The medic's guide to prescribing: Prescribing for children
Why do we need to be careful when prescribing in paediatrics? Clare M Morkane and colleagues explain in part five of the series
In this article we look at what students should know about prescribing in paediatrics. Although this subject is usually studied later in the clinical years, medical students often come across young patients in primary care and in other clinical attachments. The opportunity to treat children also arises in the foundation years in the emergency department, in general practice, and in other specialties in the foundation programmes.
If you find the idea of writing your first prescription for an adult with heart failure daunting, imagine how you will feel the first time you prescribe a drug that is unlicensed for use in children to a 2 year old. Many factors we take for granted in adult medicine suddenly become hugely important in a child. As well as calculating the correct dose for that child, and delivering it appropriately, there is the matter of compliance: sometimes no matter how hard you try, not even a spoonful of sugar helps the medicine go down.
In terms of height, weight, kidney function, liver function, and composition of the body, adults from the age of 18 to 70 can be considered a relatively homogenous population. In comparison there are striking changes as the tiny neonate grows through childhood and adolescence to become a fully grown, sexually mature, young adult of 18. Children should, therefore, not be considered as a homogenous group of patients but as variable and diverse subsets of individuals. Even children of the same biological age can exhibit differences in size or maturity that will also need to be taken into account. The following age groups are therefore used as a guide when considering prescribing in childhood:
Premature baby—less than 36 weeks' gestation
Newborn—0-27 days
Infant—from 28 days to 12 months
Child—from 12 months to 11 years
Adolescent—between 12 and either 16 or 18 years, depending on the country.
How are children different?
Firstly, and most obviously, children are smaller than adults—the younger the child the smaller it is. The smaller the child the greater the care needed to ensure that the dose of drug, usually in milligrams per kilogram, is correct.
Secondly, the child is developing physically and this will influence both drug effect and drug disposition (see box 1). The processes of pharmacokinetics (what the body does to the drug) and pharmacodynamics (what the drug does to the body) undergo age related changes, which account for many of the differences between drug doses at various stages of childhood. In particular, special care is needed in the neonatal period when the risk of toxicity is greater because of inefficient renal filtration; relative enzyme deficiencies; differing target organ sensitivity; and inadequate detoxifying systems, which cause delayed excretion.
Box 1: Factors that affect drug handling in children Absorption
Absorption is dependent on gastrointestinal function, which changes rapidly after birth
Gastric pH is increased in infants and doesn't reach adult concentrations until the second year of life
Reduced gastric emptying in neonates makes the oral route of administration unreliable in this age group. Transdermal absorption is greatly increased in neonates resulting in greater risk of toxicity via this route
Distribution
Less plasma protein binding and more volume of extracellular fluid relative to total body water in young infants results in a markedly greater volume of distribution
High bilirubin concentrations may cause drug displacement from plasma proteins—take care in neonatal jaundice
Metabolism
Clearance rates may be less at birth because of immature enzyme systems
Children have a higher metabolic rate than adults so may need higher doses on a mg/kg basis
Excretion
Renal function does not mature completely until age 6-8 months
Reduced renal excretion may occur in newborn babies
Thirdly, the child is developing mentally and socially. Small children cannot describe their symptoms or comment on the effectiveness or otherwise of drugs. They often cannot understand the reason for the drugs, therefore, administration of drugs and compliance with drug regimens can be a problem.
Fourthly, the child is growing and maturing physically, intellectually, and sexually (in adolescence). Drugs that may adversely affect growing tissues, intellectual development, and sexual maturation or reproductive potential need to be avoided if possible.
Certain drugs should be avoided altogether in the developing child. Chloramphenicol is contraindicated in newborn and premature infants because of the risk of grey baby syndrome. Other examples include tetracycline antibiotics, which are deposited in growing teeth and bones, leading to yellowing and abnormal growth, and aspirin, which in children is associated with Reye's syndrome. There are many more examples of adverse drug events particular to children, therefore, it is essential to refer to a good prescribing text to guide decisions about treatment.
