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Guidelines for the unlicensed use of Melatonin for the Treatment of Sleep Disorders in children with Visual
Impairment/Blindness, Attention Deficit Hyperactivity Disorder (ADHD), Autism, Emotional/ Behavioural
Difficulties or Attachment Disorder
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Guidelines for the unlicensed use of Melatonin for the
Treatment of Sleep Disorders in children Visual
Impairment/Blindness, Attention Deficit Hyperactivity
Disorder (ADHD), Autism, Emotional/ Behavioural
Difficulties or Attachment Disorder
New
Clinical
Chief Pharmacist
Medicines Management Committee 2015
Medicines Management Committee 2015
Equality Impact Assessment
Implementation Plan
Medicines Management Newsletter
Prescribing Update memo to prescribers
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October 2015
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October 2018
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Version number Month Year
Guidelines for the unlicensed use of Melatonin for the Treatment of Sleep Disorders in
children with Visual Impairment/Blindness, Attention Deficit Hyperactivity Disorder (ADHD),
Autism, Emotional/ Behavioural Difficulties or Attachment Disorder
Ref.
Contents
Page
1.0
Introduction
2.0
Purpose
3.0
Objectives
4.0
Definitions
5.0
Duties
6.0
Committee/Group Responsible for Approval of this Policy
7.0
Process
8.0
Monitoring Compliance
9.0
Standards/Key Performance Indicators
10.0
Equality Impact Assessment
11.0
Training
12.0
Data Protection Act and Freedom of Information Act
13.0
References
13.1
Legislation
14.0
Links to other Policies and Procedures
Appendices
Appendix 1
Melatonin Effective Shared Care Agreement
Appendix 2
Melatonin Leaflet
Review and Amendment Log
Version
Reason
V1.1 October 2015
Status
Date
Description of Change
2
1.0 Introduction
Sleep disorder is a common symptom in childhood. The underlying causes may be
behavioural, psychological or related to underlying mood disorders.
All forms of sleep disorders are more common in children with learning and behavioural
difficulties, autism, ADHD and sensory impairments (particularly visual).
Although behavioural interventions should be the primary intervention and has robust
evidence base, exogenous melatonin is the ‘first-line’ medication prescribed for
childhood insomnia and sleep disorders.
Current guidance and published data around the use of Melatonin is lacking in children.
The Children’s BNF states that clinical experience suggests that ‘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, ADHD, autism and learning
difficulties. The NICE Evidence Summary for unlicensed or off-label medicine relating to
melatonin use in children reports that there are ‘no high-quality studies’ to provide
evidence for efficacy of the UK-licensed prolonged release product used off-label in
children with sleep disorders of ADHD, but there is limited evidence for unlicensed
products.
Only one form of melatonin (Circadin® 2mg prolonged-release tablets) is currently
licensed in the UK for the short term treatment of primary insomnia, characterised by
poor quality of sleep, in adults who are aged 55 years or over. Under the license
treatment is limited to a fixed dose of 2mg daily for up to 13 weeks. Additional melatonin
products are available from special-order manufacturers or specialist importing
companies however the costing and quality of such products is variable.
The Medicines and Healthcare Products Regulatory Authority (MHRA) recognises that
melatonin use spans a wider remit than the licensed indication for Circadin® with regard
to client group and formulation. For a given clinical indication, where a product is
licensed for use in that indication it should be used in preference to any product that
does not hold a product license for use in that indication. Where there’s no licensed
product for a specific clinical indication, the use of appropriate licensed product outside
of its license (off-label) is preferred to the use of a product that does not hold any
product license.
2.0 Purpose
The aim of this document is to provide prescribers with:
 Guidelines to manage sleep disorders in children with Visual
Impairment/Blindness, Attention Deficit Hyperactivity Disorder (ADHD), Autism,
Emotional/ Behavioural Difficulties or Attachment Disorder.
