Proposal to fund modified-release melatonin for insomnia in children and adolescents with neurodevelopmental disorders

Medicines

Consultation Closed

PHARMAC is seeking feedback on a proposal to fund modified-release melatonin for children and adolescents with insomnia secondary to neurodevelopmental disorders through a provisional agreement with Aspen, from 1 July 2017.

In summary:

  • melatonin 2 mg modified-release tablets (Circadin) would be funded in the community from 1 July 2017 subject to Special Authority restrictions for the treatment of secondary insomnia in children and adolescents up to the age of 18 years with neurodevelopmental disorders (an off-label indication);
  • the Circadin brand of melatonin 2 mg modified-release tablets would be listed on the Hospital Medicines List (HML) from 1 July 2017;
  • the HML restrictions for melatonin would be widened to include the treatment of secondary insomnia in children and adolescents up to the age of 18 years with neurodevelopmental disorders; and
  • all unregistered presentations of melatonin currently listed on the HML (tab 1 mg, 2 mg and 3 mg and cap 2 mg and 3 mg) would be delisted from the HML on 1 January 2018.

Feedback sought

PHARMAC welcomes feedback on this proposal. To provide feedback, please submit it in writing by 5 pm on Friday, 26 May 2017 to:

Geraldine MacGibbon
Senior Therapeutic Group Manager/Team Leader
PHARMAC

Email: consult@pharmac.govt.nz

Fax:     04 460 4995
Post:   PO Box 10 254, 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 proposal

  • Melatonin tab modified-release 2 mg (Circadin) would be listed in Section B and in Part II of Section H (the HML) of the Pharmaceutical Schedule from 1 July 2017 at a price and subsidy of $28.22 per pack of 30 (ex-manufacturer, excluding GST).
  • A confidential rebate would apply to Circadin that would reduce its net price to the Funder.
  • Melatonin tab modified-release 2 mg would be subject to the following Special Authority restrictions in Section B of the Pharmaceutical Schedule from 1 July 2017:

Special Authority for Subsidy

Initial application only from a psychiatrist, paediatrician, neurologist or respiratory specialist, or medical practitioner on the recommendation of a psychiatrist, paediatrician, neurologist or respiratory specialist. Approvals valid for 12 months for applications meeting the following criteria:

All of the following:

  1. Patient has been diagnosed with persistent and distressing insomnia secondary to a neurodevelopmental disorder (including, but not limited to, autism spectrum disorder or attention deficit hyperactivity disorder)*; and
  2. Behavioural and environmental approaches have been tried and were unsuccessful, or are inappropriate; and
  3. Funded modified-release melatonin is to be given at doses no greater than 6 mg per day; and
  4. Patient is aged ≤18 years*.

Renewal only from a psychiatrist, paediatrician, neurologist or respiratory specialist, or medical practitioner on the recommendation of a psychiatrist, paediatrician, neurologist or respiratory specialist. Approvals valid for 12 months for applications meeting the following criteria:

All of the following:

  1. Patient is aged ≤18 years*; and
  2. Patient has demonstrated clinically meaningful benefit from funded modified-release melatonin (clinician determined); and
  3. Patient has had a trial of funded modified-release melatonin discontinuation within the past 12 months and has had a recurrence of persistent and distressing insomnia; and
  4. Funded modified-release melatonin is to be given at doses no greater than 6 mg per day.

Note: Indications marked with * are Unapproved Indications.

  • From 1 July 2017 the restrictions applying to melatonin in the HML would be amended to add the secondary insomnia indication as follows:

Restricted

Initiation – insomnia secondary to neurodevelopmental disorder

Psychiatrist, paediatrician, neurologist or respiratory specialist

Re-assessment required after 12 months

All of the following:

  1. Patient has been diagnosed with persistent and distressing insomnia secondary to a neurodevelopmental disorder (including, but not limited to, autism spectrum disorder or attention deficit hyperactivity disorder); and
  2. Behavioural and environmental approaches have been tried or are inappropriate; and
  3. Funded modified-release melatonin is to be given at doses no greater than 6 mg per day; and
  4. Patient is aged ≤18 years.

Continuation – insomnia secondary to neurodevelopmental disorder

Psychiatrist, paediatrician, neurologist of respiratory specialist

Re-assessment required after 12 months

All of the following:

  1. Patient is aged ≤ 18 years; and
  2. Patient has demonstrated clinically meaningful benefit from funded modified-release melatonin (clinician determined); and
  3. Patient has had a trial of funded modified-release melatonin discontinuation within the past 12 months and has had a recurrence of persistent and distressing insomnia; and
  4. Funded modified-release melatonin is to be given at doses no greater than 6 mg per day.

