DRUG FEVER

Ruchi A. Patel, Pharm.D.; Jason C. Gallagher, Pharm.D.

Authors and Disclosures

Posted: 01/26/2010; Pharmacotherapy. 2010;30(1):57-69. © 2010 Pharmacotherapy Publications

Abstract

Drug fever is a common condition that is frequently misdiagnosed. It is a febrile response that coincides temporally with the administration of a drug and disappears after discontinuation of the offending agent. Drug fever is usually suspected when no other cause for the fever can be elucidated, sometimes after antimicrobial therapy has already been started. In nonsensitized individuals receiving a drug for the first time, the onset of fever is highly variable and differs among drug classes, but most commonly appears after 7–10 days of drug administration and rapidly reverses after discontinuation of the drug. Early diagnosis may reduce inappropriate and potentially harmful and expensive diagnostic and therapeutic interventions. Rechallenge with the offending agent will usually cause recurrence of fever within a few hours, confirming the diagnosis. Rechallenge is controversial and should be performed with extreme caution, since there is a potential for a more severe drug reaction. We describe the mechanisms in the pathophysiology of drug fever and summarize the results of published case reports on the wide variety of agents that are implicated in causing drug fever. Special attention is paid to the role of antimicrobial agents in drug fever.

Introduction

Drug fever is a common condition that manifests with an often unclear diagnosis.^{[1, 2]} It is important for clinicians to suspect drugs as a cause of fevers of unknown origin.^[1] Since a common response among clinicians to a patient's fever is to suspect infection, drug fever can lead to overutilization of antiinfectives and other agents to treat infections that are not present, possibly increasing the risk of adverse effects and the further development of antimicrobial resistance.^[1] Fever that is due to a drug is also significant in that it may precede or accompany more serious adverse drug reactions.^{[3, 4]} Drug fever is particularly problematic when it occurs during the course of an infection, since it can mislead clinicians into believing that a successful course of therapy is failing.

To gain a better understanding of the diagnosis, mechanisms, and management of drug fever so that we could increase awareness among clinicians, we conducted a literature search using the MEDLINE database (1950–2009). Search terms were drug fever, hypersensitivity reactions, drug-induced fever, and drug reactions. References in review articles were also evaluated.

• Abstract and Introduction
• Characterization of Drug Fever
• Mechanisms of Drug Fever
• Drug Fever from Antimicrobial Agents
• Treatment
• Rechallenge
• Conclusion

• References