Oseltamivir and QT Interval

The Brazilian trial, Borba et al. [3], in which critically ill patients were given toxic doses of chloroquine (not hydroxychloroquine), also included oseltamivir. Oseltamivir (Tamiflu®) is known to prolong QT interval [1]. It is also known to cause Bradycardia, both confirmed by animal experiments [2] (citing [1] for the results in humans). The NIH COVID-19 Treatment Guidelines described the Brazilian HCQ trial in detail, but failed to mention that oseltamivir is known to prolong QT interval on its own. The NIH Guidelines also failed to mention that the study authors stressed that the findings cannot be extrapolated to non-severe cases (emphasis is mine):

“The preliminary findings of this study suggest that the higher CQ dosage should not be recommended for critically ill patients with COVID-19 because of its potential safety hazards, especially when taken concurrently with azithromycin and oseltamivir. These findings cannot be extrapolated to patients with nonsevere COVID-19.

In almost all early clinical studies using chloroquine or hydroxychloroquine for COVID-19, the participants’ cases were severe, and CQ or HCQ was co-administered with oseltamivir or lopinavir/ritonavir, another known QT prolonger.  But if QT prolongation was detected, the blame was directed only at CQ, HCQ, or HCQ + AZ.

Other studies have independently shown that HCQ + AZ have no cardiac toxicity in non-severe COVID-19 patients.

[1]    Jefferson T, Jones M, Doshi P, Spencer EA, Onakpoya I, Heneghan CJ. Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ 2014;348:g2545. https://doi.org/10.1136/bmj.g2545

[2]    Hama R. The mechanisms of delayed onset type adverse reactions to oseltamivir. Infectious Diseases 2016;48:651–60. https://doi.org/10.1080/23744235.2016.1189592

[3]    Borba MGS, Val FFA, Sampaio VS, Alexandre MAA, Melo GC, Brito M, et al. Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial. JAMA Network Open 2020;3:e208857–e208857. https://doi.org/10.1001/jamanetworkopen.2020.8857