QTc interval prolongation during favipiravir therapy in an Ebolavirus-infected patient

Chinello, Pierangelo; Petrosillo, Nicola; Pittalis, Silvia; Biava, G; Ippolito, Giuseppe; Nicastri, Emanuele

doi:10.1371/journal.pntd.0006034

Cited by 80 publications

(79 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[ 10 ] QTc prolongation was observed on the 9th day of treatment in a patient who was previously using favipiravir for Ebolavirus infection. [ 11 ] In this patient, the loading dose given was 6000 mg and 2400 mg daily thereafter. His admission potassium levels were 3.5 mmol/L, and ionized calcium was determined to be 1.08 mmol/L when QTc prolongation was evident.…”

Section: Discussionmentioning

confidence: 99%

“…Significant QT prolongation due to favipiravir was demonstrated in a patient with EVD in a previous case study. [ 11 ] Favipiravir was not shown to have a detectable effect on QT intervals in a study performed by Kumagai et al on healthy adults that used moxifloxacin as a positive control to enable high-powered statistical analysis. [ 12 ] To the best of our knowledge, the effect of favipiravir on the QTc interval in COVID-19 patients has not been evaluated in any study to date.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The effect of favipiravir on QTc interval in patients hospitalized with coronavirus disease 2019

Çap

Bilge

Işık

et al. 2020

Journal of Electrocardiology

View full text Add to dashboard Cite

Background The effect of favipiravir on the QTc interval during the treatment of Coronavirus Disease 2019 (COVID-19) patients is unclear. Thus, the current study objective was to evaluate any change in the QTc interval in patients who were hospitalized due to COVID-19 receiving favipiravir treatment. Method Patients hospitalized with COVID-19 were assessed in this single-center retrospective study. 189 patients, whose diagnosis was confirmed using real-time PCR, were included in the study. The patients were divided into three groups: those using hydroxychloroquine (Group 1, n = 66), hydroxychloroquine plus favipiravir (Group 2, n = 66), and favipiravir only (Group 3, n = 57). The QTc interval was measured before treatment (QTc-B) and 48 h after (i.e., the median) starting treatment (QTc-AT). Results The median age was 53 (39–66 IQR) and 97 (51%) of patients were female. The median QTc(Bazett)-change was 7 ms ( p = 0.028) and 12 ms ( p < 0.001) and in Group 1 and 2, respectively. In Group 3, the median QTc(Bazett)-change was observed as −3 ms and was not statistically significant ( p = 0.247). In multivariable analysis, while there was a significant relationship between QTc-AT(Bazett) and hydroxychloroquine (β coefficient = 2687, 95%CI 2599–16,976, p = 0,008), there was no significant relationship with favipiravir (β coefficient = 0,180, 95% CI -6435-7724, p = 0,858). Similarly, there was a significant relationship between the QTc-AT interval calculated using the Fredericia formula and hydroxychloroquine (β coefficient = 2120, 95% CI 0,514–14,398, p = 0,035), but not with favipiravir (β coefficient = 0,111, 95% CI -6450- 7221, p = 0,911). Conclusion In the ECG recordings received in the following days after the treatment was started in COVID-19 patients, there was a significant prolongation in the QTc interval with hydroxychloroquine, but there was no significant change with favipiravir.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The effect of favipiravir on QTc interval in patients hospitalized with coronavirus disease 2019

Çap

Bilge

Işık

et al. 2020

Journal of Electrocardiology

View full text Add to dashboard Cite

show abstract

“…Favipiravir was reported as not having caused QT prolongation after single oral doses of 1200 mg and 2400 mg [ 16 ]. However, in one case report in the treatment of Ebola virus, favipiravir prolonged the QT at higher doses [ 17 ]. Given the limited clinical experience with this agent, particularly for our patient, we decided to use strategies to mitigate and monitor the potential for QT prolongation.…”

Section: Discussionmentioning

confidence: 99%

Traveling for heart transplantation and returning with COVID-19: a logistical, clinical, and pharmacotherapeutic challenge from the Middle East

