CLINICAL PHARMACY & Chapter 10: Paediatrics

PHARMACOTHERAPY 1 Ms. Neri Margaret Fabillo

AY 2022-2023 MM/DD/YYYY
2nd Semester

OUTLINE
I. DEMOGRAPHY
II. THE NORMAL CHILD
III. DRUG DISPOSITION
IV. DRUG THERAPY IN CHILDREN
V. COUNSELLING, ADHERENCE, AND
CONCORDANCE
VI. MEDICINES IN SCHOOL
VII. MONITORING PARAMETERS
VIII. MEDICATION ERRORS
IX. LICENSING MEDICINES IN CHILDREN
X. SEVICE FRAMEWORKS

KEYNOTES
• Children are not small adults.
• Patient details such as age, weight and surface area need to
COMMON DISEASES
be accurate to ensure appropriate dosing.
• Weight and surface area may change in a relatively short time
period and necessitate dose adjustment Congenital anomalies
• Pharmacokinetic changes in childhood are important and
have a significant influence on drug handling and need to be ● The National Congenital Anomaly System (NCAS),
considered when choosing an appropriate dosing regimen for established in 1964 in the wake of the thalidomide tragedy, has
a child. monitored congenital anomalies nationally in England and
• The ability of the child to use different dosage forms changes Wales
with age, so a range should be available, for example, oral ● Registers such as NCAS are important in planning service
liquid, dispersible tablets, and capsules. delivery and alerting specialists to conditions where research is
• The availability of a medicinal product does not mean it is required.
appropriate for use in children. ● In 2007, a new classification of congenital anomalies was
• The use of unlicensed medicine in children is not illegal, introduced to include tighter rules for deciding which congenital
although it must be ensured that the choice of drug and dose anomalies should be included in the Office for National
is appropriate. Statistics report.
Note: If no learning objectives were given during the lecture, either ● In 2008, there were 175 central nervous system (CNS)
use the ones in the handout given or delete this portion altogether anomalies, for example, hydrocephalus, 282 cleft lip/palate, 932
heart and circulatory, 258 hypospadias and 225 Down's
I. DEMOGRAPHY syndrome reported to NCAS
→ Neural tube defects (spina bifida)
→ Folate supplementation prevented 72% of neural tube
● 2001 census : dependent children make up at 11.7 defects when given to women at high risk of having a child
million with a neural tube defect (MRC Vitamin Study Research
● Office for National Statistics in 2009 : population aged 16 Group, 1991.
years and under has decreased from 21% to 19% (over Cancer
the last 25 years)
● This trend is predicted to continue and by 2033 the ● Cancer is very rare in childhood
percentage of the population under 16 years old is → 1700 new cases are diagnosed in children less than 15 years
predicted to be 18%. old in the UK each year.
● Out of 14 million attendances at hospital emergency
departments reported each year in England, 2.9 million → One-third of all childhood cancers are leukaemias and of
were for children. these, about 80% are of the acute lymphoblastic type (ALL).
● 4.5 million outpatient attendances and 700,000 in-patient
→ Childhood cancer is the most common cause of death from
admissions.
illness in children aged between 1 and 15 years of age.

Asthma, eczema and hay fever

● Asthma, eczema and hay fever (allergic rhinitis) are among the
most common chronic diseases of childhood and most of
the affected children are managed in primary care.
● Incidence rates of acute asthma in children under 5 years old
were reported to be 1.5 per 1000 per week in 1991; the rates for
children aged 5–14 years old were 0.9 per 1000 per week.

