Drugs used for insomnia not listed below:

• Promethazine hydrochloride (see 3.4.1 Antihistamines)

Hypnotics should not be used regularly and are only licensed and recommended for short-term use (2-4 weeks). Z–hypnotics should not exceed four weeks use.

The intermediate-acting barbiturates have a place only in the treatment of severe intractable insomnia in patients already taking barbiturates; they should be avoided in the elderly.

The long-acting barbiturate phenobarbital is still sometimes of value in epilepsy but its use as a sedative is unjustified.

Benzodiazepines

Nitrazepam has not been included as it is not recommended due to its prolonged action which can lead to hangover effects.

Lormetazepam should not be prescribed because of its high acquisition cost.

Temazepam

• Tablets 10mg, 20mg

CNS Depressants

Zopiclone

• Tablets 3.75mg, 7.5mg (£1.47 = 28 x 7.5mg)

Indications

• Insomnia (short-term use, up to 4 weeks)

Dose

• Adult over 18 years, 7.5mg at bedtime; elderly initially 3.75mg at bedtime increased if necessary

Notes

1. Zopiclone is included as first choice because it has the lowest acquisition cost.
2. Although zopiclone is not a benzodiazepine it acts on the same receptors as benzodiazepine. It is not licensed for long-term use (maximum 4 weeks) and there is evidence of dependence in a small number of patients. It is claimed to not affect sleep architecture.
3. NICE TA77: Zaleplon, zolpidem and zopiclone for the short-term management of insomnia (April 2004). The recommendations originally included zaleplon, but this drug no longer has a marketing authorisation in the UK.

Zolpidem

• Tablets 5mg, 10mg (£1.35 = 28 x 10mg)

Indications

• Insomnia (short-term use, up to 4 weeks)

Dose

• Adult over 18 years, 10mg at bedtime; elderly or debilitated 5mg at bedtime

Notes

1. Contraindicated in obstructive sleep apnoea
2. NICE TA77: Zaleplon, zolpidem and zopiclone for the short-term management of insomnia (April 2004). The recommendations originally included zaleplon, but this drug no longer has a marketing authorisation in the UK.

Melatonin

• Immediate-release tablets 1mg (£10.89 = 30 tablets), 2mg (£10.89 = 30 tablets), 3mg (£19.81 = 30 tablets), 4mg (£10.89 = 30 tablets), 5mg (£10.89 = 30 tablets)
• Ceyesto 1mg/ml oral solution (£17.10 = 100ml, £25.65 = 150ml)
• Modified-release tablets 2mg (£3.96 = 30 tablets)

Indications and dose

• Insomnia in children with sensory impairment, neurodisability and neurodevelopmental disorders, when sleep hygiene measures have been insufficient (see note 3):
  • Immediate release tablets / Ceyesto oral solution (for children and adolescents aged 6-17 years with ADHD): 1-2mg, 30-60 minutes before bedtime, increased if necessary by 1mg every week, up to a maximum 5mg per day
  • Modified release tablets (off-label): Initially 2mg daily before bedtime, increased if necessary after 1–2 weeks to 4–6mg daily before bedtime; maximum 10mg daily
• Management of Rapid Eye Movement Behaviour Disorder (RBD) in patients living with Parkinson’s disease (see note 4):
  • Modified-release tablets (off-label): 2-12mg daily (the exact dose will be guided by the Parkinson’s specialist team) to be taken 1-2 hours before bedtime.
• Insomnia in adults aged 55 and over (short term use, up to 13 weeks) (second line)
  • Modified-release tablets. 2mg per day taken 1-2 hours before bedtime. Initial treatment should be for 3-weeks. At that time treatment should be reviewed for effectiveness and may be extended for an additional 10 weeks (maximum)
  • Melatonin should only be used when good sleep hygiene measures have failed.
• Short-term sedation under medical supervision to facilitate EEG in children and adolescents (hospital only)

Notes

1. There can be variation in the licensing of different medicines containing the same drug, check individual product SmPCs for details.
2. NICE guideline 97 (NG97) states that melatonin should not be used in patients with sleep disturbance who are living with Alzheimer’s disease.
3. Insomnia in children and adolescents:
   1. Melatonin may be prescribed in primary care only on the advice of a specialist in paediatrics or CAMHS.
   2. Some brands of immediate-release tablets can be crushed and mixed with water directly before administration (e.g. Adaflex, SmPC)
   3. Melatonin should only be used in conjunction with good sleep hygiene.
   4. Patients receiving ongoing therapy should be reviewed by the prescriber every 6 months (BNFC). In addition, periodic review by the specialist is recommended at appropriate intervals to ensure treatment remains appropriate, is not unnecessarily prolonged, and is not masking any safeguarding issues. During ongoing treatment discontinuation attempts should be regularly planned, with at least one discontinuation period occurring each 12 months.
   5. There is a lack of data (>3 years) available to inform on the likely long-term effects of melatonin use in children and adolescents. Refer to individual product SmPC.
   6. Historically, modified-release tablets (e.g. Circadin) may have been crushed to aid administration, resulting in an unlicensed immediate-release product. Where a patient cannot swallow modified-release tablets, or an immediate-release action is required, licensed immediate-release tablets (which can be crushed) are available (see note 3b).
      
