FXR Agonist (Primary Biliary Cholangitis) Pregnancy: Avoid — limited human data. Bile acids cross placenta. Use only if clearly necessary. Discuss risks/benefits with specialist.

Obeticholic Acid

Brand names: Ocaliva

Adult dose

Dose: 5 mg once daily (initial, with or without ursodeoxycholic acid); may increase to 10 mg once daily after 6 months if inadequate response

Route: Oral

Frequency: Once daily

Max: 10 mg/day

Primary biliary cholangitis (PBC). Used alongside ursodeoxycholic acid (UDCA) or as monotherapy if UDCA intolerant. Start 5 mg, assess ALP response at 6 months; increase to 10 mg if tolerated and ALP not adequately reduced. Child-Pugh A: standard dosing. Source: BNF 90; NICE TA443; EASL PBC Guidelines 2017.

Paediatric dose

Dose: Not licensed under 18 years N/A/kg

Route: N/A

Frequency: N/A

Max: N/A

PBC is rare in paediatric population. Not licensed for use under 18 years.

Dose adjustments

Renal

No dose adjustment for mild-moderate renal impairment. Severe renal impairment: limited data — use with caution.

Hepatic

Child-Pugh A: standard 5–10 mg dosing. Child-Pugh B: 5 mg weekly initially, may increase to 5 mg twice weekly — MHRA warning: decompensation and liver failure reported at standard doses in moderate-severe hepatic impairment. Child-Pugh C: 5 mg weekly — extreme caution, specialist only.

Paediatric weight-based calculator

Patient weight (kg)

PBC is rare in paediatric population. Not licensed for use under 18 years.

Clinical pearls

POISE trial (Lancet 2015): obeticholic acid 10 mg reduced ALP by 33% and total bilirubin by 18% vs placebo. Normalisation of ALP (a key surrogate for PBC progression) in 47% at 10 mg dose. NICE TA443 approved for adults with PBC who have inadequate response to or are unable to tolerate UDCA.
MHRA 2021 warning — dose modification essential in cirrhosis: cases of fatal hepatic decompensation reported in patients with moderate or severe hepatic impairment receiving standard doses (5–10 mg daily). Modified schedule mandatory for Child-Pugh B (5 mg weekly) and Child-Pugh C (5 mg weekly). Never use standard daily dosing in these patients.
Pruritus management strategy: up to 70% develop pruritus (FXR agonism increases circulating bile acids initially before reducing production). Strategy: (1) chlorphenamine or hydroxyzine for mild itch, (2) cholestyramine if moderate (take 4–6h apart from OCA), (3) dose reduction from 10 mg to 5 mg if severe, (4) rifampicin 150 mg once daily (sub-antimicrobial) if refractory — same mechanism as cholestatic pruritus treatment.
FXR mechanism: farnesoid X receptor (FXR) is the master regulator of bile acid homeostasis. OCA activates FXR → reduces CYP7A1 expression → reduces de novo bile acid synthesis from cholesterol → reduces intrahepatic bile acid load → slows hepatic damage in PBC.
ALP as surrogate endpoint: biochemical response (ALP <1.67× ULN + bilirubin within normal + ALP decrease ≥15%) is linked to reduced risk of liver transplant and death in PBC. Monitor ALP every 3–6 months — this is the primary treatment response marker. Source: BNF 90; NICE TA443; Nevens et al. Lancet 2016 (POISE); EASL PBC Guidelines 2017.

Contraindications

Complete biliary obstruction
Decompensated cirrhosis with Child-Pugh C at standard doses (use modified dosing only under expert supervision)
Hypersensitivity to obeticholic acid

Side effects

Pruritus (most common — up to 70% in trials; dose-dependent; usually manageable with antihistamines, cholestyramine, dose reduction)
Fatigue, arthralgia
Oedema
Elevated transaminases (monitor — if ALT/AST rises >10× ULN, stop)
Hypercholesterolaemia (FXR agonism reduces bile acid synthesis, may increase LDL — monitor lipids)
MHRA warning: liver failure and death in decompensated cirrhosis at standard doses — DOSE MODIFICATION MANDATORY in moderate-severe hepatic impairment

Interactions

Bile acid sequestrants (cholestyramine, colesevelam): reduce obeticholic acid absorption — take obeticholic acid at least 4–6 hours before or after bile acid sequestrant
Warfarin: monitor INR — potential interaction (FXR affects CYP expression)
UDCA (ursodeoxycholic acid): combination therapy is standard first-line — add obeticholic acid to UDCA if ALP >1.67× ULN after 12 months of UDCA; or use as monotherapy if UDCA intolerant

Monitoring

Liver function tests (ALP, ALT, AST, bilirubin, GGT) at baseline, 3 months, 6 months, then every 6 months
Pruritus score assessment at every visit (NRS 0–10)
Lipid profile (LDL cholesterol — monitor every 6–12 months)
Child-Pugh score — if liver function deteriorates, review dose modification
Clinical symptoms of decompensation (ascites, encephalopathy, variceal bleeding)

Reference: BNFc; BNF 90; NICE TA443 (obeticholic acid for PBC); Nevens et al. Lancet 2016 (POISE trial); MHRA Drug Safety Update 2021 (hepatic decompensation); EASL PBC Clinical Practice Guidelines 2017. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways