Prescribing for children V’s adults
The differences when prescribing in children
Different laws and practice guidelines apply, different pathophysiology, different pharmacokinetics and pharmacodynamics, different ‘host’ response and different adverse drug reactions can all explain why some drugs behave differently in children (Stephenson, 2005). This blog explores the differences in prescribing in children and takes account of practical considerations.
The Care quality commission (CQC, 2018) expect providers to support their non-medical prescribing clinicians to practise and provide documentation in line with established guidance (RPCS, 2016). Care should conform with the Mental Capacity Act (Gov, 2005), and children and families Act (Gov, 2014), demonstrating awareness of Gillick consent and Fraser guidelines (CQC, 2018). The World Health Organisation (WHO, 2007) has provided guidance intended to improve awareness of medicine safety issues, monitoring these, and preventing adverse drug reactions.
Legal frameworks in paediatric prescribing
Prescribing off licence
The use of adult licensed medicines in children presents a challenge to the prescriber’s accountability (Pulse today, 2016). The Human Medicines Regulations (Gov, 2012) does not prohibit the use of ‘off label’ medication in paediatrics (NICE, 2018; RCPCH, 2017). Where you are not following common practice, your reasons for prescribing the medicine should be well documented, and it may also be appropriate to show parents documentation that shows that the use of the medication is backed by a responsible body of medical opinion if this is available (Pulse today, 2016; WHO, 2007).
Pharmacokinetics for children
It is known that the neonate, has a higher intestinal pH (O’Hara, 2017) and slower gastrointestinal motility rate with lower gastric emptying (BNF, 2016) resulting in symptoms such as reduced suckling reflex or appetite, this has a direct impact on drug absorption. Conversely, the larger body surface area to weight ratio sees a relative increase in the proportion of drug absorbed via the skin, with the overall effect of drugs often producing local hypersensitivity (BNF, 2016). Alternative routes of administration i.e. rectal drugs, are problematic due to a higher frequency of pulsatile contractions of the rectum in children resulting in expulsion of solid dose forms (O’Hara, 2017).
Absorbtion
According to (Stephenson, 2005) neonates have more total body water with a limited protein binding capacity compared to adults which impacts the distribution of drugs i.e. phenytoin, salicylates and ampicillin (Batchelor and Marriott, 2015). Early in life their fat percentage doubles causing higher volumes of distribution leading to a requirement for higher mg/kg doses than in adult for lipophilic drugs such as gentamicin (O’Hara, 2017). The higher blood–brain barrier permeability in younger children effects the therapeutic window of drugs (Stephenson, 2005) opening the possibility of harm, thus supporting advice from NICE (2018) that for most drugs the adult maximum dose should not be exceeded.
Distribution
There is a larger liver to body weight ratio in infants and the foetus (Stephenson, 2005), this explains why they can often metabolise some drugs more rapidly than adults. Interestingly formula-fed infants have been shown to develop activity of CYP1A2 and CYP3A4 enzymes at a faster rate than breast fed (O’Hara, 2017), this impacts metabolism of; paracetamol, codeine, ciclosporin, diazepam and erythromycin (Rang and Dale’s, 2007). Full adult liver activity is usually achieved by 2 years of age, but prior exposure to medication can result in organ sensitivity and growth problems (BNF, 2016) with Stephenson (2005) highlighting the phenomena of Tetracyclines only staining developing tooth enamel.
Metabolism
Immature renal function in infants leads to reduced drug clearance (BNF, 2016; Stephenson, 2005), Glomerular filtration rate increases to half the adult value by three months of age and reaches rates comparable to adults by 2 years of age (Richter et al., 2001), this can account for the differences in dosing and toxicity seen in this population.
Excretion
Deciding dose for children
Since many pharmacokinetic phenomena correlate better with body surface area, doses are often standardised in m2 (NICE, 2018), so knowing the child’s weight and height and using a paediatric growth chart can help to achieve that therapeutic window. It is good practice to double check dose calculations and because of the risks, a child’s age should be written on their prescription clearly stating the strength of any capsules or tablets and indicate liquid preparations on the FP10 (BNF, 2016). Where harm occurs adverse drug reactions in adults are reported through the yellow card system in the BNF, reactions in children are submitted on the British paediatric surveillance unit orange card scheme (NICE, 2018).