   7. Other melatonin products are available and in use often for historical reasons. It is considered appropriate for GPs to initiate discussions with patients and carers about changing to a formulary recommended formulation. The discussion should include a consideration about the practicalities of taking/administering the dose. There is no need to refer to a specialist simply to ask for a review of formulation, but support is available if required.
   8. If considering off-label use of liquid preparations, consideration should be given to excipient content, including quantity and suitability, cumulative daily intake, and potential adverse effects. Refer to the Royal College of Paediatrics and Child Health (RCPCH) and Neonatal and Paediatric Pharmacists Group (NPPG) position statement on choosing an oral liquid medicine for children here.
4. Treatment of RBD in patients with Parkinson’s disease:
   1. Treatment will be initiated and supervised by a specialist with expertise in treating Rapid Eye Movement Behaviour Disorder in patients with Parkinson’s disease; the specialist will establish the patient on a stable dose of melatonin prior to asking the GP to take on long-term prescribing.
   2. The specialist will continue to oversee the ongoing management of Rapid Eye Movement Sleep Disorder (including periodic review of the need for ongoing treatment).
   3. If there are any changes in the severity of the patient's condition or concomitant medication, or if troublesome adverse reactions develop, the GP should seek advice from the specialist.

Slenyto (melatonin prolonged-release tablets)

• Slenyto prolonged-release tablets are not included in the Devon Formulary, following consideration by the Formulary Interface Group (FIG) in May 2024. The FIG recognised guidance from the General Medical Council in respect of prescribing off-label medicines. The FIG also considered that specialists and GPs have years of experience with off-label use of the 2mg modified release tablets in these patients. Overall, the FIG considered that the increase in costs to the NHS did not justify a routine recommendation for Slenyto.

Chloral hydrate

• Liquid 500mg in 5ml (unlicensed preparation)

Notes

1. Chloral hydrate liquid 500mg in 5ml is included for specialist use in paediatrics only.
2. MHRA Drug Safety Update (October 2021): Chloral hydrate, cloral betaine (Welldorm): restriction of paediatric indication
   
   1. Chloral hydrate and cloral betaine are indicated currently only for the short-term treatment of severe insomnia that is interfering with normal daily life and when other therapies (behavioural and pharmacological) have failed, as an adjunct to nonpharmacological therapies
   2. Use of these medicines in children and adolescents is not generally recommended and should be under the supervision of a medical specialist
   3. Following a national review of safety and efficacy data, the paediatric indication for chloral hydrate and cloral betaine has been further restricted to only children and adolescents with a suspected or definite neurodevelopmental disorder – this reflects current clinical practice
   4. For all patients, treatment should be for the shortest duration possible and should not exceed 2 weeks
   5. Repeated courses are not recommended and can only be administered following medical specialist re-assessment
   6. Following prolonged treatment, slowly taper the dose before discontinuation – abrupt discontinuation can lead to delirium

Dexmedetomidine

• Concentrate for solution for infusion 100 micrograms/1ml

Notes

1. For use in University Hospitals Plymouth NHS Trust only
2. For specialist use in paediatric sedation only.
3. Dexmedetomidine should only be administered by, or under the direct supervision of, personnel experienced in its use, with adequate training in anaesthesia and airway management.

Narcolepsy

Drugs used for narcolepsy not listed below:

• Modafinil (see 4.4 CNS stimulant and drugs for attention deficit hyperactivity disorder)

Pitolisant

• Tablets 4.5mg, 18mg (£310.00 = 30 tablets)

Indications

• Narcolepsy with cataplexy in adults aged 19 years and older

Dose

• Initially 9mg once daily for 1 week, then increased if necessary to 18mg once daily for 1 week, then increased if necessary to 36mg once daily, dose to be taken in the morning with breakfast, dose can be decreased (down to 4.5mg per day) or increased (up to 36mg per day) according to response and tolerance.
• Refer to SPC for information regarding use in hepatic or renal impairment

Notes

1. Narcolepsy should be diagnosed and treatment initiated by a specialist physician (this includes dose titration and stabilisation)
2. Manufacturer recommends effective contraception throughout treatment and for 21 days after stopping in women of childbearing potential. Pitolisant/metabolites may reduce the effectiveness of hormonal contraceptives; therefore, an alternative method of effective contraception should be used
3. The routine commissioning of pitolisant hydrochloride is accepted in Devon only for the treatment of narcolepsy with cataplexy in adults aged 19 years and over who would otherwise be eligible for treatment with sodium oxybate (see Commissioning Policy for more details)
4. Pitolisant is not routinely commissioned for the treatment of patients with narcolepsy without cataplexy
5. NICE TA776: Pitolisant hydrochloride is not recommended, within its marketing authorisation, to improve wakefulness and reduce excessive daytime sleepiness in adults with obstructive sleep apnoea whose sleepiness has not been satisfactorily treated by primary obstructive sleep apnoea therapy such as continuous positive airway pressure (CPAP), or who cannot tolerate it (March 2022)

Sodium oxybate

• Oral solution 500mg in 1ml (£360.00 = 180ml) (for South Devon patients, this remains secondary care only)

Indications

• Narcolepsy with cataplexy in adults (aged 19 years and older)
• Narcolepsy with cataplexy in children and adolescents (aged under 19 years) (hospital only)

Notes

1. West Devon: For adults (aged over 19 years and older), refer to individual shared care guidelines
2. South Devon: prescribing remains hospital only
3. To avoid unnecessary out of pocket expenses, practices or pharmacies should order Xyrem direct from Alloga UK via allogauk.orders@alloga.co.uk or 01773 441702 (please state which wholesaler you wish to be invoiced through)
4. The routine commissioning of sodium oxybate is accepted in Devon for the management of narcolepsy with cataplexy in adults aged 19 years and older only in line with specific criteria (see Commissioning Policy for more details).
5. Refer to NHS England clinical commissioning policy for use in children and adolescents (hospital only)