Anthony Sinclair MSc RPS GPhC
Chief Pharmacist and Head of
Birmingham Children’s Hospital,
The answer to the question, “What is in my medicine?”, is usually restricted to details about the drug that it contains. This holds true whether the medicine is a licensed tablet or injection or a specially formulated, and therefore unlicensed, liquid. Yet what the questioner may really want to know is whether their medicine is safe and will there be unwanted side-effects. For adult medicines this question can be answered with greater confidence than that for unlicensed paediatric liquid formulations. There are a number of reasons for this difference.
Walk down an aisle of any supermarket and sooner or later you will find a shopper studiously reading packaging labels to see what exactly is in their food. But surprisingly this isn’t possible to do with medicines. Many countries still take the view that the identity of the additives and excipients in medicines is a trade secret.(1)
Not just small adults…
Children are not small adults is a mantra often heard in paediatric healthcare environments. Many physiological differences set children and adults apart in the way that their bodies manage drugs, from absorption, through to excretion, and there is simply a lack of knowledge on the handling of certain excipients by the developing physiology of children and the impact that this exerts on the kinetics and dynamics of excipients such as propylene glycol, ethanol, polysorbates and paragons.(2) Deaths in neonates have been associated with administration of 99–234mg/kg/day of benzyl alcohol in large-volume licensed parenteral solutions or endotracheal solutions.(1)
Formulation is another area for concern along with the preparation of these liquid medicines. For example, in order to obtain the required drug in the right quantity it might be necessary for tablets to be crushed and suspended in a liquid. Tablets are constructions of multiple categories of ingredients, including fillers, binders, disintegrants, lubricants, coloring agents, coatings and preservatives that can influence bioavailability, and therefore clinical outcomes. These excipients might also generate adverse reactions in their own right particularly when dissolved or suspended in a liquid.
Lack of standardised formulations
The lack of standardised formulations presents a safety risk as patients are unknowingly changed from one formulation to another. Jackson and Lowey(3) report in their study that 12 hospitals in the UK supplied captopril liquid in three different formulations with shelf lives ranging from 7 to 28 days. Consistency in preparation is also an issue. A study at my own hospital(4) showed a significant difference in particle size in liquid tacrolimus between batches from the same manufacturing laboratory, which could explain otherwise unaccountable plasma level variations seen with this vital anti-transplant drug.
A final comment on formulation is to note the lack of widely accepted national standards for expiry dates for these medicines although the British Pharmacopeia is working hard to address this issue.
I am aware that practice varies across Europe as to what happens when a paediatric patient leaves hospital requiring complex medication. It could be that the care of that patient transfers to the patient’s family doctor and the supply of the liquid medicine is obtained from a community pharmacy. Usually the family doctor retains contact, for expert advice, with the hospital consultant. However, the community pharmacies seldom have links with paediatric hospital pharmacy departments. This lack of continuity between hospital pharmacy and community pharmacy and family doctor and indeed the patient, contributes to increased risks associated with these medicines, examples of which include, dosage errors, inappropriate administration and handling techniques, delays in accessing the medicines themselves and (in the UK at least) excessive costs.
- World Health Organization. Promoting safety of medicines for children;2007.
- Nunn T. Better medicines for children. Eur J Hosp Pharm 2012;19:69 doi:10.1136/ejhpharm-2012-000072
- Jackson M, Lowey, A. How to ensure the quality and safety of unlicensed oral medicines. Pharm J 2008;281:240-3.
- Birmingham Children’s Hospital and Aston University. Tacrolimus liquid bioavailability project (uncompleted);2011.