Proposal on various anti-infective medicines - amended 12 May 2017

Medicines Consultation Closed

PHARMAC is seeking feedback on a proposal to widen funded access to various pharmaceuticals in the anti-infectives therapeutic area and to list of a dispersible formulation of roxithromycin, to take effect from 1 July 2017.

In summary:

  • Antiretrovirals funding criteria would be widened to allow early treatment of people with HIV infection.
  • Azithromycin (Apo-Azithromycin, Zithromax) funding criteria would be widened to include the treatment of non-cystic fibrosis bronchiectasis in children.  [**updated 12 May 2017**]
  • Lamivudine (Zeffix) funding criteria would be widened to include prophylaxis of hepatitis B reinfection in immunocompromised patients receiving rituximab-based treatment for malignancy.
  • Ledipasvir with sofosbuvir (Harvoni) funding criteria for treatment of hepatitis C would be widened to include patients with a lower end-stage liver disease (MELD) score of 12 or greater.
  • Roxithromycin dispersible tablets (Rulide D), through a provisional agreement with Sanofi-Aventis New Zealand Ltd, would be funded for children under 12 years of age.

Feedback sought

PHARMAC welcomes feedback on this proposal. To provide feedback, please submit it in writing by Friday, 26 May 2017 to:

Lindsay Ancelet
Therapeutic Group Manager
PHARMAC

Email: consult@pharmac.govt.nz

Fax:     04 460 4995
Post:   PO Box 10254, Wellington 6143

All feedback received before the closing date will be considered by PHARMAC’s Board (or its delegate) prior to making a decision on this proposal.

Feedback we receive is subject to the Official Information Act 1982 (OIA) and we will consider any request to have information withheld in accordance with our obligations under the OIA. Anyone providing feedback, whether on their own account or on behalf of an organisation, and whether in a personal or professional capacity, should be aware that the content of their feedback and their identity may need to be disclosed in response to an OIA request.

We are not able to treat any part of your feedback as confidential unless you specifically request that we do, and then only to the extent permissible under the OIA and other relevant laws and requirements. If you would like us to withhold any commercially sensitive, confidential proprietary, or personal information included in your submission, please clearly state this in your submission and identify the relevant sections of your submission that you would like it withheld.  PHARMAC will give due consideration to any such request.

Details of the proposals

Antiretrovirals – for early treatment of HIV infection

  • Funding criteria for funding of HIV antiretroviral agents (non-nucleosides reverse transcriptase inhibitors, nucleosides reverse transcriptase inhibitors, protease inhibitors and strand transfer inhibitors) would be widened in Section B and in Part II of Section H of the Pharmaceutical Schedule from 1 July 2017 to enable early treatment of people with HIV infection.
  • To effect this change, the current Special Authority initial application for antiretrovirals for people with confirmed HIV infection would be amended as follows (additions in bold, deletions in strikethrough) (only affected criteria are shown):

Special Authority for Subsidy

Initial application - (Confirmed HIV) only from a named specialist. Approvals valid without further renewal unless notified where the patient has confirmed HIV infection. unless notified for applications meeting the following criteria:

Both:

  1. Confirmed HIV infection; and
  2. Any of the following:
    1. Symptomatic patient; or
    2. Patient aged 12 months and under; or
    3. Both:
      1. Patient aged 1 to 5 years; and
      2. Any of the following:
        1. CD4 counts < 1,000 cells/mm³; or
        2. CD4 counts < 0.25 × total lymphocyte count; or
        3. Viral load counts > 100000 copies per ml; or
    4. Both:
      1. Patient aged 6 years and over; and
      2. CD4 counts < 500 cells/mm³.

Notes: Tenofovir disoproxil fumarate prescribed under endorsement for HIV is included in the count of up to 4 subsidised antiretrovirals.

Subsidies for a combination of up to four antiretroviral medications. The combination of a protease inhibitor and low-dose ritonavir given as a booster (either as part of a combination product or separately) will be counted as one protease inhibitor for the purpose of accessing funding to antiretrovirals.

  • No changes to any of the other sets of initial Special Authority criteria for antiretrovirals, or the renewal criteria, are proposed. No changes to the Special Authority criteria for enfuvirtide are proposed.
  • Corresponding changes would be made to the relevant restrictions in Part II of Section H of the Pharmaceutical Schedule from 1 July 2017.

