Schedule H

Oral

NOT AVAILABLE in India (as per current CDSCO database)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India):

• None — Eluxadoline is NOT approved for use in India by CDSCO.

Secondary Indications – Adults Only (Off-label, if any):

Indication Irritable Bowel Syndrome with Diarrhoea (IBS-D)

Status OFF-LABEL in India

Starting dose 100 mg orally twice daily with food

Titration Reduce to 75 mg twice daily if 100 mg not tolerated

Usual maintenance dose 75–100 mg twice daily with food

Maximum dose 100 mg twice daily

Duration As clinically appropriate for symptom control

Specialist only Yes — Gastroenterologist supervision advised

Evidence basis US FDA approved; TARGET 1 and TARGET 2 RCTs (Gastroenterology 2016)

Note: Use only if imported under valid license for named-patient use through regulatory approval.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India):

• Not applicable — Drug not approved in India for any age group.

Secondary Indications – Paediatric Doses (Off-label, if any):

• Not applicable — No published paediatric dosing data available.

Parameter Recommendation

Minimum age Not recommended below 18 years

Safety/Efficacy Not established in children or adolescents

Off-label use Not advised even under specialist supervision due to lack of evidence

Severe impairment (eGFR <30) Avoid use — increased systemic exposure and adverse event risk

Dialysis (Haemodialysis/Peritoneal) Avoid use — safety data not available

• Known hypersensitivity to eluxadoline or any excipients

• History of biliary duct obstruction or sphincter of Oddi disease/dysfunction

• History of pancreatitis or structural disease of the pancreas

• Severe hepatic impairment (Child-Pugh C)

• Severe renal impairment (eGFR <30 mL/min/1.73m²) or end-stage renal disease

• Known or suspected mechanical gastrointestinal obstruction

• Alcoholism, alcohol abuse, or active alcohol addiction

• Patients without a gallbladder (post-cholecystectomy) — due to significantly elevated risk of sphincter of Oddi spasm and pancreatitis

• Mild-to-moderate hepatic impairment — requires dose reduction and close monitoring

• History of alcohol use disorder (even if currently abstinent)

• Concurrent use of strong CYP3A4 inhibitors or OATP1B1 inhibitors

• Patients at risk of constipation or fecal impaction

• Elderly patients — increased susceptibility to adverse events

• Concurrent use of medications causing CNS depression

Parameter Details

Risk Category Safety not established in human pregnancy

Animal Data Potential fetal risk observed at high doses in animal studies

Use Recommendation Use only if potential benefit clearly outweighs fetal risk; specialist guidance mandatory

Preferred Alternatives in India Loperamide (for IBS-D symptom control) under gastroenterologist supervision

Monitoring Fetal well-being monitoring if use is unavoidable

Parameter Details

Compatibility Unknown — no human data on excretion into breast milk

Theoretical Risk Low-to-moderate based on opioid receptor activity

Preferred Alternatives Consider loperamide if antidiarrhoeal required

Recommendation Avoid breastfeeding during use, or use only with specialist consultation

Infant Monitoring Drowsiness, poor feeding, failure to thrive, constipation

Parameter Recommendation

Starting dose 75 mg twice daily (lower starting dose recommended)

Titration Slower titration; assess tolerability before increasing

Special Risks Increased risk of constipation, sphincter of Oddi spasm, pancreatitis, CNS effects

Monitoring Close monitoring for GI motility disorders, abdominal pain, signs of biliary obstruction

Interacting Drug/Class Mechanism Clinical Recommendation

OATP1B1 inhibitors (cyclosporine, gemfibrozil, antiretrovirals) Inhibit hepatic uptake; markedly increase eluxadoline systemic exposure Avoid combination

Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin) May increase plasma levels of eluxadoline Use with caution; consider dose reduction

Other opioids (tramadol, morphine, codeine) Additive CNS depression and constipation Avoid concurrent use

Alcohol Increases pancreatitis risk; pharmacodynamic interaction Contraindicated

Interacting Drug/Class Effect Clinical Recommendation

Rosuvastatin Eluxadoline may inhibit BCRP and increase statin exposure Monitor for myopathy; check CK if symptoms occur

Anticholinergics (dicyclomine, oxybutynin) Additive risk of constipation and GI slowing Monitor bowel function closely

Loperamide Potentiation of antidiarrhoeal effect; risk of severe constipation Avoid combination

• Constipation

• Nausea

• Abdominal pain

• Headache

• Dry mouth

• Flatulence

Adverse Effect Clinical Action

Pancreatitis Discontinue immediately; hospitalisation required

Sphincter of Oddi spasm May cause acute biliary-type pain, elevated liver enzymes, pancreatitis; discontinue drug

Severe constipation/intestinal obstruction Discontinue; supportive management

Hypersensitivity reactions Discontinue; manage symptomatically

Phase Parameters to Monitor

Baseline Liver function tests, renal function (eGFR), complete alcohol use history, gallbladder status

After initiation Signs of pancreatitis (upper abdominal pain radiating to back, nausea, vomiting) — especially in first 1–2 weeks; bowel pattern

Long-term Periodic liver enzymes, symptom control, development of constipation, pancreatic symptoms

• NOT AVAILABLE in India (as of current CDSCO database)

• No approved branded formulations exist

• Not applicable — drug not marketed in India

• May be available only through named-patient import with regulatory approval; cost variable based on international pricing and import duties

• Eluxadoline acts via μ- and κ-opioid receptor agonism combined with δ-opioid antagonism — this unique mechanism reduces diarrhoea without causing significant systemic opioid effects or dependence.

• Strongly avoid in patients post-cholecystectomy — FDA data showed significantly elevated pancreatitis and sphincter of Oddi spasm risk in this group.

• Do not combine with loperamide or other antidiarrhoeals — risk of severe constipation and obstruction.

• In India, rifaximin and loperamide remain first-line agents for IBS-D; eluxadoline is reserved for refractory cases under specialist supervision if imported.

• Counsel patients to avoid alcohol completely during therapy due to pancreatitis risk.

• This drug is currently not marketed in India — consider only for named-patient import in carefully selected, refractory IBS-D cases.

Eluxadoline; IBS-D; not available India; opioid receptor modulator; diarrhoea; biliary contraindication; pancreatitis risk; post-cholecystectomy avoid; specialist-only; imported drug

RxIndia v0.2 — 11 Jun 2025

1. • CDSCO Drug Database (Accessed June 2025) — Drug not listed

• US FDA Prescribing Information for Eluxadoline (Viberzi)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• TARGET 1 and TARGET 2 Trials (Gastroenterology 2016)

• API Textbook of Medicine — IBS management chapter (does not mention eluxadoline as it is unavailable in India)

• Drug not listed in Indian Pharmacopoeia, NLEM, or AIIMS Essential Drug List