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Adverse effects
In large series of children with febrile illnesses, the risk of serious adverse events following
short‐term use of ibuprofen was low, and similar to that following the use of paracetamol
(Lesko & Mitchell, 1995 Level II; Lesko & Mitchell, 1999 Level II). Aspirin should be avoided in
children with a febrile illness, as it has been associated with Reye’s syndrome (encephalopathy
and liver dysfunction) (Schror, 2007).
NsNSAIDs should be avoided in children with a sensitivity reaction to aspirin or other
nsNSAIDs. A subset of children with moderate to severe asthma and nasal disease/polyps are
susceptible to NSAID‐exacerbated respiratory disease (Palmer, 2005). NsNSAIDs may be safe in
children with mild asthma as single dose diclofenac had no significant effect on respiratory
function tests (spirometry) in children with asthma (Short et al, 2000 Level III‐3) and short‐term
use of ibuprofen did not increase outpatient visits for asthma (Lesko et al, 2002 Level II). The use
of nsNSAIDs in children undergoing tonsillectomy remains controversial (see Section 4.2.2).
In a meta‐analysis that included only paediatric trials, an increased risk of bleeding requiring
either non‐surgical (OR 1.23; 95% CI 0.44 to 3.43) or surgical intervention (OR 1.46; 95% CI
0.49 to 4.0) after tonsillectomy could not be confirmed (Cardwell et al, 2005 Level I). Although
neither represented a statistically significant increase, risk of bleeding requiring surgical
intervention tended to be higher following high dose ketorolac 1mg/kg (OR 3.1; 95%CI 0.53
to 18.4) than other nsNSAIDS (OR 0.91; 95% CI 0.22 to 3.71) (Cardwell et al, 2005 Level I).

Note: reversal of conclusions
This partially reverses the Level 1 conclusion in the previous
edition of this document; earlier meta‐analyses had reported an
increased risk of reoperation for post‐tonsillectomy bleeding in
studies that included adults and children.

In a small trial, ketorolac did not increase the risk of bleeding complications after congenital
cardiac surgery (Gupta et al, 2004 Level II).
NsNSAIDs affect renal blood flow, glomerular filtration and renal drug clearance (Allegaert,
Vanhole et al, 2005). Renal failure in association with nsNSAID use has occurred in neonates
(Andreoli, 2004) and older children (Taber & Mueller, 2006), usually in the setting of other
haemodynamic compromise.
NsNSAID use for analgesia has been restricted in infants less than 3 months of age. Neonatal
bolus and short‐term use for patent ductus arteriosus closure can produce pulmonary
hypertension and alterations in cerebral (Naulaers et al, 2005), gastrointestinal and renal blood CHAPTER 10
flow (Allegaert, Vanhole et al, 2005; Aranda & Thomas, 2006). Relative effects of indomethacin
(indometacin) and ibuprofen on the risk of intraventricular haemorrhage continue to be
debated (Aranda et al, 1997; Ment et al, 2004).
10.5.3 Coxibs

Coxibs (COX‐2 specific inhibitors) have been used off‐license in children. Celecoxib was as
effective as naproxen in children with juvenile rheumatoid arthritis (Foeldvari et al, 2008 Level II).
Small‐scale efficacy studies evaluated different perioperative doses of rofecoxib (prior to its
withdrawal from the market): low dose (0.625 mg/kg) was inferior to ibuprofen (in
combination with paracetamol) (Pickering et al, 2002 Level II); 1 mg/kg was superior to placebo
(Joshi et al, 2003 Level II; Sheeran et al, 2004 Level II), and multi‐day postoperative dosing provided
superior analgesia to paracetamol (Vallee et al, 2007 Level III‐3) or hydrocodone combined with
paracetamol (Bean‐Lijewski et al, 2007 Level II). The degree of COX‐2 selectivity, pharmacokinetic

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