Terry Maguire recounts how a colleague got himself into hot water due to an adverse event
An experienced colleague recently received a damning solicitor’s letter claiming significant damages for negligence. He had dispensed Phenobarital Elixir 15mg/5ml to a child when, the correspondence claimed, the medicine was “not suitable for use in children”. The use of Phenobarital Elixir 15mg/5ml, in this case, caused a serious adverse event. The letter of claim further stated that Phenobarital Elixir 15mg/5ml “is clearly documented as unsuitable for children”. The pharmacist should have known and therefore was liable.
When asked if I was aware of this contra-indication, I had to confess I was not. As a professional pharmacist my colleague was understandably wracked with guilt about the harm to the child and he worried that his professional regulator might take a dim view. So, I wondered if his action was an acceptable standard of care.
The main interest in such a test is in whether it should be appreciated by a “reasonable” pharmacist that a prescribed medicine contained alcohol and whether that “reasonable” pharmacist had any duty to warn the patient and the prescriber.
The incident
After a short stay in hospital due to a complex and aggressive form of epilepsy, this three-year-old child was discharged. His parents approached the GP surgery requesting a liquid formulation of Phenobarbital as it was to be administered via a feeding tube. This request was passed to the practice-based pharmacist, who was waiting for the child’s hospital discharge letter which did not arrive. The child had previously been prescribed Phenobarbital tablets on many occasions and discharge letters had always stated the tablet formulation.
The pharmacist in the GP practice opted for Phenobarital Elixir 15mg/5ml since it was the only licensed liquid formulation. She created a prescription for Phenobarital Elixir 15mg/5ml, 60mg b.d. via NG tube, mitte 1,000mls, that was signed by a GP and was then brought to the pharmacy where it was dispensed without comment. Within a week the child had experienced increased seizures, raised temperature, lowered oxygen levels, vomiting, and was unable to hold down feeds. He was taken to hospital where it was confirmed he was suffering from alcohol toxicity. The Phenobarbital Elixir was discontinued and thankfully he recovered fully over a number of days.
Phenobarital Elixir 15mg/5ml has a pretty high alcohol content (38%v/v), and when used in certain patient groups – those with poor liver or kidney function or in young patients, for example – it has the potential to accumulate and cause toxicity.
It is rarely prescribed today for the management of epilepsy as more modern and more effective anti-epileptic medicines with less side-effects are normally the first choice. Interestingly the Northern Ireland Medicines Formulary, for example, does not list Phenobarbital as a first, second, or third-line choice, instead it makes no mention of it.
The Summary of Product Characteristics
The Summary of Product Characteristics (SmPC) created by the licence holder Thornton and Ross Ltd states that: “Care should be taken when given to neonates as regular dosing could result in alcohol toxicity.”
It goes on to say, “do not use more than a week in young children (less than three years old), increased risk due to accumulation”. The SmPC for Phenobarbital Elixir does not state that the formulation should not be used in children.
Patient Information Leaflet
It is a regulatory requirement that all medicines licenced in the UK have a Patient Information Leaflet (PIL) supplied with each medicine pack. The PIL is designed to inform patients and carers of the key features of the medicine and its suitability for them.
The PIL for Phenobarital Elixir 15mg/5ml states that it “contains a significant amount of alcohol”.It goes on to specify that “you must avoid other sources of alcohol. If you are alcoholic you may get a more appropriate medicine” and it cautions care in the “young, elderly, depressed, and feeble”.
It also reiterates to “take special care if you have liver disease or if the medicine is prescribed for a baby or a child” and goes on to state that “this product may be used by children”.
One further section emphasises the alcohol content and other excipients: “This medicine contains 1.6g of alcohol (ethanol) in each 5ml (ie, up to 21g based on a 65ml dose). The amount in 5ml of this medicine is equivalent to 39ml beer or 16ml wine. The alcohol in this preparation is likely to affect children. These effects include feeling sleepy and changes in behaviour. It may also affect their ability to concentrate and take part in physical activities.”
The British National Formulary for Children.
The edition of the British National Formulary (BNF) for Children current at the time of this incident (2017-2018) has the following reference to the medicine: “Some hospitals supply alcohol-free formulations of varying phenobarbital strengths.” There is no warning or caution that this formulation should not be used in children.
There is a case to be made that he should have warned the parents had he used the most accessible sources of information
The current edition of the BNF for Children (2023-2024) is very different and states clearly that “recommended practice in the UK is to use ethanol-free, unlicensed 50mg/5ml liquid for administration of Phenobarbital to children when an oral liquid is required”.
It goes on to say that, “Phenobarbital Elixir BP (15mg/5mls) contains 38% v/v of ethanol (alcohol) and so there is a potential for accumulation when ingested repeatedly, especially in young children”.
Survey
In preparing my opinion I asked 10 currently practising, “reasonable” community pharmacists if they had any experience of dispensing Phenobarbital Elixir 15mg/5mls and, if they had, were there any precautions they might take. None of these “reasonable” community pharmacists could remember having dispensed Phenobarbital Elixir in their practice and none identified the potential problem of alcohol toxicity.
Conclusion
There is little doubt that the outcome of this incident was unsatisfactory in that a child suffered a serious adverse event and this will also have had a traumatic impact on his parents.
It is my view that in general the practice-based pharmacist acted properly. The fact that the practice pharmacist did not appreciate the potential for toxicity in this patient is, in my opinion, similar to the knowledge of most “reasonable” practice pharmacists in 2018. The main accessible source of information, the BNF for Children, did not properly emphasise the risk.
Similarly, the dispensing pharmacist, acting on a prescription for a licensed medicine and where the dose was appropriate, acted as the “reasonable” community pharmacist would at that time, December 2018, and dispensed the medicine. There is a case to be made that he should have warned the parents had he used the most accessible sources of information, namely the PIL, SmPC, and the BNF for Children. It is not clear if he did read the information in these sources. Had he done so none of these sources of information, in my opinion, would have sufficiently identified the need to avoid the use of this formulation in children. His action therefore would have been no different to the average “reasonable” pharmacist.
The courts, however, might have a very different opinion.
Terry Maguire owns two pharmacies in Belfast. He is an honorary senior lecturer at the School of Pharmacy, Queen’s University Belfast. His research interests include the contribution of community pharmacy to improving public health.
