Clinical Inquiries

Do prophylactic antipyretics reduce vaccination-associated symptoms in children?

Author and Disclosure Information


Yes for acetaminophen, not so much for ibuprofen. Prophylactic acetaminophen reduces the odds of febrile reactions in the first 48 hours after vaccination by 40% to 65% and pain of all grades by 36% to 43%. In contrast, prophylactic ibuprofen reduces pain of all grades by 34% only after primary vaccination and doesn’t alter pain after boosters. Nor does it alter early febrile reactions (strength of recommendation [SOR]: B, meta-analysis of randomized clinical trials [RCTs] with moderate-to-high risk of bias).

Prophylactic administration of acetaminophen or ibuprofen is associated with a reduction in antibody response to the primary vaccine series and to influenza vaccine, but antibody responses still achieve seroprotective levels (SOR: C, bench research).




A systematic review of 13 RCTs (5077 patients) compared the effects of a prophylactic antipyretic (acetaminophen or ibuprofen, doses and schedules not described) with placebo in healthy children 6 years or younger undergoing routine childhood immunizations.1 Trials examined various schedules and combinations of vaccines. Researchers defined febrile reactions as a temperature of 38°C or higher and categorized pain as: none, mild (reaction to touch over vaccine site), moderate (protesting to limb movement), or severe (resisting limb movement).

Acetaminophen works better than ibuprofen for both fever and pain

Acetaminophen prophylaxis resulted in fewer febrile reactions in the first 24 to 48 hours after vaccine administration than placebo following both primary (odds ratio [OR] = 0.35; 95% confidence interval [CI], 0.26-0.48) and booster vaccinations (OR = 0.60; 95% CI, 0.39-0.93). Acetaminophen also reduced pain of all grades (primary vaccination: OR = 0.57; 95% CI, 0.47-0.7; booster vaccination: OR = 0.64; 95% CI, 0.48-0.84).

In contrast, ibuprofen prophylaxis had no effect on early febrile reactions for either primary or booster vaccinations. It reduced pain of all grades after primary vaccination (OR = 0.66; 95% CI, 0.49-0.88) but not after boosters (OR = 1.03; 95% CI, 0.59-1.81).

Reduced antibody response doesn’t affect seroprotective levels

Acetaminophen also generally reduced the antibody response compared with placebo (assessed using the geometric mean concentration [GMC], a statistical technique for comparing values that change logarithmically).1 GMC results are difficult to interpret clinically, however, and they differed by vaccine, antigen, and primary or booster vaccination status.

Nevertheless, patients mounted seroprotective antibody levels with or without acetaminophen prophylaxis, and the nasopharyngeal carriage rates of Streptococcus pneumoniae and Haemophilus influenzae didn’t change. Researchers didn’t publish the antibody responses to ibuprofen, nor did they track actual infection rates.

How do antipyretics work with newer combination vaccines?

A subsequent trial evaluated the immune response in 908 children receiving newer combination vaccines (DTaP/HBV/IPV/Hib and PCV13) who were randomized to 5 groups: acetaminophen 15 mg/kg at vaccination and 6 to 8 hours later; acetaminophen 15 mg/kg starting 6 to 8 hours after vaccination with a second dose 6 to 8 hours later; ibuprofen 10 mg/kg/dose at vaccination with a second dose 6 to 8 hours later; ibuprofen 10 mg/kg starting 6 to 8 hours after vaccination with a second dose 6 to 8 hours later; and placebo.2

Patients received age-appropriate vaccination and their assigned antipyretic (or placebo) at 2, 3, 4 and 12 months of age. Researchers measured the immune response at 5 and 13 months of age.

Continue to: Overall, 5% to 10% of the prophylaxis group...

Evidence-based answers from the Family Physicians Inquiries Network

Next Article: