Download MELATONIN for treatment of sleep onset insomnia and

MELATONIN – Shared Care Agreement Form
CONSULTANT REQUEST
To: Dr.
Your patient:
NHS No. (10digit):
was seen on:
with a diagnosis of:
I recommend that the following drug is continued:
This drug has been accepted as suitable for shared care by the ABHB MTC. I agree to the responsibilities set out in the
protocol SCP No. 26 (copy attached). This should be read in conjunction with the definition of shared care at:
http://www.wales.nhs.uk/sites3/Documents/371/Doc%202%20Defining%20shared%20care.pdf
I am requesting your agreement to sharing the care of this patient. The preliminary tests set out in the protocol have
been carried out. I am currently prescribing the stabilising treatment.
I would like you to undertake treatment from:
The initial treatment will be:
SUPPLY FULL DETAILS OF UNLICENSED PREPARATION
The baseline tests are:
If you undertake treatment I will reassess the patient in ____ weeks. You will be sent a written summary within 14
days. I will accept referral for reassessment at your request.
The medical staff of the department are available at all times to give you advice.
Consultant Name:
Signature:
Department:
Hospital:
Date:
Contact Telephone Nos:
GP RESPONSE (Please circle the appropriate number below detailing your response)
1. I am willing to undertake shared care as set out in SCP No. _____ for this patient.
2. I would like further information. Please contact me on: _______________________
3. I am unable to undertake shared care for this patient because: (Please state)
_________________________________________________________________________________
G.P. Signature _________________________________________ Date _________
Practice Address/Stamp ________________________________________________
PLEASE RETURN WHOLE COMPLETED FORM OR A COPY TO THE REQUESTING CONSULTANT WITHIN 1 WEEK
This Shared Care Protocol should be read in conjunction with the Summary of Product Characteristics
Status: APPROVED
Issue Date: December 2013 Reviewed Dec.2016
Approved by: ABUHB MTC
Page 1 of 7
Review Date: December 2017
Gwent Shared Care Protocol
MELATONIN
for the treatment of sleep onset insomnia and delayed sleep phase syndrome in
children (UNLICENSED USE)
Protocol No. 26
General guidance
PLEASE CHECK http://www.wales.nhs.uk/sites3/page.cfm?orgid=284&pid=5988
FOR THE LATEST VERSION OF THIS PROTOCOL
ABUHB’s Medicines and Therapeutics Committee endorsed this protocol in December 2013. It
outlines shared care arrangements for children taking melatonin for the treatment of sleep
onset insomnia and delayed sleep phase syndrome (UNLICENSED USE).
This Protocol does NOT cover the use of:
1. melatonin at doses > 10mg daily.
2. liquid melatonin formulations with acquisition costs > £0.30p/mg (i.e.
10mg/5ml, 3mg/5ml, 2mg/5ml and 2.5mg/5ml oral suspension/solutions)
This Protocol should be read in conjunction with:
 The Shared Care Agreement Form (see Page 1).
 The Summary of Product Characteristics for Circadin® 2mg modified-release (m/r) tablets
see: http://www.medicines.org.uk/emc/medicine/25643/SPC/
1. Licensed
indication
Currently the only UK-licensed preparation is the 2mg modified-release tablet Circadin®.
Circadin® is indicated as monotherapy for the short-term treatment of primary insomnia
characterised by poor quality of sleep in patients who are aged ≥ 55.
Melatonin (as either Circadin tablets or oral solution) is not licensed for use in children.
2. Background
information
NICE CG170 (Autism) states:
1.7.7 Do not use a pharmacological intervention to aid sleep unless:
 sleep problems persist despite following the sleep plan
 sleep problems are having a negative impact on the child or young person and their family
or carers.
If a pharmacological intervention is used to aid sleep it should:
 only be used following consultation with a specialist paediatrician or psychiatrist with
expertise in the management of autism or paediatric sleep medicine
 be used in conjunction with non-pharmacological interventions
 be regularly reviewed to evaluate the ongoing need for a pharmacological intervention and
to ensure that the benefits continue to outweigh the side effects and risks.
1.7.8 If the sleep problems continue to impact on the child or young person or their parents or
carers, consider:
 referral to a paediatric sleep specialist and
 short breaks and other respite care for one night or more. Short breaks may need to be
repeated regularly to ensure that parents or carers are adequately supported. Agree the
frequency of breaks with them and record this in the care plan.
The BNFc (Section 4.1.1) states:
Melatonin is a pineal hormone that may affect sleep pattern. Clinical experience suggests that when
appropriate behavioural sleep interventions fail, melatonin may be of value for treating sleep onset
insomnia and delayed sleep phase syndrome in children with conditions such as visual impairment,
cerebral palsy, attention deficit hyperactivity disorder, autism, and learning difficulties. It is also
sometimes used before MRI, CT, or EEG investigations.
