In the past decade, guidelines for appropriate dosing of hydroxychloroquine in the setting of obesity have fluctuated. The 2011 American Academy of Ophthalmology (AAO) Guidelines recommended the maximum dosage of hydroxychloroquine as 6.5 mg/kg/day (maximum dose of 400 mg), but in the setting of obesity, ideal body weight rather that real body weight should be utilized. In 2016, the AAO changed the dosing recommendations to a maximum of 5.0 mg/kg of real body (maximum dose 400 mg daily) without changes in the setting of obesity.
Melles et al. (2014) concluded that real body weight is a better predictor of retinal toxicity. Their data suggested that with utilization of either 5 mg/kg/day real body weight and 6.5 mg/kg/day ideal body weight, the predicted rate of hydroxychloroquine retinopathy decreased with an increase in BMI.
Conversely, in a 2019 study of 537 lupus patients on hydroxychloroquine, Petri et al. found that a higher BMI was associated with a higher risk of medication toxicity (P = 0.0160). Two percentage of patients with BMI less than 20 km/m2 experienced toxicity from hydroxychloroquine compared with 9.4% of patients with BMI greater than 35 kg/m2. In a 2021 study of 108 lupus nephritis patients, Pedrosa et al. determined that obese patients were prescribed a lower daily dose of hydroxychloroquine based upon real body weight (4.4 vs. 4.9 mg/kg/day) but interestingly, the median hydroxychloroquine blood level was higher in the obese patients (BMI ≥30 kg/m2) (P = 0.002). Although they did not collect data on toxicity, the authors hypothesize that obese patients are, therefore, at an increased risk and posit that dosing based on ideal body weight should be considered.
This issue was addressed in the 2016 American Academy of Ophthalmology Hydroxychloroquine Guidelines for Short, Obese patients. The authors identified 64 cases of hydroxychloroquine retinopathy in obese patients, 27% of whom had been treated with hydroxychloroquine with well tolerated doses per the 2016 AAO guidelines but still developed toxicity. The authors noted overdosing in women particularly is not uncommon. They recommended use of hydroxychloroquine to maximum of 6.5 mg/kg of ideal body weight rather than the widely utilized 5 mg/kg of real body weight. These conflicting results raise the question: perhaps toxicity could be avoided if the dose utilized satisfied both of the recommendations (i.e. the dose was lower than upper limit recommended in both situations)?
We do not have full understanding of why hydroxychloroquine levels may be higher in obesity. It has been hypothesized that hydroxychloroquine does not deposit in adipose tissue but rather other connective tissues.[31,32] More recent literature, however, has suggested this may not be true although an alternative feasible hypothesis has not been confirmed to our knowledge.[26,33]
In conclusion, while consensus on dosing hydroxychloroquine in the setting of obesity does not exist, the presence of obesity should prompt a provider to exercise caution when choosing dose of hydroxychloroquine and consider obtaining a hydroxychloroquine level.
Curr Opin Rheumatol. 2022;34(3):151-157. © 2022 Lippincott Williams & Wilkins