxicity entry above as the drug's own effect.
How the body handles this medication
- Pharmacology and site of action
- Mixed mu- and kappa-opioid receptor agonist and delta-opioid receptor antagonist, described as peripherally acting with minimal central effect; a human abuse-potential study found low drug liking and minimal pupillometry change versus oxycodone. The ATC class is antipropulsives. The label lists constipation, intestinal obstruction and perforation among its warnings.[1][2][10]
- Absorption and food
- Absolute bioavailability not determined in the label as relayed; median Tmax 1.5 hours fed and 2 hours fasted. A high-fat meal (about 800 to 1000 kcal, 50% fat) lowered Cmax by 50% and AUC by 60%. The label directs dosing with food. A Tier D encyclopedia page gives a bioavailability figure of about 1.0%, which was not verified in the label.[1][11] sec 12.3
- Metabolism and elimination
- CYP and UGT pathways have minimal involvement; no clinically meaningful CYP3A4 interaction was relayed. After a 300 mg radiolabeled dose, 82.2% of radioactivity was recovered in feces over 336 hours and under 1% in urine over 192 hours. Half-life 3.7 to 6 hours; plasma protein binding 81%.[1] sec 7, 12.3 (summarizing fetch)
- Transporters
- In vitro substrate of OAT3, OATP1B1, BSEP and MRP2; not of OCT1, OCT2, OAT1, OATP1B3, P-gp or BCRP. Ciclosporin (OATP1B1 inhibitor) raised AUC 4.4-fold and Cmax 6.2-fold; probenecid (OAT3 inhibitor) raised AUC 1.4-fold. Eluxadoline raised single-dose rosuvastatin AUC by 40% and Cmax by 18%.[1][3]
- Hepatic and renal impairment
- Eluxadoline AUC rose about 6-fold in mild, 4-fold in moderate and 16-fold in severe (Child-Pugh C) hepatic impairment; severe impairment is a contraindication and 75 mg twice daily is advised for mild or moderate. In severe renal impairment (eGFR 15 to 30) AUC was 4.7-fold higher and in ESRD not on dialysis 5.9-fold higher.[1] sec 8.6, 8.7 (summarizing fetch)
- Contraindication-linked and alcohol facts
- Contraindicated without a gallbladder, with a history of pancreatitis or structural pancreatic disease, with severe hepatic impairment, and with excessive alcohol use; pancreatitis risk is higher above 3 alcoholic drinks per day. Sphincter of Oddi spasm occurred in 0.2% (75 mg) and 0.8% (100 mg) in trials, mostly in the first week. No vitamin, mineral or supplement interaction is listed.[1][12] sec 4, 5.1, 5.2
What the research says is worth watching
General information from the medication label and the studies above. It is not personal medical advice, and any change belongs with your prescriber.
Safety / first weeks
Pancreatic symptoms
Most sphincter of Oddi spasm events occurred in the first week. Severe or persistent upper abdominal pain, especially radiating to the back, or nausea and vomiting with it, needs prompt prescriber contact [1][4][12]. This is a drug-safety matter, not a nutrient matter.
Lifestyle / label
Alcohol and gallbladder status
The label contraindicates the drug without a gallbladder and advises against excessive alcohol; risk is higher above 3 drinks per day [1][12]. Confirm both before and during therapy.
Lab / liver
Hepatic enzymes and liver function
ALT rose in 3% (100 mg) versus 1% placebo [1]. Exposure is 4-fold to 16-fold higher in hepatic impairment, with severe impairment a contraindication. Liver tests are reasonable if abdominal pain or hepatic symptoms occur; the cadence is a prescriber decision.
Symptoms / transit
Constipation and stool pattern
Constipation occurred in 8% at 100 mg, sometimes requiring hospitalization; the label advises avoiding other constipating agents and using loperamide only occasionally [1]. Persistent constipation is a reason to contact the prescriber and is also the pathway behind the yellow microbiome class flag.
Timing
Food and supplement timing
The label directs dosing with food, although a high-fat meal lowers eluxadoline exposure by 50% (Cmax) and 60% (AUC) [1]; an in silico study offers a physical-chemistry explanation [9]. The direction is nutrient-affecting-drug, so this is a timing matter, not a depletion. No mineral, vitamin or antacid separation interval is listed. No supplement dose appears in this dossier, so no upper-limit check was needed.
Special populations
Interactions, pregnancy, pediatrics, renal
OATP1B1 inhibitors such as ciclosporin raise exposure 4.4-fold (label dose reduction to 75 mg twice daily); eluxadoline raised rosuvastatin AUC by 40% [1][3]. No pregnancy studies in humans; pediatric safety is not established; AUC is 4.7-fold to 5.9-fold higher in severe renal impairment [1]. No eluxadoline-specific nutrient laboratory monitoring is supported by the evidence found.
