The new listings wrap-up is designed to provide you with information about other medicines that have been listed on the PBS for which full NPS RADAR reviews or brief items are not available.

April 2016 sees:

  • the listing of arsenic for a type of leukaemia
  • the separate listing of ribavirin and a combination of sofosbuvir, ribavirin and peginterferon for treatment of chronic hepatitis C infection. (NB: full RADAR reviews have been written for the listings of sofosbuvir, daclatasvir, and the fixed-dose combination ledipasvir with sofosbuvir for chronic hepatitis C infection).

Arsenic for acute promyelocytic leukaemia

Arsenic (Phenasen) has been listed in section 100 of the PBS for the first-line treatment of acute promyelocytic leukaemia (APL).

What is it?

The mechanisms of action for arsenic in APL are uncertain. However, arsenic has been observed to induce partial differentiation and cell death in leukaemia cells in vitro.3

Who is it for?

APL is a form of acute myeloid leukaemia with specific biological markers.4 This type of leukaemia is frequently associated with coagulation disorder and a sensitivity to certain antineoplastic medicines such as arsenic.4

Remission rates for this type of leukaemia can be as high as 80% when patients are identified and treated early.4

Safety issues

Arsenic can cause QT-interval prolongation.3 Caution should be taken when prescribing other medicines also known to prolong the QT interval. For more information on the QT interval see the NPS MedicineWise Health News and Evidence article ‘ Fatal arrythmias – drugs and the QT

Ribavirin for chronic hepatitis C – separate PBS listing

Ribavirin has been listed on the PBS General Schedule (Section 85) and S100 Highly Specialised Drugs program for use as a component of combination treatment for chronic hepatitis C virus (HCV) infection.5

Specific treatment combinations and duration depend on the viral genotype, as well as the patient’s cirrhotic status and whether they have previously received treatment for HCV infection. Treatment regimens can be found in the General Statement for Drugs for the Treatment of Hepatitis C.

This is the first time ribavirin has been listed on the PBS separately to peginterferon,6 paving the way for prescription of interferon-free hepatitis C treatments, a number of which are now listed on the PBS.

What is it?

Ribavirin is a nucleoside analogue with antiviral activity7 that interferes with RNA and DNA synthesis to inhibit protein synthesis and viral replication.8

Who is it for?

Ribavirin is PBS listed for use in the following interferon-free treatment regimens:5, 9

  • in combination with daclatasvir and sofosbuvir (12 weeks) for patients with chronic genotype 1 HCV infection with cirrhosis and who are treatment naïve or treatment experienced
  • in combination with sofosbuvir (12 weeks) for patients with chronic genotype 2 HCV infection, with or without cirrhosis, who are treatment naïve or treatment experienced
  • in combination with sofosbuvir (24 weeks) for patients with chronic genotype 3 HCV infection, with or without cirrhosis, who are treatment naïve or treatment experienced.

Safety issues

Ribavirin is contraindicated in:7

  • women who are pregnant
  • men whose partners are pregnant
  • patients with:
    • haemoglobinopathies (eg, thalassaemia major or sick-cell anaemia)
    • hypersensitivity to ribavirin or its excipients
    • history of severe pre-existing cardiac conditions, including unstable or uncontrolled cardiac disease, in the previous 6 months.

Ribavirin is also contraindicated in combination with didanosine due to reports of fatal hepatic failure, peripheral neuropathy, pancreatitis and symptomatic hyperlactataemia or lactic acidosis in clinical trials.7

When ribavirin is used in combination with other anti-HCV treatments, the relevant contraindications and precautions for those agents also apply.7

Sofosbuvir with ribavirin and peginterferon for chronic hepatitis C

The treatment regimen sofosbuvir with ribavirin and peginterferon has been PBS listed for patients with chronic genotype 1, 3, 4, 5 or 6 HCV infection, irrespective of their treatment experience and cirrhotic status.5

Further details of treatment protocols can be found in the General Statement for Drugs for the Treatment of Hepatitis C.

What is it?

Sofosbuvir is a nucleotide analogue inhibitor of the HCV-specific RNA polymerase NS5B, and prevents replication of HCV.10

Both ribavirin and peginterferon are non-specific inhibitors of viral replication. Ribavirin is a nucleoside analogue,7 while peginterferon alfa 2a shows the same antiviral activity as interferon alfa-2a in vitro, which works by activating cellular signalling and gene transcription, causing immunomodulation and inhibiting viral replication in infected cells.11

Who is it for?

