Can hydroxychloroquine (HCQ) prevent fever in patients?

Hydroxychloroquine's Role in Fever Prevention

Hydroxychloroquine can help reduce fever in patients with COVID-19 from the first day of treatment, but it is not recommended as a routine treatment solely for fever prevention. 1

Mechanism of Action and Fever Reduction

• Hydroxychloroquine (HCQ) is a lysosomotropic and lipophilic drug that penetrates cell membranes and accumulates in acidic lysosomes, increasing their pH from normal levels of 4.7-4.8 to 6.0, which may inhibit viral entry into cells 1
• In a cross-sectional study of COVID-19 patients, HCQ was effective in reducing body temperature from the first to fifth day of treatment with statistical significance (p<0.001) compared to control subjects 1
• HCQ's anti-inflammatory properties may contribute to its antipyretic effects by suppressing certain cytokine pathways, similar to what has been observed in rheumatic conditions 2

Clinical Applications for Fever Reduction

• For COVID-19 patients, HCQ showed effectiveness in reducing fever but demonstrated no significant effect on other symptoms like cough or shortness of breath 1
• In rheumatic fever, HCQ has been used to control inflammatory markers and has shown benefit in controlling pericarditis and stabilizing progressive carditis, conditions that often present with fever 2
• For Q fever, HCQ is used in combination with doxycycline primarily for treating chronic infections, not specifically for fever management 3

Treatment Recommendations and Dosing

• For COVID-19, when used for symptomatic treatment, the studied dosage was a loading dose of 400 mg twice daily followed by a maintenance dose of 200 mg twice daily for 4 days 1
• For chronic Q fever, the recommended regimen is doxycycline 100 mg twice daily with hydroxychloroquine 200 mg three times daily for extended periods (18-24 months depending on the site of infection) 3
• The combination of doxycycline and hydroxychloroquine works synergistically - hydroxychloroquine raises the pH in acidified phagosomal compartments, enhancing doxycycline's bactericidal activity 4

Important Cautions and Monitoring

• HCQ has potential cardiac side effects including QT prolongation that could lead to malignant arrhythmias and sudden cardiac death, especially with widespread use 5
• Long-term use requires monitoring for retinal toxicity with baseline ophthalmic examination and follow-up every 6 months 3
• HCQ is contraindicated in persons with glucose-6-phosphate dehydrogenase deficiency and those with retinal or visual field deficits 3
• When used for chronic Q fever, therapeutic drug monitoring is recommended to maintain serum doxycycline concentrations >5 μg/mL and hydroxychloroquine levels at 0.8-1.2 μg/mL 6, 3

Evidence Limitations

• Most evidence for HCQ's fever-reducing effects comes from small studies with methodological limitations 1
• For chronic infections like Q fever, the evidence supporting HCQ use is primarily from retrospective cohorts and in vitro studies 4
• There is insufficient evidence to recommend HCQ solely as an antipyretic agent in the absence of specific indications like COVID-19, Q fever, or rheumatic conditions 3, 4

While hydroxychloroquine has demonstrated some fever-reducing properties, particularly in COVID-19 patients, it should not be used routinely just for fever management due to its potential serious side effects and the availability of safer antipyretic alternatives.