CLINPHARM Group 2 - 2A : Andres, Balando, Bucane, Canillas, Galangue,Gonzales, Llarenas, Mengote, Muncada, Pabia, Pazon, Rosales, Samante, Severino, Vierras, Yee 1 of 9
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● Between 1993 and 2000 the incidence rates for both groups interprets overweight and obesity in terms of reference points
declined, but asthma continues to be an important childhood for body mass index (BMI, in kg/m2 ) by age and sex, and is
illness placing a burden on the health service. linked to the widely used adult overweight cut-off point of 25 and
adult obesity cut-off point of 3
Infections ● In 2004, it was estimated that 14% of boys and 17% of girls
aged 2–15 years of age were obese.
● Being overweight is linked to the development of type 2
● Major advances in the prevention of infections have been
diabetes, high blood pressure, heart disease, stroke, certain
achieved through the national childhood vaccination
cancers and other types of illnesses.
programme.
● It is recommended that a well-balanced diet providing all the
● Adverse publicity surrounding the MMR (measles, mumps and
nutrients required should include at least five portions of fruit
rubella) vaccine, involving a possible association with Crohn's
and vegetables a day.
disease and autism, resulted in a loss of public confidence in
the vaccine and a decrease in MMR coverage.
● An important gastro-intestinal infection that appears to be II. THE NORMAL CHILD
increasing is infection with verotoxin-producing Escherichia
coli (VTEC). ● Growth and development are important indicators of a child’s
→ the main cause of haemolytic uraemic syndrome, a severe general well-being.
condition which can lead to acute renal failure in children. ● Weight - one of the most widely used and obvious indicators
→ Before the 1980s it was unknown and during the 1990s of growth.
reports of infection with VTEC in children in the UK tripled ○ Separate recording charts are used for boys
from 172 in 1991 to 531 in 1999. and girls.
● Respiratory syncytial virus (RSV) is the most important cause ○ The optimum size is now that of a breast-fed
of lower respiratory tract infection in infants and young children baby.
in the UK, in whom it causes bronchiolitis, tracheobronchitis and ● Height - another important tool in development assessment. It
pneumonia. measures the child’s length.
● Should follow a percentile line; the normal rate of growth is 5
cm or more per year and any changes in this growth velocity
should be investigated.
Mental health disorders
● Head circumference - a useful parameter to monitor in
infants up to 2 years of age.
● In 2004, 1 in 10 children and young people aged 5–16 years ● Hearing, vision, motor development, and speech are also
old had a clinically diagnosed mental health disorder. monitored.
● These included 4% with an emotional disorder such as ● Child Health Clinics - carry out health and development
depression or anxiety, 6% with a conduct disorder, 2% with a checks at different points in children's lives and provide
hyperkinetic disorder and 1% with less common disorders, for information on a range of parenting topics.
example, autism, tics. ○ In the UK, development surveillance and
screening of babies and children is
well-established in these centers.
Drugs, smoking and alcohol
○ plays a vital role in childhood immunization
programs (w/c commences at 2 months of age)
● In 2008, 6% of schoolchildren smoked regularly (at least once a ● Immunization - a major success story for preventive medicine,
week) preventing diseases that potentially cause serious damage to
● Girls are more likely to smoke than boys and the prevalence a child’s health, or death,
increases with age.
● Around 14% of 15-year olds smoke regularly compared to 0.5%
of 11-year olds See Figure 10.2 for the summary of the various stages of
● In 2007, the minimum age for buying tobacco was increased development.
from 16 years old to 18 years old.
● More than half of pupils(52%) aged 11–15 years have drunk
alcohol in their lifetime.
● In 2008, a national survey identified that the mean amount of III. DRUG DISPOSITION
alcohol consumed by pupils who had drunk in the last week was
14.6 units.
● In one large survey, 17% of pupils aged 11–15 years old Pharmacokinetic Factors
admitted to being drunk in the last 4 weeks ● Absorption
● In 2008, 22% of pupils said that they had ever used drugs with → Oral absorption
33% reporting that they had ever been offered drugs. Pupils ▪ may be influenced by gastric and intestinal transit time,
were most likely to have taken cannabis (9%). gastric and intestinal pH and gastrointestinal contents.
Posture, disease state, and therapeutic interventions can
Nutrition and exercise also affect the absorption process
▪ rate of absorption is correlated with age, much slower in
● Good nutrition and physical exercise are vital both for growth neonates than in older infants and children
and development and for preventing health complications in → Intramuscular absorption
later life. ▪ Faster in infants and children than in neonatal period
● In addition, dietary patterns in childhood and adolescence have since muscle blood is increased.
an influence on dietary preferences and eating patterns in → Intraosseous absorption
adulthood. ▪ Useful route of administration in patients in whom
● In 2000, an international definition of overweight and obesity in intravenous access cannot be obtained
childhood and adolescence was proposed; the definition ▪ Rate of absorption is equivalent to the intravenous route
→ Topical absorption

