What are the recommended adult dosing regimens and safety precautions for hydroxychloroquine (including for rheumatoid arthritis, systemic lupus erythematosus, and malaria prophylaxis)?

Hydroxychloroquine Dosing and Precautions

Hydroxychloroquine dosing must not exceed 5 mg/kg of actual body weight per day to minimize irreversible retinal toxicity, with mandatory baseline and annual ophthalmologic screening after 5 years of therapy. 1, 2

Standard Dosing Regimens by Indication

Rheumatoid Arthritis

• Initial dosage: 400-600 mg daily 3
• Maintenance dosage: 200 mg once daily or 400 mg once daily (may be divided into two doses) 3
• Maximum safe dose: Do not exceed 5 mg/kg actual body weight per day 1, 2

Systemic Lupus Erythematosus

• Standard dosage: 200 mg once daily or 400 mg once daily (may be divided into two doses) 3
• Critical recommendation: Hydroxychloroquine is recommended for ALL patients with SLE due to multiple beneficial effects including prevention of disease flares and improved survival 1
• Pregnancy: Continue hydroxychloroquine at the same dose during pregnancy; strongly recommended for all pregnant women with SLE 1, 4

Chronic Discoid Lupus Erythematosus

• Dosage: 200 mg once daily or 400 mg once daily (may be divided into two doses) 3

Malaria Prophylaxis (Chloroquine-Sensitive Areas Only)

• Adults: 400 mg once weekly 3
• Pediatric patients ≥31 kg: 6.5 mg/kg (up to 400 mg maximum) once weekly 3
• Timing: Begin 2 weeks before travel, continue weekly during exposure, and for 4 weeks after leaving endemic area 3

Malaria Treatment (Uncomplicated P. vivax or P. ovale)

• Loading dose: 800 mg (4 tablets) initially 1
• Subsequent doses: 400 mg (2 tablets) at 6 hours, 24 hours, and 48 hours after initial dose 1
• Total course: 2000 mg over 48 hours 1

Critical Safety Precautions and Monitoring

Absolute Contraindications

• Hypersensitivity to 4-aminoquinoline compounds 3
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency: Check G6PD levels in men of African, Asian, or Middle Eastern origin before starting treatment 2, 4
• Pre-existing retinal or visual field deficits 4

Ophthalmologic Monitoring (Most Critical)

• Baseline examination: Mandatory before initiating therapy to rule out pre-existing maculopathy 3, 5
• Annual screening: Begin after 5 years of therapy for low-risk patients 2, 5
• Earlier screening required for high-risk patients: Those with renal disease, tamoxifen use, or daily doses >5 mg/kg actual body weight 6, 7
• Screening modalities: Use 10-2 automated visual fields PLUS at least one objective test (spectral domain OCT, multifocal ERG, or fundus autofluorescence) 5
• Asian patients: Screen wider retinal field as extramacular/pericentral patterns occur more commonly 6
• Risk increases dramatically: Retinopathy prevalence is 7.5% after 5 years, rising to nearly 20% after 20 years of treatment 6

Cardiovascular Monitoring

• Baseline ECG: Recommended before starting therapy due to QT prolongation risk 2
• Avoid in patients with: Congenital or acquired QT prolongation, cardiac disease, or proarrhythmic conditions 4
• Drug interactions: Contraindicated with ondansetron, domperidone, and citalopram due to torsades de pointes risk 4
• Annual ECGs: Consider in asymptomatic patients on long-term therapy, especially those with cardiac risk factors 4

Laboratory Monitoring

• Complete blood count and liver function tests: Annually for rheumatologic conditions 1, 2
• Renal function: Critical for dose adjustment; reduce dose by 25% if eGFR <30 mL/min per 1.73 m² 2
• Frequency varies by indication: More frequent monitoring not routinely required for stable rheumatologic disease 1

Dose Adjustment for Special Populations

• Short stature patients: Calculate dose based on ideal body weight, not actual body weight, to avoid overdosing 5
• Renal impairment: Patients require lower doses and closer monitoring due to increased systemic drug levels 4
• Hepatic impairment: Dose adjustment required if transaminase elevation occurs 4

Common and Serious Adverse Effects

Most Common (Generally Do Not Require Discontinuation)

• Gastrointestinal: Nausea, vomiting, diarrhea, abdominal pain (most frequent) 2, 4, 3
• Neurologic: Headache, dizziness 2, 4
• Dermatologic: Pruritus, urticaria 1, 4
• Ophthalmologic: Blurred vision (typically reversible with discontinuation) 4

Serious Adverse Effects Requiring Immediate Action

• Retinal toxicity: Irreversible vision loss; related to cumulative dose and duration 3, 6
• Cardiomyopathy and ventricular arrhythmias: Fatal or life-threatening cases reported 3
• Serious skin reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS syndrome, acute generalized exanthematous pustulosis 3
• Hematologic toxicity: Discontinue if myelosuppression occurs 3
• Ototoxicity: Irreversible if oral doses exceed 250 mg/day chronically 4

Conditions That May Worsen

• Psoriasis: Avoid hydroxychloroquine in patients with psoriasis; exacerbation commonly reported 1, 4, 3
• Porphyria: Avoid use; hepatotoxicity reported in patients with porphyria cutanea tarda 3

Key Clinical Pitfalls to Avoid

Dosing Errors

• Never use ideal body weight for dosing calculation: Use actual body weight to calculate the 5 mg/kg/day maximum 6, 5
• Do not confuse salt and base formulations: Hydroxychloroquine sulfate 200 mg tablets contain 155 mg base; dosing errors occur when confusing these 8
• Underdosing for acute malaria: The 800 mg loading dose is essential for treatment efficacy; lower doses lead to treatment failure 8

Monitoring Failures

• Do not wait for visible bull's-eye maculopathy: This is a late finding; screening aims to detect earlier subclinical changes 5
• Do not rely on Amsler grid testing: No longer recommended for screening 5
• Do not stop screening after 5 years: Risk continues to increase with duration; 20-year users have nearly 20% prevalence of retinopathy 6
• Do not casually discontinue for borderline findings: Goal is to safely maintain this valuable medication as long as possible 4

Drug Interactions

• Avoid concomitant QT-prolonging medications: Multiple drug classes increase arrhythmia risk 4
• Tamoxifen use increases retinal toxicity risk: Requires more frequent ophthalmologic monitoring 6, 7
• May interfere with intradermal rabies vaccine: Antibody response may be impaired 4

Special Population Considerations

• Pregnancy and lactation: Hydroxychloroquine is safe and should be continued during pregnancy in SLE patients; present in breast milk at low levels without reported adverse effects 4
• Pediatric patients: Annual retinal screening should begin immediately, not after 5 years as in adults, due to cumulative developmental effects and inability to articulate vision concerns 1