Dr. Anant Patil writes on drugs chloroquine, hydroxychloroquine, and azithromycin, all three of which have been under the spotlight now, for their roles in the treatment of COVID-19.
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Chloroquine is a well-established anti-malarial drug with anti-inflammatory action. It is also used in the treatment of rheumatoid arthritis and lupus erythematosus. Its anti-viral role came into discussion again recently in the context of COVID-19. The antiviral action of chloroquine is suggested to be because of increase in endosomal pH and interference with the terminal glycosylation of cellular receptors of SARS-CoV. [1,2] In line with the postulated mechanism, results of in-vitro studies suggest role of chloroquine in the control of 2019-nCoV infection. [2,3]
The anti-viral and anti-inflammatory activities of chloroquine make it a promising option for the treatment of COVID-19 pneumonia.  A recently published systematic review also suggests that there is sufficient pre-clinical rationale and evidence on the effectiveness of chloroquine for the treatment of COVID-19 and safety from long-term clinical use in other indications. This justifies the clinical research on chloroquine in COVID-19. 
The expert consensus by multicentre collaboration group of the Department of Science and Technology of Guangdong Province and Health Commission of Guangdong Province recommends ruling out anaemia, thrombocytopenia or leukopenia, disturbance of serum electrolytes, liver and renal impairment, QT interval prolongation and bradycardia in patients treated with chloroquine.
Visual and/or mental changes with use of chloroquine should also be monitored. Concomitant use of other drugs known to cause increase in QT interval, various anti-arrhythmics, antidepressant and anti-psychotics should also be avoided. 
Hydroxychloroquine is a hydroxyl derivative of chloroquine, also used in malaria and as a disease modifying anti-rheumatic drug. The clinical safety profile of hydroxychloroquine is better than chloroquine.  Hydroxychloroquine is also shown to be effective in inhibiting SARS-CoV-2 infection in vitro.  In another in-vitro study, hydroxychloroquine showed better anti-SARS-CoV-2 activity than chloroquine. 
A recent small, open-label, non-randomised clinical trial from France reported effectiveness of hydroxychloroquine in reduction/disappearance of viral load in patients with COVID-19. Effect of hydroxychloroquine was enhanced by azithromycin. Physicians should consider the risk of increase in QT interaction prolongation with use of these two drugs. 
Chloroquine and hydroxychloroquine are promising agents in the management of COVID-19 based on the available preliminary evidence from in-vitro and clinical studies.
Prophylaxis of high risk population against COVID-19
In the currently on-going COVID-19 pandemic, strategies for protection of high risk population (healthcare workers treating suspected/known case of COVID-19 and close contacts of laboratory positive case of COVID-19) against COVID-19 are urgently warranted.
Considering the time and cost involved in the development of new drug, it makes sense to evaluate the possibility of repositioning existing drugs by evaluating their efficacy and safety in the management of the ongoing COVID-19 pandemic. The existing drugs offer advantages for their known safety profile and drug interactions.
Recently (March 22, 2020), the National Task Force for COVID-19 by Indian Council of Medical Research (ICMR)  provided recommendation for prophylaxis of high risk population. According to this, the use of hydroxychloroquine is recommended for prophylaxis of SARS-CoV-2 infection in high risk population i.e. asymptomatic healthcare workers involved in the care of suspected/confirmed cases of COVID 19 and asymptomatic household contacts of laboratory confirmed cases.
Hydroxychloroquine should not be used for prophylaxis in children below 15 years of age, those with known cases of retinopathy, hypersensitivity to hydroxychloroquine or 4-aminoquinolines. Use of hydroxychloroquine does not prohibit patients from other recommended measures of prevention. Practice of frequent hand-washing, respiratory etiquette, and social distancing should be continued and if symptoms appear, they should immediately contact their healthcare facility.
Preventing drug misuse
Every medicine is associated with its known set of side effects, and this applies to hydroxychloroquine. It is therefore very crucial to stress the importance of avoiding injudicious use of the medicine. Everyone has a role to prevent the misuse of hydroxychloroquine.
1 The general population (i.e. community) should understand that the recent recommendation by the ICMR on use of hydroxychloroquine for prophylaxis is not for everyone. It is recommended only for high risk population mentioned above. People should refrain from taking this medicine without consultating a healthcare professional.
2 Healthcare practitioners should counsel people about possible adverse events or risk of drug interactions.
3 Pharmacists should dispense medicine only to patients having valid written prescription from a registered medical practitioner.
4 Regulatory authorities may consider more stringent monitoring of prescriptions and dispensing of hydroxychloroquine to avoid misuse/overuse during COVID-19 pandemic.
The large, multinational WHO SOLIDARITY trial, the 10 multicentre randomised controlled trial (NCT04304053)  and other studies will provide more insights about the effectiveness of different drugs in the treatment and prevention of COVID-19.
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Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.
The author, Dr. Anant Patil is Assistant Professor of Pharmacology.
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