Chloral hydrate, cloral betaine (Welldorm): restriction of paediatric indication

The paediatric indication for chloral hydrate (for children aged 2 years and older) and cloral (previously chloral) betaine (children aged 12 years and older) has been restricted to short-term treatment (maximum 2 weeks) of severe insomnia only when the child or adolescent has a suspected or definite neurodevelopmental disorder and when the insomnia is interfering with normal daily life. Chloral hydrate and cloral betaine should only be used when other therapies (behavioural and pharmacological) have failed.

From:
Medicines and Healthcare products Regulatory Agency
Published
6 October 2021
Therapeutic area:
Neurology, Paediatrics and neonatology

Advice for healthcare professionals:

  • 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 non-pharmacological therapies
  • use of these medicines in children and adolescents is not generally recommended and should be under the supervision of a medical specialist
  • 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
  • for all patients, treatment should be for the shortest duration possible and should not exceed 2 weeks
  • repeated courses are not recommended and can only be administered following medical specialist re-assessment
  • following prolonged treatment, slowly taper the dose before discontinuation – abrupt discontinuation can lead to delirium
  • report suspected adverse drug reactions associated with chloral hydrate and cloral betaine to the Yellow Card scheme

Advice to give to patients and carers:

  • chloral hydrate and cloral betaine (brand names Welldorm Elixir and Welldorm) are short-term treatments (maximum of 2 weeks) for severe insomnia that is interfering with normal daily life when other therapies (behavioural and medicines) have not worked
  • the MHRA and its independent advisors have reviewed the benefits and risks of these medicines in the paediatric population and recommended that they should only be used in children and adolescents who have a suspected or definite neurodevelopmental disorder
  • always read the leaflet that accompanies your or your child’s medicines and talk to your doctor, nurse, or pharmacist if you have any concerns

Chloral hydrate and cloral betaine

Chloral hydrate (Welldorm Elixir) and its prodrug cloral betaine (Welldorm) are older drugs that retain some limited clinical usage. In 2009, following a national review of safety and efficacy, the authorisation for these medicines was restricted to severe insomnia that is interfering with normal daily life and where other therapies have failed, as an adjunct to non-pharmacological therapies (see Drug Safety Update, June 2009).

Chloral hydrate is licensed for use in adults and in children aged 2 years and older. Cloral betaine tablets are licensed for use in adults and adolescents aged 12 years and older.

National review of paediatric indication for chloral hydrate and cloral betaine

The MHRA has conducted a further review of safety and efficacy data for these medicines and sought independent expert advice from the Commission on Human Medicines (CHM), its Neurology, Pain and Psychiatry and Paediatric Medicines Expert Advisory Groups, as well as experts in paediatric sleep disorders.

No new safety concerns were identified. However, in view of known carcinogenicity data in animals and because of concerns regarding the lack of long-term studies, a risk in humans in long-term use cannot be excluded on the basis of available data. As such, the CHM recommended that the paediatric indication of all chloral hydrate and cloral betaine products should be restricted to use only in children and adolescents with suspected or definite neurodevelopmental disorders, where the benefits of short-term use outweigh any potential risk. These changes reflect current clinical practice.

The product information is being amended to further clarify that use of chloral hydrate and cloral betaine is not recommended in children and adolescents except in these very restricted circumstances and should only be under the supervision of a specialist.

Maximum duration of treatment and other precautions

Prolonged use of chloral hydrate and cloral betaine has been associated with tolerance and the risks of dependence and abuse. The maximum treatment period for these medicines in all patients has now been defined as 2 weeks in the product information.

Repeated courses are not recommended and can only be administered following medical specialist re-assessment. Following prolonged treatment, the dose should be slowly tapered before discontinuation to avoid delirium.

The Summaries of Product Characteristics and Patient Information Leaflets should be consulted for details of correct dose and other safety information – for example see chloral hydrate 500mg/5ml oral solution.

Off-label use for sedation in children

We are aware that chloral hydrate is used for sedation in children, for example in intensive care units and before diagnostic procedures. The immature metabolism of infants and neonates results in a prolonged half-life of metabolites in these groups, with an increased risk of undesirable effects. This factor and the lack of long-term studies to demonstrate safety should be taken into account when considering prescribing in this population outside the currently licensed indication.

Guidance should be consulted on prescribers’ responsibilities when using a medicine off-label or using an unlicensed medicine.

Reporting suspected adverse drug reactions

Please continue to report suspected adverse drug reactions to the Yellow Card scheme. Healthcare professionals, patients, and caregivers are asked to submit reports using the Yellow Card scheme electronically using:

When reporting please provide as much information as possible, including information about batch numbers, medical history, any concomitant medication, onset timing, treatment dates, and product brand name.

Report suspected side effects to medicines, vaccines or medical device and diagnostic adverse incidents used in coronavirus (COVID-19) using the dedicated Coronavirus Yellow Card reporting site or the Yellow Card app.

Article citation: Drug Safety Update volume 15, issue 3: October 2021: 2.

Published 6 October 2021
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