Sofosbuvir with peginterferon and ribavirin is a first-line treatment option for patients with chronic genotype 4, 5 or 6 hepatitis C infection.5

Although this treatment regimen is also PBS listed for genotypes 1 and 3, it is not as well tolerated as first-line interferon-free regimens12 and is likely to be considered for patients who cannot tolerate,13 or fail to respond to,14 first-line treatment with direct-acting antivirals.

Safety issues

Common adverse effects of sofosbuvir with peginterferon and ribavirin include fatigue, headache, nausea, insomnia, pruritus, anaemia and influenza-like illness.10

Peginterferon and ribavirin are contraindicated in:11

  • pregnant women, or in men whose female partners are pregnant or are not using adequate contraception. Extreme care must be taken to avoid pregnancy during, and for 6 months after stopping, treatment
  • women who are breastfeeding
  • patients with known hypersensitivity to alfa interferons, to Escherichia coli-derived products, to ribavirin or any other component of the injection or tablet
  • autoimmune hepatitis or decompensated cirrhosis
  • patients with HIV co-infection with cirrhosis and a Child–Pugh score of ≥ 6, except if due only to indirect hyperbilirubinaemia caused by medicines such as atazanavir and indinavir
  • patients with a history of severe pre-existing cardiac disease, including unstable or uncontrolled cardiac disease in the previous 6 months
  • patients with haemoglobinopathies (eg, thalassaemia, sick-cell anaemia)
  • neonates and infants up to the age of 3 years, because of the excipient benzyl alcohol.

Potent P-glycoprotein inducers of the intestine (eg, rifampin, St John’s wort) should not be used with sofosbuvir.10

References

  1. Novartis Pharmaceuticals Australia Pty Limited. Xolair Product Information. North Ryde: Novartis Phamaceuticals Australia Pty Ltd, 2014. [Novartis] (accessed 14 March 2016).
  2. Australasian Society of Clinical Immunology and Allergy. ASCIA Chronic Spontaneous Urticaria (CSU) Guidelines. 2015. [Allergy.org] (accessed 18 January 2016).
  3. Phebra Pty Ltd. Phenasen Product Information. 2015.
  4. Lo-Coco F, Cicconi L, Breccia M. Current standard treatment of adult acute promyelocytic leukaemia. Br J Haematol 2015.
  5. Australian Government Department of Health Pharmaceutical Benefits Scheme. General statement for drugs for the treatment of hepatitis C. 2016. [PBS] (accessed 14 March 2016).
  6. Pharmaceutical Benefits Advisory Committee. Sofosbuvir: Public Summary Document – March 2015 PBAC Meeting. 2015. [PBS] (accessed 9 March 2016).
  7. Clinect Pty Ltd. Product Information – Ibavyr (ribavirin) tablets. 2015. [TGA] (accessed 14 March 2016).
  8. Australian Medicines Handbook. Ribavirin. Anti-infectives. Adelaide: Australian Medicines Handbook, 2016. [AMH online] (accessed 14 March 2016).
  9. Australian Government Department of Health Pharmaceutical Benefits Scheme. Ribavirin. 2016. [PBS] (accessed 14 March 2016).
  10. Gilead Sciences Pty Ltd. Sovaldi (sofosbuvir) tablets: Product Information. 2014. [TGA] (accessed 2 February 2016).
  11. Roche Products Pty Ltd. Product information – Pegasys RBV combination therapy. 2003. {TGA] (accessed 15 March 2016).
  12. Lawitz E, Mangia A, Wyles D, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med 2013;368:1878–87. [NEJM] .
  13. Gilead Sciences Pty Ltd. Public summary document – March 2015 PBAC meeting: Ledipasvir 90 mg/ sofosbuvir 400 mg fixed dose combination tablet (Harvoni). 2015. [PBS] (accessed 9 March 2016).
  14. Hepatitis C virus infection consensus statement working group. Australian recommendations for the management of hepatitis C virus infection: a consensus statement 2016. Melbourne: Gastroenterological Society of Australia, 2016. [ASHM] (accessed 10 March 2016).