Melatonin Guidelines for Primary and Secondary Care

LeicestershireMedicines StrategyGroupMelatonin Guidelines for Primary and Secondary CarePurposeMelatonin has been classified as Simple Amber 1 in the LMSG traffic light classificationfor certain conditions. This document aims to provide guidance on the use of melatoninwithin its specified indications and clarifies roles and responsibilities of secondary careand primary care.ScopeThe Simple Amber classification for melatonin covers the following:1. Sleep disorders in children with Attention Deficit Hyperactive Disorder (ADHD),autism, visual impairment, learning difficulties and developmental delay;2. Continued use in adulthood when the medication was initiated in childhood as perpoint one and proved effective;3. Prescribing of melatonin m/r tablets 2mg (Circadin ® ) and melatonin oral solution5mg/5ml only (prescribing of other preparations will remain with secondary care).Secondary Care Clinician ResponsibilitiesInitiation of prescription and titration of dose to the optimum level using theminimum effective dose (see Appendix for preferred products);Monitoring for response and adverse drug reactions (ADRs) during the titrationperiod;Liaison with the general practitioner (GP) to share the child’s care when a stabledose has been achieved and proven benefit has been established;Regular reviews (at least annually) and GP to be notified of any changes;Where necessary, arranging transfer to adult services.Melatonin Guidelines for Primary and Secondary Care1

promote sleep. In children with ADHD who are finding it difficult to settle in the evening,their ADHD medication may be optimised before considering melatonin.Melatonin is usually initiated at 2-3mg at night using the most appropriate formulationand increased depending on response to up to 10mg at night (occasionally higher dosesare used but this will be prescribed by the specialist). The medication should be given ortaken around 30-60 minutes before expected bedtime. Circadin ® is a controlled releaseformulation so should be swallowed whole 3 . The controlled release profile should helpwith sleep maintenance and thus reduce or stop night time waking. Circadin ® tabletscan be halved using a tablet cutter and this should not affect the controlled releaseprofile of the formulation. At the discretion of the clinician Circadin ® can be crushed anddispersed in water if there are swallowing difficulties or if an immediate release profile isdesired (see licensing 4 ).Circadin ® is considered first line on the basis of licensing, cost and quality of the product.Melatonin oral solution 5mg/5ml can be used in patients who are unable to takeCircadin ® or where Circadin ® does not have the desired effect. In certain circumstances,other melatonin preparations will be initiated to meet the specific needs of the patient.Prescribing of these other preparations, such as capsules, will remain in secondary care.Melatonin can be stopped abruptly should the need arise. There should be no sideeffects associated with this.Patients on melatonin will be reviewed by secondary care at least annually. There areno monitoring requirements for melatonin apart from checking for side effects andcontinued efficacy.Where appropriate, treatment should be withdrawn periodically to access continuedneed.Side effectsMelatonin is generally well tolerated. Full adverse effect profile is unclear due to smallsize of trials in children. The most commonly reported side effects are: headache,dizziness, nausea and drowsiness. Other side effects include fatigue, confusion,pruritus, hypothermia, tachycardia, nightmares, mild depression, morning grogginess,and skin rashes. Melatonin can affect seizure control in patients with epilepsy, however,information is conflicting. Children with epilepsy should be closely monitored for anyincreased incidence of seizures 5 .LicensingCircadin ® is licensed in the UK for patients over 55 years of age 3 . Its use in children andadults under 55 years is therefore off label. The MHRA and various prescribingguidelines 2,6 advise that a licensed preparation should be considered first, even if it is foran off label use. As Circadin ® is licensed in the UK, its quality is assured and therefore itis safer than using an unlicensed product.Melatonin Guidelines for Primary and Secondary Care3

