BNF for Children 2011-2012

500 10.1.1 Non-steroidal anti-inflammatory drugs BNFC 2011–201210 Musculoskeletal and joint diseasesChoice Differences in anti-inflammatory activitybetween NSAIDs are small, but there is considerablevariation in individual response and tolerance to thesedrugs. A large proportion of children will respond to anyNSAID; of the others, those who do not respond to onemay well respond to another. Pain relief starts soon aftertaking the first dose and a full analgesic effect shouldnormally be obtained within a week, whereas an antiinflammatoryeffect may not be achieved (or may not beclinically assessable) for up to 3 weeks. However, injuvenile idiopathic arthritis NSAIDs may take 4–12weeks to be effective. If appropriate responses are notobtained within these times, another NSAID should betried. The availability of appropriate formulations needsto be considered when prescribing NSAIDs for children.NSAIDs reduce the production of prostaglandins byinhibiting the enzyme cyclo-oxygenase. They vary intheir selectivity for inhibiting different types of cyclooxygenase;selective inhibition of cyclo-oxygenase-2 isassociated with less gastro-intestinal intolerance. However,in children gastro-intestinal symptoms are rare inthose taking NSAIDs for short periods. The role ofselective inhibitors of cyclo-oxygenase-2 is undeterminedin children.Ibuprofen and naproxen are propionic acid derivativesused in children:Ibuprofen combines anti-inflammatory, analgesic, andantipyretic properties. It has fewer side-effects thanother NSAIDs but its anti-inflammatory properties areweaker.Naproxen combines good efficacy with a low incidenceof side-effects.Diclofenac, indometacin, mefenamic acid, andpiroxicam have properties similar to those of propionicacid derivatives:Diclofenac has actions and side-effects similar to thoseof naproxen.Indometacin has an action equal to or superior to thatof naproxen, but with a high incidence of side-effectsincluding headache, dizziness, and gastro-intestinal disturbances.It is rarely used in children and should bereserved for when other NSAIDs have been unsuccessful.Mefenamic acid has minor anti-inflammatory properties.It has occasionally been associated with diarrhoeaand haemolytic anaemia which require discontinuationof treatment.Piroxicam is as effective as naproxen and has a longduration of action which permits once-daily administration.However, it has more gastro-intestinal side-effectsthan most other NSAIDs, and is associated with morefrequent serious skin reactions (important: see CHMPadvice, p. 505).Meloxicam is a selective inhibitor of cyclo-oxygenase-2. Its use may be considered in adolescents intolerant toother NSAIDs.Ketorolac can be used for the short-term managementof postoperative pain (section 15.1.4.2).Etoricoxib, a selective inhibitor of cyclo-oxygenase-2, islicensed for the relief of pain in osteoarthritis, rheumatoidarthritis, ankylosing spondylitis, and acute gout inchildren aged 16 years and over.For the role of aspirin in children, see section 2.9.Dental and orofacial pain Most mild to moderatedental pain and inflammation is effectively relieved byibuprofen or diclofenac. In an appraisal of the relativesafety in adults of 7 non-selective NSAIDs, the CSMassessed ibuprofen to have the lowest risk of seriousgastro-intestinal side-effects (see below).For further information on the management of dentaland orofacial pain, see p. 199.Cautions and contra-indications NSAIDs should beused with caution in children with a history of hypersensitivityto any NSAID—which includes those inwhom attacks of asthma, angioedema, urticaria or rhinitishave been precipitated by any NSAID. NSAIDsshould also be used with caution in coagulation defects.Caution may also be required in children with allergicdisorders, and also in children with connective-tissuedisorders, see Side-effects below.In children with cardiac impairment, caution is requiredsince NSAIDs may impair renal function (see also Sideeffectsbelow). All NSAIDs are contra-indicated insevere heart failure. Non-selective NSAIDs should beused with caution in uncontrolled hypertension, heartfailure, ischaemic heart disease, peripheral arterial disease,cerebrovascular disease, and when used long termin children with risk factors for cardiovascular events.The selective inhibitor of cyclo-oxygenase-2, etoricoxib,is contra-indicated in ischaemic heart disease, cerebrovasculardisease, peripheral arterial disease, and mild tosevere heart failure. Etoricoxib should be used withcaution in children with a history of cardiac failure,left ventricular dysfunction, hypertension, in childrenwith oedema for any other reason, and in childrenwith risk factors for cardiovascular events.NSAIDs and cardiovascular eventsThe risk of cardiovascular events secondary toNSAID use is undetermined in children. In adults,all NSAID use can, to varying degrees, be associatedwith a small increased risk of thrombotic events (e.g.myocardial infarction and stroke) independent ofbaseline cardiovascular risk factors or duration ofNSAID use; however, the greatest risk may be inthose patients receiving high doses long term. Asmall increased thrombotic risk cannot be excludedin children.In adults, diclofenac (150 mg daily) and ibuprofen(2.4 g daily) are associated with an increased risk ofthrombotic events. The increased risk for diclofenacis similar to that of etoricoxib. Naproxen (in adults,1 g daily) is associated with a lower thrombotic risk,and lower doses of ibuprofen (in adults, 1.2 g daily orless) have not been associated with an increased riskof myocardial infarction.The lowest effective dose of NSAID should be prescribedfor the shortest period of time to controlsymptoms, and the need for long-term treatmentshould be reviewed periodically.NSAIDs are generally contra-indicated if there is activeor previous gastro-intestinal ulceration or bleeding;however, some children may require NSAIDs for effectiverelief of pain and stiffness. For advice on theprophylaxis and treatment of NSAID-associated gastro-intestinalulcers, see section 1.3.For interactions of NSAIDs, see Appendix 1 (NSAIDs).