Acetaminophen
After sufficient evidence emerged ofan association between salicylates and Reye syndrome, acetaminophen essentially replaced aspirin as the primary treatment of fever. Acetaminophen
doses of 10 to 15 mg/kg per dose given every 4 to 6 hours orally are generally regarded as safe and effective. Typically, the onset of an antipyretic effect is within 30 to 60 minutes; approximately 80% of children will experience a decreased temperature within that time (Table 1). Although alternative dosing regimens have been suggested,41– 43 no consistent evidence has indicated that the use of an initial loading dose by either the oral (30 mg/kg per dose) or rectal (40 mg/kg per dose) route improves antipyretic efficacy. The higher rectal dose is often used in intraoperative conditions but cannot be recommended for use in routine clinical care.44,45 The use of higher loading doses in clinical practice would add potential risks for dosing confusion leading to hepatotoxicity; therefore, such doses are not recommended.
Although hepatotoxicity with acetaminophen at recommended doses has been reported rarely, hepatoxicity is most commonly seen in the setting of an acute overdose. In addition, there is
significant concern over the possibility of acetaminophen-related hepatitis in the setting of a chronic overdose. The most commonly reported scenarios are those of children receiving multiple
supratherapeutic doses (ie, 15 mg/kg per dose) or frequent administration of appropriate single doses at intervals of less than 4 hours, which has resulted in doses of more than 90 mg/kg per day for several days.46,47 Giving an adult preparation of acetaminophen to a child may result in supratherapeutic dosing. In 1 case series,46 half of the children with hepatotoxicity had received adult preparations of acetaminophen. One safety concern is the effect of acetaminophen on asthma-related symptoms; although asthma has also been associated with acetaminophen use, causality has not been demonstrated.48–5