What is the recommended dosing for hydroxychloroquine (HCQ) in patients with conditions like rheumatoid arthritis or lupus, and how does it differ for malaria treatment and patients with impaired renal function?

Hydroxychloroquine Dosing

For rheumatoid arthritis and lupus, hydroxychloroquine should be dosed at ≤5 mg/kg actual body weight per day (typically 200-400 mg daily) to minimize retinal toxicity risk, with dose reduction of 25% required when eGFR <30 ml/min per 1.73 m². 1

Standard Dosing for Rheumatic Diseases

Systemic Lupus Erythematosus (SLE)

• Starting dose: 200 mg once daily or 400 mg once daily (or in two divided doses) 1, 2
• Maximum safe dose: ≤5 mg/kg actual body weight per day to keep retinopathy risk below 2% over 10 years 1
• Optimal maintenance: 200 mg/day (approximately 3.0-3.5 mg/kg/day) achieves prolonged remission in 72% of patients while maintaining safety 3
• Hydroxychloroquine is recommended for all patients with SLE due to multiple beneficial effects including reduced flares, organ damage prevention, and improved survival 1

Rheumatoid Arthritis

• Initial dose: 400-600 mg daily as single or divided doses 2
• Chronic maintenance: 200-400 mg daily as single or divided doses 2
• The action is cumulative and may require weeks to months for maximum therapeutic effect 2
• Daily doses exceeding 5 mg/kg actual body weight increase retinopathy incidence 2

Chronic Discoid Lupus Erythematosus

• Dose: 200 mg once daily or 400 mg once daily (or in two divided doses) 2

Dosing in Renal Impairment

Critical adjustment required for kidney disease:

• eGFR <30 ml/min per 1.73 m²: Reduce dose by 25% 1
• Reduced renal function is the greatest additional risk factor for retinopathy because the drug is excreted in urine, increasing systemic HCQ levels 1
• Patients with renal insufficiency need lower doses and closer monitoring 1
• eGFR <60 ml/min per 1.73 m² is a risk factor requiring earlier ophthalmologic screening (after 1 year instead of 5 years) 1

Malaria Dosing (Distinct from Rheumatic Disease)

Malaria Prophylaxis

• Adults: 400 mg once weekly 2
• Pediatric patients ≥31 kg: 6.5 mg/kg actual body weight (up to 400 mg) once weekly 2
• Start 2 weeks before travel, continue weekly during exposure, and for 4 weeks after leaving endemic area 2

Treatment of Uncomplicated Malaria

• Adults: 800 mg initially, then 400 mg at 6,24, and 48 hours (total 2,000 mg) 2
• Pediatric patients ≥31 kg: 13 mg/kg initially, then 6.5 mg/kg at 6,24, and 48 hours (total 31 mg/kg, up to 2,000 mg) 2

Critical Safety Considerations

Retinal Toxicity Risk Factors

The primary risk factors for retinopathy are:

• Daily dose >5 mg/kg actual body weight 1
• Duration of treatment (risk increases to 7.5% after long-term use, >20% after 20 years) 1
• Chronic kidney disease (eGFR <60 ml/min per 1.73 m²) 1
• Concomitant tamoxifen use 1
• Pre-existing retinal or macular disease 1

Ophthalmologic Screening Schedule

• Baseline examination within first few months of therapy 1
• Annual screening beginning after 5 years for low-risk patients 1
• Annual screening beginning after 1 year for high-risk patients (eGFR <60 ml/min per 1.73 m², dose >5 mg/kg/day, concomitant tamoxifen, or chloroquine use) 1
• East Asian patients require screening beyond central macula due to different retinopathy phenotype (pericentral vascular arcade involvement) 1

Pre-Treatment Screening

• G6PD testing preferred in men of African, Asian, or Middle Eastern origin before starting therapy due to hemolysis risk 1
• Baseline ECG recommended due to QT prolongation risk 4

Administration Instructions

• Take with food or milk to reduce gastrointestinal side effects 2
• Do not crush or divide tablets 2

Common Pitfalls to Avoid

Dosing based on ideal rather than actual body weight: The evidence clearly demonstrates that actual body weight should be used for dose calculation, as retinopathy risks were statistically similar across BMI groups (15-35 kg/m²) when actual body weight was used 1

Using doses of 2-3 mg/kg/day: Lower doses may not achieve adequate blood levels and are associated with higher flare rates in lupus nephritis 1

Failing to adjust for renal impairment: This is the greatest modifiable risk factor for toxicity and must not be overlooked 1

Inadequate monitoring in East Asian patients: Standard central macular screening may miss early pericentral toxicity in this population 1

Stopping HCQ for borderline ophthalmologic findings: The goal is to safely maintain this valuable medication as long as possible, not to discontinue it casually 1