 Recommendations on prescribing melatonin cost-effectively by considering the
brand and formulation choices available
 Guidelines on the transfer of melatonin prescribing from consultant to GP in
primary care as part of an Effective Shared Care Arrangement (ESCA).
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3.0 Objectives
These guidelines are intended to:
 ensure the appropriate prescribing of melatonin in the treatment of sleep
disorders in children with visual impairment/blindness, ADHD, autism, emotional/
behavioural difficulties or attachment disorder
 ensure cost-effective prescribing of melatonin
 support the prescribing of melatonin across the health economy via an ESCA.
4.0 Definitions
Melatonin – the hormone of the pineal gland is normally made in response to dropping
light levels and after morning exposure to daylight. When given to humans it has a rapid
half-life of half to one hour, producing a transient, mild sleep inducing effect. It lowers
alertness, body temperature and performance during the three or four hours after a low
dose has been administered.
MHRA – Medicines and Healthcare Regulatory Agency
NICE – National Institute of Clinical Excellence
Specials Manufacturing – ‘Specials’ are products which have been specially
manufactured or imported for the treatment of an individual patient after being ordered
by a doctor, dentist, nurse independent prescriber, pharmacist independent prescriber,
supplementary prescriber.
ESCA – Effective Shared Care Agreement
5.0 Duties
Adherence to this policy is the responsibility of all staff who are involved in the
prescribing of medication to children in mental health services.
6.0 Committee/Group Responsible for Approval of this Policy
The Medicines Management Committee is responsible for approval of this policy.
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4
7.0 Process
7.0 Management of Poor Sleep in Children
7.1
Non-pharmacological Therapy
Consider the use of a sleep diary; sleep information and advice sheet prior to the use
of any drug treatment. Traditional, non-pharmacological sleep hygiene methods must
have been tried and failed; such as:

Behavioural interventions - Advice on good sleep habits and behavioural
techniques for managing sleep difficulties can give good effects and should
always be tried prior to starting medication.

Cognitive behavioural therapy may be more effective than hypnotics in
improving sleep in the long term. CBT has been shown to improve sleep quality,
reduce hypnotic drug use and improve health related quality of life among long
term hypnotic users with chronic sleep difficulties.

Self-help strategies (DVDs, audio-CDs) have a small but potentially worthwhile
benefit.
Non-pharmacological strategies may have limited application where a patient’s
condition is impaired.
Measurement and documentation of effectiveness of Intervention (clinician and
patient/carer reports)
Parents should keep a sleep diary both prior to commencing medication and once
medication is started. Review of the diary should occur at follow-up to inform
decisions regarding dosage and continuation. Effectiveness of interventions should
be documented in the clinical notes at review.
7.2 Pharmacological Treatment with Melatonin
Consider initiating treatment with melatonin when non-pharmacological sleep
hygiene methods have been tried and failed.

Dose:
- The usual starting dose of melatonin for sleep disorders is 1-2 mg in children
above the age of two.
- The dose may be doubled if there is insufficient benefit after 1-2 weeks.
- Maximum Dose - doses higher than 10 mg are not considered to be of
greater efficacy.
- If no benefit is seen after 2 weeks, then melatonin should be stopped.
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
Contraindications:
- Hypersensitivity to active substances or excipients (see Circadin SPC).

Cautions in use:
- The manufacturer of Circadin® advises caution in patients with renal disorders
and not to use melatonin patients with liver disorders.
- No evidence of safety in pregnancy or breastfeeding.
- The frequency of seizures should be monitored in children or adolescents with
epilepsy given melatonin.
- The manufacturer of Circadin® advises melatonin should not be used in
patients with autoimmune and some rare hereditary glucose tolerance
disorders.
- Not to be used by children under one year of age.

Adverse effects:
- Melatonin is generally well tolerated.
- In clinical studies the most common adverse events were headache,
dizziness, drowsiness, pharyngitis, back pain and fatigue. These occurred at
a similar frequency to placebo.
- There was no evidence of withdrawal effects following treatment
discontinuation.