Overlap map, to prevent double counting
Gut microbiome risk (class extrapolation)
Shares evidence with: Loperamide dossier (series 6, batch b011)
Note: The same Hillman 2025 source [8] underlies the loperamide microbiome entry (where loperamide was in the cohort) and this yellow class extrapolation. It is one study, not two confirmations, and it does not show an eluxadoline effect.
Gut microbiome risk
Shares evidence with: Pancreatitis, sphincter of Oddi spasm and hepatic enzyme rise
Note: Both draw on the same label [1], but on different statements (constipation rates versus pancreatic and hepatic events). No shared study.
Mitochondrial burden
Shares evidence with: ATP production
Note: Both are ungraded for the same reason: identical PubMed listings and the same unborrowed class material. One gap viewed twice, not two independent gaps.
Oxidative stress (yellow)
Shares evidence with: Mitochondrial burden; ATP production
Note: The only redox evidence is the rat colitis study [14], which measured colonic MDA, glutathione and catalase. Those are tissue redox markers, not mitochondrial or ATP measurements, so the study is not counted toward either ungraded entry. Same Tier B source is not reused in any other entry.
Iron
Shares evidence with: Oxygen delivery/utilization
Note: Same hematologic query set and the same null label, side-effect and regulatory-document reading, including the narrative-review null [15]. Any effect on hemoglobin would be mediated through iron; neither is counted as an independent confirmation.
Copper
Shares evidence with: Iron
Note: No shared source. Graded separately per Hard Rule 7; both ungraded.
ATP production
Shares evidence with: Pharmacokinetic basis (transporters)
Note: The only PubMed hit for the ATP query was the transporter paper [3], used in the pharmacokinetic basis, not as ATP-production evidence.
All references used above
- VIBERZI (eluxadoline) tablets, DailyMed prescribing information, version 28, last updated July 16, 2024. — Regulatory label (Tier A). Read through a summarizing fetch tool across three queries; wording and numbers are as relayed, including section numbers 5.1, 5.2, 5.4, 6, 7, 8.1, 8.4, 8.6, 8.7 and 12.3. Source of pharmacokinetic, transporter, impairment, adverse-reaction and alcohol statements. The statement that no vitamin, mineral, microbiome, mitochondrial or oxidative content exists is the fetch tool's report of absence, not a line-by-line read.
- WHO Collaborating Centre, ATC/DDD Index: eluxadoline, A07DA06, DDD 0.2 g oral. — Reference index. Group A07DA antipropulsives.
- Davenport JM, et al. Effect of uptake transporters OAT3 and OATP1B1 and efflux transporter MRP2 on the pharmacokinetics of eluxadoline. J Clin Pharmacol 2015;55(5):534-542. — In vivo transporter interaction study (Tier A for pharmacokinetics; eluxadoline administered). PMID 25491493; DOI 10.1002/jcph.442. Ciclosporin raised AUC 4.4-fold and Cmax 6.2-fold; probenecid AUC 1.4-fold and Cmax 1.3-fold; OATP1B1 hepatic uptake major, OAT3 and MRP2 minor. Abstract only, from a reconstructed OpenAlex record (which lists the year as 2014, the online date); sample size not seen.
- Postmarketing cases of eluxadoline-associated pancreatitis in patients with or without a gallbladder. Aliment Pharmacol Ther 2018. — Retrospective FDA adverse event report review, 119 cases, May 2015 to February 2017. DOI 10.1111/apt.14504; PMID 29349789. Author list not captured. Abstract only, from a reconstructed OpenAlex record. Tier A for the drug's toxicity; spontaneous reports.
- Risk of pancreatitis following treatment of irritable bowel syndrome with eluxadoline. Clin Gastroenterol Hepatol 2018. — Adverse-event database analysis, 597 eluxadoline reports. DOI 10.1016/j.cgh.2017.08.006; PMID 28804032. The abstract was not available from OpenAlex; the figures (16.4% versus 0.2 to 0.5%) are from a PubMed listing summary and were not independently read.Secondhand abstract summary; treat the figures as provisional.
- Post-marketing reports of pancreatitis in eluxadoline-treated patients pre and post US label change. Ther Adv Gastroenterol 2021. — Pharmacovigilance database review, 2,191 adverse events, January 2016 to June 2018. DOI 10.1177/17562848211001725; PMID 33953798. Abstract only, from a reconstructed OpenAlex record, which gives 274 pancreatitis cases; the PubMed listing summary said 273, a small discrepancy left unresolved. Manufacturer-linked database.
- Safety of eluxadoline in patients with irritable bowel syndrome with diarrhea. Am J Gastroenterol 2017. — Pooled phase 2 and 3 safety analysis, 2,776 patients. DOI 10.1038/ajg.2016.542; PMID 27922029. Abstract only, from a reconstructed OpenAlex record (which lists 2016, the online date).
