Excessive Dosing Still Occurring in Outpatient Hydroxychloroquine Prescriptions

Hydroxychloroquine Medicine Isolated on White
Taking a retina-threatening level of the drugs is most commonly associated with low body weight and having obtained the prescription from a dermatologist.

A summary of current practice patterns, 2 years after the 2016 American Academy of Ophthalmology’s (AAO) recommendations for hydroxychloroquine prescriptions, found that excessive dosing remains prevalent in 27% of outpatient hydroxychloroquine prescriptions, with dermatologist prescriber and low actual body weight the main risk factors, according to a study published in Ophthalmology.

“Alternative dosing strategies may be used to titrate dosage and improve patient safety,” according to researchers. 

The study shows hydroxychloroquine retinal toxicity is associated with high daily dose and cumulative drug exposure, which prompted the AAO to recommend an ideal body weight (IBW)-based maximum daily dose for ophthalmic safety in 2011. After several large-scale studies found falling rates of excess dosing among hydroxychloroquine initiators, the AAO revised its recommendation in 2016 to a daily dose of no more than 5 mg/kg actual body weight (ABW).

In this retrospective chart review, investigators looked at 6539 outpatient hydroxychloroquine prescriptions in 2018 based on patients at the Cleveland Clinic Foundation from January 1 to December 31, 2018.

They found that the prevalence of excess dosing based on the 2016 AAO ABW recommendations was 27%, and the factors most associated with this were lower weight and dermatologist prescriber. Systemic autoimmune condition (85%) was the most common drug indication, while rheumatologists prescribed 75% of prescriptions. Mean daily dose was 340 ± 95 mg daily (4.3 ± 1.4 mg/kg/day with the most common daily 35 doses 400 mg (65%) and 200 mg (27%), as a single dose (46%) or 2 doses (54%).

Female sex and lower weight (<78.12 kg, sample median) were associated with excess dosing in univariate logistic models, while lower weight patients accounted for 99% of all excessively dosed prescriptions. Among specialists, dermatologists were most likely to prescribe excess doses (P <.013 after Bonferroni correction). “Primary dermatologic conditions were nearly twice as likely as systemic autoimmune conditions to be treated with an excessive dose (OR, 1.93; 95% CI, 1.37-47 2.72). Among the 104 patients treated for dermatologic conditions by either a dermatologist or rheumatologist, dermatologists prescribed higher daily doses (383 ± 78 vs 330 ± 99 mg, P =.003, or 5.1 ± 1.6 vs 4.2 ± 1.3 mg/kg/day, P =.005),” the study says.

Two factors not associated with excessive dosing: Age and duration of use. 

Researchers found that Black patients were less likely to be excessively dosed than White patients and that Asian patients had a higher weight-based daily dose compared with White and Black  patients (P =.002 and P <.001, respectively), and were twice as likely as Black patients to be excessively dosed. Asian patients also have a “predilection to present with an extramacular retinopathy pattern.” 

Asian patients therefore “represent a vulnerable population due to the combination of possibly increased excessive dosing risk and an atypical disease pattern,” according to researchers.

The study’s limitations include that some subgroups in the study were small, possibly impacting how the researchers detected differences. The study’s retrospective nature might have affected results as well, particularly with the medication list, which might not be a “fully accurate indicator of instructed use.” Also, the conclusions in this study are from a multihospital system, which might not be representative of all types of practices. Finally, “AAO 2016 recommendations are intended for ophthalmic safety but have no bearing on therapeutic dosing, which must be assessed on an individual case basis by the prescriber.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Chen R, Chen AX, Greenlee TE, et al. Hydroxychloroquine prescription practices after 2016 AAO recommendations. Ophthalmol. Published online March 16, 2021. doi:10.1016/j.ophtha.2021.03.022