- Vivid dreams and nightmares have been reported
- Some reports suggest melatonin improves seizure control when used in
patients with epilepsy; others indicate that it may worsen seizure control.
When used in patients with epilepsy, it is important to closely monitor the
effect of melatonin on seizure frequency.
- No robust large controlled clinical studies have been conducted in children
and adults with learning disabilities and epilepsy taking melatonin, so its
safety in this group has not been established.
- Many of the children who have received melatonin in the published RCTs had
developmental problems. The scope for detecting subtle adverse effects in
this population was limited.
Common side effects reported included:
headache, depression, restlessness, confusion, nausea, tachycardia and
pruritis.

Drug Interactions:
- Melatonin’s metabolism is mainly mediated via CYP1A enzymes. Therefore
interactions may occur between melatonin and other drugs affecting or
metabolised by CYP1A enzymes e.g. fluvoxamine, cimetidine, ciprofloxacin
and other quinolones, carbamazepine, omeprazole, oestrogens (oral
contraceptives and HRT), rifampicin, theophylline and. Increase in blood
pressure with nifedipine and reduced prothrombin with warfarin have been
reported.
- There is a large amount of data in the literature regarding the effect of
adrenergic agonists/antagonists, opiate agonists/antagonists, antidepressant
medicinal products, prostaglandin inhibitors, benzodiazepines, tryptophan and
V1.1 October 2015
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-
-
alcohol, on endogenous melatonin secretion. Whether or not these active
substances interfere with the dynamic or kinetic effects of Circadin or vice
versa has not been studied.
Alcohol should not be taken with melatonin, because it reduces the
effectiveness of melatonin on sleep.
Melatonin may enhance the sedative properties of benzodiazepines and nonbenzodiazepine hypnotics, such as zaleplon, zolpidem and zopiclone.
Circadin has been co-administered in studies with thioridazine and
imipramine, active substances which affect the central nervous system. No
clinically significant pharmacokinetic interactions were found in each case.
However, Circadin co-administration resulted in increased feelings of
tranquility and difficulty in performing tasks compared to imipramine alone,
and increased feelings of “muzzy-headedness” compared to thioridazine
alone.
7.3 Continuation of behavioural interventions in combination with medication is more
effective than medication alone.
7.4 Melatonin Brand/Formulation choices
In August 2008 the MHRA issued guidance on the use of melatonin. Many nonpharmaceutical grade products of melatonin are being imported from countries where
melatonin products are classed as food supplements, not medicines, they are not
required to be manufactured to the standard of Good Manufacturing Practice (GMP)
normal for pharmaceuticals. It is believed that at least 50 melatonin preparations are
being imported into, or manufactured in the UK. To encourage the use of melatonin
manufactured according to GMP the MHRA advised that if imported melatonin was used
then the special clinical need should be provided to the importer for submission to the
MHRA.
Melatonin 2 mg prolonged release (Circadin®) is now licensed as monotherapy for the
short term treatment of primary insomnia in adults aged 55 years and over. The MHRA
advised … ‘It is therefore important to ensure that the licensed product available in
the UK is used where possible.”
If this dosage or formulation of Circadin® is not appropriate a melatonin product
manufactured according to GMP should be used, although this will be an unlicensed
product.
First line –The licensed product Melatonin 2 mg MR (Circadin®) for an unlicensed
indication, if the dose is appropriate.
It is recommended that melatonin be given on an empty stomach, since the absorption
may be delayed when taken with large meals. It should be taken one to two hours
before bedtime.
Please note patients who experience difficulties in swallowing the tablet, breaking or
sub-division and crushing the tablet alters the release characteristics approximate to an
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immediate release dose form. The in-vitro release from a crushed or powdered tablet is
expected to provide an immediate release profile similar to that from an unlicensed
immediate release tablet or (unlicensed) oral solution and as such provides a viable
alternative to either of these options. However, to the extent that Circadin® is a licensed
product, its use outside of licence (in so far as the tablet is broken or crushed) is
considered preferable to an unlicensed presentation of melatonin.
