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Hydroxychloroquine/remdesivir/tocilizumab Increase in corrected QT interval and off-label use: case report

In a report of 2 patients, a 16-year-old girl (patient 1) was described who exhibited an increase in corrected QT interval during offlabel therapy with hydroxychloroquine for coronavirus 2019 disease (COVID-19). Additionally, she received off-label therapy with tocilizumab and remdesivir for COVID-19 [routes not stated]. The obese girl, who had intermediate-risk orbital alveolar rhabdomyosarcoma, had been receiving chemotherapy with vincristine and irinotecan at hospital. During week 10 of chemotherapy, she was diagnosed with COVID-19 disease. Initially, she was stable with ongoing diarrhoea and vomiting [aetiologies unknown]. She developed fever on hospital day 3. On admission, she started receiving unspecified prophylactic anticoagulant therapy and oxygen as needed for comfort. On hospital day 6, she started receiving off-label hydroxychloroquine 400mg twice daily, followed by 200mg twice daily, for COVID-19. The off-label hydroxychloroquine was used as a bridge to compassionate use of remdesivir. However, on hospital day 7, she experienced clinical deterioration with increased work of breathing, fatigue and hypoxia, which necessitated transfer to the ICU for support with heated high-flow nasal cannula. She exhibited an increase in the corrected QT interval from 416 to 440 during an ECG, while had been receiving hydroxychloroquine. She was noted to have cardiac complication i.e. an increase in the corrected QT interval secondary to hydroxychloroquine [time to reaction onset stated]. The girl had been receiving chemotherapy. Due to rising IL-6 levels (severe cytokine storm) and impending respiratory failure, she received off-label therapy with tocilizumab 800mg daily on hospital day 7 and day 8. Subsequently, the fever and CRP improved; however, she remained febrile, and she required high levels of oxygen support. On hospital day 10, off-label use of remdesivir 100mg daily for 5 doses was started for the treatment of COVID-19. Meanwhile, hydroxychloroquine was discontinued. The dosing of remdesivir was limited by elevated alanine transferase [aetiology unknown]. She was weaned from oxygen support, and on hospital day 14, she was moved out of the ICU [outcome of ADR not stated]. Stokes CL, et al. Severe COVID-19 disease in two pediatric oncology patients. Pediatric Blood and Cancer 67: 1-4, No. 9, Sep 2020. Available from: URL: http:// doi.org/10.1002/pbc.28432

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Reactions 19 Sep 2020 No. 1822