title: An open-label randomized clinical trial of prophylactic paracetamol coadministered with 7-valent pneumococcal conjugate vaccine and hexavalent diphtheria toxoid, tetanus toxoid, 3-component acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b vaccine.
abstract: BACKGROUND
  In two clinical trials, low-grade fever was observed more frequently after coadministration than after separate administration of two recommended routine pediatric vaccines. Since fever is an important issue with vaccine tolerability, we performed this open-label study on the efficacy and safety of prophylactic use of paracetamol (acetaminophen, Benuron®) in children administered routine 7-valent pneumococcal conjugate vaccine (PCV-7) coadministered with hexavalent vaccine (diphtheria-tetanus-acellular pertussis-hepatitis B, poliovirus, Haemophilus influenzae type b vaccine [DTPa-HBV-IPV/Hib]) in Germany.
  
  
  METHODS
  Healthy infants (N = 301) who received a 3-dose infant series of PCV-7 and DTPa-HBV-IPV/Hib plus a toddler dose were randomly assigned 1:1 to prophylactic paracetamol (125 mg or 250 mg suppositories, based on body weight) at vaccination, and at 6-8 hour intervals thereafter, or a control group that received no paracetamol. Rectal temperature and local and other systemic reactions were measured for 4 days post vaccination; adverse events were collected throughout the study.
  
  
  RESULTS
  In the intent-to-treat population, paracetamol reduced the incidence of fever ≥38°C, but this reduction was only significant for the infant series, with computed efficacy of 43.0% (95% confidence interval [CI]: 17.4, 61.2), and not significant after the toddler dose (efficacy 15.9%; 95% CI: -19.9, 41.3); results were similar in the per protocol (PP) population. Fever >39°C was rare during the infant series, such that there were too few cases for assessment. After the toddler dose, paracetamol effectively reduced fever >39°C, reaching statistical significance in the PP population only (efficacy 79%; 95% CI: 3.9, 97.7). Paracetamol also reduced reactogenicity, but there were few significant differences between groups after any dose. No vaccine-related serious adverse events were reported.
  
  
  CONCLUSIONS
  Paracetamol effectively prevented fever and other reactions, mainly during the infant series. However, as events were generally mild and of no concern in either group our data support current recommendations to administer paracetamol to treat symptoms only and not for routine prophylaxis.
  
  
  BACKGROUND
  NCT00294294.
authors.forename: Markus A
authors.initials: MA
authors.lastname: Rose
authors.forename: Christine
authors.initials: C
authors.lastname: Juergens
authors.forename: Beate
authors.initials: B
authors.lastname: Schmoele-Thoma
authors.forename: William C
authors.initials: WC
authors.lastname: Gruber
authors.forename: Sherryl
authors.initials: S
authors.lastname: Baker
authors.forename: Stefan
authors.initials: S
authors.lastname: Zielen
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage; D016667:Bacterial Capsules; D002675:Child, Preschool; D004165:Diphtheria / Q000517:prevention & control; D004168:Diphtheria Toxoid / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D005858:Germany; D018073:Haemophilus Vaccines / Q000008:administration & dosage*; D019741:Haemophilus influenzae type b / Q000276:immunology; D006509:Hepatitis B / Q000517:prevention & control; D006801:Humans; D007223:Infant; D008297:Male; D011008:Pneumococcal Infections / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000008:administration & dosage*; D017955:Poliovirus / Q000276:immunology; D011054:Poliovirus Vaccine, Inactivated / Q000008:administration & dosage*; D013742:Tetanus / Q000517:prevention & control; D013745:Tetanus Toxoid / Q000008:administration & dosage*; D014611:Vaccination / Q000379:methods; D018074:Vaccines, Conjugate / Q000008:administration & dosage*; D014917:Whooping Cough / Q000517:prevention & control
chemical_list: D018712:Analgesics, Non-Narcotic; D004168:Diphtheria Toxoid; D018073:Haemophilus Vaccines; C044237:Haemophilus influenzae type b polysaccharide vaccine; D022242:Pneumococcal Vaccines; D011054:Poliovirus Vaccine, Inactivated; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate; D000082:Acetaminophen