Effects of prophylactic and therapeutic paracetamol treatment during vaccination on hepatitis B antibody levels in adults: two open-label, randomized controlled trials.

Anne M C M Doedée,Hester E De Melker,Fiona R M Van Der Klis,Henk Van Loveren,Greet J Boland,Arja De Klerk,Riny Janssen,Jeroen L A Pennings,Guy A M Berbers,Lise Lotte Gluud

doi:10.1371/journal.pone.0098175

Abstract

Worldwide, paracetamol is administered as a remedy for complaints that occur after vaccination. Recently published results indicate that paracetamol inhibits the vaccination response in infants when given prior to vaccination. The goal of this study was to establish whether paracetamol exerts similar effects in young adults. In addition, the effect of timing of paracetamol intake was investigated. In two randomized, controlled, open-label studies 496 healthy young adults were randomly assigned to three groups. The study groups received paracetamol for 24 hours starting at the time of (prophylactic use) - or 6 hours after (therapeutic use) the primary (0 month) and first booster (1 month) hepatitis B vaccination. The control group received no paracetamol. None of the participants used paracetamol around the second booster (6 months) vaccination. Anti-HBs levels were measured prior to and one month after the second booster vaccination on ADVIA Centaur XP. One month after the second booster vaccination, the anti-HBs level in the prophylactic paracetamol group was significantly lower (p = 0.048) than the level in the control group (4257 mIU/mL vs. 5768 mIU/mL). The anti-HBs level in the therapeutic paracetamol group (4958 mIU/mL) was not different (p = 0.34) from the level in the control group. Only prophylactic paracetamol treatment, and not therapeutic treatment, during vaccination has a negative influence on the antibody concentration after hepatitis B vaccination in adults. These findings prompt to consider therapeutic instead of prophylactic treatment to ensure maximal vaccination efficacy and retain the possibility to treat pain and fever after vaccination.Trial RegistrationControlled-Trials.com ISRCTN03576945

Highlights

Paracetamol is an analgesic and antipyretic drug widely used in children and adults [1]
Study participants were randomly divided in a control, prophylactic or therapeutic paracetamol group
The ratio in the therapeutic paracetamol group was not different from the ratio in the control group (p = 0.17). These results indicate that only prophylactic paracetamol treatment during the primary vaccinations affects the initial immune response resulting in a diminished effect of the second booster vaccination

Summary

Introduction

Paracetamol (acetaminophen) is an analgesic and antipyretic drug widely used in children and adults [1]. In the Netherlands, the advice is to be cautious with the use of paracetamol during vaccination and only children who experienced fever or persistent screaming after vaccination are advised to use paracetamol prior to further vaccinations [3]. Despite this advice to restrict paracetamol to those children with previous reactions, many parents give paracetamol to their children prior to or just after the vaccine administrations. Data on use of paracetamol by adults during vaccination are not available

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