odevixibat sesquihydrate: clinical use

Prescribing considerations

• Initiate and supervise treatment through a clinician experienced in PFIC or Alagille syndrome.
• Confirm that enterohepatic circulation and canalicular bile-salt transport are sufficiently preserved for the mechanism to work.
• Clinical experience is limited in severe hepatic impairment and in older adults.
• Diarrhoea may necessitate hydration support and treatment review.

Contraindications and cautions

• Hypersensitivity to odevixibat or any formulation excipient.
• Patients with complete absence or lack of functional BSEP, such as BSEP3 PFIC2, are not expected to respond; this is a lack-of-efficacy consideration rather than a labelled contraindication.

Monitoring

• Liver tests before treatment and subsequently according to clinical practice: ALT, AST, GGT, alkaline phosphatase and total bilirubin.
• Vitamins A, D and E and INR before treatment and during follow-up.
• Hydration and clinical severity during diarrhoea.
• Clinical response, recognising that impaired gastrointestinal motility or disrupted enterohepatic circulation may reduce efficacy.

Clinical pharmacology

Odevixibat is a potent, selective and reversible ileal bile acid transporter inhibitor acting locally in the distal ileum. Oral absorption is minimal, with estimated relative bioavailability below 1%; it increases faecal bile-acid clearance and reduces serum bile-acid concentrations.

Formulation and product differences

• The 200- and 600-microgram capsules are larger and are primarily intended to be opened and sprinkled, although they may be swallowed whole.
• The 400- and 1,200-microgram capsules are smaller and are primarily intended to be swallowed whole, although they may also be opened and sprinkled.
• All strengths contain pellets that can be administered using supported soft-food or liquid techniques.

Capsule

Route: Oral

Strengths: 200 micrograms, 400 micrograms, 600 micrograms, 1200 micrograms