Hydroxychloroquine dosing in immune-mediated diseases: implications for patient safety

Abstract

Objective Evidence suggests that hydroxychloroquine (HCQ) retinal toxicity is more common than previously thought. Adhering to careful weight-based dosing can significantly reduce the risk of this adverse event and is recommended in recentguidelines. We used electronic health record data from a large health system to examine HCQ dosing over a five-year period and to identify risk factors associated with higher dosage of HCQ. Methods We constructed a longitudinal, retrospective cohort of patients with HCQ prescriptions (1,681 patients with 3,490 prescribing events) between 2012–2016. We measured HCQ dosing patterns relative to guidelines (<6.5 mg/kg and <5.0 mg/kg) over time and used longitudinal multivariate mixed effects logistic regression to identify sociodemographic, clinical and health system factors associated with receiving higher than recommended doses of HCQ. Results The proportion of patients receiving doses above 6.5 mg/kg decreased from 12% in 2012 to 7% by 2016. Similarly, the proportion of patients with doses above 5.0 mg/kg fell from 38% in 2012 to 30% in 2016. Low body weight (< 68 kg) was strongly associated with receiving doses of HCQ above 6.5 mg/kg across all time points, even after adjusting for other factors (ORs ranging from 13.2–21.0). Conclusion Although the proportion of patients receiving higher than recommended HCQ doses has declined over a period of five years, a substantial number of individuals remain at increased risk for toxicity. Given the widespread use of HCQ in immune-mediated diseases, our study suggests that interventions aimed to ensure appropriate dosing are warranted to improve patient safety.

Sharp decline in hydroxychloroquine dosing—analysis of 17,797 initiators from 2007 to 2016

“…While this may reflect the local practice pattern, it is also conceivable that the requirement to be seen by an ophthalmologist may have selected patients with higher initial dosing more frequently even in the recent years. In contrast, another university center study captured all patients ( n = 1681) who received any HCQ prescription between 2012 and 2016 and reported a substantial decline in excess dosing, similar to ours [18]. Our study is over ten times larger than this study and spans twice its duration, and we were able to address initial dosing trends.…”

“…As such, our study captured a diverse patient population as well as prescription dosing by multiple providers and provider specialties and provides population-level data on HCQ prescribing patterns in relation to HCQ dosing guidelines. Furthermore, our study was substantially longer and larger than previous single-center studies, providing higher precision in our results [18, 19]. However, our data lacked information regarding disease activity for patients with SLE, RA, and other conditions, limiting our ability to assess its potential relationship with initial HCQ dosing.…”

“…Two previous, small-scale, single-center studies ( n = 554 and n = 1681) have reported conflicting findings of HCQ dosing trends [18, 19]. The first study captured all rheumatology patients ( n = 554) who initiated HCQ between 2009 and 2016 and were seen by an ophthalmologist in a university health care system and reported no change in HCQ trend [19].…”

Systematic benefit-risk assessment for the use of chloroquine or hydroxychloroquine as a treatment for COVID-19: Establishing a dynamic framework for rapid decision-making

“…One of the most serious toxic effects of hydroxychloroquine/ chloroquine are ocular side effects, notably retinopathy [22][23][24][25][26], although the risk for hydroxychloroquine is considered to be lower [27]. Both duration of use and weight-based dosing (dose per kg) are important parameters for the risk of developing retinopathy [26].…”

Hidroxicloroquina como alternativa para o tratamento da infecção causada pelo SARS-CoV-2: O que se sabe até agora?

“…Entre esses fatores podemos destacar: dose diária e duração do uso, nefrotoxicidade e interações medicamentosas. Entretanto a existência de efeitos colaterais em indivíduos que fazem uso da HCQ é muito baixa quando administrada em baixas doses, sendo necessária a implementação de estratégias que permitam a administração de doses apropriadas de acordo com o paciente (Rodríguez-Hurtado, Sáez-Moreno, Rodríguez-Ferrer, 2015;Marmor et al, 2016;Gianfrancesco et al, 2017).…”