Hydroxychloroquine: Recommended Uses and Limitations
Hydroxychloroquine is NOT recommended for COVID-19 treatment or prevention, but is indicated for malaria, rheumatoid arthritis, systemic lupus erythematosus, and chronic discoid lupus erythematosus. 1, 2
FDA-Approved Indications
Hydroxychloroquine is officially indicated for:
Malaria:
- Treatment of uncomplicated malaria due to P. falciparum, P. malariae, P. vivax, and P. ovale
- Prophylaxis in geographic areas where chloroquine resistance is not reported
- Not recommended for complicated malaria or chloroquine-resistant strains 2
Autoimmune Conditions:
- Acute and chronic rheumatoid arthritis in adults
- Systemic lupus erythematosus in adults
- Chronic discoid lupus erythematosus in adults 2
COVID-19 Use: Strong Recommendation Against
Multiple high-quality guidelines explicitly recommend against hydroxychloroquine use for COVID-19:
- The European Respiratory Society (2021) recommends NOT to offer hydroxychloroquine to patients with COVID-19, including both hospitalized patients and outpatients 1
- The WHO (2021) issued a strong recommendation against hydroxychloroquine as prophylaxis in individuals who do not have COVID-19 1
This recommendation is based on:
- Large randomized controlled trials (UK RECOVERY and WHO SOLIDARITY) showing no survival benefit 1
- Pooled mortality data showing OR 1.08 (95% CI 0.97-1.19), effectively excluding meaningful benefit 1
- No significant positive trends in clinical outcomes including time to improvement, clinical resolution, hospitalization, ICU admission, or ventilation 1
- Increased risk of adverse events (OR 4.23,95% CI 3.30-5.42) 1
Dosing for Approved Indications
Rheumatoid Arthritis:
- Initial: 400-600 mg daily (single or divided doses)
- Maintenance: 200-400 mg daily
- Do not exceed 5 mg/kg/day based on actual body weight to minimize retinopathy risk 2
Lupus Erythematosus:
- Similar dosing to rheumatoid arthritis, adjusted based on response 2
Malaria:
- Prophylaxis: 400 mg once weekly for adults (starting 2 weeks before travel)
- Treatment: 800 mg initially, followed by 400 mg at 6,24, and 48 hours (total 2,000 mg) 2
Safety Considerations
Major Side Effects:
Retinopathy: Most significant dose-limiting toxicity with long-term use
- Risk factors: daily dose >5 mg/kg, duration >10 years, age >65 years, female sex, chronic kidney disease, concurrent tamoxifen use
- Regular ophthalmologic screening every 6-12 months recommended 3
Cardiac: QT interval prolongation and conduction abnormalities
- Increased risk when combined with other QT-prolonging medications like azithromycin 3
Common side effects: Gastrointestinal symptoms (nausea, vomiting, diarrhea), headache, dizziness, skin rashes 3
Hematologic: Risk of hemolytic anemia in G6PD deficiency patients 3
Monitoring Recommendations
Baseline: Complete ophthalmologic exam, ECG, liver function tests, complete blood count, G6PD screening in high-risk populations, renal function tests 3
During treatment: Regular monitoring of liver function, complete blood count, renal function, and ophthalmologic examination every 6-12 months 3
Key Contraindications
- Retinal or visual field changes
- Hypersensitivity to 4-aminoquinoline compounds
- Long-term therapy in children
- Caution in patients with G6PD deficiency, hepatic disease, alcoholism, or taking hepatotoxic drugs 3, 2
Despite early interest in hydroxychloroquine for COVID-19 due to its in vitro antiviral activity against SARS-CoV-2 4, 5, multiple large clinical trials have conclusively demonstrated no benefit while showing increased adverse effects, leading to strong recommendations against its use for this indication.