If an unlicensed product is clinically indicated, rather than the licensed product, e.g.
because of swallowing difficulties with tablets, or because of the release characteristics,
then a number of Specials Manufacturing Companies are able to supply melatonin
capsules or liquid that are manufactured in the UK according to GMP. Further
information and advice is available from the Trust’s pharmacy department.
Liquid preparations should only be prescribed for selected patients that truly cannot
tolerate solid oral preparations. If only a liquid preparation is suitable, ensure this is
prescribed as per the Drug Tariff version i.e. Melatonin 5mg/5ml oral solution x 200ml.
Patients prescribed other non-tariff strengths (i.e. 2.5mg/5ml or 10mg/5ml) or
formulations (i.e. suspension), should be changed (with equivalent volume of dose
amendment) to the tariff listed strength and formulation.
Changing from immediate release melatonin to prolonged release melatonin
When the dose of melatonin capsules is equivalent to a dose of Circadin then this can
be changed to the same dose e.g. 6mg of unlicensed melatonin capsules to 3 x 2mg of
Circadin.
For patients not on an equivalent dose, this can be changed to the next nearest dose
e.g. 2.5mg capsules to 2mg tablets or 3mg capsules to 2 x 2mg Circadin.
Patients who have difficulty swallowing tablets or who open capsules should not be
changed.
7.5 Documentation
The off-label or unlicensed use of melatonin is documented in the patient’s clinical notes
recording that it has been discussed with the patient’s carers in line with the guidance
provided in the Unlicensed Medication Policy. Appropriate consent should be obtained
and filed in the patient’s notes. Patient information leaflets are available on the Trust
intranet – See Appendix 2.
7.6 Effective Shared Care Agreement
Once stabilised, shared care is appropriate, in accordance with the ESCA (see appendix
1).
7.7 Review of therapy
It is recommended that the patients are followed up two weeks after initiation to assess
benefit of treatment and then every six months to ensure continuing benefit of melatonin.
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Standard monitoring of growth and sexual development is recommended when treating
children i.e. height, weight and pubertal development progress.
Monitoring of side effects should be done on a regular basis and reviewed at each
appointment. GPs should also be involved in the review of side effects and this
information be relayed back to the consultant.
Length of trial for effectiveness
The aim is to establish healthy sleep habits with the lowest effective dose. At least six
months of an improved sleep pattern should elapse before withdrawal takes place.
Drug holidays if tolerance is suspected
Tolerance is characterised by the administration of a drug in higher doses to achieve the
same effect. It is not listed on the Summary of Product Characteristics (SPC) for
Circadin®. However, some clinical experience from the National Child and Adolescent
Learning Disability Psychiatry Network suggests that the efficacy may be lost if
melatonin is prescribed for longer than two years. It suggests that if the melatonin is
withdrawn prior to this, sensitivity may be re-established and melatonin successfully reintroduced at a lower dose.
Withdrawal of treatment
Withdrawal may occur over a period of 3-4 weeks. However, for some children if
withdrawal is not successful treatment may be necessary long term.
8.0 Monitoring compliance
To ensure that the MHRA guidance is adhered to, the safe prescribing of melatonin in
children will be reviewed every six months by analysing prescribing data available from
e-PACT.
9.0 Equality Impact Assessment
The Black Country Partnership NHS Foundation Trust is committed to ensuring that the
way we provide services and the way we recruit and treat staff reflects individual needs,
promotes equality and does not discriminate unfairly against any particular individual or
group. The Equality Impact Assessment for this policy has been completed and is
readily available on the Intranet. If you require this in a different format e.g. larger print,
Braille, different languages or audio tape, please contact the Equality & Diversity Team
on 0121-612-8067 or email [email protected].