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 ▪ Percutaneous absorption, inversely related to the
thickness of the stratum corneum and directly related to
skin hydration, is generally much greater in the newborn
and young infant than in the adult
● Renal excretion
▪ Needle-free subcutaneous jet injection brings many
→ Below 3-6 months of age, the glomerular filtration rate is
benefits; they give comparable levels to standard
lower than that of adults but may be partially compensated
subcutaneous injections and overcome the problems of
by a greater reduction in tubular reabsorption
needle phobia.
→ After 8 months, renal excretion of drugs is comparable with
▪ Another route is ophthalmic topical absorption; significant
that observed in older children and adults
amounts of drugs may be absorbed from ophthalmic
preparations through ophthalmic or nasolacrimal duct
absorption
→ Rectal absorption
▪ Useful in patients who are vomiting or in infants or
children reluctant or unable to take oral medication
→ Buccal absorption
▪ Useful route in patients who cannot tolerate oral
medications
▪ Highly lipophilic drugs can rapidly cross the buccal
mucosa
→ Intranasal absorption
▪ Medicines can be administered intranasally for their local ● Other factors
action → Nutritional status and disease states can influence drug
▪ Highly lipophilic analgesics are used via this route for handling
treatment of acute pain, particularly in situations where → High plasma clearance of antibiotics has been demonstrated
intravenous access is difficult in children with cystic fibrosis, increased elimination of
→ Inhalation absorption furosemide has been reported in children with nephrotic
▪ Direct delivery of drug therapies to the lungs. syndrome, while prolonged elimination of furosemide has
● Distribution been reported in infants with congestive cardiac failure.
→ Factors that determine drug distribution within the body are
subject to change with age; these include vascular perfusion,
body composition, tissue binding characteristics and the IV. DRUG THERAPY IN CHILDREN
extent of plasma protein binding
→ Total body water and extracellular fluid volume decrease with DOSAGE
age ● Doses of medicines in children should be obtained from a
paediatric dosage handbook and should not be extrapolated
from the adult dose.
→ [United Kingdom] the BNF-C is a national formulary which
includes prescribing guidelines and drug monographs.
▪ contains information on licensed, unlicensed and off-label
use of medicines.
● Most formularies use a single dose convention and indicate
the number of times the dose should be repeated in a 24-h
period. Other formularies indicate the total daily dose and the
number of doses this is divided into.
● The changing requirement for drug dosage during
childhood corresponds most closely with changes in body
→ Protein Binding surface area (BSA).
▪ Despite normal blood pH, free fatty acid and bilirubin
levels in infants, binding to plasma proteins is reduced as → Nomograms which allow the surface area to be easily
a result of low concentrations of both globulins and derived are available.
albumin. ● Practical problems in using the Surface Area method:
▪ Binding values are reached within the third year of life for
acidic drugs, for basic drugs, adult values are not reached a. Accurate height and weight may be difficult to obtain in a
until between 7 and 12 years of life sick child.
● Drug Metabolism b. Manufacturers rarely provide dosage information on a
→ At birth, majority of enzymes responsible for drug surface area basis.
metabolism are either absent or present in reduced amounts
compared with adults ● Practical problems in using the Surface Area method:
→ In the 1-9 year age group, metabolic clearance of drugs is
greater than in adults. Children in this age group may require ● The surface area formula for children has been used to
a higher dosage than adults produce the percentage method, giving the percentage of
adult dose required at various ages and weights, although use
should be reserved for exceptional circumstances. (See table
10.5.)