Antiretrovirals background

A large range of antiretrovirals are currently funded subject to restrictions for people with confirmed HIV infection, for prevention of maternal transmission and for post-exposure prophylaxis following non-occupational exposure to HIV. For people with confirmed HIV infection over the age of 12 months, a disease threshold (measured by CD4 counts or viral load) must be met for access to funded treatment.

The full set of current Special Authority criteria and the list of currently funded treatments can be found in the Pharmaceutical Schedule(external link).

In February 2014 the Anti-infective Subcommittee of PTAC recommended removing the disease threshold criteria, which would allow access to funded treatment for early HIV infection, with a medium priority. This recommendation was endorsed by PTAC at its May 2014 meeting.

We estimate that the proposed change would result in approximately 3,000 people accessing treatment earlier in their disease course.

More information, including links to Subcommittee minutes, can be found in the Application Tracker record for antiretrovirals at:

https://connect.pharmac.govt.nz/apptracker/s/global-search/antiretrovirals(external link)

Azithromycin – for treatment of non-cystic fibrosis bronchiectasis in children [** updated 12 May **]

  • Funding criteria for azithromycin 250 mg and 500 mg tablets (Apo-Azithromycin) and granules for oral liquid 200 mg per 5 ml (40 mg per ml) (Zithromax) would be widened in Section B and in Part II of Section H of the Pharmaceutical Schedule from 1 July 2017 to allow funding of more than 5 days’ treatment in children with non-CF bronchiectasis and people with Mycobacterium infections.

  • To effect this change, the current restrictions for azithromycin (see background section, below) in Section B of the Pharmaceutical Schedule would be replaced by the following (**differences to 8 May 2017 proposal indicated by deletions in strikethrough and additions in bold**):

AZITHROMYCIN – Maximum of 5 days treatment per prescription; can be waived by Special Authority see SAQQQQ  Subsidy by endorsement; can be waived by Special Authority see SAQQQQ

Endorsement for a maximum of 5 days’ treatment for the following indications: Mycoplasma genitaliuminfections when first-line treatments have failed, pertussis and chlamydia, and the prescription is endorsed accordingly.

Special Authority for Waiver of Rule

Initial application – (bronchiolitis obliterans syndrome, cystic fibrosis and Mycobacteriuminfections) from any relevant specialist. Approvals valid without further renewal unless notified for applications meeting the following criteria:

Any of the following:

  1. Patient has received a lung transplant and requires treatment or prophylaxis for bronchiolitis obliterans syndrome*; or
  2. Patient has cystic fibrosis and has chronic infection with Pseudomonas aeruginosa or Pseudomonas-related gram negative organisms*; or
  3. Patient has a Mycobacteriuminfection.

Indications marked with * are Unapproved Indications

Initial application – (non-cystic fibrosis bronchiectasis*) only from a respiratory specialist or paediatrician. Approvals valid for 12 months for applications meeting the following criteria:

All of the following:

  1. For prophylaxis of exacerbations of non-cystic fibrosis bronchiectasis*; and
  2. Patient is aged 18 and under; and
  3. Either:
    1. Patient has had 3 or more exacerbations of their bronchiectasis, within a 12 month period; or
    2. Patient has had 3 acute admissions to hospital for treatment of infective respiratory exacerbations within a 12 month period.

Indications marked with * are Unapproved Indications

Renewal – (non-cystic fibrosis bronchiectasis*) only from a respiratory specialist or paediatrician. Approvals valid for 12 months for applications meeting the following criteria:

All of the following:

  1. The patient has completed 12 months of azithromycin treatment for non-cystic fibrosis bronchiectasis; and
  2. Following initial 12 months of treatment, the patient has not received any further azithromycin treatment for non-cystic fibrosis bronchiectasis for a further 12 months, unless considered clinically inappropriate to stop treatment; and
  3. The patient will not receive more than a total of 24 months’ azithromycin cumulative treatment (see note).

Note: no further renewals will be subsidised. A maximum of 24 months of azithromycin treatment for non-cystic fibrosis bronchiectasis will be subsidised.

Indications marked with * are Unapproved Indications

  • A similar restriction would apply in Part II of Section H of the Pharmaceutical Schedule from 1 July 2017, as follows.

