What are the indications and dosages for hydroxychloroquine (HCQ) in various medical conditions?

Hydroxychloroquine: Indications and Dosing

FDA-Approved Indications

Hydroxychloroquine is FDA-approved for malaria (treatment and prophylaxis in non-resistant areas), rheumatoid arthritis, systemic lupus erythematosus, and chronic discoid lupus erythematosus in adults. 1

Malaria

• Prophylaxis (adults): 400 mg once weekly, starting 2 weeks before travel, continuing during exposure, and for 4 weeks after leaving endemic area 1
• Prophylaxis (pediatric ≥31 kg): 6.5 mg/kg (up to 400 mg) once weekly, same schedule as adults 1
• Treatment of uncomplicated malaria (adults): 800 mg initially, then 400 mg at 6,24, and 48 hours (total 2,000 mg) 1
• Treatment (pediatric ≥31 kg): 13 mg/kg initially (up to 800 mg), then 6.5 mg/kg at 6,24, and 48 hours (total 31 mg/kg, up to 2,000 mg) 1
• Not recommended for chloroquine-resistant strains, complicated malaria, or in pediatric patients <31 kg 1

Rheumatoid Arthritis (Adults)

• Initial dosage: 400-600 mg daily (single dose or divided twice daily) 1
• Chronic maintenance: 200-400 mg daily (single dose or divided twice daily) 1
• Critical safety threshold: Daily doses exceeding 5 mg/kg actual body weight increase retinopathy incidence 1
• Therapeutic effect is cumulative and may require weeks to months 1

Systemic Lupus Erythematosus (Adults)

• Recommended dosage: 200 mg once daily OR 400 mg once daily (or divided twice daily) 1
• EULAR guideline recommendation: Hydroxychloroquine is recommended for ALL patients with SLE at a dose not exceeding 5 mg/kg real body weight 2
• Long-term use: Should be continued indefinitely (lifelong) due to beneficial effects on reducing renal flares, limiting organ damage, and improving outcomes 3
• Renal benefits: Associated with higher rates of renal response, fewer renal flares, and reduced accrual of renal damage 2, 3

Chronic Discoid Lupus Erythematosus (Adults)

• Recommended dosage: 200 mg once daily OR 400 mg once daily (or divided twice daily) 1

Administration Guidelines

• Take with food or milk to minimize gastrointestinal side effects 1
• Do not crush or divide tablets 1

Critical Safety Monitoring

Retinal Toxicity Screening

The most important safety concern is irreversible retinal toxicity, which is dose and duration-dependent. 2

• Baseline ophthalmologic examination required before starting therapy 2, 4
• Annual screening begins after 5 years of continuous therapy for low-risk patients 2, 4, 5
• Earlier screening required for high-risk patients (chronic kidney disease, pre-existing retinal disease, cumulative dose >1000g, duration >5-7 years) 2, 5
• Risk of retinopathy: <2% with ≤5 mg/kg dosing up to 10 years, increases to ~10% after 10 years, exceeds 10% after 20 years 2
• Screening modalities: 10-2 automated visual fields PLUS at least one objective test (multifocal ERG, spectral domain OCT, or fundus autofluorescence) 5

Cardiac Monitoring

• Fatal cardiomyopathy and ventricular arrhythmias have been reported 1
• Avoid in patients with: Congenital/acquired QT prolongation, cardiac disease, bradycardia <50 bpm, uncorrected electrolyte abnormalities 1
• Monitor cardiac function as clinically indicated during therapy 1
• Correct electrolyte imbalances before initiating treatment 1

Renal Dosing Adjustments

• Reduce dose by 25% in patients with eGFR <30 mL/min/1.73 m² 4
• Hydroxychloroquine dose of 6.5 mg/kg/day (or 400 mg/day, whichever is lower) is generally safe with normal baseline examination 2

Pre-treatment Screening

• Check G6PD levels in men of African, Asian, or Middle Eastern origin before starting treatment 4
• Baseline measurements: Body weight, blood pressure, serum creatinine, estimated GFR, serum albumin, complete blood count 2, 3

COVID-19 Use (Not Recommended)

Current evidence does NOT support routine use of hydroxychloroquine for COVID-19 treatment or prophylaxis. 4

• Multiple early pandemic guidelines (2020) suggested various HCQ regimens for COVID-19, but these were based on in-vitro data and expert consensus during conditions of uncertainty 2
• Subsequent evidence: Randomized controlled trials showed no benefit for mortality, mechanical ventilation need, or ICU admission 6, 7, 8
• One RCT found no reduction in viral load or symptom duration in mild COVID-19 8
• Safety concerns included QTc prolongation and potential increased mortality with higher doses 2, 7

Important Contraindications and Warnings

• Absolute contraindication: Known hypersensitivity to 4-aminoquinoline compounds 1
• Avoid in: Psoriasis (may worsen), porphyria (hepatotoxicity risk), patients on QT-prolonging drugs 1
• Never discontinue abruptly in SLE patients as this may trigger disease flares 3
• Most common adverse effects: Nausea, vomiting, diarrhea, abdominal pain 1