- Hillman EBM, et al. Changing gastrointestinal transit time alters microbiome composition and bile acid metabolism: a cross-over study in healthy volunteers. Neurogastroenterol Motil 2025. — Randomized cross-over, 18 healthy volunteers, loperamide and senna. DOI 10.1111/nmo.70075; PMID 40394972. Abstract only, from a reconstructed OpenAlex record.Excluded cohort: eluxadoline was not studied. Tier C for this drug and used only as the labeled class extrapolation.
- Computational study: In silico food-drug interaction, a case study of eluxadoline and fatty meal. Int J Mol Sci 2020;21(23):9127. — Molecular modeling (Tier B, mechanistic, in silico). DOI 10.3390/ijms21239127; PMID 33266221. Abstract only, from a reconstructed OpenAlex record. Compares eluxadoline with loperamide and reports reduced eluxadoline absorption with fat.
- Levy-Cooperman N, et al. Abuse potential and pharmacodynamic characteristics of oral and intranasal eluxadoline, a mixed mu- and kappa-opioid receptor agonist and delta-opioid receptor antagonist. J Pharmacol Exp Ther 2016;359(3):471-481. — Two crossover human studies in recreational opioid users. DOI 10.1124/jpet.116.236547; PMID 27647873. Abstract only, from a reconstructed OpenAlex record. Used for the receptor description and the low central effect statement.
- Wikipedia: Eluxadoline. — Tier D for evidence purposes. Read through a summarizing fetch tool. Used only to locate references and for the quoted bioavailability figure of about 1.0%, which was not verified against the label.Tier D. Not used to support any grade.
- Drugs.com: Viberzi (eluxadoline) food, alcohol, vitamin and supplement interactions. — Tier D consumer page, read through a summarizing fetch tool. Used only as a circulating-claim check and to confirm the alcohol statement.Tier D. Not used to support any grade.
- Drugs.com: Viberzi side effects. — Tier D consumer page, read through a summarizing fetch tool. Used only as a circulating-claim check for hematologic and nutrient content.Tier D. Not used to support any grade.
- Anwer MK, Ahmed MM, Aldawsari MF, et al. Eluxadoline loaded solid lipid nanoparticles for improved colon targeting in rat model of ulcerative colitis. Pharmaceuticals (Basel) 2020;13(9):255. — In vivo animal study with eluxadoline in the cohort (Tier B): Wistar rats, acetic acid colitis, n=6 per group, free eluxadoline and nanoformulation versus sham, colitis control and prednisolone; colonic MDA, glutathione and catalase. DOI 10.3390/ph13090255; PMID 32961713. Full text read through a summarizing fetch of the open-access MDPI page over three queries; figures not seen; separate values for the free-drug group were not given in the text read. Funded by an institutional research deanship; authors declare no conflict of interest.Disease-model study with no healthy drug-only arm; supports only the yellow reverse-direction oxidative stress entry.
- Barshop K, Staller K. Eluxadoline in irritable bowel syndrome with diarrhea: rationale, evidence and place in therapy. Ther Adv Chronic Dis 2017;8(11):153-160. — Narrative review (Tier C, not stratified for laboratory outcomes). Passage read through a summarizing fetch: no significant trends in hematologic, metabolic or renal laboratory findings in eluxadoline groups of the phase 3 trials. DOI 10.1177/2040622317714389. No values, so cited only as a secondhand null observation.Secondhand; supports no grade.
- European Medicines Agency. Truberzi (eluxadoline) EPAR public assessment report. — Regulatory assessment (Tier A for regulatory content). Read through a summarizing fetch of an excerpt that was truncated before the full clinical safety section; the nonclinical toxicology section relayed 13-week cynomolgus monkey oral studies up to 200 mg/kg/day and a 2-week intravenous study up to 20 mg/kg/day without adverse clinical pathology or haematology findings. Clinical laboratory tables were not seen.
- FDA Center for Drug Evaluation and Research, NDA 206940 approval package: summary review (206940Orig1s000SumR.pdf). — Regulatory review (Tier A for regulatory content). Read through a summarizing fetch; relayed nonclinical genotoxicity (Ames, human lymphocyte chromosome aberration, mouse lymphoma, rat micronucleus all negative), carcinogenicity and fertility statements and no statement on hemoglobin, anemia, iron, vitamins, copper, mitochondria, oxidative stress or microbiome.
- FDA Center for Drug Evaluation and Research, NDA 206940 approval package: clinical pharmacology review (206940Orig1s000ClinPharmR.pdf). — Regulatory review (Tier A for regulatory content). Opened through a summarizing fetch of a long PDF; the tool reported no statement on hemoglobin, hematology, iron, vitamins, copper, mitochondria, oxidative stress or microbiome. Absence is the tool's report, not a page-by-page read.