Kim Annink

164 Chapter 7 allopurinol in adults (72). High doses of allopurinol, pre-existing renal failure and co- medication with ampicillin or amoxicillin seem to increase the risk for AHR. The rate of occurrence for AHR is frequently cited to be approximately 0.1% in adults treated with allopurinol and this number origins from a report in which 3 out of 1835 hospitalized adults treated with allopurinol had probable AHR (73). More appropriately and more recently, a population-based study reported an annual incidence rate of 4.68 per 1000 new allopurinol users in Taiwan (74). Taking into account that the odds-ratio for AHR in Chinese compared to Caucasian is 70 (75), the incidence is probably less than 1 in 10,000 new Caucasian users. In all antenatal (n=138) and postnatal (n=58) treated infants with HIE, as in other term (n=178) and preterm (n=348) infants, no serious adverse reactions to allopurinol have been reported (46,47,50,58,59,65-68,76). Consequently, a recent Cochrane review on postnatal allopurinol for HIE concluded that there are no major concerns about safety based on the available data (51). Nevertheless, because of the high pH of an allopurinol preparation suitable for intravenous administration, perivascular or intra-arterial infusion of allopurinol must be strictly avoided. 4.5% of the allopurinol treated mothers had irritation of the perivascular tissue (71). Conclusions and recommendations In conclusion, the neuroprotective effect of allopurinol has been tested by postnatal administration in neonates with HIE and by antenatal administration in mothers with imminent fetal hypoxia. In newborn animals as well as in neonates, allopurinol seems to inhibit the formation of superoxide and scavenge free radicals that both can lead to brain damage. Based on available literature about antenatal and postnatal administration of allopurinol in animals and human neonates, allopurinol might reduce brain damage caused by perinatal asphyxia in term born neonates, but only in those with moderate HIE. Moreover, allopurinol in neonates appears to be safe: even when supra-therapeutic concentrations are reached no adverse events have been seen, but rare side effects may not yet have become apparent. In summary, the literature is inconclusive whether allopurinol is a suitable neuroprotective therapy in infants with HIE. Antenatal administration may result