From the Guidelines
Drug-induced fever is primarily caused by hypersensitivity reactions, altered thermoregulation, or direct drug toxicity, and can be triggered by various medications, including antibiotics, anticonvulsants, antipsychotics, and biologics. The exact mechanism of drug-induced fever is complex and not fully understood, but it is believed to involve an immune-mediated response, with the release of cytokines and other inflammatory mediators playing a key role 1. The diagnosis of drug-induced fever is typically established by a temporal relationship between the fever and the administration of the suspected medication, and management involves discontinuing the offending agent and providing supportive care.
Some common culprits of drug-induced fever include:
- Antibiotics, such as beta-lactams and sulfonamides
- Anticonvulsants, such as phenytoin and carbamazepine
- Antipsychotics, such as haloperidol
- Biologics, such as monoclonal antibodies
The fever pattern in drug-induced fever is often continuous, rather than intermittent, and may be accompanied by other symptoms such as rash, eosinophilia, or other hypersensitivity reactions 1. It is essential to maintain a high index of suspicion for drug-induced fever, especially when other causes of fever have been ruled out or when fever persists despite appropriate treatment for presumed infections.
In terms of specific medications, penicillin is a common cause of drug-induced anaphylaxis, which can also present with fever 1. Other medications, such as aspirin and nonsteroidal anti-inflammatory drugs, can also cause anaphylactic reactions, which may be accompanied by fever 1. However, the relationship between these medications and drug-induced fever is not fully understood and requires further study.
Overall, the key to managing drug-induced fever is to discontinue the suspected medication and provide supportive care, with antipyretics and other symptomatic treatments used as needed. By maintaining a high index of suspicion for drug-induced fever and taking a thorough medication history, healthcare providers can help to identify and manage this potentially life-threatening condition.
From the FDA Drug Label
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as ibuprofen tablets. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling
The cause of drug-induced fever (DIF) may be related to Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), which can present with fever, among other symptoms, as seen in patients taking NSAIDs like ibuprofen tablets 2.
From the Research
Causes of Drug-Induced Fever
The causes of drug-induced fever (DIF) can be attributed to various mechanisms, including:
- Immunologic reactions mediated by drug-induced antibodies 3
- Pharmacologic action of the drug 3, 4
- Effects on thermoregulation 3, 5
- Local complications following parenteral administration 3
- Idiosyncratic responses 3
- Hypersensitivity reactions 6, 4
- Damage to tissues 4
- Increase in the rate of metabolism 4
- Interference with heat dissipation peripherally 4
Commonly Implicated Drugs
Certain drugs are more commonly associated with DIF, including:
- Antibiotics, such as penicillins and cephalosporins 7, 6, 4
- Antituberculars 4
- Quinidine 4
- Procainamide 4
- Methyldopa 4
- Phenytoin 4
Characteristics of Drug-Induced Fever
DIF typically:
- Occurs after 7-10 days of drug administration 3, 6, 4
- Resolves within 48 hours of discontinuing the offending drug 3
- Recurs within a few hours of rechallenge with the offending agent 3, 6
- May be accompanied by general symptoms mimicking sepsis 7
- Can be complicated by rhabdomyolysis, multi-organ failure, and disseminated intravascular coagulation 5