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 ● Gels, sprays and liquids can also be administered into the
buccal cavity, using drugs such as midazolam to treat
seizures.

Oral Route
● Most convenient but in an uncooperative child it can be the
least reliable.
● Use of an oral syringe can provide controlled administration,
ensure accurate measurement of the calculated dose and
avoids the need for dilution of preparations with syrup.
● Concentrated formulations may be administered as oral
drops in a very small volume.
→ Although convenient, there could be significant dosage
errors if drops are not delivered accurately.
● In general, liquid preparations are more suitable for
children under 7 years of age.
● In selecting a method of dosage calculation, the therapeutic
index of the drug should be considered. ● The osmolality and tonicity of preparations may be important
● Oral liquids with high-osmolality or extremes of pH may
→ For NARROW THERAPEUTIC INDEX (eg. cytotoxic
irritate the stomach and should be diluted for
agents): where recommendations are quoted per square
administration.
metre, dosing must be based on the calculated surface area.
Exception: children less than 1 year of age (it must be based ● Sugar-free preparations may be necessary in the diabetic
on weight). child or be desirable in other children for the prevention of
dental caries.
→ For WIDE THERAPEUTIC INDEX (eg. penicillin): single
→ Artificial sweetening agent Aspartame: use with caution in
doses may be quoted for a wide age range. Between these
children with Phenylketonuria.
two extremes, doses are quoted in milligrams per kilogram
and this is the most widely used method of calculation. → Other substitutes Sorbitol and Glycerol: may not
contribute to dental caries but produce diarrhea in large
● Whichever method is used, the resulting dosage should be doses.
rounded sensibly to facilitate dose measurement and
● Injection solutions can sometimes be administered orally,
administration and subsequently modified according to
although their concentration and pH must be considered
response or adverse effects.
together with the presence of unsuitable excipients.
● It is important to note that none of the available methods of → Powders or small capsules may be prepared and used
dosage calculation account for the change in dosage interval as an alternative.
that may be required because of age-related changes in drug
→ Lactose must be used with caution in children with lactose
clearance.
intolerance.
● Where possible, the use of therapeutic drug monitoring to ● It is also important to advise parents when it is not
confirm the appropriateness of a dose is recommended. appropriate to crush solid dosage forms (e.g.
sustained-release preparations).
● However, it should be recognised that addition of a medicine
CHOICE OF PREPARATION to a food or liquid may be the only way of rendering an
unpalatable medicine acceptable.
The choice of preparation and its formulation will be
influenced by: → Whenever possible, evidence that this is pharmaceutically
1. The intended route of administration, acceptable should be sought.
2. The age of the child, availability of preparations, ● If an age-appropriate formulation is not available, for
3. Other concomitant therapy and, possibly, example, for a medicine used off-label, a liquid oral
4. Underlying disease states. preparation may be prepared extemporaneously, often by
crushing the ‘adult’ tablets and suspending the powder in
Buccal Route commercial or locally produced suspending agents.
● Drugs may be absorbed rapidly from the buccal cavity (the
cheek pouch)
Nasogastric and Gastrostomy Administration
● They may dissolve when administered and be swallowed
and absorbed from the stomach. ● Medicines may be administered into the stomach via a
nasogastric tube in the unconscious child or when
● ‘Melt®’ technology, [for example, desmopressin, piroxicam, swallowing is difficult.
ondansetron], in which the drug and flavourings are
freeze-dried into a rapidly dissolving pellet, can be very ● A gastrostomy tube may be placed into the stomach
useful. transcutaneously if the problem is long term, for example, in
some children with cerebral palsy.
→ The ‘melt’ dissolves instantly into a very small volume
which is difficult for the child to reject.

