What is the list of medications that can induce fever, also known as drug-induced (DI) fever or drug-related hyperthermia?

From the Guidelines

Drug-induced fever can be caused by a wide range of medications, including antipsychotics, anesthetics, antibiotics, anticonvulsants, and biologics, with the most notable ones being haloperidol, halothane, phenytoin, and interferons, as reported in the 2008 guidelines from the American College of Critical Care Medicine and the Infectious Diseases Society of America 1. The list of medications that can induce fever is extensive and includes:

• Antipsychotics: haloperidol, phenothiazines, thioxanthenes, and butyrophenones 1
• Anesthetics: halothane, succinylcholine, and inhalation anesthetics 1
• Antibiotics: although not explicitly listed in the provided evidence, other sources suggest that antibiotics such as beta-lactams, sulfonamides, vancomycin, and minocycline can cause drug-induced fever
• Anticonvulsants: phenytoin, carbamazepine, and phenobarbital
• Biologics: interferons, interleukins, and monoclonal antibodies
• Other medications: allopurinol, heparin, iodinated contrast media, procainamide, quinidine, methyldopa, and NSAIDs It is essential to note that the diagnosis of drug-induced fever is usually established by the temporal relationship between the fever and the start and stop of the medication, and the fever often resolves within 48-72 hours after discontinuing the offending drug 1. The mechanism of drug-induced fever varies by medication but often involves hypersensitivity reactions, altered thermoregulation, or direct cytokine effects. Management primarily involves stopping the suspected medication and providing supportive care while the fever resolves. In some cases, withdrawal of certain drugs, such as alcohol, opiates, barbiturates, and benzodiazepines, can also be associated with fever, often with associated tachycardia, diaphoresis, and hyperreflexia 1.

From the Research

Medications that can Induce Fever

The following medications can cause drug-induced fever:

• Antibiotics, such as vancomycin 2, imipenem/cilastatin 3, penicillins, and cephalosporins 4
• Anticonvulsants 3
• Antineoplastics 3
• Antituberculars 4
• Quinidine 4
• Procainamide 4
• Methyldopa 4
• Phenytoin 4

Mechanisms of Drug-Induced Fever

Drug-induced fever can occur through several mechanisms, including:

• Immunologic reaction mediated by drug-induced antibodies 5, 2
• Interference with heat dissipation peripherally 4
• Increase in the rate of metabolism 4
• Evasion of a cellular or humoral immune response 4
• Mimicry of endogenous pyrogen 4
• Tissue damage 4

Characteristics of Drug-Induced Fever

Drug-induced fever typically:

• Occurs after 7 to 10 days of drug administration 5, 4
• Persists as long as the drug is continued 4
• Disappears soon after stopping the drug 5, 4
• Rapidly reappears if the drug is restarted 5, 2, 3