Atallah

Hamour

Mallah

et al. 2020

Drugs Ther Perspect

View full text Add to dashboard Cite

Heart transplantation (HT) has become a standard option for patients with end-stage heart failure (HF). However, the scarcity of donor availability remains a major hurdle for receiving this novel therapy, especially in the context of the rapidly spreading severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) pandemic. We report the case of a patient in the United Arab Emirates (UAE) with advanced HF who was glucose-6-phosphate dehydrogenase deficient and had a history of type 2 diabetes mellitus with diabetic retinopathy and nephropathy, chronic kidney disease stage II, and hyperlipidemia. He was referred for HT abroad and was subsequently caught in the midst of the COVID-19 pandemic in New York, the US state most affected by the crisis at the time. Despite limited experience with favipiravir, we judged it to be the most appropriate agent with this patient’s complex history given the lower risk for QT prolongation, no need for renal-dose adjustment, and no reported drug–drug interactions. Given the limited clinical experience with this agent, particularly for our patient, we decided to adopt strategies to mitigate and monitor the potential for QT prolongation. We outline the logistical, clinical, and pharmacological challenges that the poly-morbid patient and our HT program in the Middle-East faced under those novel circumstances.

show abstract

“…Because of its competitive anti-heparin potential and interference with viral replication and entry into the cell, the anti-trypanosomal agent, Suramin (Germanin or Bayer-205) has been proposed to treat EVD ( 229 ). A pyrazine carboxamide derivative namely Favipiravir (an anti-flu medicine), which was used earlier as an inhibitor of influenza virus replication, has been found useful in both therapy and prophylaxis during EBOV epidemic in West Africa ( 238 – 240 ). Favipiravir and the pyrazine carboxamide derivative T-705 showed positive results in treating patients with medium to high viremias, although these drugs were not found to be effective with very high viremias, but revealed acceptable results during EBOV infection in mouse ( 219 , 221 , 241 ).…”

Section: Advances In Developing Drugs and Therapies Against Ebovmentioning

confidence: 99%

Advances in Designing and Developing Vaccines, Drugs, and Therapies to Counter Ebola Virus

et al. 2018

View full text Add to dashboard Cite

Ebola virus (EBOV), a member of the family Filoviridae, is responsible for causing Ebola virus disease (EVD) (formerly named Ebola hemorrhagic fever). This is a severe, often fatal illness with mortality rates varying from 50 to 90% in humans. Although the virus and associated disease has been recognized since 1976, it was only when the recent outbreak of EBOV in 2014–2016 highlighted the danger and global impact of this virus, necessitating the need for coming up with the effective vaccines and drugs to counter its pandemic threat. Albeit no commercial vaccine is available so far against EBOV, a few vaccine candidates are under evaluation and clinical trials to assess their prophylactic efficacy. These include recombinant viral vector (recombinant vesicular stomatitis virus vector, chimpanzee adenovirus type 3-vector, and modified vaccinia Ankara virus), Ebola virus-like particles, virus-like replicon particles, DNA, and plant-based vaccines. Due to improvement in the field of genomics and proteomics, epitope-targeted vaccines have gained top priority. Correspondingly, several therapies have also been developed, including immunoglobulins against specific viral structures small cell-penetrating antibody fragments that target intracellular EBOV proteins. Small interfering RNAs and oligomer-mediated inhibition have also been verified for EVD treatment. Other treatment options include viral entry inhibitors, transfusion of convalescent blood/serum, neutralizing antibodies, and gene expression inhibitors. Repurposed drugs, which have proven safety profiles, can be adapted after high-throughput screening for efficacy and potency for EVD treatment. Herbal and other natural products are also being explored for EVD treatment. Further studies to better understand the pathogenesis and antigenic structures of the virus can help in developing an effective vaccine and identifying appropriate antiviral targets. This review presents the recent advances in designing and developing vaccines, drugs, and therapies to counter the EBOV threat.

show abstract

QTc interval prolongation during favipiravir therapy in an Ebolavirus-infected patient

Cited by 80 publications

References 18 publications

The effect of favipiravir on QTc interval in patients hospitalized with coronavirus disease 2019

The effect of favipiravir on QTc interval in patients hospitalized with coronavirus disease 2019

Traveling for heart transplantation and returning with COVID-19: a logistical, clinical, and pharmacotherapeutic challenge from the Middle East

Advances in Designing and Developing Vaccines, Drugs, and Therapies to Counter Ebola Virus

Contact Info

Product

Resources

About