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An event is serious (based on the ICH definition) when the patient outcome is:
* death
* life-threatening
* hospitalisation
* disability
* congenital anomaly
* other medically important event
* Drug interaction
In a retrospective study conducted between 23 May 2020 and 15 July 2020 to evaluate the effect of azithromycin, hydroxychloroquine and favipiravir combination on the corrected QT interval (QTc) in patients with COVID-19, two patients including a male patient [not all sexes stated; ages not stated] were described; out of whom, the male patient had QTc interval prolongation following concurrent administration of off label azithromycin and hydroxychloroquine, and the remaining patient had QTc interval prolongation following concurrent administration of off label azithromycin, hydroxychloroquine and favipiravir for COVID-19 pneumonia [routes and times to reaction onsets not stated].
Case 1: The male patient was admitted due to COVID-19-related symptoms. Following a positive real-time reverse transcription-PCR for COVID-19, he was diagnosed with COVID-19 disease. Therefore, he started receiving off label treatment with hydroxychloroquine and azithromycin. He received hydroxychloroquine loading dose of 400mg twice a day on the first day followed by 200mg twice a day for a total of 5 days and, azithromycin with loading dose of 500 mg/day on the first day followed by 250 mg/day for a total of 5 days. An ECG performed on the day 5 of treatment demonstrated a QTc interval of >500ms. This, prolongation of QTc interval was identified due to direct effect of both the individual drug, and also due to the synergistic effect of the hydroxychloroquine and azithromycin. The synergistic effect indicated the pharmacodynamic interaction between hydroxychloroquine and azithromycin. He completed the off label therapy with hydroxychloroquine and azithromycin.
Case 2: The patient, who had diabetes mellitus was admitted due to COVID-19 related symptoms. Following a positive real-time reverse transcription-PCR for COVID-19 and chest CT scan, the patient was diagnosed with COVID-19 pneumonia. Therefore, the patient started receiving off label treatment with hydroxychloroquine, azithromycin and favipiravir. The patient received hydroxychloroquine loading dose of 400mg twice a day on the first day followed by 200mg twice a day for a total of 5 days, azithromycin with loading dose of 500 mg/day on the first day followed by 250 mg/day for a total of 5 days, and favipiravir with loading dose of 1600mg twice day on the first day followed by 600mg twice day for a total of 5 days. An ECG performed on the day 5 of treatment demonstrated a QTc interval of more than 500ms. This, prolongation of QTc interval was identified due to direct effect of individual drugs, and also due to the synergistic effect i.e. pharmacodynamic interaction of hydroxychloroquine and azithromycin, and undefined interaction with favipiravir. The patient completed the off label therapy of hydroxychloroquine, azithromycin and favipiravir [outcomes not stated].
Reference
- Cerik IB, et al. Impact of Adding Favipiravir to Hydroxychloroquine and Azithromycin Treatment on QTc Interval in COVID-19. Turkiye Klinikleri Cardiovascular Sciences 33: 15-21, No. 1, 2021. Available from: URL: 10.5336/cardiosci.2020-80082 [DOI]