“Children are not small adults.” This mantra is often repeated when discussing paediatric pharmacotherapy. While paediatric doses were traditionally extrapolated directly from adult doses, it is now known that many drugs display vastly different pharmacokinetic profiles in adult and paediatric populations. However, many drugs have not been formally tested for safety and efficacy in children. Until recently, children were often excluded from clinical trials due to ethical concerns. So, while we know that children are physiologically and developmentally different to adults, there is often a lack of solid evidence to guide therapy in this population.
The Australian Commission on Safety and Quality in Health Care acknowledges that medication errors are one of the most common and preventable adverse events encountered in the healthcare setting. Paediatric populations have been highlighted as being at a greater risk of harm from these errors compared to adults.
Formulations specifically designed for use in adult populations present a heightened level of risk when utilised in children. The most obvious example of this is the practice of manipulating solid dose forms to obtain smaller doses. This may be a simple case of splitting tablets, or more complex manipulations involving the preparation of a suspension from crushed tablets or the contents of a capsule. These manipulations have the potential to introduce marked variability in the final product due to stability issues or inaccurate measurements. It is good practice to utilise paediatric formulations wherever appropriate. However, this is not always possible. Calculated doses should be reviewed to ensure that they are able to be administered safely. This may require rounding of the dose for practical purposes. Parents and carers should be counselled to enable them to safely continue required therapy beyond discharge.
Certain drugs may present a greater risk of harm than others. Medications with a narrow therapeutic index are more likely to result in toxicity or ineffectiveness if inappropriate doses are administered. For example, the conversion of codeine to the active metabolite morphine is difficult to predict in paediatric populations. Reduced clearance may also lead to morphine accumulation. The Therapeutic Goods Administration (TGA) conducted a safety review in 2017 and now advises that codeine should not be used in children under 12 years of age. On the other hand, some drugs require relatively greater doses in children due to different distribution profiles. For example, the volume of distribution of gentamicin decreases throughout childhood as the percentage water content of the body naturally reduces with age. This means that younger children require higher doses per kilogram body weight to achieve therapeutic peaks. Medications with a wider therapeutic index are preferred as pharmacokinetic changes are likely to have less impact on the safety and efficacy of therapy.
While all paediatric populations are at greater risk of adverse outcomes from medication errors, the first 28 days of life may be considered particularly high risk. Body weight can fluctuate significantly during the neonatal period. This may necessitate multiple dose recalculations which presents an opportunity for error to occur. The rapid development that occurs during this phase is also likely to result in significant changes to drug metabolism which can be difficult to predict.
With these issues in mind, it is worth considering the Position statement on paediatric prescribing recently published by the Commission. This statement highlights dose calculation errors as a particular area of concern. The following measures are recommended to improve the safety and efficacy of pharmacotherapy in paediatric populations:
- Ensure that each prescription contains the following information;
- Age and/or date of birth
- Current body weight
- Basis for the dose calculation
- Dose in units of mass (e.g. Xmg per dose, given X times per day)*
- Clinicians must use this information to review the appropriateness of the prescribed dose when prescribing, dispensing, and administering medication;
- Use a calculator to verify all dose calculations; and
- Discuss and clarify with parents and carers the reason for each medication as well as the appropriate way to administer the prescribed dose.
*Expressing the dose in units of mass may not be appropriate for some medications including eye drops, ear drops, topical products, inhalers, and insulin.
It is vital that current paediatric references are available at the point of prescribing, dispensing, and administration. Consultation of references is especially important when treating special patient populations such as those with renal or hepatic impairment, or children who are significantly outside of the average weight for age range. Calculations using ‘total body weight’ may result in overdose for some medicines in children who are obese or overweight. Although dosing information is limited in this group, some medications may require the use of ‘ideal body weight’ to avoid toxicity. Doses used in long-term therapy will also need adjustment as the child grows. However, the upper dose limits for adults should not be exceeded. This is particularly relevant to consider for older children and those weighing more than 40-50kg.
Prescribing medications in paediatric populations is associated with higher risks. Adoption of the recommendations outlined in the Commission’s position statement can reduce dosing errors and prevent patient harm.
- Australian Commission on Safety and Quality in Health Care. Position statement on paediatric prescribing. Sydney: ACSQHC; 2018.
- Batchelor HK, Marriott JF. Formulations for children: problems and solutions. Br J Clin Pharmacol. 2015; 79(3): 405-18.
- O’Hara K. Paediatric pharmacokinetics and drug doses. Aust Prescr. 2016; 39(6): 208-10.