GY48LS6

Статус Emergency use authorization (EUA) FDA отозван 15 июня 2020 г.

Mechanisms may include inhibition of viral enzymes or processes such as viral DNA and RNA polymerase, viral protein glycosylation, virus assembly, new virus particle transport, and virus release. Other mechanisms may also involve ACE2 cellular receptor inhibition, acidification at the surface of the cell membrane inhibiting fusion of the virus, and immunomodulation of cytokine release.

Pre-clinical in vitro data suggest hydroxychloroquine has activity against SARSCoV-2.

One in vitro study suggests that hydroxychloroquine may be more potent than chloroquine.

• Hydroxychloroquine exhibited a higher in vitro antiviral effect compared to chloroquine when drug was added prior to the viral challenge.
• The EC50 values for chloroquine were greater than 100 microM at 24 hours and 18.01 microM at 48 hours.
• The EC50 values for hydroxychloroquine were 6.25 microM at 24 hours and 5.85 microM at 48 hours.

An open-label, non-randomized clinical trial compared hydroxychloroquine treatment to an untreated negative control group.

• Preliminary data showed the proportion of patients that had negative PCR results significantly differed between treated patients and untreated controls.
• On day 6, 70% of hydroxychloroquine-treated patients were virologically cured compared to 12.5% in the untreated control group.

A parallel-group, randomized trial of hospitalized patients with nonsevere COVID-19 compared 5 days for hydroxychloroquine to standard treatment.

• Fever recovery time was shortened in the hydroxychloroquine group (2.2 days) compared to standard therapy (3.2 days).
• Cough recovery time was shortened in the hydroxychloroquine group (2 days) compared to standard therapy (3.1 days).

A prospective review assessed virologic and clinical outcomes of 11 hospitalized patients who received hydroxychloroquine and azithromycin.

• Within 5 days, 1 patient died, 2 were transferred to the ICU, and 1 patient had therapy discontinued due to QT prolongation.
• Nasopharyngeal swabs were still positive for SARS-CoV-2 in 8 of 10 patients 5 to 6 days after treatment initiation.

Some protocols have recommendations for use.

Additional data regarding clinical efficacy for COVID-19 are being evaluated.

Safety Concerns:

• Risk of cardiac arrhythmias (e.g., QT prolongation)
• Risk of retinal damage, especially with long term use
• Caution in patients with G6PD deficiency
• Caution in diabetics
• Significant drug interactions

к.м.н. Отделенов В.А., к.м.н. Мирзаев К.Б., PhD Киселев Ю.Ю., д.м.н., проф., Гиляревский С.Р., д.м.н., проф., член-корр. РАН Сычев Д.А. Рекомендуемые подходы к наблюдению за интервалом QT при приеме гидроксихлорохина при COVID-19. 26 апреля 2020. Информационный центр по вопросам фармакотерапии у пациентов с новой коронавирусной инфекцией COVID-19 «ФармаCOVID» на базе ФГБОУ ДПО РМАНПО Минздрава России.

Zhichao Feng, Jennifer Li, et al. The Use of Adjuvant Therapy in Preventing Progression to Severe Pneumonia in Patients with Coronavirus Disease 2019: A Multicenter Data Analysis. MedRxiv.April 10, 2020. DOI: 10.1101/2020.04.08.20057539.

Wei Tang, Zhujun Cao, et al. Hydroxychloroquine in patients with COVID-19: an open-label, randomized, controlled trial. DOI: 10.1101/2020.04.10.20060558.

Zhaowei Chen, Jijia Hu, et al. Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial. DOI: 10.1101/2020.03.22.2004075.

Andrew A. Lover. Quantifying treatment effects of hydroxychloroquine and azithromycin for covid-19: a secondary analysis of an open label non-randomized clinical trial. DOI: 10.1101/2020.03.22.20040949. 

Jinoos Yazdany and Alfred H.J. Kim. Use of Hydroxychloroquine and Chloroquine During the COVID-19 Pandemic: What Every Clinician Should Know. Ann Intern Med. 2020 Mar 31 : M20-1334. doi: 10.7326/M20-1334. PMID: 32232419.

Credible Meds. COVID-19 experimental therapies and TdP risk.

CHEN Jun, LIU Danping, LIU Li, LIU Ping, XU et al.. A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19). J Zhejiang Univ (Med Sci) 2020, Vol. 49. DOI: 10.3785/j.issn.1008-9292.2020.03.03.

Molina JM, Delaugerre C, Goff JL, et al. No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe 17 COVID-19. Med Mal Infect 2020. DOI:https://doi.org/10.1016/j.medmal.2020.03.006. PMID: 32240719.

Gautret P, Lagier J, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents 2020 Mar 20. PMID: 32205204.

Yao X, Ye F, Zhang M, et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis 2020 Mar 9. PMID: 32150618.

Dong L, Hu S, Gao J. Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discov Ther 2020;14:58-60. PMID: 32147628.

Italian Society of Infectious and Tropical Diseases. Handbook for the care of people with disease-COVI 19. Edition 2.0, March 13, 2020.

Colson P, Rolain J, Lagier J, et al. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int J Antimicrob Agents 2020. PMID: 32145363.

Ben-Zvi H, Kivity S, Langevitz P, et al. Hydroxychloroquine: from malaria to autoimmunity. Clin Rev Allergy Immunol 2012;42:145-153. PMID: 21221847.