Hydroxychloroquine: balancing the need to maintain therapeutic levels with ocular safety: an update

Abdulaziz, Nada; Shah, Anjali R.; McCune, W. Joseph

doi:10.1097/bor.0000000000000500

Cited by 47 publications

(28 citation statements)

References 38 publications

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“…Rigorous pharmacoepidemiologic studies are needed to ascertain potential benefits of HCQ in TID. In addition, the appropriate dosing, as well as relative risks and benefits of long term HCQ use should be carefully assessed considering the concerns for ocular toxicity, especially in individuals with impaired kidney function (20). Whether longitudinally HCQ use results in less IF/TA deserves further study.…”

Section: Discussionmentioning

confidence: 99%

Brief Report: Tubulointerstitial Damage in Lupus Nephritis: A Comparison of the Factors Associated With Tubulointerstitial Inflammation and Renal Scarring

Jimenez

Mowrey

Putterman

et al. 2018

Arthritis & Rheumatology

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Section: Discussionmentioning

confidence: 99%

Brief Report: Tubulointerstitial Damage in Lupus Nephritis: A Comparison of the Factors Associated With Tubulointerstitial Inflammation and Renal Scarring

Jimenez

Mowrey

Putterman

et al. 2018

Arthritis & Rheumatology

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“…Numerous factors have been shown to affect blood levels of HCQ, such as genetic variants of the CYP enzyme family, age, gender, body weight, gastric emptying, and co-administration with immunosuppressants, such as corticosteroids (Al-Rawi et al., 2018 ; Lee et al., 2016 , 2017 ). Even though it has been reported that renal clearance of unchanged drug was approximately 16 to 30% and did not correlate with creatinine clearance (Miller et al., 1991 ), renal insufficiency has been reported to increase the risk of toxicity (Abdulaziz et al., 2018 ).…”

Section: Methodsmentioning

confidence: 99%

“…In view of the above, HCQ levels of 2250 ng/ml, even though rather conservatory, were used as an upper limit, considering also the cardiotoxic effects of the drug, possible co-administered medications and impaired clearance due to co-morbidities (Abdulaziz et al., 2018 ).…”

Section: Methodsmentioning

confidence: 99%

Optimization of hydroxychloroquine dosing scheme based on COVID-19 patients’ characteristics: a review of the literature and simulations

et al. 2020

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1. During the recent COVID-19 outbreak hydroxychloroquine (HCQ) has been proposed as a safe and effective therapeutic option. However, a wide variety of dosing schemes has been applied in the clinical practice and tested in clinical studies. 2. An extended literature survey was performed investigating the pharmacokinetics, the efficacy and safety of HCQ in COVID-19 treatment. Population pharmacokinetic models were retrieved from the literature and after evaluation and assessment one was selected in order to perform simulations. 3. The most commonly applied dosing schemes were explored for patients with different weights and different levels of HCQ clearance impairment. Model-based simulations of HCQ concentrations revealed that high initial doses followed by low and sparse doses may offer significant benefits to patients by decreasing the viral load without reaching levels considered to produce adverse effects. For instance, the dosing scheme proposed for a 70 kg adult with moderate COVID-19 symptoms would be 600 mg upon diagnosis, 400 mg after 12 h, 300 mg after 24 h, 200 mg after 36 h, followed by 200 mg BID for 4 d, followed by 200 mg OD for 5 d. 4. Based on the results from simulations performed and the currently published knowledge regarding HCQ in COVID-19 treatment, this study provides evidence that a high loading dose followed by sparse doses could offer significant benefits to the patients.

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“…Four additional models describe plasma concentrations or merged blood and plasma concentrations. [16][17][18][19] Blood concentrations are known to be more reproducible (because higher, with lesser analytical sensitivity issues). We therefore used the model by Carmichael et al 3 for subsequent simulation after independent validation.…”

Section: Wha This Study Addsmentioning

confidence: 99%

Model informed dosing of hydroxycholoroquine in COVID‐19 patients: Learnings from the recent experience, remaining uncertainties and gaps

Thémans

Dauby

Schrooyen

et al. 2020

Brit J Clinical Pharma

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In the absence of a commonly agreed dosing protocol based on pharmacokinetic (PK) considerations, the dose and treatment duration for hydroxychloroquine (HCQ) in COVID-19 disease currently vary across national guidelines and clinical study protocols. We have used a model-based approach to explore the relative impact of alternative dosing regimens proposed in different dosing protocols for hydroxychloroquine in COVID-19. Methods: We compared different PK exposures using Monte Carlo simulations based on a previously published population pharmacokinetic model in patients with rheumatoid arthritis, externally validated using both independent data in lupus erythematous patients and recent data in French COVID-19 patients. Clinical efficacy and safety information from COVID-19 patients treated with HCQ were used to contextualize and assess the actual clinical value of the model predictions. Results: Literature and observed clinical data confirm the variability in clinical responses in COVID-19 when treated with the same fixed doses. Confounding factors were identified that should be taken into account for dose recommendation. For 80% of patients, doses higher than 800 mg day on day 1 followed by 600 mg daily on following days might not be needed for being cured. Limited adverse drug reactions have been reported so far for this dosing regimen, most often confounded by co-medications, comorbidities or underlying COVID-19 disease effects. Conclusion: Our results were clear, indicating the unmet need for characterization of target PK exposures to inform HCQ dosing optimization in COVID-19. Dosing optimization for HCQ in COVID-19 is still an unmet need. Efforts in this sense are a prerequisite for best benefit/risk balance.

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Hydroxychloroquine: balancing the need to maintain therapeutic levels with ocular safety: an update

Abstract: The most important changes in practice guidelines include dose calculation based on total body weight, dose reduction after long-term use, and intensified screening with techniques including optical coherence tomography (OCT) after 5 years.

Cited by 47 publications

References 38 publications

Brief Report: Tubulointerstitial Damage in Lupus Nephritis: A Comparison of the Factors Associated With Tubulointerstitial Inflammation and Renal Scarring

Brief Report: Tubulointerstitial Damage in Lupus Nephritis: A Comparison of the Factors Associated With Tubulointerstitial Inflammation and Renal Scarring

Optimization of hydroxychloroquine dosing scheme based on COVID-19 patients’ characteristics: a review of the literature and simulations

Model informed dosing of hydroxycholoroquine in COVID‐19 patients: Learnings from the recent experience, remaining uncertainties and gaps

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