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 ● Enteral nutrition may also be administered through such → Dilution of parenteral preparations for infusion may also
tubes. cause inadvertent fluid overload in children.
● Drugs such as phenytoin may adsorb to the plastic of the → Dilution of parenteral preparations for infusion may also
tubes and interact with enteral feeds, requiring special cause inadvertent fluid overload in children.
administration techniques to ensure bioavailability.
→ In fluid-restricted or very young infants, it is possible that
● Suitability of drugs for nasogastric or gastrostomy tube the volume of diluted drug can exceed the daily fluid
administration should always be checked. requirement.
***In order to appreciate this problem, the paediatric practitioner
should become familiar with the fluid volumes that children can
Intranasal Route
tolerate.
● Several drugs, such as desmopressin, diamorphine, fentanyl
→ As a guide these volumes can be calculated using the
and midazolam, have been shown to be absorbed from the
following formula:
nasal mucosa.
★ 100 mL/kg for the first 10 kg,
● This route may avoid the need for injections but
★ plus 50 mL/kg for the next 10 kg,
administration may be difficult in the uncooperative child and
★ plus 20 mL/kg thereafter.
drugs administered may irritate the mucosa or be painful.
Worked examples are given in Table 10.6.

Rectal Route
● Although the rectal route can be useful, it is limited by the
range of products available and the dosage inflexibility
associated with rectal preparations.
● Some oral liquid preparations such as chloral hydrate and
carbamazepine can be administered rectally.
● The route is useful in the unconscious child in the operating
theatre or intensive care unit and it is not uncommon to
administer preoperative analgesics such as diclofenac and
paracetamol and the antiemetic ondansetron using ● Lack of suitable paediatric formulations
suppository formulations.
→ A large number of parenteral products are only available
● Parents and teachers may express concerns about using this in adult dose sizes.
route, fearing accusations of child abuse, but it is an
important route of administration for diazepam or → The concentrations of these products can make it difficult
paraldehyde in the fitting child. to measure the small doses required in paediatrics.
→ Increasingly, buccal administration of midazolam may be → ‘Ten times’ errors are common particularly when drawing
preferred. the dose from a single ampoule or vial that contains
sufficient for an adult patient.
● When oral and rectal routes are inappropriate, the parenteral
route may be necessary. ● Displacement volume
→ Reconstitution of powder injections in accordance with
manufacturers' directions usually makes no allowance for
Parenteral Route the displacement volume of the powder itself. Hence, the
● Intravenous access final volume may be greater than expected and the
concentration will, therefore, be less than expected.
→ Scalp veins, commonly used in newborn infants, are often
very prominent in this age group, allowing easy access. → This can result in the paediatric patient receiving an
underdose, which becomes even more significant in
→ It is also more difficult for the infant to dislodge a cannula younger patients receiving smaller doses or more
from this site than from a site on the arm or foot. concentrated preparations.
→ Likewise the umbilical artery offers a useful route for → Paediatric units usually make available modified
monitoring the patient but can also be used for drug reconstitution directions which take account of
administration in some circumstances. displacement volumes.
→ ***Vasoconstrictive drugs, such as adrenaline ● Rates of infusion
(epinephrine), dopamine and isoprenaline, should not be
given by this route. → The greater the distance between the administration port
and the distal end of the delivery system, and the slower
● Fluid overload the flow rate, the longer the time required for the drug to
→ In infants and children, the direct administration of be delivered to the patient.
intravenous fluids from the main infusion container is
associated with the risk of inadvertent fluid overload. → In very young infants and children, it may take several
hours for the drug to reach the patient, depending on the
→ This problem can be avoided by the use of a paediatric point of injection.
administration set and/or a volumetric infusion device to
control the flow rate. → This is an important consideration if dosage adjustments
are being made in response to plasma level monitoring.
*** A paediatric administration set incorporates a graduated
volumetric chamber with a maximum capacity of 150 mL. → Bolus injections should always be given as close to the
patient as possible.

