Onset of Action for Acetaminophen in Reducing Fever

Acetaminophen begins to reduce fever within 4 hours of administration, with a mean temperature reduction of 0.26°C during this timeframe. 1

Mechanism and Effectiveness

Acetaminophen works as an antipyretic by lowering body temperature in febrile patients, though its effectiveness varies between individuals 1
The medication is modestly successful in achieving normothermia in most patients, but those with temperatures exceeding 38°C may be relatively unresponsive to treatment 1
In critically ill patients, acetaminophen produces a slightly higher absolute temperature reduction (mean 0.86°C vs 0.56°C in untreated patients) and a slightly more rapid cooling rate (mean 0.20°C vs 0.13°C per hour) 2

The antipyretic effect begins within hours of administration 1
A small placebo-controlled trial found that acetaminophen might lower body temperature by a mean of 0.26°C within 4 hours of starting treatment 1
The full effect may not be apparent until 24 hours after initiation of treatment, when high-dose acetaminophen (6000 mg daily) resulted in 0.4°C lower body temperatures compared to placebo 3

Standard dosing for fever reduction is typically 15 mg/kg every 4 hours 1
Higher doses of acetaminophen (6000 mg daily) may have a more significant effect on lowering body temperature than lower doses (3900 mg daily) 1, 3
For prevention of fever in patients with history of febrile conditions, acetaminophen can be given prophylactically 1

The response to acetaminophen is variable between patients, with some showing minimal response 2
Acetaminophen's fever-reducing effect is similar regardless of whether the fever is caused by viral or bacterial infections 4
While acetaminophen can reduce fever, there is no evidence that using medications to lower body temperature improves clinical outcomes in conditions like stroke, though treating fever makes intuitive sense 1
In pediatric patients with febrile seizures, acetaminophen administration has been shown to significantly reduce the recurrence rate of seizures during the same fever episode (9.1% vs 23.5% without antipyretics) 5

After administering acetaminophen for fever, temperature should be monitored to assess response 1
If fever persists despite acetaminophen administration, especially in temperatures >38°C, additional evaluation for the source of fever may be warranted 1
The absence of fever response to acetaminophen should not be used to differentiate between viral and bacterial infections, as studies show no significant difference in response between these etiologies 4