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10.0 Training
Training on this policy should be given to all new members of staff who are expected to
work under it. Staff should ensure they maintain a working knowledge of this policy and
read as often as required to ensure competence under it. Staff should be re-trained on
this policy when an incident occurs. Where specific training needs are identified, please
contact the CAMHS manager.
11.0 Data Protection Act and Freedom of Information Act
All staff have a responsibility to ensure that they do not disclose information concerning
the Trust’s activities or about service users in its care to unauthorised individuals. This
responsibility applies whether you are currently employed or after your employment
ends and in certain aspects of your personal life e.g. use of social networking sites etc.
The Trust seeks to ensure a high level of transparency in all its business activities but
reserves the right not to disclose information where relevant legislation applies.
12.0 References
1 Wassmer E and Whitehouse WP. Melatonin and sleep in children with
neurodevelopmental disabilities and sleep disorders. Current
Paediatrics;2006:16:132-8
2 Arendt J. Melatonin. British Medical Journal 1996;312:1242-3
3 Melatonin in paediatric sleep disorders. London New Drugs Group
September 2008
4 BNF for Children 2011-12
5 Prescribing Guidelines: Melatonin. South Staffs and Shropshire
Healthcare Foundation Trust
6 Regional Drug and Therapeutics Centre. Melatonin for sleep disorders
in adults. New Drug Evaluation No. 90 June 2008
7 National Children and Adolescent Learning Disability Psychiatry
Network. 2008
8 Alder Hey Royal Liverpool Children’s NHS Trust. Guidelines on
melatonin. 2000
9 Drug Procurement Advise. Restrictions on the import of unlicensed
melatonin products following the grant of a marketing authorisation for
Circadin® 2mg tablets. MHRA August 2008
10 Summary of Product Characteristics (SPC) – Circadin, Flynn
Pharmaceuticals.
http://www.medicines.org.uk/emc/medicine/25643/SPC/
11 ESUOM2: Sleep disorders in children and young people with attention
deficit hyperactivity disorder: melatonin
12 In-vitro Release (Dissolution) of Circadin® from Intact, Divided and
Crushed Melatonin Tablets. Data on File. Flynn Pharmaceuticals
13 Dudley and Walsall Mental Health Trust: Guidance on The Prescribing
of Melatonin in Children for the Treatment of Sleep Disorders
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13.0 Links to other Policies and Procedures
BCPFT Unlicensed Medicines policy
BCPFT Medicines Policy
V1.1 October 2015
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Appendix 1
Effective Shared Care Agreement for Melatonin
For the treatment of sleep disorders in children with visual impairment or blindness,
attention deficit hyperactivity disorder, autism (Unlicensed Use). Melatonin is licensed for
the short term treatment of insomnia in patients age over 55 years.
Patient’s
Name:
NHS Number:
Date of Birth:
Date Treatment
Started:
Name of drug:
(Add Date)
One copy of information leaflet given to patient
One copy of agreement sent to general
practitioner
One copy filed in patients notes
Name of Initiating
Doctor:
Consultant:
Speciality:
Fax Number:
PRIMARY CARE SECTION TO BE COMPLETED BY GENERAL PRACTITIONER
I agree*/don’t agree* to enter into a shared care arrangement for the treatment of the above
patient with this medicine (*delete as appropriate)
GP Name:
Signature:
Date:
Once signed please detach this sheet and fax to the number shown above.
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ADVICE AND SUPPORT (Please contact the specialist who initiated the treatment)
Contact details
Specialist:
Consultant Psychiatrist – CAMHS (West Bromwich)
Consultant Psychiatrist – CAMHS (Wolverhampton)
Other:
Prescribing and Medicines Management Team (West
Bromwich)
Prescribing and Medicines Management Team,
Wolverhampton
Chief Pharmacist at Black Country Partnership NHS
Foundation Trust
V1.1 October 2015
Telephone No.
0121 612 6620
01902 444021
0121 612 2802
01902 575209
0121-612-8609
13
Effective Shared Care Agreement for Melatonin
For the treatment of sleep disorders in children with visual impairment or blindness,
attention deficit hyperactivity disorder, autism (Unlicensed Use). Melatonin is licensed for
the short term treatment of insomnia in patients age over 55 years.
