title: Evaluation of the potential cardiotoxicity of the antihistamines terfenadine, astemizole, loratadine, and cetirizine in atopic children.
abstract: BACKGROUND
  Adverse cardiac effects have been related to the use of H1-receptor antagonists terfenadine and astemizole.
  
  
  OBJECTIVE
  We have investigated the cardiac effects of the H1-receptor antagonists terfenadine, astemizole, loratadine and cetirizine, used in recommended doses, concomitantly or not with the antibiotic erythromycin.
  
  
  METHODS
  A group of 80 children aged 5 to 12 years was studied. All children had been diagnosed with perennial allergic rhinitis based on symptoms, clinical signs and a positive immediate skin test to Dermatophagoides pteronyssinus. The children had no personal history of cardiac disease or hepatic dysfunction, and they had a normal electrocardiogram (ECG) at the beginning of the study. Forty children had allergic rhinitis and sinusitis, and were assigned to subgroups of ten children who received terfenadine, astemizole, loratadine, or cetirizine, concomitantly with erythromycin, for 14 days. Erythromycin was started to treat presumed bacterial infection in children with complete radiologic opacification of the maxillary sinus(es). The remaining 40 children had no sinusitis, and were assigned to subgroups of 10 children who received terfenadine, astemizole, loratadine, or cetirizine for 14 days.
  
  
  RESULTS
  No significant changes in the QT interval and QTc (QT corrected by Bazzett's equation) were observed among children who received astemizole, loratadine or cetirizine, with or without erythromycin. Children who have received terfenadine and erythromycin showed significantly prolonged QT interval (mean pretreatment and posttreatment values 0.32s and 0.34s, respectively). Analysis of the QTc interval, however, showed no significant differences in the group treated with terfenadine and erythromycin (mean values 0.39s and 0.39s, respectively).
  
  
  CONCLUSIONS
  Our results show that H1-receptor antagonists terfenadine, astemizole, loratadine and cetirizine, administered with or without erythromycin, to atopic children in recommended doses, do not induce adverse cardiac effects. Although the association between terfenadine and erythromycin has caused a statistically significant increase in QT interval measurements, the magnitude of these changes was below levels considered cardiotoxic or clinically relevant.
authors.affiliation: Department of Pediatrics, Paulista School of Medicine, Federal University of São Paulo, SP, Brazil.
authors.forename: L F
authors.initials: LF
authors.lastname: Delgado
authors.forename: A
authors.initials: A
authors.lastname: Pferferman
authors.forename: D
authors.initials: D
authors.lastname: Solé
authors.forename: C K
authors.initials: CK
authors.lastname: Naspitz
mesh_terms: D018926:Anti-Allergic Agents / Q000009:adverse effects*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016589:Astemizole / Q000009:adverse effects*; D017332:Cetirizine / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D004347:Drug Interactions; D004562:Electrocardiography / Q000187:drug effects; D004917:Erythromycin / Q000627:therapeutic use*; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006634:Histamine H1 Antagonists / Q000009:adverse effects*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000209:etiology / Q000503:physiopathology*; D017336:Loratadine / Q000009:adverse effects*; D008297:Male; D016593:Terfenadine / Q000009:adverse effects*
chemical_list: D018926:Anti-Allergic Agents; D000900:Anti-Bacterial Agents; D006634:Histamine H1 Antagonists; D004917:Erythromycin; D017336:Loratadine; D016593:Terfenadine; D016589:Astemizole; D017332:Cetirizine