Currently, melatonin oral solution 5mg/5ml is unlicensed. In a paediatric setting, it iscommon to prescribe unlicensed preparations as long as there is a clinical need andthere is not a licensed product to fully meet this need 6 . A letter of special clinical needmay be required.Cost (based on a dose of 4mg once daily)Product Cost per original pack Cost per year^Melatonin m/r tablets 2mg £15.39 for a pack of 30 £345Circadin ®7Melatonin oral solution £100 - £141.66 for 200ml £672-£947.525mg/5ml 7,8bottle**melatonin oral solution 5mg/5ml is a specials product so its price can vary depending on where itis procured from. There is a cap on its price though as it features in part VIIIB of the drug tariff.If a sugar-free, colour-free and/or lactose free preparation is required, this can be stated on theprescription for the same price.Background and Further InformationSleep disturbance in children with neurological or behavioural disorders is common andcan be a major source of distress for the patient and family. Furthermore, sleepdisturbance can have an impact on the child’s behaviour and ability to concentrateduring the day. In ADHD for example, up to 50% of children could have sleep relatedproblems.Melatonin is an endogenous hormone produced by the pineal gland in the brain. It isimportant in the regulation of circadian rhythms in humans and animals and a number ofstudies have shown that exogenous melatonin has beneficial effects on the sleeppatterns of these groups of children 5 . Many paediatricians and child psychiatrists areusing melatonin for difficult sleep problems in the UK.Further Advice and SupportSupervising consultant or Dr C S PrasannaChild and Adolescent Mental HealthServiceLeicestershire Partnership NHS TrustTel: 0116 225 2900Fax 0116 225 2899email:chikkagoragatta.prasanna@leicspart.nhs.ukSupervising Consultant or Dr AdrianBrookeConsultant Paediatrician/Lead ConsultantFYPCLeicestershire Partnership NHS TrustTel: 0116 225 6743Fax: 0116 225 3850email: Adrian.brooke@leicspart.nhs.ukMelatonin Guidelines for Primary and Secondary Care4

References1. Leicestershire Medicines Strategy Group (LMSG) [WWW]. Available from:http://www.lmsg.nhs.uk/start/default.asp [accessed on 21/09/2012]2. Dealing with specials (June 2010). Pharmacy Professional, p.27-323. Summary of Product Characteristics: Circadin [WWW]. Available from: www.medicines.org.uk[accessed on 21/09/2012].4. “Specials” – Guidelines for good practice and points to consider (October 2010). LeicestershireMedicines Strategy Group (LMSG) [WWW]. Available from:http://www.lmsg.nhs.uk/start/default.asp [accessed on 21/09/2012]5. UK Medicines Information (September 2008) Melatonin in paediatric sleep disorders. London: UKMedicines Information.6. National Prescribing Centre Prescribing Specials – Five guiding principals for prescribers[WWW].Available from:http://www.npc.nhs.uk/improving_safety/prescribing_specials/ [accessed on21/09/2012]7. Drug Tariff [WWW]. Available from http://www.nhsbsa.nhs.uk/PrescriptionServices.aspx[accessedon 21/09/2012]8. Personal communication. Rosemont Pharmaceutical. September 2012.9. Shared care agreement for methylphenidate, dexamfetamine and atomoxetine for use in attentiondeficit disorder in children and adolescents. Available from:http://www.lmsg.nhs.uk/start/default.asp [accessed on 21/09/2012]Written by Tejas Khatau – Lead Pharmacist Families Young People and Children’sServices (Leicestershire Partnership NHS Trust).In consultation with Dr Prasanna, Dr Brooke, Anthony Oxley, Dr Bretherton, Dr Karim,Teresa Norris, Sarah Baines, Chris Tinegate, Zeibun Patel, David Harris (UHL),LMSG approved: October 2012Review Date: October 2014Version controls logVersion Section Description of amendments Date Author /amended by1.1 Appendix Appendix added with list of preferred products 29/10/12 TK/HH1.2 Cost Liquid 1mg/ml changed to oral solution 5mg/5ml to 31/1/13 HHmatch Drug Tariff. All other references to liquidchanged to oral solution.1.3 Prescribing Doses higher than 10mg daily will be prescribed by thespecialistSept 2013HHMelatonin Guidelines for Primary and Secondary Care5