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 ● Dead space
→ Following administration via an injection port, a residual
amount of drug solution can remain trapped at the port.
→ If dose volumes are small the trapped fluid may represent
a considerable proportion of the intended dose.
→ Similarly, the volume of solution required to prime the
intravenous lines or the in-line filters (i.e. the dead space)
can be a significant proportion of the intended dose.
→ This problem can be minimised by ensuring that drugs are
flushed at an appropriate rate into the main infusion line
after administration via an injection port or through a filter,
and by priming the lines initially with a compatible solution.
→ It is important to remember that flushing volumes can add
a significant amount to the daily fluid and sodium intake,
and it may be important to record the volume of flushing
solutions used in patients susceptible to fluid overload.
● Excipients
→ Analogous to oral preparations, excipients may be present
in parenteral formulations and can be associated with V. COUNSELING, ADHERENCE, AND COINCIDENCE
adverse effects. → Parents and carers are the one responsible for the
▪ Benzyl alcohol, polysorbates and propylene glycol are administration of medicines to their children, the
commonly used agents which may induce a range of concordance and adherence must be considered.
adverse effects in children including metabolic → Non-adherence Factors:
acidosis, altered plasma osmolality, central nervous ▪ Taking the medicine
system depression, respiratory depression, cardiac ▪ Complicated dosage regimens
arrhythmias and seizures. ▪ Misunderstanding of instructions
▪ Apparent ineffectiveness or side effects of the treatment
→ Knowledge of the products that contain these ingredients → Adherence: better when fewer medicines are prescribed.
may influence drug selection. ▪ Formulation
▪ Taste
▪ Appearance
Pulmonary Route ▪ Ease of administration of treatment
● The use of aerosol inhalers for the prevention and treatment → Many health professionals often counsel the parent/carer
of asthma presents particular problems for children because where possible treatment goals should be set in a
of the coordination required. collaboration with the child.
→ Parents consider 8-10 years old children, the start of
● The availability of breath-activated devices and spacer involving them in the counseling process as well as verbal
devices and large-volume holding chambers has greatly instruction.
improved the situation. → If a drug is used in an “off-label”, it may cause confusion and
● It must be remembered that drugs can be absorbed into the distress. Thus, care is needed to ensure that the information
systemic circulation after pulmonary administration or may provided is appropriate for both the parent and child.
be absorbed by the enteral route when excess drug is
swallowed. VI. MEDICINE IN SCHOOL
● High-dose corticosteroid inhalation may suppress the ● Children who are acutely ill will be treated with medicines at
adrenal cortical axis and growth by this mechanism.
home or in hospital, although during their recovery phase it may
be possible to return to school.
DOSAGE REGIMEN SELECTION ● Children with chronic illness such as asthma or epilepsy, and
A summary of the factors to be considered when selecting a drug children recovering from acute illnesses, may require medicines
dosage regimen or route of administration for a paediatric patient to be ­administered whilst at school.
is shown in Table 10.7. ● Some medical emergencies may occur at school or on school
trips such as anaphylaxis (associated with food allergy or insect
stings), severe asthma attack and seizures

Policies and Guidance

● Policies and procedures are required to ensure that
prescribed medicines are labeled, stored and administered
safely and appropriately, and that teachers and care
assistants are adequately trained and understand their
responsibilities.
● Advice has been provided for schools and their employers on
how to manage medicines in school. The advice considers

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 staffing issues such as employment of staff, insurance and
training.
● Other issues covered include drawing up a health care plan for
a pupil, confidentiality, record keeping, the storage, access and
disposal of medicines, home-to-school transport, and on-site
and off-site activities
● It also provides general information on four common
conditions that may require management at school: asthma,
diabetes, epilepsy and anaphylaxis.

