Understanding the dynamics of hydroxychloroquine blood levels in lupus nephritis

Pedrosa, Tatiana do Nascimento; Pasoto, Sandra Gofinet; Aikawa, Nádia E.; Yuki, Emily Figueiredo Neves; Borba, Eduardo F.; Filho, Júlio César Rente Ferreira; Carricondo, Pedro Carlos; Zanetti, Caio Bosquiero; Conde, P; Duarte, Nilo José Coelho; Fontoura, Nicole; Romano, Paschoalina; Carvalho, Valdemir Melechco; Silva, Clóvis A.; Bonfá, Eloísa

doi:10.1177/0961203320912832

Cited by 20 publications

(24 citation statements)

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“…The inclusion and exclusion criteria of this study provided a homogenous population of LN patients with at least 3 months of stable use of HCQ under prescribed 2016-AAO dose warranting enough time to reach HCQ steady state. 12 The use of whole blood samples for HCQ measurement and the exclusion of conditions that could interact with HCQ or interfere in its concentration 5 , 6 , 11 , 12 , 16 were relevant to provide a more accurate measurement and minimize confounding variables. The inclusion of LN patients only with adequate HCQ blood levels (≥613.5 ng/mL) provided a more consistent population for this study excluding non-adherence behavior.…”

Section: Discussionmentioning

confidence: 99%

“…Inclusion criteria at entry were: LN defined according to the American College of Rheumatology (ACR); 10 age ≥18 years; stable use of HCQ at the prescribed 2016-AAO recommended dose per RBW 5 for at least three months, with a maximum of prescribed HCQ dose of 400 mg per day (for high BMI), and baseline HCQ blood levels ≥613.5 ng/mL 6 to ensure a known adherent population. Exclusion criteria were: severe chronic renal insufficiency, 11 alcoholism, 12 infections, 11 liver and heart failures, use of drugs that could interfere in HCQ blood levels or interact with HCQ, such as, tamoxifen, digoxin and antacids.…”

Section: Methodsmentioning

confidence: 99%

“…Whole blood samples were assessed for HCQ measurements using a liquid chromatography-tandem mass spectrometry method as previously described. 6…”

Section: Methodsmentioning

confidence: 99%

“…Recently, our group demonstrated that stable patients with lupus nephritis (LN) under 2016-AAO dose sustained adequate HCQ blood levels (≥613.5 ng/mL) with a low risk of flare. 6 Moreover, Petri et al. (2020) 7 showed that high mean and maximal blood levels of HCQ were associated with retinopathy particularly in obese patients, reinforcing the need of low HCQ doses for specific groups of SLE patients.…”

Section: Introductionmentioning

confidence: 99%

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The influence of obesity on hydroxychloroquine blood levels in lupus nephritis patients

Pedrosa

Kupa

Pasoto

et al. 2021

Lupus

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Introduction In 2016 the American Academy of Ophthalmology(2016-AAO) recommended a maximum daily HCQ use of 5.0 mg/kg real body weight(RBW) taking into consideration minimizing eye toxicity. Retinopathy in systemic lupus erythematosus(SLE) patients was recently associated with obesity and this condition is progressively more common in these patients. However, the impact of obesity in HCQ blood levels remains controversial. Objective To determine if the 2016-AAO recommendation based on RBW with and without maximum daily dose restriction results in adequate and safe blood levels in obese lupus nephritis(LN) patients. Methods A cross-sectional study was performed with 108 LN patients under the prescribed 2016-AAO dose for at least 3 months. LN patients were assessed for demographic characteristics, body mass index(BMI), disease parameters, HCQ dose, concomitant treatment and HCQ blood levels measured by liquid chromatography-tandem mass spectrometry. Obesity was defined as BMI ≥30kg/m2. Results Obesity was identified in 35/108(32%) LN patients. The calculation of HCQ daily dosage revealed that obese patients were under a lower prescribed daily dose according to the real body weight (RBW) [4.4(2.9-5.4) vs. 4.9(4-5.5)mg/Kg/day, p < 0.001] due to the maximum limit used. Regardless of that the median of HCQ blood levels was significantly higher in obese compared to non-obese patients (1562 ± 548.6 vs. 1208 ± 448.9 ng/mL, p = 0.002). Further analysis of patients under the 20016-AAO recommendation by RBW without the restriction of maximum daily dose confirmed that in spite of comparable daily dose in 14 obese patients and 61 non-obese patients [4.8 (4.5-5.4) vs. 5.0(4.5-5.5) mg/kg, p = 0.312], the median of HCQ blood levels was significantly higher in obese patients than in non-obese (1734 ± 457.3 vs. 1189 ± 449.4 ng/mL, p < 0.001). Conclusion Obese patients under the 2016-AAO prescribed dose of HCQ based on RBW with and without maximum daily dose restriction have a very high HCQ blood levels compared to non-obese patients, with a potential increased risk of ocular toxicity. The use of 2016-AAO dose of HCQ according to the ideal body weight for this group of patients should be considered.Clinicaltrials.gov #NCT0312243.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Whole blood samples were assessed for HCQ measurements using a liquid chromatography-tandem mass spectrometry method as previously described. 6…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The influence of obesity on hydroxychloroquine blood levels in lupus nephritis patients