Patient’s Name:
NHS Number:
Date of Birth:
Date treatment commenced:
Name of drug, form and dosage:
AREAS OF RESPONSIBILITY FOR THE SHARING OF CARE
This shared care agreement outlines suggested ways in which the responsibilities for managing the
prescribing of melatonin can be shared between the specialist and general practitioner (GP). GPs are
invited to participate. If the GP is not confident to undertake these roles, then he or she is under no
obligation to do so. In such an event, the total clinical responsibility for the patient for the diagnosed
condition remains with the specialist.
Sharing of care assumes communication between the specialist, GP and patient. The intention to share
care is usually explained to the patient by the specialist prescriber initiating treatment. It is important that
patients/carers are consulted about treatment and are in agreement with it.
The prescriber of the medication legally assumes clinical responsibility for the drug and
the consequences of its use.
RESPONSIBILITIES and ROLES
Specialist Responsibilities
1. Initiate melatonin and stabilise patient on a maintenance dose, selecting
appropriate product and providing patient with appropriate formulation. (See
BCFPT Guidance: The Prescribing of Melatonin in Children for the Treatment of
Sleep Disorders.
2. Discuss the benefits and side effects of treatment with the patient, including that
the medication is unlicensed.
3. Transfer all appropriate information of the treatment to the GP for effective
continuity of care.
4. Ensure that the patient has enough medication, at least two weeks supply during
transfer of care. Clearly indicate the name, strength and formulation of the
chosen melatonin preparation and any future dose changes in the letter to the
patient’s GP. The recommended brand is Circadin® 2mg MR tablet.
5. Have a mechanism in place for regular review treatment to monitor the
parameters as listed below and patient’s response to the medication (see
paragraph 4 below).
6. Inform GP on the outcomes of medication review.
7. Report adverse events to the CSM and GP.
8. Ensure that clear backup arrangements exist for GPs to obtain advice and
support.
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General Practitioner Responsibilities
1. Reply to the request for shared care as soon as possible (within two weeks).
2. Prescribe melatonin within the dose ranges and period of treatment specified or
recommended. Adjust the dose as advised by the specialist.
3. Report to and seek advice from the specialist on any aspect of patient care that is
of concern and may affect treatment with melatonin.
4. Refer patients to the specialist if their condition deteriorates.
5. Liaise with the patient’s nominated community pharmacy, if required, regarding
supply.
6. Stop treatment on the advice of the specialist or immediately if an urgent need to
stop treatment arises.
7. Report adverse events to the specialist and CSM.
8. Inform specialist of all relevant medical information regarding the patient and any
changes to the patient’s medication irrespective of indication.
Patient's / Carer’s Role
1. Inform specialist or GP of any other medication being taken, including over-thecounter products.
2. Report to the specialist or GP if he or she does not have a clear understanding of
the treatment.
3. Share any concerns in relation to the treatment with melatonin and report any
adverse effects or problems to the specialist or GP.
4. Attend appointments for review of treatment arranged by the specialist or GP.
SUPPORTING INFORMATION
1. Therapeutic Use
Melatonin is a hormone that is produced by the pineal gland in the brain. Melatonin is produced
naturally by the body during the hours of darkness and is involved in the promotion of sleep. It is used
in the treatment of sleep disorders in children with visual impairment or blindness, cerebral palsy,
attention deficit hyperactivity disorder, autism, epilepsy and in the treatment of sleep disorders in
patients with learning disabilities or dementia.
Treatment must be initiated by or under the supervision of a physician with appropriate knowledge
and experience of childhood behavioural disorders or learning disabilities. It may be used in short
courses of a few weeks to help re-establish a good sleep routine, or as a continuous medication. For
some patients where it appears to lose its effect after a while, it should be given for blocks of a few
weeks with a few days break before restarting
2. Choice of products and NHS Cost.
Only one brand of melatonin is licensed in the UK (Circadin® - Melatonin 2mg prolonged-release
tablets). Licensed preparation is to be preferred over an unlicensed one and use in many
circumstances may be “off-label”.
