Guidelines for Hydroxychloroquine Use in Various Conditions
Hydroxychloroquine should be used for specific FDA-approved indications including rheumatoid arthritis, systemic lupus erythematosus, chronic discoid lupus erythematosus, and malaria (treatment and prophylaxis), but is strongly recommended against for COVID-19 treatment or prevention. 1, 2
FDA-Approved Indications
Rheumatologic Conditions
- Rheumatoid arthritis: 400-600 mg daily initially, followed by 200-400 mg daily maintenance dose 1
- Systemic lupus erythematosus: 200-400 mg daily (single or divided doses) 1
- Chronic discoid lupus erythematosus: 200-400 mg daily (single or divided doses) 1
Malaria
- Prophylaxis:
- Adults: 400 mg once weekly
- Pediatric patients ≥31 kg: 6.5 mg/kg (up to 400 mg) once weekly
- Begin 2 weeks before travel, continue during travel, and for 4 weeks after leaving endemic area 1
- Treatment of uncomplicated malaria: Refer to full prescribing information for dosing 1
COVID-19 Use (Not Recommended)
The WHO and European Respiratory Society have issued a strong recommendation against hydroxychloroquine for:
- COVID-19 treatment (hospitalized or outpatient)
- COVID-19 prophylaxis in individuals without COVID-19 3, 2
This recommendation is based on high-certainty evidence showing:
- No or little effect on mortality and hospitalization
- No or little effect on laboratory-confirmed SARS-CoV-2 infection
- Increased risk of adverse effects leading to drug discontinuation 3
Dosing and Safety Considerations
Optimal Dosing
- Maximum recommended dose: ≤5.0 mg/kg based on actual body weight 3
- Higher doses increase retinopathy risk to ~10% after 10 years of use 3
- For patients with eGFR <30 ml/min per 1.73 m², reduce dose by 25% 3
Monitoring Requirements
Baseline assessment:
Ongoing monitoring:
Risk Factors for Toxicity
Retinal Toxicity
- Daily dose >5 mg/kg actual body weight
- Treatment duration >10 years
- Age >65 years
- Female sex
- Chronic kidney disease
- Concurrent tamoxifen use 3, 2
Other Toxicities
- Cardiac: QT prolongation, conduction abnormalities, cardiomyopathy (especially with chloroquine) 3, 2
- Hematologic: Hemolytic anemia (especially in G6PD deficiency) 3, 2
- Neurologic: Headache, dizziness, confusion, convulsions 3
- Dermatologic: Skin rashes, lichenoid eruptions 3
Contraindications
- Hypersensitivity to 4-aminoquinoline compounds
- Pre-existing retinopathy or visual field changes
- Long-term therapy in children 2, 1
Special Populations
Pregnancy
- Generally considered safe during pregnancy if clinically indicated
- In one study of 133 pregnancies in women treated with hydroxychloroquine, no difference in live birth rates or complications was observed compared to untreated women 3
Patients with Lupus Nephritis
- Hydroxychloroquine is recommended as part of general management in patients with lupus nephritis
- Associated with reduced incidence of flares and organ damage accrual 3
- Blood hydroxychloroquine level above 0.6 mg/l may be associated with lower risk of lupus nephritis flare 3
Common Pitfalls and Caveats
Retinal toxicity can be irreversible - Proper dosing and regular screening are essential to prevent permanent vision loss 3, 4
Drug interactions - Hydroxychloroquine has potentially significant interactions with:
Self-medication risks - Indiscriminate use, especially for COVID-19, has led to shortages, self-treatment, and fatal overdoses 5, 6
Chloroquine substitution - While structurally similar and less expensive, chloroquine carries a higher risk of toxicity, particularly cardiac effects 3
By following these guidelines and monitoring protocols, hydroxychloroquine can be used safely and effectively for its approved indications while minimizing the risk of serious adverse effects.