Restricted

Initiation – bronchiolitis obliterans syndrome, cystic fibrosis and Mycobacteriuminfections

Any of the following:

  1. Patient has received a lung transplant and requires treatment or prophylaxis for bronchiolitis obliterans syndrome*; or
  2. Patient has cystic fibrosis and has chronic infection with Pseudomonas aeruginosa or Pseudomonas-related gram negative organisms*; or
  3. Patient has a Mycobacteriuminfection.

Indications marked with * are Unapproved Indications

Initiation - non-cystic fibrosis bronchiectasis*

Respiratory specialist or paediatrician

Re-assessment required after 12 months

All of the following:

  1. For prophylaxis of exacerbations of non-cystic fibrosis bronchiectasis*; and
  2. Patient is aged 18 and under; and
  3. Either:
    1. Patient has had 3 or more exacerbations of their bronchiectasis, within a 12 month period; or
    2. Patient has had 3 acute admissions to hospital for treatment of infective respiratory exacerbations within a 12 month period.

Indications marked with * are Unapproved Indications

Continuation - non-cystic fibrosis bronchiectasis*
Respiratory specialist or paediatrician

Re-assessment required after 12 months

All of the following:

  1. The patient has completed 12 months of azithromycin treatment for non-cystic fibrosis bronchiectasis; and
  2. Following initial 12 months of treatment, the patient has not received any further azithromycin treatment for non-cystic fibrosis bronchiectasis for a further 12 months, unless considered clinically inappropriate to stop treatment; and
  3. The patient will not receive more than a total of 24 months’ azithromycin cumulative treatment (see note).

Note: A maximum of 24 months of azithromycin treatment for non-cystic fibrosis will be subsidised in the community.

Indications marked with * are Unapproved Indications

Initiation – other indications
Re-assessment required after 5 days

For any other condition.

Continuation – other indications
Re-assessment required after 5 days

For any other condition.

Azithromycin background

Azithromycin is a macrolide antibiotic with anti-inflammatory and immunomodulatory properties. It is currently listed in Section B of the Pharmaceutical Schedule subject to the restrictions outlined below. Similar restrictions apply in Section H.

AZITHROMYCIN – Maximum of 5 days’ treatment per prescription; can be waived by endorsement

For endorsement, patient has either:

  1. Received a lung transplant and requires treatment or prophylaxis for bronchiolitis obliterans syndrome*; or
  2. Cystic fibrosis and has chronic infection with Pseudomonas aeruginosa or Pseudomonas related gram negative organisms*

Indications marked with * are Unapproved Indications

In May 2016, PHARMAC consulted on a proposal to widen the funding criteria for azithromycin to include the treatment of non-cystic fibrosis (CF) bronchiectasis in children and amend funded access for other indications. The consultation letter, which contains background information for the proposal, can be found on PHARMAC’s website.

At the time, PHARMAC received a number of responses to the proposal to amend the funding restrictions for azithromycin. The feedback raised significant concerns that we considered required further clinical advice. Advice on these matters was sought from PTAC at its August 2016 meeting. PTAC recommended some changes to the criteria that had been proposed in May 2016, which are reflected in the proposal set out in this consultation. These changes include:

  • limiting funded access to azithromycin for non-CF bronchiectasis to prescriptions written by respiratory specialists and paediatricians and including a 12 month stand-down period between azithromycin treatments (unless deemed clinically inappropriate to stand-down) with no more than 24 months’ cumulative treatment from all courses combined
  • limiting funded access to azithromycin for bronchiolitis obliterans syndrome and cystic fibrosis to prescriptions written by any relevant specialist.
  • expanding the Mycobacterium avium intracellulare complex infection criteria to include all Mycobacterium infections.

We estimate that approximately 350 additional people would be eligible for more than 5 days’ funded treatment under the proposed criteria for long-term indications.

Funding for 5 days’ azithromycin treatment for any indication
[*additional information not included in proposal circulated/published 8 May 2017 *]

In August 2016, PTAC also recommended that a proposal to restrict 5 day courses of azithromycin not be progressed and referred the issue to the Anti-Infective Subcommittee. 

