A child's fever can be reduced more quickly and safely by alternating acetaminophen and ibuprofen instead of administering either agent alone, according to Dr. E. Michael Sarrell and his colleagues at Tel Aviv University in Israel.
About 19%–30% of all visits to primary care pediatricians are on account of fever, and acetaminophen and ibuprofen are the most commonly prescribed therapeutics to bring elevated temperatures down. According to Dr. Sarrell and his colleagues, “Antipyretic use therefore plays a major role in daily pediatric practice, and it must be both effective and safe.”
As a consequence, they designed a study to determine which agent—or if both intermittently—may be more effective.
In a double-blind, controlled clinical trial 464 children aged 6–36 months with a fever of at least 38.4° C presenting at one of three pediatric centers in Israel were randomized to 12.5 mg/kg of acetaminophen syrup every 6 hours (154 patients), an ibuprofen suspension of 5 mg/kg every 8 hours (155 patients), or alternating acetaminophen/ibuprofen every 4 hours (155 patients) for a total of 3 days. Within each arm, one-half of the children received an initial loading dose of 25 mg/kg of acetaminophen or 10 mg/kg of ibuprofen to more quickly attain an effective drug serum concentration (Arch. Pediatr. Adolesc. Med. 2006; 160:197–202).
The type of loading medication had no effect on children's response, but the type of maintenance medication did—and significantly so. The alternating regimen reduced children's fevers more rapidly, led to less stress among children, and required less medication during the first 3 days of treatment than either acetaminophen or ibuprofen alone.
For example, 1 day after initiation of treatment, infants who received the alternating regimen had a 1.07° C drop in temperature (vs. a drop of 0.19° C with acetaminophen and an increase of 0.02° C with ibuprofen), a 52.4% reduction in stress levels (vs. 39.6% with acetaminophen and 35.7% with ibuprofen), and required 22.6% fewer treatment doses from day 1 to day 2 (vs. 11.2% with acetaminophen and 2.2% with ibuprofen). Moreover, only 10% of children who received the alternating treatment experienced a recurrence in fever on day 5 as opposed to 21% of children on acetaminophen and 17% of children on ibuprofen.
Because their treatment was more effective, children on acetaminophen/ibuprofen missed significantly fewer days of day care (which presumably meant that parents missed fewer days of work) than did children who were on acetaminophen or ibuprofen alone (1.76, 2.64, and 2.58 days, respectively).
No child experienced any serious adverse effects related to treatment, and there were no statistically significant differences between groups for abnormal laboratory values.