Hydroxychloroquine in the post-COVID-19 era: will this pandemic upset decades of clinical practice?

Pothen, Lucie; Yıldız, Halil; Samnick, Mathilde Mbouck; Yombi, Jean Cyr

doi:10.1007/s10067-020-05572-9

Cited by 3 publications

(3 citation statements)

References 51 publications

(70 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Te combination of azithromycin and hydroxychloroquine was associated with a greater reporting of prolonged-QT intervals and/or torsade de pointe-associated ventricular tachycardia reporting than either drug in monotherapy (999/165 300 (0.6%) versus 9/607 (1.5%), reporting odds ratio, 2.48 [95% CI, 1.28-4.79]). HCQ is considered one of the safest drugs available to treat autoimmune diseases, despite long-term administration, including in patients with systemic lupus erythematosus, RA, primary Sjogren's syndrome, antiphospholipid syndrome, and sarcoidosis [5,7,9,75]. HCQ is usually administered orally at 200 mg/ day to 400 mg/day, with a maximum dose of 5 mg/kg/day, and is well tolerated at this dosage [5,7,9,75].…”

Section: Discussionmentioning

confidence: 99%

“…HCQ is considered one of the safest drugs available to treat autoimmune diseases, despite long-term administration, including in patients with systemic lupus erythematosus, RA, primary Sjogren's syndrome, antiphospholipid syndrome, and sarcoidosis [5,7,9,75]. HCQ is usually administered orally at 200 mg/ day to 400 mg/day, with a maximum dose of 5 mg/kg/day, and is well tolerated at this dosage [5,7,9,75]. Our experience of HCQ is that, with simple precautions around use (hypokalaemia and a normal ECG), HCQ is an extremely safe drug [76].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Hydroxychloroquine: Pharmacokinetics and Toxicity

Brouqui,

Chabrière,

Raoult

2024

Journal of Clinical Pharmacy and Therapeutics

View full text Add to dashboard Cite

Background/Purpose(s). We have extensively used HCQ at 200 mg three times a day (tid) to treat various infections such as Q fever and Whipple’s disease. Serum levels of between 1 μg/ml and 2 μg/ml serum level are recommended to achieve the safety and efficacy of these treatments. Our aim in this paper is to describe our experience regarding the pharmacokinetics and toxicity of HCQ in another infection caused by SARS-CoV-2. Methods. As recommended, we performed electrocardiograms before administering HCQ off-label. The HCQ concentration in the serum was monitored to ensure the effectiveness and safety of the treatment. We retrospectively analysed HCQ serum concentrations measured over time and toxicity data in patients with COVID-19 who were treated with HCQ at the IHU Marseille Infection. We did not treat patients with HCQ contraindications with this medication. Results. We measured HCQ concentrations in 1310 serum samples from 989 patients with COVID-19. The mean ± SD HCQ concentration increased in patients’ sera during treatment from day 1 (0.10 μg/ml ± 0.08) to day 11 (0.85 μg/ml ± 0.44), confirming that HCQ accumulates in the body during short-term therapy. However, the observed concentrations did not exceed the therapeutic range for other indications (0.80–1.20 μg/mL in Q fever patients treated for between 18 and 24 months). In patients treated with HCQ, major side effects included intestinal disorders (nausea, vomiting, and gastric pain) and QT prolongation. No conduction disorders (including torsades de pointes and ventricular arrhythmia), cardiomyopathy, retinopathy, or HCQ-related deaths were observed. Conclusions. In patients treated over a short time period with 200 mg tid of HCQ, therapeutic concentrations in serum were obtained in most patients without significant side effects or complications. Although patients must be carefully evaluated for HCQ contraindications, HCQ 200 mg tid for ten days can be considered an appropriate and safe dosage in patients with COVID-19.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hydroxychloroquine: Pharmacokinetics and Toxicity

Brouqui,

Chabrière,

Raoult

2024

Journal of Clinical Pharmacy and Therapeutics

View full text Add to dashboard Cite

show abstract

“…In particular, expert reviews of repurposed drug therapies and vaccines have allowed the recommendation of hydroxychloroquine and MMR vaccination as potential therapeutic and preventive options during the pandemic [14]. While the clinical implications of such reviews are uncertain, there are ethical concerns over the risks of non-specific drug therapies [15].…”

Section: Research Methodology Perspective Prospmentioning

confidence: 99%

Biomedical Researchers Confronting the Covid-19 Pandemic

Gajović

2021

CAJMHE

View full text Add to dashboard Cite

The COVID-19 pandemic represents a global challenge to be confronted by the biomedical community. This article aimed to explore how knowledgeable and competent researchers may contribute to fighting the pandemic, and to discuss the ethics and impact of this endeavor. Many medical researchers and in particular clinical practitioners are engaged in collecting new evidence and creating new knowledge by undertaking pandemic-related research. This research is frequently unplanned, and subsequently numerous obstacles to starting new but necessary studies must be overcome. To contribute research evidence in hard times represents a highly ethical move. Moreover, these new studies need ethical approvals, financial resources, and institutional frameworks. Another pandemic-related challenge is how to generate expert opinions during the period when solid evidence is missing. Unlike research studies providing necessary scientific evidence, expert opinions do not need ethical approvals or disclosures of competing interests. The apparent contrast of evidence-based versus opinion-based decision-making during the pandemic reconfirms that quality research studies have no alternatives at all times.