Initiation – insomnia where benzodiazepines and zopiclone are contraindicated

Both:

  1. Patient has insomnia and benzodiazepines and zopiclone are contraindicated; and
  2. For in-hospital use only.
  • All unregistered presentations of melatonin, i.e. tab 1 mg, 2 mg and 3 mg and cap 2 mg and 3 mg, would be delisted from the HML from 1 January 2018.

Background

Melatonin is a naturally occurring hormone produced by the pineal gland. It is associated with the control of circadian rhythms and entrainment to the light-dark cycle. It is also associated with a hypnotic effect and increased propensity for sleep.

The Circadin brand of melatonin 2 mg modified-release tablets is registered in New Zealand for use as monotherapy for the short-term treatment of primary insomnia characterised by poor quality of sleep in patients who are aged 55 or over. Circadin is the only registered brand of melatonin in New Zealand.

In November 2012, PHARMAC’s Pharmacology and Therapeutics Advisory Committee (PTAC) reviewed an application from the supplier to fund melatonin 2 mg modified-release tablets for primary insomnia in patients aged ≥55 years, as well as clinician-initiated applications for melatonin in two off-label indications: insomnia secondary to dementia and insomnia secondary to neurodevelopmental or psychiatric disorders in children and adolescents.

PTAC recommended that funding for primary insomnia in patients aged ≥55 years and for insomnia secondary to dementia be declined, but recommended that melatonin 2 mg modified-release tablets be funded for insomnia secondary to neurodevelopmental disorders in children and adolescents with a low priority.

Details of the applications for the different indications and links to the minutes of PTAC’s reviews, as well as to the consultation and notification letters referred to below, can be found on the Application Tracker on PHARMAC’s website at:

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

In February 2014 PTAC reviewed feedback from the Paediatric Society and the Royal Australian and New Zealand College of Psychiatrists in relation to funding of melatonin for insomnia secondary to neurodevelopmental disorders in children and adolescents. PTAC again recommended that melatonin 2 mg modified-release tablets be funded for this patient group, subject to Special Authority criteria, with a low priority.

In May 2014, PHARMAC issued a consultation on a proposal to fund melatonin 2 mg modified-release tablets (Circadin) for secondary insomnia in children and adolescents with neurodevelopmental disorders from 1 July 2014, subject to Special Authority criteria essentially as recommended by PTAC in February 2014.

A number of clinical issues were raised during consultation, and a decision on the proposal was delayed due to the need to consider these issues and seek further advice from PTAC.

PHARMAC sought further advice from PTAC in August 2014. PTAC’s recommendation was for funding with a low priority as well as some suggested changes to the previously recommended Special Authority criteria. Of note, PTAC addressed a number of concerns that had been raised during the original consultation and advised that:

  • Modified-release melatonin would have a similar efficacy to immediate-release melatonin, providing a reduction in sleep latency of around 30 minutes.
  • In clinical situations where patients cannot swallow whole tablets it would be reasonable to crush the modified-release tablets, noting that this was not recommended on the datasheet and would nullify the modified-release properties. The Committee considered that it would be preferable to crush the registered modified-release presentation compared with using an unregistered immediate-release presentation, given the lack of quality controls for the unregistered presentations (including a lack of controls around whether or not a particular brand contains the stated quantity of melatonin). The Committee considered there was no evidence to suggest that dose adjustment would be needed if the modified-release tablets were crushed. The Committee noted that overseas guidance recommends crushing Circadin tablets to give an immediate-release profile.
  • There was no particular clinical situation where it would only be clinically feasible for an immediate-release presentation of melatonin to be used. Given that there are no regulatory, safety, efficacy, or quality controls for immediate-release melatonin in New Zealand, the Committee considered that it would be preferable to fund in the community, and list on the HML, only the registered brand of melatonin.

In November 2014, PHARMAC notified that our budget position had changed, which meant that we were not in a position to invest in melatonin at that time.

We are pleased to have now reached a new provisional agreement with the supplier, Aspen, for the funding of melatonin 2 mg modified-release tablets subject to criteria essentially as proposed by PTAC in August 2014.

The proposal also includes delisting the unregistered presentations of melatonin that are currently listed on the HML, given that this proposal would result in a registered presentation of melatonin being listed.

Information on the use of melatonin, including off-label use, can be found in the August 2015 issue of Best Practice Journal at https://www.bpac.org.nz/BPJ/2015/August/melatonin.aspx(external link)