Download Safe use of NSAIDs in infants and children

Safe use of NSAIDs in infants
and children
likely to manifest in those with recopxed
risk factors, such as volume depletion or
borderline renal function. Most trials of
ibuprofen have not evaluated these outcomes systematically in febrile illness, but
there are case reports of such toxicities
occurring in ~hildren.~
NSAlDs are effective in alleviating pain and inflammation in infants and children.
The use of ibuprofen and paracetamol
in combination or in an alternating regiThey are generally well tolerated when used for appropriate indications, in
men in the setting of febrile illness is discouraged.' The physiological effects of the
combination may potentiate the risk of
recommended paediatric doses, and with consideration of relevant precautions.
toxicity with each agent, and the efficacy
NSAIDs have we1 known analgesic, anti- superior tolerability profile. NSAIDs, such and safety of this practice have not been
pyretic and anti-inflammatory effects. as ibuprofen, are used for analgesia in the well e~aluated.~
The combined use of
This article discusses the main indica- postoperative period, either to decrease these antipyretics needs further investigations for their use in infants (excluding opioid requirements or to provide adjunc- tion, as there is evidence that it may also
neonates) and children, adverse effects tive analgesia with regular paracetamol. lead to an increased incidence of adverse
that occur in this age group and the
effects as a result of parental confusion
principles guiding the choice of NSAID.
about correct dosing.'s5
NSAlDs for fever?
The role of NSAIDs in the treatment of
NSAlDs for pain and inflammation febrile illness in children is more contro- Adverse effects and precautions
The main indication for NSAIDs in chil- versial. Most children tolerate low grade Serious toxicity associated with NSAIDs
dren is the treatment of inflammatory fever (less than 38.5"C) well and do not appears to be rare in children. The specpain. This includes a variety of chronic require pharmacological treatment for trum of adverse effects that occur in adults
inflammatory conditions, most often fever. Antipyretic therapy does not pre- may also occur in children, although there
juvenile idiopathic arthritis (JIA), where vent febrile convulsions, and there is are some differences.
NSAIDs are used for both their analgesic some evidence that such therapy may
and anti-inflammatory properties. Onset prolong the course of some infections.'
Gastrointestinal effects
If antipyretic therapy is needed (e.g. Adverse gastrointestinal eff& related to
of the analgesic effect of NSAIDs is relatively rapid but the anti-inflammatory for a symptomatic child with high fever), - the use of NSAIDs are a signilicant probeffects may take longer (up to six to eight paracetamol is the preferred pharmaco- lem in adults. Although the magnitude of
weeks for optimal relief of chronic inflam- the rap^.^ Ibuprofen has equivalent anti- this problem in children is poorly documation) and require higher doses than pyretic efficacy to paracetamol when used mented, it is thought to be considerably
those used for analgesia (see Table).
at recommended doses, but it is unclear less. Mild gastrointestinal symptoms (e.g.
NSAIDs are also &&e analgesics for whether ibuprofen is equally effective in abdominal pain) are commonly reported
the treatment of mild to moderate acute relieving important clinical outcomes, in children receiving NSAIDs, but clinipain where inflammation may be the prin- such as the child's discomfort and symp- cally significant gastroduodenal pathciple underlying mechanism. In single toms (a Cochrane review is currently ology is uncommon. In many children
doses they have analgesic &cacy compa- investigating this question). It is also who develop gastrointestinal symptoms,
rable to that of paracetamol, which is the unclear whether ibuprofen has any safety underlying disease, psychosocial factors
preferred first line agent because of its advantage. Although short term use of and concomitant medication may account
ibuprofen for fever control appears to be for these effects.
Dr Gazarian is Senior Lecturer, Schwl of Women's and relatively safe, the comparative safety of
To minimise gastrointestinal effects,
Children's Health, University of NSW, and Paediatric
longer term and more widespread use for NSAIDs should always be given with
Clinical Pharmacologist and Rheumatologist, Sydney
febrile illness in young children with typi- food. Concurrent treatment with gastroChildren's Hospital, Randwick
cal underlying comorbidities (e.g. dehy- protective drugs is generally not necessary.
Ms Graudins is QualityUse of Medicines Pharmacist,
dration, mild renal impairment) has not NSAIDs should be used with caution (and
been clearly established. Known toxicities at the lowest effective dose) in children
Sydney Children's Hospital, Randwick, and Conjoint
of NSAIDs include gastrointestinal and who have underlymg gut pathology (e.g.
Lecturer, School of Women's and Children's Health,
University of NSW, Sydney, NSW.
renal adverse effects, with the latter more inflammatory bowel disease).
MediineToday I November 2006, Volume 7, Number 11 71
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72 MediineToday I November 2006, Volume 7, Number 11
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continued
be used with caution in other asthmatic
patients. If safety concerns exist and
NSAIDs are definitely needed in a child
with asthma, the first dose should be
administered under medical supervision.
Skin reactions
A variety of skin reactions including pruritis, urticaria, erythema multiforme and
phototoxic reactions have been described.
Pseudoporphyria is a distinctive type of
photodermatitis that occurs fairly commonly in children with JIA receiving
naproxen (prevalence of 12?'0);~
individuals with fair skin are particularly susceptible. All signs except scarring resolve
with discontinuation of therapy, so early
recognition is important.
