Cutaneous adverse reactions to amoxicillin-clavulanic acid suspension in children: the role of sodium benzoate

Curr Drug Saf. 2012 Apr;7(2):87-91. doi: 10.2174/157488612802715636.

Abstract

Background: In Europe amoxicillin plus clavulanic acid is the most commonly prescribed antibiotic and sodium benzoate is contained in the suspension formulation as a preservative.

Objective: We studied the relevance of sodium benzoate as the culprit agent. In a group of children with a history of adverse reactions to amoxicillin plus clavulanic acid suspension.

Study design: A total of 89 children were enrolled over a period of 3 years (2006 - 2009). Single blind oral provocation tests (OPTs) with amoxicillin plus clavulanic acid, sodium benzoate and placebo were performed. 20 children with recurrent idiopathic urticaria were investigated as a control group.

Results: according to personal history: 70% of reactions were late in developing while 23% of reactions were immediate and for 5% of the cases it was not possible to define the timing. 8 children (8/89=9%) resulted positive to the provocation tests with amoxicillin plus clavulanic acid; ten children (10/89=11%) had positive results with sodium benzoate; 3% had a double positivity (i.e. excipient and active drug). The timing of reactions significantly differs between the Amoxicillin plus clavulanic acid and sodium benzoate groups (p=0.002).

Conclusion: Sodium benzoate probably acts through a non-immunologic mechanism and care should be given to children allergic to sodium benzoate containing pharmaceutical formulations.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Amoxicillin-Potassium Clavulanate Combination / administration & dosage
  • Amoxicillin-Potassium Clavulanate Combination / adverse effects*
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects
  • Child
  • Child, Preschool
  • Drug Eruptions / etiology*
  • Female
  • Humans
  • Male
  • Preservatives, Pharmaceutical / adverse effects
  • Preservatives, Pharmaceutical / chemistry
  • Recurrence
  • Single-Blind Method
  • Sodium Benzoate / adverse effects*
  • Sodium Benzoate / chemistry
  • Suspensions
  • Time Factors
  • Urticaria / chemically induced*

Substances

  • Anti-Bacterial Agents
  • Preservatives, Pharmaceutical
  • Suspensions
  • Amoxicillin-Potassium Clavulanate Combination
  • Sodium Benzoate