Schedule H

Oral

• Tablets: 5 mg, 10 mg (film-coated)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Primary Biliary Cholangitis (PBC)

Use as combination therapy with ursodeoxycholic acid (UDCA) in patients with inadequate response, or as monotherapy when UDCA is not tolerated.

Dosing by Hepatic Status:

Patient Category Starting Dose Titration Usual Maintenance Dose Maximum Dose

No cirrhosis OR Compensated cirrhosis (Child-Pugh A) 5 mg once daily After ≥3 months, increase to 10 mg once daily if inadequate response and drug is tolerated 5–10 mg once daily 10 mg/day

Decompensated cirrhosis (Child-Pugh B or C) 5 mg once weekly May increase to 5 mg twice weekly (doses ≥3 days apart), then to 10 mg twice weekly based on tolerance 5–10 mg twice weekly 10 mg twice weekly (not exceeding 20 mg/week)

Clinical Notes:

• Assess therapeutic response using serum alkaline phosphatase (ALP) and bilirubin levels at 3 months

• Dose-limiting pruritus may necessitate dose reduction, temporary drug interruption, or concomitant antipruritic therapy

• Always confirm Child-Pugh classification prior to dose selection

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

Indication Dose Duration Notes Evidence

Non-Alcoholic Steatohepatitis (NASH) — OFF-LABEL 10–25 mg once daily Ongoing (trial-based) Specialist (hepatologist) supervision mandatory; not standard practice in India Phase III REGENERATE trial; routine use not recommended pending long-term safety data

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

NOT APPROVED for paediatric use in India

• Safety and efficacy have not been established in patients below 18 years of age

• No licensed paediatric indication exists

Secondary Indications – Paediatrics (Off-label, if any)

Indication Dose Notes

Juvenile PBC (rare) — OFF-LABEL Not established Only under hepatologist supervision as compassionate use in exceptional circumstances

Age Restriction Statement:

Use is not recommended in individuals under 18 years of age except under specialist hepatology supervision in rare, carefully selected cases.

Mild to moderate impairment No dose adjustment required

Degree of Impairment Recommendation

Mild (Child-Pugh A) Start at 5 mg once daily; titrate based on response after ≥3 months

Moderate (Child-Pugh B) Start at 5 mg once weekly; titrate slowly (5 mg twice weekly → 10 mg twice weekly); close monitoring essential

Severe (Child-Pugh C) Start at 5 mg once weekly; titrate with extreme caution; increased risk of hepatic decompensation and mortality

Decompensated cirrhosis Specialist supervision mandatory; intensive hepatic monitoring required throughout therapy

• Complete biliary obstruction (mechanical or functional)

• Known hypersensitivity to obeticholic acid or any formulation excipients

• Decompensated cirrhosis without appropriate dose modification and hepatologist oversight

• Child-Pugh B or C hepatic impairment without dose adjustment (daily dosing contraindicated)

• Moderate to severe hepatic impairment — mandatory dose modification required

• Pruritus — dose-dependent; may be severe and treatment-limiting

• Portal hypertension — risk of worsening with incorrect dosing

• Concurrent use of hepatotoxic medications

• Use in NASH — remains investigational; requires hepatologist discretion

• History of variceal bleeding or hepatic encephalopathy

Parameter Details

Risk statement No adequate human pregnancy data; animal studies indicate fetal toxicity at high doses without major teratogenicity

Use in pregnancy Only if potential benefit clearly outweighs risk; specialist consultation required

Preferred alternative Ursodeoxycholic acid (UDCA) is preferred for PBC management during pregnancy

Monitoring Serial liver function tests; fetal growth surveillance via ultrasound

Parameter Details

Compatibility Unknown if excreted in human breast milk

Recommendation Avoid if possible; consider discontinuing breastfeeding or the drug based on clinical necessity

Preferred alternative Ursodeoxycholic acid (if compatible with disease severity)

Infant monitoring Observe for feeding difficulties, gastrointestinal disturbances, or poor weight gain

• Starting dose: 5 mg once daily (or 5 mg once weekly if cirrhotic)

