What are the uses and dosages of hydroxychloroquine (HCQ) for various medical conditions?

Hydroxychloroquine Uses and Dosages

Hydroxychloroquine (HCQ) is primarily indicated for malaria treatment and prevention, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and chronic discoid lupus erythematosus, with specific dosing regimens for each condition based on actual body weight to minimize retinal toxicity risk.

FDA-Approved Indications

• Malaria: Both treatment of uncomplicated malaria (due to P. falciparum, P. malariae, P. vivax, and P. ovale) and prophylaxis in geographic areas where chloroquine resistance is not reported 1
• Rheumatoid Arthritis: Treatment of both acute and chronic rheumatoid arthritis in adults 1
• Systemic Lupus Erythematosus (SLE): Treatment of SLE in adults 1
• Chronic Discoid Lupus Erythematosus: Treatment in adults 1

Dosing Recommendations

For Malaria

• Prophylaxis:

  • Adults: 400 mg once weekly 1
  • Pediatric patients ≥31 kg: 6.5 mg/kg actual body weight (up to 400 mg) once weekly 1
  • Start 2 weeks before travel to endemic area, continue during stay and for 4 weeks after leaving 1

• Treatment of Uncomplicated Malaria:

  • Adults: 800 mg initially, followed by 400 mg at 6 hours, 24 hours, and 48 hours (total 2,000 mg) 1
  • Pediatric patients ≥31 kg: 13 mg/kg (up to 800 mg) initially, followed by 6.5 mg/kg (up to 400 mg) at 6,24, and 48 hours 1

For Rheumatoid Arthritis

• Initial dosage: 400-600 mg daily as a single dose or divided into two doses 1
• Maintenance dosage: 200-400 mg daily as a single dose or divided into two doses 1
• Maximum recommended dose: 5 mg/kg/day based on actual body weight to minimize retinopathy risk 1, 2

For Systemic Lupus Erythematosus

• 200 mg once daily, or 400 mg once daily or in two divided doses 1
• Recommended for all patients with SLE due to multiple beneficial effects 2

For Chronic Discoid Lupus Erythematosus

• 200 mg once daily, or 400 mg once daily or in two divided doses 1

For Dermatomyositis (Off-label)

• Primarily used for cutaneous manifestations at 200 mg twice daily (5 mg/kg) 2

Administration Guidelines

• Administer orally with food or milk 1
• Do not crush or divide tablets 1
• The action is cumulative and may require weeks to months for maximum therapeutic effect 1

Monitoring and Safety Considerations

Retinal Toxicity

• Daily doses exceeding 5 mg/kg (actual weight) increase the risk of retinopathy 2, 1

• Risk factors for retinopathy include:

  • High daily dosage relative to body weight 2
  • Cumulative dose and duration of treatment (>5 years) 2
  • Reduced renal function 2
  • Concomitant tamoxifen use 2
  • Pre-existing retinal or macular disease 2

• Ophthalmologic monitoring:

  • Baseline examination recommended 2
  • Annual screening beginning after 5 years of therapy for low-risk patients 2
  • Earlier and more frequent screening for high-risk patients 2

Cardiac Effects

• Risk of cardiomyopathy and ventricular arrhythmias including QT prolongation 1
• Avoid in patients with congenital or acquired QT prolongation 1
• Monitor cardiac function as clinically indicated 1

Other Considerations

• Check G6PD levels in men of African, Asian, or Middle Eastern origin before starting treatment 2
• Reduce dose by 25% in patients with eGFR <30 ml/min per 1.73 m² 2

COVID-19 Considerations (Historical Context)

• HCQ was investigated for COVID-19 treatment in 2020 based on in-vitro activity against SARS-CoV-2 2
• Various dosing regimens were proposed in early guidelines:
  • 600 mg loading dose, 300 mg 12 hours later, followed by 300 mg twice daily on days 2-5 2
  • Used alone or in combination with other agents 2
• Current evidence does not support routine use for COVID-19 treatment 2

Mechanism of Action

• In rheumatic diseases: Increases pH within intracellular vacuoles, interfering with antigen processing in macrophages and other antigen-presenting cells 3
• Immunomodulatory rather than immunosuppressive effects 2
• Inhibits toll-like receptors and reduces production of cytokines 4

Common Pitfalls to Avoid

• Exceeding recommended dosage: Never exceed 5 mg/kg/day based on actual body weight to minimize retinal toxicity 2, 1
• Inadequate monitoring: Regular ophthalmologic screening is essential for long-term use 2
• Ignoring drug interactions: Be cautious with medications that prolong QT interval 1
• Discontinuing abruptly: In SLE patients, discontinuation can lead to disease flares 2
• Inadequate patient education: Patients should be informed about potential side effects and the importance of regular monitoring 2