The Anti-infective Subcommittee, at its October 2016 meeting, considered that inappropriate use of azithromycin is contributing to antimicrobial resistance, particularly for respiratory tract infections treated in primary care.  Members considered that an appropriate mechanism to address inappropriate usage is needed, whilst maintaining clinically appropriate funded access. PHARMAC continues to consider appropriate mechanisms and would welcome any thoughts from interested parties on this issue.

This proposal, if approved, would retain a maximum of 5 days funded treatment per prescription for any indication which could be waived by Special Authority for certain indications.  

More information, including links to advisory committee minutes and previous consultation and notification letters, can be found in the Application Tracker record for azithromycin at: https://connect.pharmac.govt.nz/apptracker/s/global-search/antiretrovirals(external link)

Lamivudine – for prophylaxis of hepatitis B reinfection in immunocompromised patients receiving treatment for malignancy

  • Funding criteria for lamivudine 100 mg tablets and oral liquid 5 mg per ml (Zeffix) would be widened in Section B of the Pharmaceutical Schedule from 1 July 2017 to include prophylaxis of hepatitis B reinfection in immunocompromised patients receiving rituximab in combination with immunosuppressive chemotherapy for malignancy as shown.(additions in bold, deletions in strikethrough; note that some minor changes have been made for consistency of language that do not change the intent of the existing criteria). No changes are proposed for the renewal criteria.

Special Authority for Subsidy

Initial application only from a gastroenterologist, infectious disease specialist, paediatrician, general physician or medical practitioner on the recommendation of a gastroenterologist, infectious disease specialist, paediatrician or general physician. Approvals valid for 1 year for applications meeting the following criteria:

Any of the following:

  1. Hepatitis B virus (HBV) DNA-positive cirrhosis prior to liver transplantation; or
  2. Hepatitis B surface antigen (HBsAg)-positive and has had a liver, kidney, heart, lung or bone marrow transplant; or
  3. Hepatitis B virus naïve patient HBV-naïve patient who has received a liver transplant from a an anti-HBc (H hepatitis B core antibody (anti-HBc)-positive donor; or
  4. Hepatitis B surface antigen HBsAg-positive patient who is receiving chemotherapy for a malignancy, or high dose steroids (at least 20 mg/day for at least 7 days), or who has received such treatment within the previous two months; or
  5. Hepatitis B surface antigen HBsAg-positive patient who is receiving anti-tumour necrosis factor treatment; or
  6. Hepatitis B core antibody (anti-HBc) Anti-HBc-positive patient who is receiving rituximab in combination with immunosuppressive chemotherapies for a malignancy. plus high dose steroids (e.g. R-CHOP)
  •  A similar restriction would apply in Part II of Section H of the Pharmaceutical Schedule from 1 July 2017.

Lamivudine background

Lamivudine is an anti-viral agent that is highly active against hepatitis B virus (HBV). It is currently funded for the treatment of hepatitis B in a range of clinical situations (as outlined above, excluding the marked up changes). This includes anti-hepatitis B core antibody (anti-HBc)-positive patients who are receiving rituximab in combination with high dose steroids.

In November 2015, the Anti-infective Subcommittee of PTAC considered information submitted to PHARMAC in relation to the funding of lamivudine for hepatitis B surface antigen (HBsAg)-negative/anti-HBc-positive patients who are receiving rituximab in the absence of high dose corticosteroids. The Subcommittee recommended that access to lamivudine be widened to include prophylaxis of hepatitis B reactivation in immunocompromised patients receiving rituximab-based treatment for malignancy, with a high priority – in effect, regardless of high dose corticosteroid status. This recommendation was endorsed by PTAC at its February 2016 meeting.

We estimate that approximately 70 additional people each year would be eligible for treatment under the proposed criteria.

