Fever in Patients Taking Hydroxychloroquine
A patient on hydroxychloroquine who develops fever requires immediate evaluation for infection or disease flare, as hydroxychloroquine does not prevent fever and provides no antipyretic benefit—the fever indicates an underlying condition requiring diagnosis and treatment. 1, 2
Initial Assessment and Key Considerations
Hydroxychloroquine is not an antipyretic agent and does not prevent or treat fever. The medication is FDA-approved only for malaria, systemic lupus erythematosus, and rheumatoid arthritis, with no evidence supporting its use as a fever preventative or general therapeutic agent. 1, 3
Evaluate for the Most Likely Causes
For patients with malaria history:
- Obtain thick and thin blood smears immediately to assess for malaria recurrence or reinfection. 4
- If the smear is positive, continue or adjust antimalarial therapy based on chloroquine sensitivity patterns in the region. 4
- If symptoms persist beyond 48-72 hours despite chloroquine treatment, consider chloroquine-resistant malaria and switch to second-line agents (sulfadoxine-pyrimethamine, mefloquine, or quinine). 4
For patients with rheumatoid arthritis or lupus:
- Assess for disease flare with inflammatory markers (ESR, CRP) and disease-specific activity measures. 5
- Evaluate for secondary bacterial infection, as immunosuppressed patients are at higher risk. 4
- Check liver function tests, as hydroxychloroquine can rarely cause hepatotoxicity with fever and aminotransferase elevations, particularly in patients with acute intermittent porphyria or porphyria cutanea tarda. 4
Critical Safety Monitoring
Check baseline and serial liver function tests in any febrile patient on hydroxychloroquine, as the drug concentrates in the liver and can trigger hypersensitivity reactions manifesting as fever with elevated transaminases. 4
Assess for cardiac complications if fever is accompanied by palpitations or syncope, as hydroxychloroquine causes QT interval prolongation and can lead to ventricular arrhythmias, particularly when combined with other QT-prolonging medications. 4, 6
Treatment Approach
- Administer antipyretics (acetaminophen/paracetamol) for symptomatic fever control and ensure adequate hydration. 4
- Do not discontinue hydroxychloroquine solely due to fever unless hepatotoxicity or hypersensitivity reaction is confirmed. 4, 5
- Initiate empiric antibiotics if bacterial superinfection is suspected based on clinical presentation (productive cough, focal consolidation, elevated procalcitonin). 4
- For malaria-specific treatment: If blood smear confirms parasitemia, administer chloroquine 600 mg base initially, then 300 mg at 6,24, and 48 hours. 4
Common Pitfalls to Avoid
Do not assume hydroxychloroquine provides any fever protection. There is no evidence that long-term hydroxychloroquine use prevents febrile illnesses, and any fever in these patients represents a new pathologic process requiring full evaluation. 1, 2, 7
Do not attribute fever to hydroxychloroquine itself unless accompanied by other signs of drug reaction (rash, eosinophilia, elevated liver enzymes), as fever is not a common adverse effect of the medication. 4
Do not use hydroxychloroquine to treat viral infections like COVID-19, as multiple randomized controlled trials have demonstrated no mortality benefit, no time-to-recovery benefit, and increased risk of adverse cardiac events. 1, 6