Pedrosa

Kupa

Pasoto

et al. 2021

Lupus

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“…Elsewhere, clinical trials have evaluated smaller doses. For prevention or prophylaxis, where the viral burden is much lower, the daily doses being evaluated are similar to those widely recommended and generally very well tolerated in rheumatological conditions [37,62,[121][122][123][124][125][126].…”

Section: The Case For Evaluating Large Doses In Covid-19mentioning

confidence: 99%

COVID-19 prevention and treatment: A critical analysis of chloroquine and hydroxychloroquine clinical pharmacology

et al. 2020

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• Chloroquine and hydroxychloroquine have been used for over 60 years in the treatment of malaria, amoebic liver abscess, and several rheumatological conditions, but their clinical pharmacology is not well understood. COVID-19 is a new potential indication, although these drugs have only moderate in vitro activity against the SARS-CoV-2 virus and there is no convincing evidence at this time of significant clinical efficacy. • Chloroquine and hydroxychloroquine both have unusual pharmacokinetic properties with enormous apparent volumes of distribution (chloroquine > hydroxychloroquine) and very slow elimination from the body (terminal elimination half-lives > 1 month). • The free plasma concentrations that drive potentially serious adverse reactions (hypotension, cardiac conduction disturbances, delayed ventricular repolarization, and neurotoxicity) are determined largely by distribution processes. • Hydroxychloroquine was slightly safer than chloroquine in preclinical testing and is considered better tolerated over the long term. Both drugs are dangerous when overdosed, and parenteral administration needs careful control. • There are different salts, each with a different base equivalent. This has led to confusion and sometimes mistakes in dosing. As different salts are available in different places, malaria treatment is usually recommended in terms of base equivalent. Tablets of the two most widely available forms, chloroquine diphosphate 250 mg salt and hydroxychloroquine sulphate 200 mg salt, both contain 155 mg base.

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Reference Range of Hydroxychloroquine Blood Levels That Can Reduce Odds of Active Lupus and Prevent Flares

Garg,

Chewning,

Hutson

et al. 2023

Arthritis Care & Research

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ObjectiveRecent data show that lower hydroxychloroquine (HCQ) doses are associated with two‐six‐fold higher risk of lupus flare. Thus, establishing an effective a reference range of HCQ blood levels with upper and lower bounds for efficacy may support individualizing HCQ dosing to prevent flares.MethodsHCQ levels in whole blood and SLE disease activity index (SLEDAI) were measured during the baseline visit and again during a standard of care routine follow‐up visit. Active cross‐sectional lupus at baseline was defined as SLEDAI ≥6; a within subject flare was defined as a subsequent 3‐point increase in SLEDAI with clinical symptoms requiring therapy change. We examined associations between active lupus and HCQ blood levels at baseline, and flares and HCQ levels during 6‐12‐month routine lupus follow‐up visit using mixed regression analysis.ResultsAmong 158 baseline patient‐visits, 19% had active lupus. A 71% lower odds of active lupus was noted in patients with levels within 750‐1200 ng/ml range (adjusted OR 0.29, 95% CIs 0.08‐0.96). Using convenience sampling strategy during a pandemic, we longitudinally followed 42 patients. Among those patients, 17% flared during their follow‐up visit. Maintaining HCQ levels within 750‐1200 ng/ml reduced the odds of flare by 26% over 9 months median follow‐up.ConclusionAn effective reference range of HCQ blood levels, 750‐1200 ng/ml, was associated with 71% lower odds of active lupus, and maintaining levels within this range reduced odds of flares by 26%. These findings could guide clinicians to individualize HCQ doses to maintain HCQ levels within this range to maximize efficacy.This article is protected by copyright. All rights reserved.

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Understanding the dynamics of hydroxychloroquine blood levels in lupus nephritis

Cited by 20 publications

References 49 publications

The influence of obesity on hydroxychloroquine blood levels in lupus nephritis patients

The influence of obesity on hydroxychloroquine blood levels in lupus nephritis patients

COVID-19 prevention and treatment: A critical analysis of chloroquine and hydroxychloroquine clinical pharmacology

Reference Range of Hydroxychloroquine Blood Levels That Can Reduce Odds of Active Lupus and Prevent Flares

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