Allergic reactions to long-term benzathine penicillin prophylaxis for rheumatic fever. International Rheumatic Fever Study Group

Lancet. 1991 Jun 1;337(8753):1308-10.


1790 patients from 11 countries were enrolled in a prospective international study to determine the incidence of allergic reactions to monthly intramuscular benzathine penicillin (penicillin G benzathine) injections to prevent recurrences of rheumatic fever. After 32,430 injections during 2736 patient years of observation, 57 of the 1790 patients (3.2%) had an allergic reaction. 4 had anaphylaxis, an incidence of 0.2% (1.2/10,000 injections), all in patients over 12 years of age, and 1 patient died, a fatality incidence of 0.05% (0.31/10,000 injections). These rates are similar to those described for patients without rheumatic fever who receive short-term treatment with parenteral penicillin. Rheumatic fever recurred in 8 of 1790 patients (0.45%) who received benzathine penicillin prophylaxis compared with 11 of 96 (11.5%) who did not comply with treatment. Life-threatening allergic reactions are rare in patients on long-term parenteral benzathine penicillin to prevent recurrences of rheumatic fever; the long-term benefits of such prophylaxis by far outweigh the risk of a serious allergic reaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anaphylaxis / chemically induced
  • Anaphylaxis / epidemiology
  • Child
  • Child, Preschool
  • Developing Countries
  • Drug Hypersensitivity / epidemiology*
  • Drug Hypersensitivity / etiology
  • Humans
  • Incidence
  • Injections, Intramuscular
  • Penicillin G Benzathine / administration & dosage
  • Penicillin G Benzathine / adverse effects*
  • Penicillin G Benzathine / therapeutic use
  • Prospective Studies
  • Recurrence
  • Rheumatic Fever / prevention & control*
  • Time Factors


  • Penicillin G Benzathine