Safety considerations with chloroquine, hydroxychloroquine a
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Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) has spread rapidly around the globe in recent months. With deaths from its associated disease, coronavirus disease 2019 (COVID-19), projected to reach into the millions and a vaccine unlikely in the near term, the search is on for existing drugs that might prevent COVID-19 or improve outcomes for patients who have COVID-19. Chloroquine and its derivative hydroxychloroquine, which have been used for decades in the treatment and prevention of malaria as well as chronic inflammatory diseases such as rheumatoid arthritis and systemic lupus erythematosus, have received much attention as potential therapies.

Chloroquine and hydroxychloroquine are generally well-tolerated, but clinicians and patients should be aware of serious adverse events that can occur, even during short courses of treatment.

Potential risks of treatment include prolongation of the QTc interval (especially in patients with preexisting cardiac disease or if co-prescribed with azithromycin), hypoglycemia, neuropsychiatric effects, drug-drug interactions, and idiosyncratic hypersensitivity reactions. Genetic variability in the metabolism of these drugs is considerable and influences their safety and effectiveness. Chloroquine and hydroxychloroquine are extremely toxic in overdose.

The use of either chloroquine or hydroxychloroquine and azithromycin for treatment or prevention of SARS-CoV-2 infection is currently supported primarily by in vitro data and weak studies involving humans. Physicians and patients should be aware of several uncommon but potentially life-threatening adverse effects should these drugs be used before better-designed studies determine their benefit, if any, in treating or preventing COVID-19. Harms of treatment can be mitigated by careful patient selection and monitoring.

Disclaimer: A search of PubMed from 1966 until 2020 was conducted for publications related to adverse events involving chloroquine, hydroxychloroquine and azithromycin. No restrictions were placed on article type; however, reviews were prioritized where available and their bibliographies were examined for articles that might have been missed in the broader search.

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