What dose should I prescribe?
Children are not miniature adults. It is not acceptable to extrapolate from the adult dose. In paediatrics dose calculations are based on the individual patient, taking into account age, weight, body surface area, and condition. Some drugs—for example, amoxicillin—may be prescribed according to specified age brackets and indication alone. Other drugs—for example, antineoplastic agents—require more complex calculations and protocols for treatment. Children also grow up, and, therefore, for longer term treatment the prescriber must review and alter the dose as required. Before any prescription is made it is important to check with a drug's summary of product characteristics or a reference text. The BNF for Children (http://bnfc.org) is one such reference that brings together the available evidence in paediatric prescribing.
Sometimes doses may be so small that miscalculations or misplacements of the decimal point are easy mistakes to make but not so easy to resolve. Prescribing errors occur in 1.5% of all prescriptions in the United Kingdom and administration errors in 3-8% of doses given. Great care should therefore be taken (see the case history in box 2).
Box 2: Case history
Kirsty, a previously well 12 year old girl presented to the emergency department with symptoms and signs of diabetic ketoacidosis and an intravenous infusion of insulin was started. Six hours after the start of the infusion, blood gases showed an unchanged pH. Review by a senior identified that insulin had been prescribed at a 10th of the recommended dose because of a dilution error.
What went wrong?
Insulin should have been mixed with 0.9% sodium chloride to a concentration of 1 unit/ml and infused at a rate of 0.1 units/kg/hr. In this situation, however, instead of 50 units mixed with 50 ml, Kirsty was prescribed only 5 units/50 ml. Hence she received only 0.01 units/kg/hr. Always check dose calculations.
Which preparation should be used?
The formulation prescribed should be appropriate for the child, taking into account age and the underlying disease. It is most convenient to give drugs orally. Liquid preparations are ideal for young children, and the tastier they are the better. If sugar-free preparations are available they should be used—this keeps the dentist happy as well. Liquid suspensions contain undissolved particles—they should always be shaken before use.
For oral and parenteral preparations it is important to ensure that an appropriate measuring device, syringe, or calibrated measuring spoon is available to measure the small quantities that may be required. A household teaspoon might vary in volume from 2.5 to 7.8 ml and is far from ideal for giving precise doses of liquid drugs. The available forms of tablets or capsules may make it impossible to give the correct dose without using part of a tablet. Parents should be discouraged from adding drugs to feeds because interactions may occur, especially with milk, and the child may not always finish the bottle.
The rectal route is rarely used in the UK, however, it is useful when patients are vomiting or fitting—in particular, the rapid absorption of rectal diazepam is invaluable for controlling seizures. Likewise the intramuscular route is discouraged where possible in neonates and young children because of the lack of suitable muscle and unpredictable absorption.
Aerosol inhalers are commonly used for asthma. Spacers significantly improve delivery of inhaled drugs in children who lack the coordination to use a pressurised metered dose inhaler. Masks should be used in young children, and parental education is essential in ensuring effective administration. Bear in mind that developmental age may vary from chronological age, it is, therefore, important to tailor the route of administration to the child's capabilities.
Unlicensed and off-label drugs
The purpose of licensing is to ensure that drugs are evaluated for efficacy, safety, and quality. Most drugs used in children have been developed for use in adults. Drug companies are reluctant to develop drugs for use in children for many reasons, including the practicalities of organising studies in young patients (in terms of staff, facilities, and drug preparations required), difficult recruitment of patients (the population of children with specific diseases may be small), and poor financial rewards.
For these reasons many drugs are either not licensed (unlicensed) for use in children or are prescribed outside the terms of the product license ("off-label" prescribing). Indeed, a study in five European countries found that almost half of the drugs used in paediatric wards were unlicensed or "off label." This means that the risks and benefits of the drug have not been scrutinised by the licensing body. A consequence of this is that no age related profiles of adverse drug reactions or guidelines for dosing exist, and drugs of appropriate strengths and doses ready to administer are lacking. Conversely, there may be a huge practical experience of the use of some drugs in children, especially in specialist centres.
