Drug-Induced Fever

Mechanisms and Clinical Manifestations

Simple drug-induced hypersensitivity fever can occur with tetrabenazine, typically developing after several days of drug administration 1
The lag time between initiating a drug and fever development averages 21 days (median 8 days) 2, 3
Fever typically resolves within 1-3 days after drug discontinuation but may take up to 7 days 2, 3
Trihexyphenidyl can cause anticholinergic syndrome with hyperthermia as a feature 4
Anticholinergic syndrome presents with hyperthermia, hot/dry/erythematous skin, mydriasis, dry mucous membranes, and hypoactive bowel sounds 4
Patients may develop tachycardia, mild hypertension, agitated delirium, and tachypnea 4

Drug-induced fever is a diagnosis of exclusion after ruling out infectious causes 2, 5
The diagnosis is usually established by temporal relationship between starting the drug and onset of fever 2
Fever persists as long as the drug is continued and typically resolves within 1-3 days after discontinuation 2, 1
Physostigmine may be considered for severe anticholinergic toxicity 4
Patients should be cautioned about increased susceptibility to heat stroke while taking trihexyphenidyl 4

Evaluate temporal relationship between drug initiation and fever onset 2
Look for other symptoms of NMS (muscle rigidity, altered mental status) or anticholinergic syndrome (dry skin/mucous membranes, mydriasis) 4
Consider discontinuation of the suspected medication if clinically appropriate 2, 3
Monitor for resolution of fever after drug discontinuation 2
Avoid rechallenging patients who experienced severe reactions 2