• Titration: Proceed slowly with careful clinical assessment

• Additional risks: Heightened susceptibility to pruritus; increased risk of hepatic decompensation; reduced hepatic reserve

• Monitoring: Closer surveillance of liver function parameters recommended

Interacting Drug Mechanism/Effect Management

Bile acid sequestrants (cholestyramine, colesevelam, colestipol) Bind obeticholic acid in GI tract, reducing absorption Administer obeticholic acid at least 4–6 hours before OR 4–6 hours after bile acid sequestrant

Warfarin May alter INR (increased or decreased anticoagulation) Monitor INR frequently upon initiation, dose change, or discontinuation; adjust warfarin dose accordingly

Interacting Drug Effect Management

CYP1A2 substrates (theophylline, clozapine) Obeticholic acid may mildly inhibit CYP1A2; risk of increased substrate levels Monitor drug levels if narrow therapeutic index

Statins (particularly simvastatin) Potential additive hepatotoxicity risk Monitor liver function tests closely

Antidiabetic agents (insulin, sulfonylureas) Improvement in hepatic function may alter glucose metabolism and insulin sensitivity Monitor blood glucose; adjust antidiabetic therapy as needed

Immunosuppressants (cyclosporine) Limited co-administration data Clinical monitoring recommended; watch for altered efficacy or toxicity

• Pruritus (reported in up to 70% of patients; often dose-limiting)

• Fatigue

• Abdominal pain or discomfort

• Arthralgia

• Nausea

• Oropharyngeal pain

• Dizziness

• Hepatic failure — rare; higher risk in advanced cirrhosis with inappropriate dosing

• Decompensated cirrhosis — may manifest as new or worsening ascites, hepatic encephalopathy

• Jaundice and worsening cholestasis

• Variceal bleeding (in predisposed patients)

→ Immediate drug discontinuation and urgent hepatology consultation required if serious hepatic adverse events occur

Baseline:

• Liver function tests: ALT, AST, ALP, total and direct bilirubin

• Serum albumin and INR (especially in cirrhotic patients)

• Renal function (serum creatinine, eGFR)

• Child-Pugh classification

After initiation/dose change:

• Liver function tests: Monthly for first 3 months

• Pruritus assessment: At each visit

• INR: If on warfarin therapy

Long-term:

• Liver function tests: Every 3–6 months

• Clinical assessment for signs of hepatic decompensation (ascites, encephalopathy, variceal bleeding)

• Periodic imaging as indicated for disease progression surveillance

• Ocanic® (Abbott)

• Obetoza® (Zuventus)

• Lumizioco® (Lupin)

Strength Approximate Price per Tablet

Note: Not included in NLEM; available in private market only. Prices may vary by location and supplier.

1. Always determine Child-Pugh classification before prescribing — daily dosing in Child-Pugh B or C patients has resulted in fatal hepatic decompensation

1. Pruritus is the most common treatment-limiting adverse effect — proactive patient counselling and early antipruritic strategies improve adherence

1. Primary role is as add-on therapy to UDCA in patients with inadequate biochemical response (ALP >1.67× ULN or elevated bilirubin)

1. Monitor liver function intensively during the first 3 months — most serious adverse events occur early

1. Avoid use in NASH outside clinical trials unless under hepatologist supervision with documented informed consent

1. Weekly dosing schedule for decompensated cirrhosis must be strictly adhered to; doses should be separated by at least 3 days

Obeticholic acid; PBC; primary biliary cholangitis; FXR agonist; hepatology; biliary cirrhosis; NASH-off-label; hepatotoxicity-risk; pruritus; cirrhosis-caution; UDCA-adjunct

RxIndia v1.0 — 31 Mar 2025

• CDSCO approved product information

• Abbott India prescribing information (Ocanic®)

• AIIMS Delhi hepatology protocols — PBC management guidelines

• ICMR guidance on chronic liver disease management

• API Textbook of Medicine — chronic cholestatic liver diseases chapter

• REGENERATE trial data (for NASH off-label evidence only)