Little is known about its long-term effects in children, and there is uncertainty as to the effect on
other circadian rhythms including endocrine or reproductive hormone secretion. Treatment with
melatonin should be initiated and supervised by a specialist, but may be continued by general
practitioners under a shared-care arrangement. The need to continue melatonin therapy should
be reviewed every 6 months.
Attention Deficit Hyperactivity Disorder
In NICE’s ESUOM2 of January 2013 (Sleep disorders in children and young people with
attention deficit hyperactivity disorder: melatonin) no high-quality studies were identified
This Shared Care Protocol should be read in conjunction with the Summary of Product Characteristics
Status: APPROVED
Issue Date: December 2013
Approved by: ABUHB MTC
Page 2 of 7
Review Date: December 2015
that provided evidence for the efficacy of Circadin® tablets used off-label in children with
sleep disorders and ADHD.
Limited evidence for unlicensed melatonin products was identified from 2 small (n = 105
and 19) short-term randomised controlled trials (RCTs) and one small, long-term follow-up
study (n = 94). The evidence suggests that unlicensed melatonin products, taken for 10
days to 4 weeks, may reduce sleep onset latency (the time taken for a child to go to sleep)
in children with sleep onset insomnia and ADHD by approximately 20 minutes. In addition
melatonin may improve average sleep duration by 15 to 20 minutes. However, there are
limitations to these small studies, and longer term efficacy is unclear.
These RCTs included stimulant and non-stimulant treated children aged 6 to 14 years with
ADHD and suffering from sleep onset insomnia. The studies used daily doses of between 3
and 6mg of unlicensed melatonin described as 'fast-release' or 'short-acting', administered
shortly before bedtime. Associated improvement in ADHD-related behaviour, cognition or
quality of life was not robustly demonstrated.
Unlicensed melatonin used in the RCTs appeared well tolerated in the short to medium
term with only transient mild to moderate adverse effects reported.
The BNFc (Section 4.1.1) also states that apart from Circadin®, unlicensed immediate-release
preparations are also available and that the manufacturer should be specified in the sharedcare guideline because of variability in clinical effect of unlicensed formulations.
The modified release tablets formulation was developed, in order to circumvent the fast
clearance of the hormone and to provide a melatonin profile in the blood more closely
matched to the normal physiological profile, cutting the tablet into smaller segments (or
crushing) to aid swallowing may be advised by the specialist - in such situations the advice in
the Circadin® package leaflet (i.e. tablets should not be crushed or cut in half) should be
ignored.
In August 2008 the MHRA advised that as a licensed modified-release melatonin product
(Circadin®) had become available in the UK in June 2008, Circadin® should be used whenever
possible because imported melatonin may be of non-pharmaceutical grade from the USA,
where it is classed as a supplement rather than a medicine. The MHRA recognised, however,
that there may be individual patients for whom the UK product cannot meet their clinical
needs. In particular, there may be some need for alternative dosage forms, or strengths, or
for an immediate-release product. http://www.mhra.gov.uk/NewsCentre/CON023251
Note prescribers will need to provide written details of the special clinical need to the
importer for submission to the MHRA. Details have to be provided with every order and not
just the first occasion. Patient identification is not required in letters from clinicians in order
to maintain patient confidentiality.
Acquisition Costs: Only preparations in bold are covered by this Protocol
Drug Tariff Part VIIIB - Arrangements for
payment for Specials and Imported Unlicensed
Medicines
minimum
volume
Price for minimum
volume (Oct 2016)
total mg
in min vol
Price per
mg
Melatonin 5mg/5ml oral solution
200ml
£60.19
200
£0.30
Melatonin 10mg/5ml oral solution
100ml
£116.72
200
£0.58
Melatonin 10mg/5ml oral suspension
100ml
£142.34
200
£0.71
Melatonin 5mg/5ml oral suspension
100ml
£73.86
100
£0.74
Melatonin 3mg/5ml oral solution
100ml
£74.27
60
£1.24
Melatonin 2mg/5ml oral solution
100ml
£64.22
40
£1.61
Melatonin 2.5mg/5ml oral solution
100ml
£85.01
50
£1.70
Melatonin 3mg/5ml oral suspension
100ml
£133.80
60
£2.23
Melatonin 2mg/5ml oral suspension
100ml
£116.33
40
£2.91
Melatonin 2.5mg/5ml oral suspension
100ml
£160.28
50
£3.21
Qty
Price for 30 (Oct
2016)
Total mg
Price per
mg
30 x 2mg
£15.39
60
£0.26
Melatonin 2mg M/R tablets (Circadin®)
This Shared Care Protocol should be read in conjunction with the Summary of Product Characteristics
Status: APPROVED
Issue Date: December 2013
Approved by: ABUHB MTC
Page 3 of 7
Review Date: December 2015
3. Contraindication
s & Cautions
The only listed contra-indication to Circadin® is:
Known sensitivity to melatonin or to any of the excipients.