Responsibility for Common Medicines

● Responsible pupils should be allowed to administer their own
medication.
● Asthmatics should carry their ‘reliever’ inhaler (e.g. salbutamol
or terbutaline), a spare should be available in school, and easy
access before and during sports.
● Medicines with a two or three times daily administration
schedule should be supplied wherever possible so that dosing
during school hours is avoided.

Special Schools
● Some children with severe, chronic illness will go to special
rather than mainstream schools where their condition can
receive attention from teachers and carers who have undergone
appropriate training.
● Pupils may also attend another institution for respite care.
Particular attention to communication of changes to drug
treatment between parents, primary care doctors, hospital
doctors and school staff is required if medication errors are to
be avoided.

VII. MONITORING PARAMETERS

● Paediatric vital signs (Table 10.8) and haematological and

biochemical parameters (Table 10.9) change throughout
childhood and differ from those in adults.

Assessment of Renal Function

● There are a number of methods of measuring renal function
in children. These include the use of 51Cr-EDTA, 99mTc-DTPA
and using serum and urine creatinine concentrations over a
timed period. Serum creatinine and estimated creatinine
clearance are the most frequently used and most practical
methods for day-to-day assessment of renal function.
● In adults, several formulae and nomograms are available for
calculating and estimating renal function. Cockcroft and Gault
equation and the estimated GFR (eGFR) equation are validated
only for patients aged 18 years and over.

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● A number of validated models are available for use in children: clinical trials in children but may also exclude them from
epidemiological studies of ADRs to prescribed drugs.

MEDICATION ERROR

● In contrast to ADRs, medication errors occur as a result of

human mistakes or system flaws.

● Medication errors are now recognised as an important cause of

adverse drug events in pediatric practice.

● They can produce a variety of problems ranging from minor

discomfort to death.

The incidence of medication errors and the risk of serious

errors occurring in children are significantly greater than in
adults. The causes are many and include:

● Heterogeneous nature of the pediatric population and

the corresponding lack of standard dosage·
● Calculation errors by the prescriber, pharmacist, nurse or
caregiver.
* Whichever equation is chosen, it should be borne in mind that ● Lack of available dosage forms and concentrations
there are limitations to their use; for example, they should not appropriate for administration to children, necessitating
be used in rapidly changing renal function, anorexic or obese additional calculations and manipulations of commercially
patients, and they should not be taken as an accurate measure available products or preparation of extemporaneous
but as a guide to glomerular filtration rate formulations from raw materials.
● Lack of familiarity with pediatric dosing guidelines.
ADVERSE DRUG REACTIONS ● Confusion between adult and pediatric preparations.
● The incidence of ADRs in children outside the neonatal ● Limited published information.
period is thought to be less than at all other ages; however, ● Need for precise dose measurement and appropriate
the nature and severity of the ADRs that children experience drug delivery systems; absence leads to administration
may differ from those experienced by adults. errors and use of inappropriate measuring devices. •
● ADRs in infants and older children typically occur at lower Ten-fold dosing errors are particularly important and
doses than in adults, and symptoms may be atypical. potentially catastrophic; but reports still appear regularly
in the published literature
Examples include:
•enamel hypoplasia and permanent discolouration of
the teeth with tetracyclines LICENSING MEDICINES FOR CHILDREN
•growth suppression with long-term corticosteroids in
prepubertal children
•paradoxical hyperactivity in children treated with Medicines licensing process
phenobarbital
•hepatotoxicity associated with the use of sodium
valproate. There are three major risk factors: ● All medicines marketed in the UK must have been granted a
– age under 3 years product licence (PL) under the terms of the Medicines Act 1968
–child receiving other anticonvulsants
–developmental delay ● The aim of licensing is to ensure that medicines have been
•increased risk of Reye's syndrome with the assessed for safety, quality and efficacy. In the UK, evidence
submitted by a pharmaceutical company is assessed by the
use of salicylates in children with mild viral
Medicines and Healthcare products Regulatory Agency (MHRA)
infection. Reye's syndrome is a with independent advice from the Commission on Human
life-threatening illness associated with Medicines (CHM) and its paediatric medicines expert group.
drowsiness, coma, hypoglycaemia, seizures
and liver failure. The mechanism of this ● The licensed indications for a drug are published in the SmPC.
toxicity remains unknown but aspirin should
generally be avoided in children under 16
years of age.
● The reporting of ADRs is particularly important because the
current system of drug development and authorisation not
only deprives children of useful drugs because of the lack of

