What is the appropriate adult dosing, monitoring requirements, contraindications, and alternative therapies for Plaquenil (hydroxychloroquine)?

Hydroxychloroquine (Plaquenil) Clinical Management

Adult Dosing

The standard dose for rheumatic diseases is ≤5 mg/kg actual body weight per day, which maintains retinopathy risk below 2% over 10 years. 1, 2

• For systemic lupus erythematosus, start at 200-400 mg once daily, not exceeding 5 mg/kg actual body weight per day 2
• Use actual body weight for dose calculation—this is critical, as retinopathy risks are similar across BMI groups (15-35 kg/m²) when actual body weight is used 2
• Reduce dose by 25% when eGFR <30 ml/min per 1.73 m²—this is the greatest modifiable risk factor for toxicity 2, 3
• Lower doses (2-3 mg/kg/day) are inadequate and associated with higher flare rates in lupus nephritis 2

Ophthalmologic Monitoring Requirements

Baseline examination is not required before initiating treatment, but structured screening must begin based on risk stratification. 3

Standard-Risk Patients

• Begin annual screening after 5 years of treatment 1, 3
• Risk of retinopathy is <1% during first 5 years, <2% at 5-10 years with appropriate dosing 3

High-Risk Patients (Screen After 1 Year)

• eGFR <60 ml/min per 1.73 m² 2
• Concomitant tamoxifen use 2
• Pre-existing retinal or macular disease 2
• Daily dose >5 mg/kg actual body weight 2

Required Screening Tests

• 10-2 visual field testing 3
• Spectral-domain OCT 3
• Fundus autofluorescence 3
• East Asian patients require screening beyond central macula due to pericentral vascular arcade involvement 2

Critical Monitoring Caveat

• Retinopathy may progress even after drug cessation if detected late 3
• Risk increases dramatically with duration: 7.5% in long-term users, >20% after 20 years 3

Additional Monitoring

Pre-treatment G6PD testing is preferred in men of African, Asian, or Middle Eastern origin due to hemolysis risk. 2, 4

• Baseline ECG recommended due to QT prolongation risk 2
• Monitor renal function regularly and adjust dose if impairment develops 4
• Check electrolytes regularly, especially with concurrent glucocorticoids, as corticosteroid-induced hypokalemia increases QT prolongation risk 4
• Some clinicians perform yearly ECGs in asymptomatic patients 3
• Target blood hydroxychloroquine level >0.6 mg/L for optimal disease control 3, 4

Contraindications and Precautions

Absolute contraindications are limited, but specific populations require dose adjustment or enhanced monitoring. 2, 3

• Known hypersensitivity to hydroxychloroquine 1
• G6PD deficiency (relative contraindication—requires testing before initiation) 2, 3
• Pre-existing retinal or macular disease (requires earlier screening, not absolute contraindication) 2
• Severe renal impairment (requires 25% dose reduction, not contraindication) 2, 3

Pregnancy and Breastfeeding

• Hydroxychloroquine is safe during pregnancy and should be continued—it decreases lupus activity without harm to the fetus 3, 4
• 133 pregnancies resulted in 117 live births with no difference in complications compared to untreated patients 3

Common Side Effects

Gastrointestinal symptoms (nausea, vomiting, diarrhea) are the most common side effects and are usually mild and reversible. 3

• These account for most treatment intolerances 3
• Ototoxicity can occur when doses exceed 250 mg/day 3
• Cardiomyopathy manifesting as heart failure can occur with high cumulative exposure 3
• Conduction abnormalities including heart block can occur with prolonged use 3

Alternative Therapies

Hydroxychloroquine is the backbone therapy for SLE and should not be avoided for fear of retinopathy—the goal is to safely maintain this valuable medication as long as possible. 1, 2

• Hydroxychloroquine provides reduced flares, prevention of organ damage, improved survival, and lower cardiovascular/thrombotic events 4, 5
• In SLE, discontinuation probabilities are only 8% at 12 months and 24% at 24 months, compared to 37% and 54% in rheumatoid arthritis 6
• Early hydroxychloroquine use in antinuclear antibodies-positive individuals may delay progression to SLE 5

When Hydroxychloroquine Cannot Be Used

• For rheumatoid arthritis: methotrexate, sulfasalazine, leflunomide are alternatives 6
• For SLE: no single alternative provides the comprehensive benefits of hydroxychloroquine—combination immunosuppression may be required 5
• The drug should not be stopped casually for borderline findings 1

Critical Pitfalls to Avoid

• Never use ideal body weight for dosing—always use actual body weight 2
• Never fail to adjust for renal impairment—this is the greatest modifiable risk factor 2
• Never delay screening in high-risk patients—begin after 1 year, not 5 years 2, 3
• Never miss pericentral screening in East Asian patients—standard central screening will miss early toxicity 2
• Never underdose to avoid toxicity—doses of 2-3 mg/kg/day are associated with higher flare rates 2