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CORRESPONDENCE
Year : 2020  |  Volume : 152  |  Issue : 1  |  Page : 124-126

Optimal dosing & time: Issues to get hydroxychloroquine safety & efficacy against COVID-19/SARS-CoV-2


Department of Internal Medicine, Health Sciences Center, Federal University of Santa Catarina, Florianopolis, Brazil

Date of Submission18-Jun-2020
Date of Web Publication17-Sep-2020

Correspondence Address:
Fabricio Souza Neves
Department of Internal Medicine, Health Sciences Center, Federal University of Santa Catarina, Florianopolis
Brazil
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmr.IJMR_2609_20

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How to cite this article:
Neves FS. Optimal dosing & time: Issues to get hydroxychloroquine safety & efficacy against COVID-19/SARS-CoV-2. Indian J Med Res 2020;152:124-6

How to cite this URL:
Neves FS. Optimal dosing & time: Issues to get hydroxychloroquine safety & efficacy against COVID-19/SARS-CoV-2. Indian J Med Res [serial online] 2020 [cited 2021 Jul 27];152:124-6. Available from: https://www.ijmr.org.in/text.asp?2020/152/1/124/292027



Sir,

Due to its in vitro antiviral characteristics and immunomodulatory properties, chloroquine (CQ) and hydroxychloroquine (HCQ) are candidates for the prevention and treatment of severe acute respiratory syndrome (SARS) for more than a decade[1]. The coronavirus disease 2019 (COVID-19) pandemic with SARS-CoV-2 renovated its interest, but clinical studies until now showed only a few (if any) benefits from CQ/HCQ in the treatment of COVID-19[2].

It is important to note that a possible explanation to this failure is based on the pharmacokinetic characteristics of these drugs. CQ and HCQ have large volumes of distribution due to their extensive sequestration by tissues, and therefore, a prolonged time is needed to reach stable plasmatic concentrations (the steady state). Both CQ and HCQ are used as immunomodulatory drugs in the treatment of systemic lupus erythematosus, and clinical improvement is obtained only after some weeks of treatment. This correlates with time to reach steady state. It was estimated that HCQ at a dose of 310 mg/day would take 14 days to reach 90 per cent of the plasma steady state[3]. Higher daily doses would lead to higher steady-state concentrations and shorten the time to achieve them. However, very high dosage is also associated with increased toxicity[4]. This pharmacokinetic profile makes CQ/HCQ more suitable for pre-exposure prophylaxis than for the treatment of COVID-19.

Chatterjee et al[5] in their case-control study about pre-exposure prophylaxis of COVID-19 with HCQ in healthcare workers demonstrated that HCQ provided significantly additional protection against COVID-19 beginning after four weeks of use of maintenance dose of HCQ 400 mg once weekly, in a progressive dose-response relationship. A single loading dose of HCQ 400 mg twice a day (bid) was also used.

These are encouraging results. Obviously, the use of personal protective equipment (PPE) cannot be neglected (the study shows the highest odds ratio with its use), but we are now able to consider an additional element of protection with HCQ in prophylactic use for those who are in high-risk of infection (healthcare workers).

To contribute to this effort, I additionally suggest the use of HCQ (400 mg bid) on the first day, followed by 400 mg three times a week in the first week, and then the maintenance dose of HCQ 400 mg once weekly. This scheme with a slightly higher loading dose in the first week may warrant earlier clinical benefits (after the first seven days)[6]. It would be useful for populations who already are at risk of COVID-19 infection, to get faster clinical benefits probably without significant risk of adverse effects.

Conflicts of Interest: None.



 
   References Top

1.
Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R. Effects of chloroquine on viral infections: An old drug against today's diseases? Lancet Infect Dis 2003; 3 : 722-7.  Back to cited text no. 1
    
2.
Sarma P, Kaur H, Kumar H, Mahendru D, Avti P, Bhattacharyya A, et al. Virological and clinical cure in COVID-19 patients treated with hydroxychloroquine: A systematic review and meta-analysis. J Med Virol 2020; 92 : 776-85.  Back to cited text no. 2
    
3.
Browning DJ. Pharmacology of chloroquine and hydroxychloroquine. Hydroxychloroquine and chloroquine retinopathy. New York: Springer; 2014.  Back to cited text no. 3
    
4.
Tett SE, Cutler DJ, Day RO, Brown KF. Bioavailability of hydroxychloroquine tablets in healthy volunteers. Br J Clin Pharmacol 1989; 27 : 771-9.  Back to cited text no. 4
    
5.
Chatterjee P, Anand T, Singh KJ, Rasaily R, Singh R, Das S, et al. Healthcare workers & SARS-CoV-2 infection in India: A case-control investigation in the time of COVID-19. Indian J Med Res 2020; 151 : 459-67.  Back to cited text no. 5
    
6.
Al-Kofahi M, Jacobson P, Boulware DR, Matas A, Kandaswamy R, Jaber MM, et al. Finding the dose for hydroxychloroquine prophylaxis for COVID-19: The desperate search for effectiveness. Clin Pharmacol Ther 2020; 10.1002/cpt.1874.  Back to cited text no. 6
    




 

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