More information, including links to Subcommittee minutes, can be found in the Application Tracker record for lamivudine at:

https://connect.pharmac.govt.nz/apptracker/s/global-search/Lamivudine(external link)

Ledipasvir with sofosbuvir – reduction in MELD score requirement

  • The funding criteria for ledipasvir with sofosbuvir (Harvoni) tab 90 mg with sofosbuvir 400 mg would be amended from 1 July 2017 as follows (additions in bold, deletions in strikethrough):

Special Authority for Subsidy

Access criteria:

Chronic hepatitis C – Advanced disease– ribavirin is not contraindicated. Applications from any relevant practitioner. Approvals valid for 12 weeks for applications meeting the following criteria:

All of the following:

  1. Patient has chronic hepatitis C (any genotype); and
  2. Ribavirin treatment is not contraindicated; and
  3. Any of the following:
    1. Patient has decompensated cirrhosis with a MELD score of 15 12 or greater; or
    2. Patient has been accepted onto a list for a liver transplant or has received a liver transplant; or
    3. Patient has essential mixed cryoglobulinaemia with associated purpuric skin rash and; Either
      1. Cryoglobulinaemic glomerulonephritis; or
      2. Systemic vasculitis.

Chronic hepatitis C – Advanced disease - ribavirin is contraindicated. Applications from any relevant practitioner. Approvals valid for 24 weeks for applications meeting the following criteria:

All of the following:

  1. Patient has chronic hepatitis C (any genotype); and
  2. Ribavirin treatment is contraindicated; and
  3. Any of the following:
    1. Patient has decompensated cirrhosis with a MELD score of 15 12 or greater; or
    2. Patient has been accepted onto a list for a liver transplant or has received a liver transplant; or
    3. Patient has essential mixed cryoglobulinaemia with associated purpuric skin rash and; Either
      1. Cryoglobulinaemic glomerulonephritis; or
      2. Systemic vasculitis.

Ledipasvir with sofosbuvir background

Ledipasvir and sofosbuvir (Harvoni) is a combination treatment of two antiviral agents that is active against all genotypes (1-6) of the hepatitis C virus.

Ledipasvir with sofosbuvir (Harvoni) is funded for patients with chronic hepatitis C with advanced disease who meet the access criteria (as detailed above without the marked up changes) on application to the Hepatitis C Treatment Panel.

Another similar combination treatment, paritaprivir, ritonavir and ombitasvir with dasabuvir (Viekira Pak) is active against genotype 1 of the hepatitis C virus and it is listed without any funding criteria restrictions.

In June 2016, when PHARMAC announced our decision to fund Harvoni and Viekira Pak for hepatitis C from 1 July 2016, we advised that we had received feedback requesting that access to ledipasvir with sofosbuvir (Harvoni) be widened via reduction of the end-stage liver disease (MELD) score. We advised that we would continue to consider the possibility of widening access. The notification letter can be found here.

We now propose that the MELD score requirement be reduced from 15 to 12, ie. less severe end-stage liver disease.

We estimate this proposal would result in an additional 35-45 people with hepatitis C genotypes 1-6 being able to access treatment with ledipasvir with sofosbuvir (Harvoni) earlier in the course of their disease.

Roxithromycin dispersible tablet for children

Roxithromycin (Rulide D) 50 mg dispersible tablet would be listed in Section B and Part II of Section H of the Pharmaceutical Schedule from 1 July 2017 at the following price and subsidy (ex-manufacturer, excluding GST):

Chemical and presentation Brand Pack size Proposed price and subsidy
Roxithromycin tab dispersible 50 mg Rulide D 10 $7.19

Roxithromycin dispersible tablets would be restricted to children under 12 years of age.

Roxithromycin dispersible tablet background

Roxithromycin is a macrolide antibacterial agent used in the treatment of various infections.  PHARMAC currently funds roxithromycin 150 mg and 300 mg tablets, however these formulations are considered not suitable for use in young children due to doses required and the ability to swallow whole tablets. This proposal would list a 50mg dispersible formulation of roxithromycin that dissolves in a spoonful of water and is suitable for young children.

In December 2014, the Anti-infective Subcommittee considered an application from a Paediatric Infection Disease Physician regarding access to roxithromycin dispersible tablets and the Subcommittee recommended listing with a high priority. The Subcommittee considered that access to roxithromycin dispersible tablets would be particularly beneficial for children with penicillin allergy and intolerance to erythromycin and would also be useful for other indications. This recommendation was ratified by PTAC at its May 2015 meeting.

More information, including links to the PTAC and Subcommittee minutes, can be found in the records for roxithromycin dispersible tablets on PHARMAC’s Application Tracker at: https://connect.pharmac.govt.nz/apptracker/s/global-search/roxithromycin(external link)

We estimate that this proposal would result in up to 21,500 patients accessing treatment with roxithromycin dispersible tablets.