Cautions:
1. Melatonin may cause drowsiness.
2. Autoimmune diseases – the manufacturer of Circadin® advises avoid, as no information is
available.
3. As Circadin® 2mg tablets contain lactose, patients with rare hereditary problems of
galactose intolerance, the LAPP lactase deficiency or glucose-galactose malabsorption
should not take them.
4. Dosage regimen
Sleep onset insomnia and delayed sleep phase syndrome
Child 1 month to 18 years: initially 2 to 3mg daily before bedtime increased if necessary after
1 to 2 weeks to 4 to 6mg daily before bedtime. Maximum dose: 10mg daily.
Consider medication holidays especially if dose is becoming less effective.
Circadin 2mg tablets should be taken 1-2 hours before bedtime (and after food) if swallowed
whole.
Melatonin oral solution (5mg/5ml) and crushed Circadin® tablets should be taken 30 minutes
before bedtime.
5. Drug
Interactions
Check BNFc Appendix
1 before coprescribing any other
drug.
Drugs likely to INCREASE levels of melatonin:
Fluvoxamine – Increases melatonin levels (by 17-fold higher AUC and a 12-fold higher
serum Cmax), avoid concomitant administration.
Oestrogens (e.g. contraceptive), cimetidine, quinolones and caffeine.
Drugs likely to DECREASE levels of melatonin:
Carbamazepine and rifampicin may reduce plasma concentrations of melatonin.
Cigarette smoking may also decrease melatonin levels.
Alcohol reduces the effectiveness of melatonin..
Melatonin may decrease the antihypertensive effect of nifedipine and may possibly
potentiate the effects of warfarin.
Melatonin may enhance the sedative properties of benzodiazepines and other hypnotics,
such as zopiclone.
Agomelatine (Non Formulary in ABHB) is a melatonin MT1 and MT2 receptor agonist.
6. Adverse drug
reactions
All serious adverse
events should be
reported to MHRA
using the Yellow Card.
There are no adverse reactions to melatonin, as reported in clinical trials with Circadin® 2mg
(and related to treatment) with very common (≥ 1/10) and common (≥1/100 to <1/10)
frequencies.
Frequency
Uncommon
(≥1/1,000 to
<1/100)
Adverse event
Management
abdominal pain, dyspepsia, dry mouth, mouth ulceration,
weight gain, hypertension, chest pain, malaise, dizziness,
restlessness, nervousness, irritability, anxiety, migraine,
proteinuria, glycosuria, pruritus, rash, dry skin
Seek specialist
advice if
severe or
persistant.
7. Baseline
investigations
To be undertaken by specialist:
Accurate pre-treatment height and weight on a growth chart.
Non pharmacological sleep hygiene methods must have failed.
8. Ongoing
monitoring
To be undertaken by specialist:
i) Height and weight – six monthly. These measurements need to be communicated to the
child’s GP practice (see Section 12)
Advice can be obtained from the local Child Psychiatry and Community Paediatric Services
9 to 5pm Monday to Friday
9. Specialist contact
details
This Shared Care Protocol should be read in conjunction with the Summary of Product Characteristics
Status: APPROVED
Issue Date: December 2013
Approved by: ABUHB MTC
Page 4 of 7
Review Date: December 2015
Child psychiatry:
01633 436832
01633 436831
01633 436830
01633 436944
Learning
Disabilities:
01633 623553
Community
Paediatrics:
via responsible
Consultant
Secretary
Adult psychiatry:
contact local General Adult
Community Mental Health
Team see:
http://howis.wales.nhs.uk/site
splus/866/page/52574
10. Pharmaceutical
aspects
Circadin 2mg tablets should normally be swallowed whole to maintain prolonged release
properties however crushing the tablets may be advised by the specialist to facilitate
swallowing e.g. with yoghurt.
11. Criteria for shared
care
Prescribing responsibility will only be transferred when:
 Treatment is for a specified indication.
 Treatment has been initiated and established by the Specialist Centre.
 The patient’s initial reaction to and progress on the drug is satisfactory.
 The patient’s general physical, mental and social circumstances are such that he/she
would benefit from shared care arrangements.
12. Responsibilities of
Specialists
(Secondary Care)
i.
13. Responsibilities of
patients/carers
 To attend hospital and GP clinic appointments Failure to attend will result in the
medication being stopped.
 To report any adverse events immediately to their specialist or GP.
