Proposal relating to anti-infective agent - azithromycin

Medicines

Consultation Closed

PHARMAC is seeking feedback on a proposal to widen access to azithromycin for prevention of exacerbations of non-cystic fibrosis bronchiectasis in children and to amend access for other indications from 1 July 2016. Azithromycin is an antibiotic used to treat various infections.

In summary, from 1 July 2016, this proposal would result in:

  • azithromycin being funded, subject to Special Authority criteria (& HML restrictions), for:
    • prevention of exacerbations of non-cystic bronchiectasis for children
    • lung transplant patients requiring treatment or prophylaxis for bronchiolitis obliterans syndrome
    • mycobacterium avium intracellulare complex infections
    • cystic fibrosis patients with chronic infection with Pseudomonas aeruginosa or Pseudomonas related gram negative organisms, and
  • short courses of azithromycin (5 days treatment only) being funded for the following indications; Mycoplasma genitalium infection when first-line treatments have failed, pertussis and chlamydia; subject to endorsement on prescription.

For the avoidance of doubt, use for any other indications would not be subsidised via the Pharmaceutical Schedule.

Feedback sought

PHARMAC welcomes feedback on this proposal. To provide feedback, please submit it in writing by Wednesday, 25 May 2016 to:

Adrienne Martin
Senior Therapeutic Group Manager/Team Leader
PHARMAC
PO Box 10254
Wellington 6143

Email: adrienne.martin@pharmac.govt.nz
Fax: 04 460 4995

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 proposal

Current criteria

  • Azithromycin 250 mg tab (Apo-Azithromycin), 500 mg tab (Apo-Azithromycin) and grans for oral liquid 200 mg per 5 ml, 15 ml (Zithromax) are currently subject to the following access criteria in Section B of the Pharmaceutical Schedule:

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

  • A similar restriction currently applies in Part II of Section H of the Pharmaceutical Schedule (the Hospital Medicines List; HML).

Proposed changes

  • From 1 July 2016, the access criteria in Section B of the Pharmaceutical Schedule applying to azithromycin (all formulations, as described above) would be:

AZITHROMYCIN – Subsidy by endorsement for a maximum of 5 days treatment for the following indications; mycoplasma genitalium infections when first-line treatments have failed, pertussis and chlamydia. Endorsement rule can be waived by Special Authority see below.

Special Authority for Waiver of Endorsement Rule

Initial application - (bronchiolitis obliterans syndrome, cystic fibrosis and mycobacterium avium intracellulare complex infections) from any relevant practitioner. Approvals valid without further renewal unless notified where the patient has any of the following:

  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*; or
  3. Mycobacterium avium intracellulare complex infections.

Indications marked with * are Unapproved Indications

Initial application – (non-cystic fibrosis bronchiectasis*) from any relevant practitioner. Approvals valid for 12 months for applications meeting the following criteria:

Indications marked with * are Unapproved Indications

Renewal application – (non-cystic fibrosis bronchiectasis*) from any relevant practitioner. Approvals valid for 12 months for applications meeting the following criteria:

  1. The treatment remains appropriate and the patient is benefitting from treatment; and
  2. The patient will not be prescribed more than a further 12 months’ treatment (see note).

Note: no further renewals will be subsidised.

Indications marked with * are Unapproved Indications

  • A similar restriction would apply in Part II of Section H (the Hospitals Medicines List; HML).

Background

Azithromycin is a macrolide antibiotic with anti-inflammatory and immunomodulatory properties.

Bronchiectasis is a lung disease characterised by irreversible bronchial dilation and chronic inflammation, resulting in a chronic wet cough. Impaired clearance of the lower airways leads to chronic bacterial infection and inflammation, a process that has been referred to as a “vicious circle.” If progressive, this process may lead to respiratory failure and the need for lung transplantation or to death. The course of the disease is highly variable, with frequent exacerbations having a major influence on quality of life.

Although the exact cause is often not known, bronchiectasis is most commonly caused by recurrent or severe respiratory infections. Overcrowding and socioeconomic deprivation are also thought to be important contributing factors.

Bronchiectasis can occur at any age but is most likely to begin in childhood. We estimate that there are approximately 350 children who would be eligible for treatment under this proposal.

Children of Māori and Pacific backgrounds are disproportionately affected by the disease. In New Zealand, Pacific children aged under 15 years have an estimated incidence rate of bronchiectasis of 17.8 per 100 000. This compares to 4.8 and 1.5 per 100 000 for Māori and New Zealand European children respectively, of the same age.[1] The risk of being hospitalised due to bronchiectasis has been reported to be almost 11 times higher for a Pacific child aged under 14 years and four times higher for a Māori child, than for a New Zealand European.[2]

If implemented, the proposal is expected to increase the health gains for children with non-cystic bronchiectasis and in addition there would also be cost savings to DHBs, associated with treatment, due to a reduction in health care costs from reduced hospital admissions for exacerbations.

Clinical advice

A funding application for azithromycin for non-cystic fibrosis bronchiectasis has undergone extensive review by PHARMAC’s clinical advisory groups, including the Pharmacology and Therapeutics Advisory Committee (PTAC), the Respiratory Subcommittee and the Anti-infective Subcommittee of PTAC.

Consideration of funding for azithromycin highlighted concern about the risks of azithromycin resistance, and that, as an important antibiotic, use of azithromycin should be maintained for specific indications. Therefore, to ensure that funded access to azithromycin is targeted to those groups most likely to benefit, or for indications where there were no other suitable available alternatives, and acknowledging the importance of antimicrobial stewardship, the current access criteria were reviewed.

The most recent review of the funding for both, azithromycin for non-cystic fibrosis bronchiectasis and the current access criteria, was by PTAC at its August 2015 meeting. In summary PTAC made the following recommendations:

  • that azithromycin be funded for non-cystic fibrosis bronchiectasis in children (aged 18 and under) who have had 3 or more exacerbations of their bronchiectasis or 3 acute admissions to hospital for treatment of infective respiratory exacerbations within a 12 month period, for a maximum treatment duration of 24 months, with a high priority
  • that short courses of azithromycin of 5 days treatment should be restricted to the following indications; mycoplasma genitalium infection when first-line treatments have failed, pertussis, and chlamydia
  • that longer courses of azithromycin should be restricted to the following indications; patients who have received a lung transplant and require treatment or prophylaxis for bronchiolitis obliterans syndrome, patients with cystic fibrosis and have chronic infection with Pseudomonas aeruginosa or Pseudomonas related gram negative organisms, and patients with mycobacterium avium intracellulare complex infections
  • that the application for azithromycin for prevention of exacerbations in adult non-cystic fibrosis bronchiectasis should be declined, noting that an alternative treatment (erythromycin) is available for these patients.

Please note that although PTAC has recommended to PHARMAC that funding of azithromycin for prevention of exacerbations in adult non-cystic fibrosis bronchiectasis should be declined, this funding application remains open, and could be further considered if new information became available. A recommendation to decline from PTAC would usually not result in a medicine being funded. However, PHARMAC routinely seeks further advice from PTAC where new evidence becomes available.

Full details of the minutes are available from the following link 

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


[1] Twiss et al Arch Dis Child 2005;90(7):737-40

[2] BPJ 46 2012 – Bronchiectasis: Rates still increasing among Pacific peoples