Prophylactic acetaminophen (paracetamol) has been advocated to reduce frequency and severity of fever and other adverse reactions associated with pediatric immunization. Because fever is a natural part of the immune response, a new study investigated the effects of prophylactic acetaminophen following vaccination on both fever reduction and antibody production. A total of 459 healthy infants were randomized to acetaminophen prophylaxis vs. as needed antipyretic treatment following immunization against pneumococcus, H. influenzae type b, diphtheria-tetanus-acellular pertussis, hepatitis B, inactivated poliovirus, and oral human rotavirus vaccines. The prophylactic group received 3 doses within the first 24 hours after the primary vaccination, and most of these children also received prophylaxis after a booster vaccination. Temperature was checked on a scheduled basis during the first 4 days regardless of symptoms.

Fever (temperature ≥ 38 degrees C [100.4 degrees F]) occurred after primary vaccination in 42% receiving acetaminophen vs. 66% in control group (p < 0.05, NNT 5). Rates of fever after the booster vaccination were 36% with acetaminophen vs. 58% with control (p < 0.05, NNT 5). There were no significant differences in severe fever (≥ 39.5 degrees C [103.1 degrees F]), which was rare in both groups. However, antibody geometric mean concentrations were significantly lower in the prophylactic group compared to controls and remained lower even after the booster dose. Prophylactic acetaminophen use led to statistically significant reductions in the proportion of patients meeting prespecified measures of immune response for 3 of 10 pneumococcal subtypes and hemophilus influenza b, but not for any of the other immunizations given (level 3 [lacking direct] evidence) (Lancet 2009 Oct 17;374(9698):1339).