Recommended Dose of Chloroquine/Hydroxychloroquine for Chronic Rheumatoid Arthritis
For chronic rheumatoid arthritis, hydroxychloroquine is strongly preferred over chloroquine, with a recommended dose of 200-400 mg daily (given once daily or in two divided doses), not exceeding 5 mg/kg actual body weight per day to minimize retinal toxicity risk. 1, 2, 3, 4
Initial Dosing Strategy
- Start with 400-600 mg daily as a single dose or two divided doses during the initial treatment phase, recognizing that hydroxychloroquine's action is cumulative and may require weeks to months for maximum therapeutic effect 4
- Transition to chronic maintenance dosing of 200-400 mg daily (once daily or in two divided doses) after initial disease control is achieved 1, 4
- The absolute maximum safe dose is ≤5 mg/kg actual body weight per day, as daily doses exceeding this threshold significantly increase the incidence of retinopathy 1, 2, 3, 4
Critical Dosing Considerations
Use Actual Body Weight, Not Ideal Body Weight
- Calculate the dose based on actual body weight, as retinopathy risks are statistically similar across BMI groups (15-35 kg/m²) when actual body weight is used for dosing 3
- This is a common pitfall—do not use lean body weight or ideal body weight for hydroxychloroquine dosing in the modern era 3
Dose Adjustment for Renal Impairment
- Reduce the dose by 25% when eGFR <30 ml/min per 1.73 m², as reduced renal function is the greatest additional risk factor for retinopathy 2, 3
- Patients with eGFR <60 ml/min per 1.73 m² require earlier ophthalmologic screening (after 1 year instead of 5 years) 3
Why Hydroxychloroquine Over Chloroquine
Hydroxychloroquine is conditionally recommended over chloroquine for rheumatoid arthritis because it has a more favorable safety profile with lower retinal toxicity risk at therapeutic doses 1, 5
- Chloroquine dosing for RA (when used historically): 3.5-4.0 mg/kg per day based on lean body weight 5
- Hydroxychloroquine dosing for RA: 6.0-6.5 mg/kg per day based on lean body weight in older literature, but modern guidelines use ≤5 mg/kg actual body weight 5, 3
- The 2021 ACR guidelines for RA treatment do not specifically recommend chloroquine, focusing instead on hydroxychloroquine as the antimalarial of choice 1
Mandatory Safety Monitoring
Ophthalmologic Screening
- Baseline ophthalmologic examination is mandatory before initiating therapy 2, 3
- Annual screening beginning after 5 years for low-risk patients 2, 3
- Annual screening beginning after 1 year for high-risk patients, including those with eGFR <60 ml/min per 1.73 m², concomitant tamoxifen use, or pre-existing retinal/macular disease 3
- East Asian patients require screening beyond the central macula due to a different retinopathy phenotype (pericentral vascular arcade involvement) 3
Pre-Treatment Screening
- Check G6PD levels in men of African, Asian, or Middle Eastern origin before starting treatment, as hydroxychloroquine is absolutely contraindicated in G6PD deficiency 2, 3
- Baseline ECG is recommended due to QT prolongation risk 2, 4
Common Pitfalls to Avoid
- Do not use doses lower than 200 mg daily for RA, as lower doses (2-3 mg/kg/day) may not achieve adequate blood levels and are associated with inadequate disease control 3
- Do not fail to adjust for renal impairment, as this is the greatest modifiable risk factor for toxicity 3
- Do not crush or divide the tablets—they must be taken whole with food or milk 4
- Do not discontinue hydroxychloroquine casually—the goal is to safely maintain it as long as possible given its disease-modifying benefits 3
Additional Considerations
- Hydroxychloroquine can be used concomitantly with corticosteroids, salicylates, and other antirheumatic agents 4
- Common side effects include gastrointestinal disturbance, headache, dizziness, blurred vision, and pruritus, which generally do not require discontinuation 2
- Vortex keratopathy (corneal deposits) may occur but is distinct from retinal toxicity 2
- Hydroxychloroquine may exacerbate psoriasis in susceptible patients 2