Prescribers should always consider licensed preparation first and unlicensed products are restricted to
where there is need for dose titration or when patients are not be able to take solid dosage. Liquid
V1.1 October 2015
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preparations should only be prescribed for selected patients that truly cannot tolerate solid oral
preparations.
Prescriptions should state the drug, strength, form, frequency and quantity to be supplied e.g.
Melatonin MR 2mg tablets, one at night crushed and mixed with water, 28 tablets.
The MHRA advice is to prescribe in the following order of preference:
I.
If there is a licensed product available it should be used, even if it is for an unlicensed use. This
means Circadin® 2mg sustained release tablets. These are in packs of 21, not 28, so prescribe
quantities with care. This should be the preparation of choice unless there are clear reasons why it
will be inappropriate.
II.
Liquid preparations
If only a liquid preparation is suitable, ensure this is prescribed as per the drug tariff version i.e.
Melatonin 5mg/5ml oral solution x 200ml.
Patients prescribed other non-tariff strengths (i.e. 2.5mg/5ml or 10mg/5ml) or formulations (i.e.
suspension), should be changed (with equivalent volume of dose amendment) to the tariff listed
strength and formulation.
3. Dose and Administration
See BCPFT Guidance: Guidelines for the unlicensed use of Melatonin for the Treatment of Sleep
Disorders in children with Visual Impairment/Blindness, Attention Deficit Hyperactivity Disorder
(ADHD), Autism, Emotional/ Behavioural Difficulties or Attachment Disorder
Changing from immediate release melatonin to prolonged release melatonin
When the dose of melatonin capsules is equivalent to a dose of Circadin® then this can be changed
to the same dose e.g. 6mg of unlicensed melatonin capsules to 3 x 2mg of Circadin®.
For patients not on an equivalent dose, this can be changed to the next nearest dose e.g. 2.5mg
capsules to 2mg tablets or 3mg capsules to 2 x 2mg Circadin® or 1 x 2mg Circadin®.
Patients who have difficulty swallowing tablets or who open capsules should not be changed. If in
doubt seek advice from the specialist who initiated treatment.
4. Monitoring Requirements: The need to continue melatonin therapy should be reviewed every 6
months.
Parameter
Frequency of monitoring
Action
Height
Weight
Pubertal development
6 monthly
6 monthly
6 monthly
By Specialist
By Specialist
By Specialist
5. Side Effects
Melatonin appears to have very few adverse effects such as worsening of seizures and exacerbation
of asthma, so should be used with caution in patients with a history of seizures and respiratory
disorders. Other reported side effects include headaches, dizziness, nausea and excessive
drowsiness. There is limited information about the long term adverse effects, so routine screening for
side effect is recommended. All suspected reactions (including those considered not to be serious
and even where the causal link is uncertain) should be reported to the CSM.
6. Drug Interactions
Melatonin’s metabolism is mainly mediated via CYP1A enzymes. Therefore interactions may occur
between melatonin and other drugs affecting or metabolised by CYP1A enzymes e.g. fluvoxamine,
cimetidine, ciprofloxacin and other quinolones, carbamazepine, omeprazole, oestrogens (oral
V1.1 October 2015
16
contraceptives and HRT), rifampicin, theophylline and. Increase in blood pressure with nifedipine and
reduced prothrombin with warfarin have been reported.
There is a large amount of data in the literature regarding the effect of adrenergic
agonists/antagonists, opiate agonists/antagonists, antidepressant medicinal products, prostaglandin
inhibitors, benzodiazepines, tryptophan and alcohol, on endogenous melatonin secretion. Whether or
not these active substances interfere with the dynamic or kinetic effects of Circadin or vice versa has
not been studied.