Delivery of medicines in children
The BNF and NICE strongly recommend avoiding painful intramuscular injections in favour of an oral syringe, and although flavoured liquid preparations are practical for children, they may contain sugar and contain excipients, which encourages dental decay, so sugar-free medicines are preferred for long-term (NICE, 2018). Parents should be advised not to add any medicines to the infant’s feed, since the drug may interact with the milk or other liquid in it; moreover, the ingested dosage may be reduced if the child does not drink all the contents (BNF, 2016; NICE, 2018). Dosing intervals can cause uncertainties for parents, guardians and teachers, example of this is antibacterial drugs which are generally given at regular intervals throughout the day, lower dose intervals with some flexibility should be allowed in children, i.e. the night-time dose may be given at the child’s bedtime.
In conclusion, due to the obvious ethical barriers there is significantly less research into paediatric pharmacology. There is however plenty of published guidance and legislation on how to use what knowledge is available. There are more practical prescribing challenges and certainly more time will be needed to counsel parents and guardians to help delivery effective care.
References
Batchelor, H.K., Marriott, J.F., 2015. Paediatric pharmacokinetics: key considerations. Br J Clin Pharmacol 79, 395–404.
BNF, 2016. British National Formulary. BMJ Group, British Medical Association & Royal Pharmaceutical Society, London.
CQC, 2018. Common themes arising from inspections of online healthcare providers of primary care. Care Quality Commission https://www.cqc.org.uk/sites/default/files/20171013_online_healthcare_providers_additional_guidance_issues_from_inspection.pdf (accessed 3.8.18).
Gov, 2014. Children and Families Act 2014 http://www.legislation.gov.uk/ukpga/2014/6/contents/enacted (accessed 4.17.18).
Gov, 2012. The Human Medicines Regulations 2012 http://www.legislation.gov.uk/uksi/2012/1916/contents/made (accessed 4.17.18).
Gov, 2005. Mental Capacity Act 2005 http://www.legislation.gov.uk/ukpga/2005/9/contents (accessed 4.17.18).
NICE, 2018. Prescribing in children. NICE-The National Institute for Health and Care.
https://bnf.nice.org.uk/guidance/prescribing-in-children.html (accessed 3.8.18).
O’Hara, K., 2017. Pharmacokinetic changes with growth and development between birth and adulthood. Journal of Pharmacy Practice and Research, Wiley Online Library 47, 313–318.
Pulse today, 2016. Paediatric prescribing guidelines and tips http://www.pulsetoday.co.uk/paediatric-prescribing-guidelines-and-tips/10923680.article (accessed 3.8.18).
Rang, H., Dale’s, M., 2007. Rang & Dale’s Pharmacology, 6th ed. Churchill Livingstone, Elsevier.
RCPCH, 2017. Children’s medicines and unlicensed medicines statement. Royal college of paediatrics and child health. https://www.rcpch.ac.uk/medicines#Unlicensed_medicines_statement (accessed 3.8.18).
Richter, V., Greiner, B., et al, 2001. Determination of in vivo absorption, metabolism, and transport of drugs by the human intestinal wall and liver with a novel perfusion technique. Clin Pharmacol Ther 70, 217–227.
RPCS, 2016. A Competency Framework for all Prescribers. Royal Pharmaceutical https://www.rpharms.com/Portals/0/RPS%20document%20library/Open%20access/Professional%20standards/Prescribing%20competency%20framework/prescribing-competency-framework.pdf (accessed 12.11.17).
Stephenson, T., 2005. How children’s responses to drugs differ from adults. British Journal of Clinical Pharmacology 59, 670–673.
WHO, 2007. Promoting safety of medicines for children. World Health Organisation. http://www.who.int/medicines/publications/essentialmedicines/Promotion_safe_med_childrens.pdf (accessed 4.17.18).
