Widening access to ursodeoxycholic acid

Medicines

Decision

PHARMAC is pleased to announce the approval of a proposal to widen access to ursodeoxycholic acid (Ursosan) from 1 July 2013.

This proposal was the subject of a consultation letter dated 3 May 2013.

In summary, the effect of the decision is that:

  • The access criteria will be widened to include funded access to ursodeoxycholic acid for patients with:
    • Alagille syndrome;
    • Progressive familial intrahepatic cholestasis (PFIC);
    • Chronic severe drug induced cholestatic liver injury; and
    • Total parenteral nutrition induced cholestasis (TPN-IC) in paediatric patients
  • The existing criteria will be amended by separating the criteria for patients with cholestasis associated with pregnancy from the criteria for patients with cirrhosis and reducing the bilirubin level relating to decompensated cirrhosis from 170µmol/L to 100µmol/L.

Details of the decision

  • Access to ursodeoxycholic acid (Ursosan) in Section B of the Pharmaceutical Schedule will be as follows from 1 July 2013:

Initial application – (Alagille syndrome or progressive familial intrahepatic cholestasis) - from any relevant practitioner. Approvals valid without further renewal unless notified for applications meeting the following criteria:

Either:

  1. Patient has been diagnosed with Alagille syndrome; or
  2. Patient has progressive familial intrahepatic cholestasis

Initial application – (Chronic severe drug induced cholestatic liver injury) – from any relevant practitioner. Approvals valid for 3 months for applications meeting the following criteria:

Both:

  1. Patient has chronic severe drug induced cholestatic liver injury; and
  2. Cholestatic liver injury not due to Total Parenteral Nutrition (TPN) use in adults; and
  3. Treatment with ursodeoxycholic acid may prevent hospital admission or reduce duration of stay

Initial application – (Cirrhosis) – from any relevant practitioner. Approvals valid for 6 months for applications meeting the following criteria:

Both:

  1. Primary biliary cirrhosis confirmed by antimitochondrial antibody titre (AMA) > 1:80, and raised cholestatic liver enzymes with or without raised serum IgM or, if AMA is negative, by liver biopsy; and
  2. Patient not requiring a liver transplant (bilirubin > 100 µmol/l; decompensated cirrhosis)

Initial application – (Pregnancy) – from any relevant practitioner. Approvals valid for 6 months where the patient diagnosed with cholestasis of pregnancy.

Initial application – (Haematological transplant) – from any relevant practitioner. Approvals valid for 6 months for applications meeting the following criteria:

Both:

  1. Patient at risk of veno-occlusive disease or has hepatic impairment and is undergoing conditioning treatment prior to allogenic stem cell or bone marrow transplantation; and
  2. Treatment for up to 13 weeks.

Initial application – (Total parenteral nutrition induced cholestasis) from any relevant practitioner. Approvals valid for 6 months for applications meeting the following criteria:

Both:

  1. Paediatric patient has developed abnormal liver function as indicated on testing which is likely to be induced by Total Parenteral Nutrition (TPN); and
  2. Liver function has not improved with modifying the TPN composition.

Renewal (Chronic severe drug induced cholestatic liver injury) from any relevant practitioner. Approvals valid for 6 months where the patient continues to benefit from treatment.

Renewal – (Pregnancy/Cirrhosis) – from any relevant practitioner. Approvals valid for 2 years where the treatment remains appropriate and the patient is benefiting from treatment.

Renewal – (Total parenteral nutrition induced cholestasis) from any relevant practitioner. Approvals valid for 6 months where a paediatric patient continues to require TPN and who is benefiting from treatment, defined as a sustained improvement in bilirubin levels.

Note: Ursodeoxycholic acid is not an appropriate therapy for patients requiring a liver transplant (bilirubin > 100 µmol/l; decompensated cirrhosis). These patients should be referred to an appropriate transplant centre. Treatment failure – doubling of serum bilirubin levels, absence of a significant decrease in ALP or ALT and AST, development of varices, ascites or encephalopathy, marked worsening of pruritus or fatigue, histological progression by two stages, or to cirrhosis, need for transplantation.

  • The restrictions to ursodeoxycholic acid (Ursosan) in Part II of Section H of the Pharmaceutical Schedule will be widened to include the following indications from 1 July 2013:

RESTRICTED

Alagille syndrome or Progressive Familial Intrahepatic Cholestasis

Either:

  1. Patient has been diagnosed with Alagille syndrome; or
  2. Patient has progressive familial intrahepatic cholestasis

Chronic severe drug induced cholestatic liver injury

Both:

  1. Patient has chronic severe drug induced cholestatic liver injury; and
  2. Cholestatic liver injury not due to Total Parenteral Nutrition (TPN) use in adults; and
  3. Treatment with ursodeoxycholic acid may prevent hospital admission or reduce duration of stay

Cirrhosis

Both:

  1. Primary biliary cirrhosis confirmed by antimitochondrial antibody titre (AMA) > 1:80, and raised cholestatic liver enzymes with or without raised serum IgM or, if AMA is negative by liver biopsy; and
  2. Patient not requiring a liver transplant (bilirubin > 100 µmol/l; decompensated cirrhosis

Pregnancy

Patient diagnosed with cholestasis of pregnancy.

Haematological Transplant

Both:

  1. Patient at risk of veno-occlusive disease or has hepatic impairment and is undergoing conditioning treatment prior to allogenic stem cell or bone marrow transplantation; and
  2. Treatment for up to 13 weeks.

Total Parenteral Nutrition Induced Cholestasis

Both:

  1. Paediatric patient has developed abnormal liver function as indicated on testing which is likely to be induced by TPN; and
  2. Liver function has not improved with modifying the TPN composition

Feedback received

We appreciate all of the feedback that we received and acknowledge the time people took to respond. All consultation responses received by 17th May 2013 were considered in their entirety in making a decision on the proposed changes. Most responses were supportive of the proposal, and the following issues were raised in relation to specific aspects of the proposal:

Theme Comment

A group of responders expressed disappointment at the decision to decline funding for cystic fibrosis patients with liver disease and would like a review of the decision.

PHARMAC has not decided to decline funding for cystic fibrosis patients with liver disease. The Gastrointestinal Subcommittee of PTAC asked that further evidence be sought on use of ursodeoxycholic acid for these patients, including expert opinion, and this will be reviewed at its next meeting.

Once we have the Subcommittee’s advice we will be in a position to inform interested parties about progress of decision-making on funding of ursodeoxycholic acid for this patient group.

More information

If you have any questions about this decision, you can call our toll free number (9 am to 5 pm, Monday to Friday) on 0800 66 00 50.