Hydroxychloroquine in the treatment of COVID-19: How to use it waiting for conclusive scientific evidence

To the Editor

To date, there is no effective treatment against the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 disease. Numerous clinical studies are evaluating the utility of antiviral and immunomodulatory drugs, where antimalarials such as chloroquine and hydroxychloroquine (HCQ) are one of the alternatives studied.¹

So far, clinical experience in the use of HCQ arises mainly from treatment in patients with systemic lupus erythematosus (SLE), whose long-term effects show multiple benefits. However, high cumulative doses have been associated with serious adverse effects, especially in the retina and myocardium.²

Many healthcare protocols propose the use of HCQ in the treatment of COVID-19.¹ However, it is important to consider adverse myocardial effects, such as the development of severe arrhythmias.^3,4

In the COVID-19 patient, possible cardiac involvement is mainly related to 4 factors: 1) underlying heart disease (often silent in older patients); 2) myocardial involvement caused by the infection and the inflammatory response itself, which leads to myocarditis with elevated troponins; 3) acute toxicity probably associated with the use of antimalarials in high doses, more evident in chloroquine treatments and 4) concomitant use of other treatments that, together with HCQ, prolong the corrected QT interval (QTc), with the risk of serious ventricular arrhythmias.^3–5

In the absence (pending) of conclusive scientific evidence, what considerations should be taken into account when using HCQ in the treatment of COVID-19? It is necessary to change the way in which HCQ is usually used in patients with SLE, adapting its prescription and control of potential adverse effects to this new therapeutic scenario. The following considerations aim to optimize the HCQ treatment of COVID-19:

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  When the doctor considers that HCQ can be useful, it should be initiated as early as possible after diagnosing the infection, due to the decrease in viral replication and dissemination demonstrated in vitro and in vivo.¹

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  Using HCQ in an acute treatment (5 days), with loading dose (400 mg/every 12 h) the first day and 4 days of maintenance (200 mg/every 12 h), after requesting an informed medical consent (with COVID-19 being an indication not contemplated in the SmPC).

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  Minimize the risk of prolonged QTc. For this, a baseline electrocardiogram (ECG) must be performed prior to the start of treatment. If the QTc is greater than or equal to 500 ms, HCQ should not be started. If the QTc is less than 470 ms in men or less than 480 ms in women, treatment can be initiated, repeating the ECG in 48 h. If the QTc is greater than or equal to 500 ms or an increase greater than or equal to 60 ms is observed, treatment should be discontinued.⁴

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  Avoid or discontinue the simultaneous use of drugs that prolong the QTc, particularly azithromycin, clarithromycin, levofloxacin, moxifloxacin, ciprofloxacin, haloperidol, quetiapine, risperidone, domperidone and ondansetron, among others.^4,5

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  Keep a close watch on potassium, calcium and magnesium levels due to their arrhythmogenic potential, as well as glycemia in patients with diabetes due to the risk of hypoglycaemia.⁴

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  Consider not administering or discontinuing HCQ in advanced stages of infection due to the possibility of a COVID-19-induced myocarditis.^3,5

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  It is not necessary to adjust the dose based on renal or hepatic function, nor does it require ophthalmological control before or after treatment.⁶

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  Pending the result of several active studies, HCQ should not be indicated prophylactically as there is no evidence to support its preventive use or post-exposure to avoid COVID-19 infection.

In short, when prescribing HCQ in COVID-19, different precautions should be taken from those currently considered for SLE patients. It should be indicated in its window of opportunity and consider the existing multifactorial myocardial involvement, seeking to avoid cardiovascular adverse effects. The results of different controlled and randomized studies that confirm or refute the usefulness of HCQ in the treatment of COVID-19 will contribute to define its role in this clinical setting.

Funding

The authors declare that they have not received funding to carry out this study.