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Comment & Response
October 21, 2020

QT Interval in Patients With COVID-19—Reply

Author Affiliations
  • 1Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
  • 2Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
JAMA Cardiol. 2021;6(3):358. doi:10.1001/jamacardio.2020.4958

In Reply We thank Bianco et al for their interesting and important inquiry regarding the safety of crushing hydroxychloroquine. For many medications, including chloroquine and hydroxychloroquine with dose-dependent toxic effects, rapid absorption is known to cause harm.1 The manufacturer information recommends against crushing film-coated hydroxychloroquine (Plaquenil) tablets, yet drug-information resources, such as Lexicomp, include recommendations to mix with food or into suspension if unable to swallow the tablet.2 The film coating on these tablets was added primarily to enhance compliance due to its bitter taste, rather than pharmacokinetic considerations.3 However, the relationship between absorption, maximum serum concentration, and disruption of the coating requires further elucidation. Interestingly, in the DISCOVERY trial protocol,4 nasogastric administration of hydroxychloroquine was not only allowed, but the loading dose of hydroxychloroquine was also increased. In the absence of readily available therapeutic drug monitoring, we agree that pharmacokinetic studies related to nasogastric administration in critically ill patients are important in confirming bioequivalence and safety.

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