Alcohol should not be taken with melatonin, because it reduces the effectiveness of melatonin on
sleep.
Melatonin may enhance the sedative properties of benzodiazepines and non-benzodiazepine
hypnotics, such as zaleplon, zolpidem and zopiclone.
Circadin has been co-administered in studies with thioridazine and imipramine, active substances
which affect the central nervous system. No clinically significant pharmacokinetic interactions were
found in each case. However, Circadin co-administration resulted in increased feelings of tranquility
and difficulty in performing tasks compared to imipramine alone, and increased feelings of “muzzyheadedness” compared to thioridazine alone.
References







BNF for children. 2014-2015
NHS Quality Improvement Scotland. Evidence Note. No. 14. Dec 2006
Regional Drug and Therapeutics Centre: Drug Update. No. 44. November 2005.
Great Manchester Interface Prescribing Group. Shared Care Guideline for Melatonin for Sleep
Disorder
LNDG review: Melatonin in paediatric sleep disorders (Sep 2008)
http://www.nelm.nhs.uk/en/NeLMArea/ Evidence/Drug-Specific-Reviews/Melatonin-in-paediatricsleep-disorders/?query=melatonin&rank=4
Dudley and Walsall Mental Health Trust. Guidance on The Prescribing of Melatonin in Children for
the Treatment of Sleep Disorders
BCPFT Guidance: Guidelines for the unlicensed use of Melatonin for the Treatment of Sleep
Disorders in children with Visual Impairment/Blindness, Attention Deficit Hyperactivity Disorder
(ADHD), Autism, Emotional/ Behavioural Difficulties or Attachment Disorder
Version Control
Version
Date of Issue
1.0
September 2015
V1.1 October 2015
Author/s
Brief Description of Changes
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Melatonin for children
Appendix 2 - Melatonin Leaflet
What is melatonin?
Melatonin is a natural hormone that
regulates the sleep/wake cycle.
When children have a disturbed
sleep cycle, melatonin can help
restore a more natural sleep pattern.
Melatonin work best in combination
with good night-time routines and is
not intended to be a long-term
treatment.
Who needs melatonin?
Melatonin is mainly used for children
with cerebral palsy, Attention Deficit
Hyperactivity Disorder (ADHD),
autism, learning disabilities or visual
impairment.
How will melatonin be
prescribed?
Once the most effective dose for
your child has been found, the
specialist will give you a prescription
for Circadin™ which can be taken to
your usual chemist. Repeat
prescriptions for Circadin™ will
continue to be supplied by the
specialist until such time as it is
considered appropriate for your GP
to take over the prescribing.
V1.1 October 2015
Who can prescribe melatonin?
Only specialist paediatricians and psychiatrists can
initiate treatment and prescribe for the first few
months of treatment. Initially you may be given a
liquid version of melatonin to help find the best dose
to treat your child. Once the most effective dose has
been found, your child will be transferred to tablets.
The prescribing responsibility may then be shared
with your GP. The specialist will review the continued
need for melatonin every six months. Attempts will be
made to wean your child off melatonin once a good
sleep routine is established or if melatonin is no
longer considered effective.
What form of melatonin will be supplied?
Melatonin is available as a modified-release tablet
called Circadin™. However, this is licensed for use
only in people aged over 55. This does not mean that
it is unsafe to use Circadin™ in younger people, just
that the manufacturer has not applied to the
Medicines Healthcare Products Regulatory Agency
for a licence. Many medicines are not licensed for
use in children but are considered safe and effective.
There is evidence to support the use of melatonin in
younger people available at NICE Evidence
Summary for melatonin in children and young people.
How does my child take
melatonin?
Circadin™ tablets should normally
be swallowed whole with a glass of
water one to two hours before
bedtime. This is because they are a
modified (slow) release tablet; this
means that the melatonin is released
over a period of time. Depending on
the dose prescribed, you may need
to cut the tablets in half. Tabletcutters are available from your
chemist.
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