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Unlicensed and ‘off-label’ medicines
The recommendations that relate to the use of
medicines for children and young people include;
● The term ‘off-label’ is often used to describe this.
Because many of these medicines will have been ● All children and young people should receive medicines
produced in ‘adult’ dose forms, such as tablets, it is often that are safe and effective, in formulations that can be
necessary to prepare extemporaneously a suitable liquid easily administered and are appropriate to their age,
preparation for the child. having minimum impact on their education and lifestyle.
● Medicines should be prescribed, dispensed and
● The drug to be used has no product license or MA, administered by professionals who are well trained,
perhaps because it is only just undergoing clinical trials in informed and competent to work with children to improve
adults, has been imported from another country, has health outcomes and minimise harm and any side effects
been prepared under a ‘specials’ manufacturing license of medicines.
or is being used.
● Children and young people and their parents or carers
● As with ‘off-label’ use, there must always be information should be well informed and supported to make choices
to support the quality, efficacy and safety of the medicine about their medicines and competent in the
as well as information on the intended use. administration of medicines

Markers of good practice are defined as:

● The use of medicines in children is based on the best

available evidence of clinical use and cost-effectiveness
Recent Legislation on Medicines for Ghildren and safety, ideally derived from clinical trials but also
including, where appropriate, medicines that are not
licensed for their age group or for their particular health
problem (‘off-label’) or those that do not have a licence at
● Both Europe and the USA have orphan drugs regulations all (‘unlicensed’) in order to achieve the best possible
designed to offer incentives for the development of health outcomes and minimise harm and side effects.
medicines for rare diseases. Although not exclusively for ● In all settings and whatever the circumstances, children
paediatric conditions, the regulations have assisted the and young people have equitable access to clinically safe
development of important drugs such as antiretrovirals and cost-effective medicines in age-appropriate
(HIV/AIDS), alendronate (osteogenesis imperfecta), formulations.
α-galactosidase (Fabry's disease), sodium ● Appropriate information and decision support are
phenylbutyrate (hyperammonaemia) and ibuprofen available for professionals who prescribe, dispense and
injection (closure of patent ductus arteriosus) administer medicines for children and young people.
● Children, young people and their parents/carers receive
● The WHO has a ‘Make medicines child size’ programme
consistent, up-to-date, comprehensive, timely information
to stimulate the development of age-appropriate
on the safe and effective use of medicines.
formulations of medicines for children, particularly for
● In all settings, professionals enable parents, young
those which appear in the List of Essential Medicines for
people and, where appropriate, children to be active
Children.
partners in the decisions about the medicines prescribed
● In June 2010, the first ever WHO model formulary for for them.
children was released to provide information on how to ● Primary and secondary care providers should ensure that
use over 240 essential medicines for treating illness and the use of medicines in children is incorporated in their
disease in children from 0 to 12 years of age clinical governance and audit arrangements.
● The contribution of pharmacists to the effective and safe
use of medicines in children is maximised.
SERVICE FRAMEWORK

● The service framework for paediatric intensive care

defines the nature of paediatric intensive care, the
elements of a high-quality paediatric intensive care
service and a policy framework for the future organisation
of services
● National service frameworks (NSFs) are long-term
strategies for improving specific areas of care.

Two paediatric service frameworks have been

published;

1. for paediatric intensive care (Department of Health, 2002)

2. for children, young people and maternity services (Department

of Health, 2004) and continue to influence practice.

CLINPHARM Title of Lecture 9 of 9

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