Patient harm

Safety concerns related to phenobarbital liquid oral formulations are system wide and have potential to affect all patient groups using phenobarbital.

Confusion between concentrations of phenobarbital liquid preparations can result in administration of doses that are either higher or lower than intended.

• Lower doses may result in increased seizure activity
• Higher doses may lead to gastro-intestinal disturbances, sedative effects, and respiratory depression requiring non-invasive ventilation.

A lack of awareness related to the clinical suitability of alcohol containing formulations, may lead to higher than recommended levels of ethanol; there is potential for accumulation of ethanol when ingested repeatedly, especially in young children with low or immature metabolic capacity.

High risk scenarios

Phenobarbital liquid use by neonatal or paediatric groups where there is the potential for selecting an ethanol containing product during clinical and supply processes.

Poor communication and documentation failures at transfer of care has the potential to contribute to inadvertent switches in formulation and/or strength.

Supply shortages and/or unavailability of stock may lead to alternative formulations being utilised .  Without adequate planning and communication there is potential for a temporary switch in product inadvertently being continued, after the usual formulation is available.

Clinical use

Liquid formulations of oral  phenobarbital are used as an anticonvulsant in the treatment of all forms of epilepsy except absence seizures.

Switching formulations

The National Institute for Health and Care Excellence (NICE) recommends a consistent supply of a particular manufacturer’s antiepileptic drug preparation, unless it is decided, in consultation with the child, young person, adult and their family and/or carers as appropriate, that this is not a concern.

Children

The Neonatal and Paediatric Pharmacy Group (NPPG) and the Royal College of Paediatrics and Child Health (RCPCH) recommends phenobarbital (ethanol free) 50mg/5mL as the standard concentration that should be used in children.

Available formulations

A wide range of liquid oral phenobarbital formulations are available on the NHSBSA dictionary of medicines and devices (dm+d); exacerbating the risk of inadvertent product selection.

Phenobarbital is also available in tablet and injectable formulations

Ethanol containing liquids

Phenobarbital Elixir BP 15 mg/5 mL is the only licensed liquid oral formulation of phenobarbital liquid available in the UK.  This product contains 38% v/v of ethanol (alcohol). There is potential for accumulation of alcohol when ingested repeatedly, especially in young children.  This product is not suitable for use in children.

Ethanol free products

Other liquid oral preparations (unlicensed) which do not contain ethanol are available for use.  There are multiple strengths and formulations available.

The range of concentrations of unlicensed preparations listed in the NHSBSA drug tariff has been rationalised to only the 50mg/5ml strength to prevent confusion between product strengths:

• Phenobarbital 50mg/5ml oral solution (AF) 150ml
• Phenobarbital 50mg/5ml oral suspension (AF) 100ml

Risks

Multiple formulations and strengths within prescribing, stockholding and dispensing systems may lead to inadvertent selection of a different formulation than intended.

Stockholding a range of preparations, due to the clinical need for patients to be maintained on a consistent formulation, increases the risk of confusion and inadvertent selection of an incorrect formulation.

Failure to adequately communicate information relating to the specific formulation and dose supplied at discharge, and subsequent prescribing requirements following transfer of care, may lead to inadvertent product switches.

A lack of awareness of potential harms associated with higher than recommended levels of alcohol when using products with a high volume of alcohol.

Mitigation

Opportunities exist to minimise potential harm from an inadvertent formulation switch or supply of a clinically incorrect formulation of phenobarbital liquid.

Standardisation

Rationalise the range of formulations used in local/regional clinical guidelines/protocols and formularies to limit the risk of confusion between products.  System wide rationalisation will prevent the need for local stockholding of multiple formulations.

Ensure prudent use of prescribing systems, formularies and dispensing systems functionality to minimise the range of formulations available for selection. Phenobarbital (ethanol free) 50mg/5mL should be included as standard.

Awareness and knowledge

Ensure healthcare professionals responsible for the prescribing, supply and administration of medicines are aware of the risks of selecting the wrong formulation of phenobarbital liquid and potential harm of selecting an alcohol containing formulation.

Ensure the patient/caregiver is made aware of the specific formulation that is intended for their use and, that a switch in formulation is not expected without discussion/direction from a healthcare professional.

Prescribing and validation

Ensure the clinically appropriate formulation is prescribed;

• clinical guidelines/protocols should specify the clinically appropriate formulation for each patient group
• prescribers initiating phenobarbital oral solution in children should prescribe the phenobarbital alcohol free 50mg/5mL liquid preparation.
• prudent use of electronic prescribing clinical support functionality may support assurance that clinically appropriate formulations are prescribed

Ensure the intended phenobarbital liquid formulation choice is communicated at transfers of care;

• clinical guidelines/protocols should highlight the importance of clear documentation of the formulation.
• prudent use of electronic prescribing and electronic patient record systems can facilitate assurance that required details are inputted at the point of prescribing/validation.
• ensure the patient/caregiver is made aware of the formulation that is intended for their use and that a switch in formulation is not expected without discussion/direction from a healthcare professional

Switching of products should be carefully managed with clear documentation of the intended brand to be used, dose, frequency and arrangements for monitoring and follow up. This information should be communicated at all transfers of care.

Supply

Ensure supply standards / procedures / protocols are reviewed to incorporate strategies which minimise the risk of supplying the incorrect formulation;

• any ambiguity of the prescription in relation to the intended formulation needs to be escalated and the correct formulation ascertained prior to supply
• the patient/caregiver should be used where possible as a confirmation of intended formulation
• prudent use of electronic dispensing system functionality can be used to limit the number of formulations available for selection and highlight, where necessary those products containing ethanol
• prudent use of electronic dispensing system functionality to highlight ‘ethanol containing product’ and/or ‘unsuitable for children’ at the point of selection and/or dispensing labels.

Ensure the patient/caregiver is made aware of the specific formulation that is intended for their use including whether it is ethanol containing or ethanol free.  Advise that a switch in formulation is not expected without discussion/direction from a healthcare professional.

Ensure segregation of different strength products to minimise the risk of selection errors.

Further resources

The NHS Business Services Authority (NHSBSA) Children’s Standard Liquid Concentration dashboard can help healthcare professionals working in primary care to determine the extent to which liquid phenobarbital prescribed for patients under the age of 18 follow the nationally recommended concentration. Prescribers, prescribing advisors and other members of the team can identify patients on non-standard concentrations and review them. This will help to switch to the national standard where appropriate.

Acknowledgments

Information on prevalent risks associated with phenobarbital liquid was provided by the Patient Safety Team at NHS England.

Thanks to the Neonatal and Paediatric Pharmacists Group (NPPG) and the Patient Safety team at NHS England for their contributions.