Hydroxychloroquine Side Effects and Management

Introduction to Hydroxychloroquine Side Effects

Hydroxychloroquine is generally well-tolerated with a relatively low rate of drug-related adverse effects, but requires vigilant monitoring for retinopathy, cardiotoxicity, and less common neuromuscular complications 1, 2

Gastrointestinal symptoms such as nausea, vomiting, and diarrhea are usually mild and reversible, and account for most treatment intolerances 3, 2

The risk of retinopathy is less than 1% during the first 5 years when dosed at ≤5 mg/kg actual body weight daily, less than 2% at 5-10 years with appropriate dosing, 0.5% after 6 years, increasing to 7.5% in long-term users, and more than 20% after 20 years of treatment 1, 8, 3, 2, 9, 7
The American Academy of Ophthalmology recommends no baseline ophthalmologic examination required before initiating treatment, begin annual screening after 1 year in high-risk patients, and begin annual screening after 5 years in standard-risk patients 1, 8, 3, 2, 7, 6
Screening must include 10-2 visual field testing, spectral-domain OCT, and fundus autofluorescence 7
Retinopathy may progress even after drug cessation if detected late, making early detection crucial 7

Conduction abnormalities including heart block can occur with prolonged use 4, 5
Some clinicians perform yearly ECGs in asymptomatic patients, especially with chloroquine 4, 5
Cardiomyopathy manifesting as heart failure can occur with high cumulative exposure 1, 8, 3, 2

The risk of hemolysis in patients with G6PD deficiency is increased, and G6PD levels should be measured before starting hydroxychloroquine in men, especially those of African, Asian, or Middle Eastern origin 1, 8, 3, 2
Ototoxicity can occur when doses exceed 250 mg/day 4
Interference with selected vaccines can occur 4

The daily dose should not exceed 5 mg/kg actual body weight to minimize retinopathy risk, and doses of 2-3 mg/kg/day may not achieve adequate blood levels and are associated with higher flare rates 1, 8, 3, 9, 6
In patients with eGFR <30 ml/min/1.73 m², the dose should be reduced by 25% 1, 8, 3, 2, 9
The target blood hydroxychloroquine level should be >0.6 mg/L for optimal disease control 1, 8, 3

Hydroxychloroquine is safe during pregnancy, and is associated with decreased lupus activity without harm to the fetus 5, 2, 9
The American College of Rheumatology recommends hydroxychloroquine use during pregnancy, with 133 pregnancies resulting in 117 live births with no difference in complications compared to untreated patients 5