What is the proper use and dosage of Hydroxychloroquine (HCQ) for medical conditions?

Hydroxychloroquine: Proper Use and Dosage

For rheumatic diseases, hydroxychloroquine should be dosed at ≤5.0 mg/kg based on actual body weight to minimize retinal toxicity while maintaining therapeutic efficacy. 1

Approved Indications and Standard Dosing

Rheumatoid Arthritis

• Initial dose: 400-600 mg daily (single or divided doses) 2
• Maintenance dose: 200-400 mg daily (single or divided doses) 2
• Maximum safe dose: ≤5.0 mg/kg actual body weight daily to keep retinopathy risk below 2% over 10 years 1
• Lower doses (200 mg daily) show equivalent efficacy to 400 mg daily but with three times fewer side effects 3

Systemic Lupus Erythematosus (SLE)

• Recommended dose: 200 mg once daily OR 400 mg once daily or in two divided doses 2
• Critical importance: All SLE patients should receive hydroxychloroquine due to reduced mortality, decreased organ damage, and lower flare rates 1
• Therapeutic blood level target: >0.6 mg/L associated with lower lupus nephritis flare risk 1

Chronic Discoid Lupus Erythematosus

• Recommended dose: 200 mg once daily OR 400 mg once daily or in two divided doses 2

Malaria Prophylaxis (≥31 kg patients)

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

Critical Dosing Adjustments

Renal Impairment

• eGFR <30 mL/min/1.73 m²: Reduce dose by 25% 1
• Renal insufficiency is the greatest additional risk factor for toxicity due to reduced drug excretion 1

Body Weight Considerations

• Short stature patients: Calculate dose based on ideal body weight to avoid overdosage 4
• Dosing based on actual body weight shows similar retinopathy risk across BMI 15-35 kg/m² 1

Administration Guidelines

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

Mandatory Monitoring Protocol

Pre-Treatment Screening

• G6PD testing: Required for men of African, Asian, or Middle Eastern origin before initiating therapy to prevent hemolysis 1
• Baseline ophthalmologic examination: Document retinal status before starting treatment 1, 4

Ongoing Ophthalmologic Surveillance

• Low-risk patients: Annual screening beginning after 5 years of therapy 1, 5, 4
• High-risk patients (start screening after 1 year): 1
  • Concomitant tamoxifen use
  • eGFR <60 mL/min/1.73 m²
  • Dose >5 mg/kg/day
  • Concomitant chloroquine use

Screening Methodology

• Preferred tests: Optical coherence tomography (OCT) plus automated 10-2 visual fields 1, 4
• OCT detects anatomic changes earlier and more specifically than visual fields 1
• Multifocal electroretinography (mfERG) or fundus autofluorescence may substitute for visual fields 4
• Amsler grid testing is no longer recommended 4

Retinopathy Risk Stratification

Risk by Duration and Dose

• ≤5.0 mg/kg/day for ≤10 years: <2% retinopathy risk 1
• Higher doses after 10 years: ~10% retinopathy risk 1
• After 20+ years: Risk can exceed 20% 1
• Annual risk with normal screening: <5% even after 20 years of use 1

Primary Risk Factors

• High daily dose relative to body weight 1
• Cumulative dose exposure 1
• Reduced renal function (increases systemic drug levels) 1
• Concomitant tamoxifen use 1

Management of Borderline Findings

Do not discontinue hydroxychloroquine for uncertain or borderline retinal findings. 1

• Retinopathy develops slowly over several years, allowing time for confirmation 1
• Recheck suspicious findings after a few months or obtain retina consultation with advanced testing (mfERG, fundus autofluorescence) 1
• Decision to discontinue requires shared decision-making between patient, prescribing physician, and ophthalmologist, weighing disease severity against visual loss risk 1

Critical Safety Warnings

Cardiac Toxicity

• Contraindications: Congenital/acquired QT prolongation, cardiac disease, bradycardia <50 bpm, uncorrected electrolyte abnormalities 2
• Fatal cardiomyopathy and ventricular arrhythmias (including torsades de pointes) reported with both acute and chronic use 2, 6
• Avoid concomitant QT-prolonging drugs (particularly azithromycin, which showed concerning QT prolongation in COVID-19 studies) 2, 6
• Monitor cardiac function clinically; correct electrolytes before initiating therapy 2

Gastrointestinal Effects

• Most common adverse effects: nausea, vomiting, diarrhea 6
• Usually resolve with dose reduction or discontinuation 6

Overdose Manifestations

• Symptoms manifest rapidly (minutes to hours) 6
• Cardiovascular shock and collapse are most prominent 6
• Neurotoxic effects include psychosis and seizures 6
• Deaths result primarily from cardiovascular collapse 6

COVID-19 Context

Hydroxychloroquine is NOT recommended for COVID-19 treatment or prophylaxis. 5

• Current evidence does not support routine use per WHO guidance 5
• Investigated dosing regimens (600 mg loading, then 300 mg twice daily days 2-5) showed no proven benefit 5
• Increased cardiotoxicity concerns emerged during COVID-19 trials, particularly with azithromycin co-administration 6

Key Clinical Pitfalls to Avoid

1. Do not exceed 5 mg/kg/day based on actual body weight—this sharply increases retinopathy risk 1, 5
2. Do not delay ophthalmologic screening beyond 5 years in low-risk patients 1, 5
3. Do not stop therapy prematurely for borderline findings without confirmation and multidisciplinary discussion 1
4. Do not prescribe without baseline ophthalmologic examination 1, 4
5. Do not ignore renal function—dose reduction mandatory when eGFR <30 mL/min/1.73 m² 1
6. Do not combine with other QT-prolonging medications without careful cardiac monitoring 2