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Drug Fever

Author

Listed:
  • Dominique Vodovar

    (Ambroise Paré Hospital
    Lariboisière Hospital
    Paris-Diderot University)

  • Christine LeBeller

    (European Georges Pompidou Hospital)

  • Bruno Mégarbane

    (Lariboisière Hospital
    Paris-Diderot University)

  • Agnes Lillo-Le-Louet

    (European Georges Pompidou Hospital)

  • Thomas Hanslik

    (Ambroise Paré Hospital
    Versailles-Saint Quentin University)

Abstract

Background: Although known as a rare adverse drug reaction (ADR), drug fever (DF) remains an important issue in medicine, with the risk of leading to inappropriate and potentially harmful diagnostic and therapeutic interventions. Only sparse data regarding DF have been published. Objective: The aim of the study was to investigate which drugs were associated with DF, and report outcomes. Methods: Cases of DF without skin reactions were selected from all ADRs reported from 1986 to 2007 in the French National Pharmacovigilance Database. Drugs potentially responsible for DF were assessed using a qualitative case-by-case analysis (Naranjo’s criteria) and quantitative measurement (proportional reporting ratio [PRR]). A drug was implicated as the cause of DF when the following criteria were validated: three or more cases and PRR of at least two with a Chi-squared value of at least four. Results: A total of 167 DF cases involving 115 drugs were eligible. Based on the PRR, 22 drugs were significantly associated with DF. Antibacterials represented the most frequently reported drugs, including amikacin (PRR 39.6 [95% CI 23.6, 69.0], oxacillin (9.1 [3.6, 23.4]), cefotaxime (5.5 [2.0, 15.3]), ceftriaxone (5.4 [2.6, 11.3]), rifampicin (4.0 [1.8, 9.2]), vancomycin (4.0 [1.4, 11.5]), ciprofloxacin (3.1 [1.2, 8.0]), isoniazid (3.9 [1.4, 11.4]), pristinamycin (3.1 [1.0, 9.1]) and cotrimoxazole (2.6 [1.2, 5.8]). Median time [interquartile range] from drug administration to fever onset was 2 days [1.0–10.5]. A diagnosis of DF was made following cessation of the suspected drugs (3 days [1.0–11.5] after fever onset. Drug rechallenge was performed (38.0%), resulting in recurrence of DF in all cases. DF resulted in life-threatening events (0.6%), hospitalization or prolonged hospital stay (24.5%) and persistent disability (0.6%). Final outcome was favourable in 96.9% of cases after drug discontinuation. Conclusion: Diagnosing DF is challenging. Based on this large series, antibacterials remain the major class of drugs responsible for DF.

Suggested Citation

  • Dominique Vodovar & Christine LeBeller & Bruno Mégarbane & Agnes Lillo-Le-Louet & Thomas Hanslik, 2012. "Drug Fever," Drug Safety, Springer, vol. 35(9), pages 759-767, September.
    • Handle: RePEc:spr:drugsa:v:35:y:2012:i:9:d:10.1007_bf03261972
    DOI: 10.1007/BF03261972
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