show abstract

Efficacy of Ivermectin, Chloroquine/Hydroxychloroquine, and Azithromycin in Managing COVID-19: A Systematic Review of Phase III Clinical Trials

Sansone,

Boschiero,

Marson

2024

Biomedicines

View full text Add to dashboard Cite

Background: During the coronavirus disease (COVID)-19 pandemic several drugs were used to manage the patients mainly those with a severe phenotype. Potential drugs were used off-label and major concerns arose from their applicability to managing the health crisis highlighting the importance of clinical trials. In this context, we described the mechanisms of the three repurposed drugs [Ivermectin-antiparasitic drug, Chloroquine/Hydroxychloroquine-antimalarial drugs, and Azithromycin-antimicrobial drug]; and, based on this description, the study evaluated the clinical efficacy of those drugs published in clinical trials. The use of these drugs reflects the period of uncertainty that marked the beginning of the COVID-19 pandemic, which made them a possible treatment for COVID-19. Methods: In our review, we evaluated phase III randomized controlled clinical trials (RCTs) that analyzed the efficacy of these drugs published from the COVID-19 pandemic onset to 2023. We included eight RCTs published for Ivermectin, 11 RCTs for Chloroquine/Hydroxychloroquine, and three RCTs for Azithromycin. The research question (PICOT) accounted for P—hospitalized patients with confirmed or suspected COVID-19; I—use of oral or intravenous Ivermectin OR Chloroquine/Hydroxychloroquine OR Azithromycin; C—placebo or no placebo (standard of care); O—mortality OR hospitalization OR viral clearance OR need for mechanical ventilation OR clinical improvement; and T—phase III RCTs. Results: While studying these drugs’ respective mechanisms of action, the reasons for which they were thought to be useful became apparent and are as follows: Ivermectin binds to insulin-like growth factor and prevents nuclear transportation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), therefore preventing cell entrance, induces apoptosis, and osmotic cell death and disrupts viral replication. Chloroquine/Hydroxychloroquine blocks the movement of SARS-CoV-2 from early endosomes to lysosomes inside the cell, also, this drug blocks the binding between SARS-CoV-2 and Angiotensin-Converting Enzyme (ACE)-2 inhibiting the interaction between the virus spike proteins and the cell membrane and this drug can also inhibit SARS-CoV-2 viral replication causing, ultimately, the reduction in viral infection as well as the potential to progression for a higher severity phenotype culminating with a higher chance of death. Azithromycin exerts a down-regulating effect on the inflammatory cascade, attenuating the excessive production of cytokines and inducing phagocytic activity, and acts interfering with the viral replication cycle. Ivermectin, when compared to standard care or placebo, did not reduce the disease severity, need for mechanical ventilation, need for intensive care unit, or in-hospital mortality. Only one study demonstrated that Ivermectin may improve viral clearance compared to placebo. Individuals who received Chloroquine/Hydroxychloroquine did not present a lower incidence of death, improved clinical status, or higher chance of respiratory deterioration compared to those who received usual care or placebo. Also, some studies demonstrated that Chloroquine/Hydroxychloroquine resulted in worse outcomes and side-effects included severe ones. Adding Azithromycin to a standard of care did not result in clinical improvement in hospitalized COVID-19 participants. In brief, COVID-19 was one of the deadliest pandemics in modern human history. Due to the potential health catastrophe caused by SARS-CoV-2, a global effort was made to evaluate treatments for COVID-19 to attenuate its impact on the human species. Unfortunately, several countries prematurely justified the emergency use of drugs that showed only in vitro effects against SARS-CoV-2, with a dearth of evidence supporting efficacy in humans. In this context, we reviewed the mechanisms of several drugs proposed to treat COVID-19, including Ivermectin, Chloroquine/Hydroxychloroquine, and Azithromycin, as well as the phase III clinical trials that evaluated the efficacy of these drugs for treating patients with this respiratory disease. Conclusions: As the main finding, although Ivermectin, Chloroquine/Hydroxychloroquine, and Azithromycin might have mechanistic effects against SARS-CoV-2 infection, most phase III clinical trials observed no treatment benefit in patients with COVID-19, underscoring the need for robust phase III clinical trials.

show abstract

Hydroxychloroquine in the post-COVID-19 era: will this pandemic upset decades of clinical practice?

Cited by 3 publications

References 51 publications

Hydroxychloroquine: Pharmacokinetics and Toxicity

Hydroxychloroquine: Pharmacokinetics and Toxicity

Biomedical Researchers Confronting the Covid-19 Pandemic

Efficacy of Ivermectin, Chloroquine/Hydroxychloroquine, and Azithromycin in Managing COVID-19: A Systematic Review of Phase III Clinical Trials

Contact Info

Product

Resources

About