14. Responsibilities of
 To return the Shared Care Agreement Form (Page 1) to the requesting specialist within
To undertake a full assessment of the sleep problem to determine its precise nature and
any factors that might be contributing to it (such as the sleep environment, comorbidities
and current medication) as recommended by NICE CG170.
ii. To consider initiating melatonin, where sleep problems persist (despite parents and
carers following a sleep plan) and where the sleep problems are having a negative impact
on the child or young person and their family or carers.
iii. To undertake the baseline clinical evaluations (as detailed in Section 7).
iv. To provide a patient information leaflet indicating the risks and benefits associated with
melatonin, and to discuss these with the child or young person and their family or carers.
v. To discuss the goals of treatment with the parent/carer as well as the parameters for
continuation and cessation of melatonin. The principle of trial cessation of melatonin
(‘drug holidays’) in evaluating continued need should be covered. Parents/carers should
also be advised that once the patient reaches adulthood continued specialist monitoring,
required for shared care, is not currently available in Gwent.
vi. To advise the patient/carer on potential side effects and the action to be taken should
they occur.
vii. To confirm patient/carer understanding and consent to treatment.
viii. To initiate melatonin and to increase the dose according to response. Circadin 2mg
tablets (‘OFF LABEL’) should be considered before the 5mg/5ml oral solution
(UNLICENSED). If an unlicensed alternative to Circadin® is required, to provide written
details of the special clinical need to the importer for submission to the MHRA.
ix. Once melatonin has been evaluated as effective and well tolerated (for a period of at
least 3 months), to send the GP a Shared Care Agreement Form (Page 1) inviting them to
participate in shared care management of the patient.
x. To monitor the patient in accordance with the schedule above (see Section 8).
xi. To inform the general practitioner of dosage schedule, monitoring measurements and
progress of treatment (including six monthly height and weight measurements) after each
appointment.
xii. To inform the general practitioner if the patient fails to attend and clearly indicating that
the patient is taking melatonin.
To re-evaluate the need to continue melatonin therapy every 6 months. This may be
performed in a specialist-nurse-led clinic. Use of ‘medication holidays’ should be considered
as part of this evaluation, especially if dose is becoming less effective.
This Shared Care Protocol should be read in conjunction with the Summary of Product Characteristics
Status: APPROVED
Issue Date: December 2013
Approved by: ABUHB MTC
Page 5 of 7
Review Date: December 2015
Primary Care
15. Responsibilities
of all prescribers
16. Supporting
documentation /
information
one week of receipt.
 To issue ongoing prescriptions for melatonin as per dose recommended by specialist.
 To contact the patient/carer if they fail to attend appointments with specialist and if
necessary refuse to issue further prescriptions until specialist supervision has occurred.
 Any suspected serious adverse reaction to an established drug should be reported to
MHRA via the “yellow card scheme.” http://yellowcard.mhra.gov.uk/
BNF/BNFc Section 4.1.1 Hypnotics
Local Patient information leaflet in development
January 2013 NICE Evidence summaries: unlicensed/off-label medicines ESUOM2 : Sleep
disorders in children and young people with attention deficit hyperactivity disorder: melatonin
http://www.nice.org.uk/mpc/evidencesummariesunlicensedofflabelmedicines/ESUOM2.jsp
August 2013 NICE CG170 Autism - management of autism in children and young people
http://guidance.nice.org.uk/CG170
Parent/Carer information
The National Autistic Society – Sleep and autism: helping your child
http://www.autism.org.uk/living-with-autism/understanding-behaviour/sleep-and-autismhelping-your-child.aspx
Cerebra (a charity set up to help improve the lives of children with brain related conditions)
have a team of sleep practitioners covering parts of the UK who can offer help and advice on
sleep issues. Their sleep service includes a sleep questionnaire and diary:
http://www.cerebra.org.uk/English/gethelp/sleepservice/Pages/default.aspx
This Shared Care Protocol should be read in conjunction with the Summary of Product Characteristics
Status: APPROVED
Issue Date: December 2013
Approved by: ABUHB MTC
Page 6 of 7
Review Date: December 2015
APPENDIX 1
SLEEP DIARY
Week Beginning
Monday
………./………/………
Activities in the
hour before
bedtime?
Time taken to
bed?
Number of times
gets out of bed?
Time and place
fell asleep?
What helped
him/her settle?
Number of times
up overnight and
for how long?
Activities when
up in the night?
Time he/she got
up in morning?
Did he/she
require waking in
the morning?
Day time naps –
how many and
for how long?
Status: APPROVED
Approved by: ABUHB MTC
Tuesday
Wednesday
Thursday
Friday
This Shared Care Protocol should be read in conjunction with the Summary of Product Characteristics
Issue Date: December 2013
Page 7 of 7
Review Date: December 2015
Saturday
Sunday