Prescribing an off-label or unlicensed drug is not illegal, and it is important to emphasise that the lack of approval for paediatric use does not mean the drug is contraindicated. It just means that not enough trial data exists or has been presented for a licence to be granted. The licensing of a drug puts constraints on drug companies, but not individual prescribers. So the responsibility of ensuring that there is adequate information supporting the quality, effectiveness, and safety of a drug ultimately lies with the person prescribing the drug. Expert opinion from previous use together with careful individual consideration usually guides this decision.
How to maximise compliance
Non-compliance with treatment is widespread in paediatrics, and vigilance is needed to ensure the best possible treatment for patients. Formulation, taste, appearance, and ease of administration are all contributing factors. To maximise the potential of a child taking the drug, you should find the most suitable formulation available, and, if possible, the prescription should be tailored to the child's daily routine.
Because parents often play an essential role in the administration of drugs to their children, compliance of the parent as well as the child needs to be considered. So a thorough explanation of the purpose of the drug and comprehensive instructions for its administration are essential. Also remember that different considerations are necessary for older children or adolescents, who may be responsible for their own drugs. Poor compliance can be a particular problem in this age group because of peer pressure and the desire to fit in. A way of minimising this is to keep the number of drugs prescribed to a minimum, and avoid doses at lunch time if at all possible.
Other considerations
Children, and especially toddlers, enjoy exploring the world with their mouths—almost any item will be sucked or chewed given the chance. It is important to remember that pink tablets that look like sweets or a tasty bottle of cough medicine are equally likely to be desired. It is important that parents keep such items high on shelves or locked in a medicine cabinet.
Unintentional poisoning in childhood is a common and serious problem, and, unfortunately, children are sometimes deliberately poisoned by adults. If this does occur parents should be encouraged not to try to induce vomiting but to get their child to hospital as soon as possible, taking all the drug containers with them. Toxic doses can be calculated by weight, and expert advice from the National Poisons Information Service can be sought (www.toxbase.org).
Prescribing do's and don'ts Do's
Only prescribe within the limits of your competence
Check the weight and age of child are correct
Always state the age of the child on a prescription
Make a clear, accurate, and legible record of all drugs prescribed
Have an awareness of serious contraindications and adverse effects of drugs prescribed
Take an adequate history, including previous adverse drug reactions and use of non-prescription drugs
Ensure patients or parents have been given appropriate information on adverse effects
Get doses checked by someone else when they are calculated
Report all suspected adverse drug reactions using the yellow card system
Don'ts
Put a zero after a decimal point. This reduces the risk of a 10 times overdose when writing prescriptions—for example, 10 micrograms not 10.0 micrograms. When decimals are unavoidable a zero should be written in front of the decimal point—for example, 0.5 ml not .5 ml
Don't abbreviate nanograms and micrograms when writing prescriptions
Don't use the terms cubic centimetres, cc, or cm3; the term millilitre (ml) is used in medicine and pharmacy
Finally
It is important to bear in mind all the factors that influence the prescribing of drugs in children—however, as junior doctors you are never alone. Paediatric reference texts such as BNF for Children also provide a wealth of guidance on all aspects of prescribing.
Clare M Morkane, fourth year medical student, Cardiff University, Heath Park, Cardiff CF14 4XN
Katie G Binns, fourth year medical studentWales College of Medicine, Department of Clinical Pharmacology, Division of Medical Sciences, Medical School, University of Birmingham, Birmingham B15 2TT
Jamie J Coleman, specialist registrar in clinical pharmacology and honorary lecturer in medicine
Email: email
Student BMJ 2007;15:293-336 September ISSN 0966-6494
Competing interests: None declared.
The series editor is Jamie J Coleman ( j.j.coleman@bham.ac.uk).
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