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CNS effects
A substantial proportion of children
receiving long term NSAID therapy may
experience CNS effects, with headache
being the most common. Less common
symptoms include fatigue, sleep disturbance and hyperactivity. Ibuprofen has
been reported to cause aseptic meningitis,
particularly in patients with systemic
lupus erythematosus.'
-
Platelets
NSAIDs inhibit platelet aggregation and
may prolong bleeding time for some
patients, especially with long term use.
-Clinically significant bleeding has not
been associated with NSAIDs in children
after tonsille~tomy,'~
however, whether
NSAIDs increase the risk of significant
bleeding in the postoperative period generally remains controversial. Risk may
.
vary with different procedures and so the
. - tmanagement of an individual child
' should be discussed
the relevant sur- with
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Choosing an NSAID
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"Ttf*~ifferences
in anti-inflammatory activity
iY[
,,K,between ditrerent NSAIDs are small, with
-2 unpredictable variability in individual
A- patient response, but there are ditrerences
($1-'
'in the type and hequency of adverse effects
r sao
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misril9gnI bdnd
Itti,., -,
(see Table). For an individual patient, the
initial choice of NSAID should be based
on which agent is likely to provide the most
favourable bene£it to risk ratio for the condition being treated. Additional considerations include the availabilityof a palatable
paediatric formulation, convenience of
dosing schedule and afjfordability.NSAID
combinations should be avoided because
toxicity is likely to be increased without a
proven increase in benefit.
The NSAIDs currently available for
use in children are listed in the Table.
Only naproxen and ibuprofen are available in liquid form. Naproxen suspension is the only liquid NSATD listed on
the PBS (authority required, for chronic
inflammatory arthropathies where the
patient is unable to take a solid dose
form). [This suspension was temporarily
unavailable in Australia from mid-2002,
reinstated in the Australian market in late
2005, and relisted on the PBS in early
2006.1 Naproxen suspension is the most
widely used NSAID for treating chronic
childhood arthropathies worldwide. It
has a well established efficacy and safety
profile in children, has a convenient dosing schedule and is affordable. Ibuen is somewhat less effective as an
anti-inflammatory agent but has a more
favourable toxicity profile. Aspirin is
now used much less often in children
because of its association with a greater
frequency of adverse effects (including
Reye's syndrome). Currently, the main
role of aspirin is in the treatment of Kawasaki disease and rheumatic fever, and as
an antiplatelet agent. '
. '
The COX-2 inhibitors &Gently marketed in Australia are not approved for
use in children. Unlike adults, children
have a neghgible risk of significant gas>ropathy with NSAID therapy and so
,,&ere is no good rationale for considering
''off-label use in the majority of children.
The recent safety concerns with COX-2
inhibitors in the adult population and the
lack of data from the paediatric population showing any advantage in efficacy
or safety over currently available NSAIDs
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.
,
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mean that the use of these agents in children outside a clinical trial setting is not
1. Knoebel EE, Narang AS, Ey JL. Fevec to treat
or not to treat. Clin Pediatr (Phila) 2002,41: 9-16:
2. Litalien C, Jacqz-&grain E. Risks and benefits
of nonsteroidal anti-inflammatorydrugs in
children: a comparison with paracetamoL Paediatr
Drugs 2001; 3: 817-858.
3. American Academy of Pediatrics, Committee
on Drugs. Acetaminophen toxicity in
Pediatrics 2001; 108: 1020-1024.
4. Carson SM. Alternating acetaminophen and
ibuprofen in the febrile child: examination of the
evidence regarding efficacy and safety. Pediatr
Nurs 2003; 29: 379-382.
5. Li SF, Lacher B, Crain EF. Acetaminophen and
ibuprofen dosing by parents. Pediatr Emerg Care
2000,16: 394-397.
6. Szer IS, Goldstein-Schainberg C, Kurtin PS.
Paucity of renal complicationsassociated with
nonsteroidal antiintlammatrory drugs in children
with chronicarthritis. J Pediatr 1991; 119: 815-817.
7. Haftel HM,Mitchell JM, Adams BS. Incidence
of renal toxicity h m anti-inflammatorymedications
in a pediatric rheumatologypopulation: role of
routine screening of urine. J Rheumatol2000;
27(suppl58): 73.
8. JenkinsC, Costello J, Hodge L. Systematic
review of prevalence of aspirin induced asthma
and its implicationsfor clinical practice. BMJ 2004,
VU
328: 434-440. -- - - - - .9. Debley JS, Carter ER, Gibson RL, Rosenfeld M,
Redding GJ. The prevalence of ibuprofen-sensitive
asthma in children: a randomized controlled
bronchoprovocation challenge study. J Pediatr
2005; 147: 233-238.
10. Cardwell M, Siviter G, Smith A. Non-steroidal
anti-inflammatorydrugs and penoperative
bleeding in paediatrictonsillectomy. Cochrane
r
DatabaseSyst Rev2005; (2): ~ ~ 0 0 3 5 9 1 .
.,
III.J'II,
This article is for general information purposes only.
Both the full product information and the Australian
Medicines Handbook should be consulted before
prescribing the aforementioned medications.
DECLARATION OF INTEREST: None.
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MedicineToday I November 2006, Volume 7, Number 11
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