Clinical Therapeutics
August 2015 Volume 37, Issue 8 , Supplement, e1-e170
http://www.clinicaltherapeutics.com/current

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High dose favipiravir: first experience in a patient with Ebola
A.M. Borobia, M. Mora-Rillo, G. Ramírez Olivencia, M. Lago, M. Arsuaga, F. De la Calle, F. Arnalich, J.R. Arribas, A.J. Carcas
DOI: http://dx.doi.org/10.1016/j.clinthera.2015.05.054
Abstract
Background
On October 2014, the first case of human-to-human transmission of Ebola virus (EVOB) outside Africa was admitted in our hospital. Patient received supportive treatment and experimental treatment with convalescent plasma and antiviral was considered. Favipiravir (Toyama-Chemical) is a RNA polymerase inhibitor approved in Japan for the treatment of influenza, but with no previous experience in human EVOB infected patients.
Methods
The rational for favipiravir dose and schedule was based on recent in vitro and in vivo data in mice (Oesterech, 2014) showing an EBOV-IC90: 17 μg/mL and therapeutic efficacy: 300 mg/kg/d. Preclinical toxicology studies in monkeys settled a NOAEL of 100 mg/kg/d. Also pharmacokinetic data in healthy volunteers (loading dose/maintenance: 1200/600 BID) provided by Company was took in consideration: Cmax: 30–56 μg/mL, t1/2: 3.4–5.8 hr and plasma albumin binding: 53%. Based on this limited information, we decided a loading dose of 50 mg/kg BID (3 doses) and maintenance dose of 25 mg/kg TID. This schedule aimed to maintain a free Cmin above IC90 and as close as possible to 60 μg/mL of total concentration. Similar doses had been recommended after our decision (Mentré, 2014).
Results
Favipiravir was initiated on day 9 of illness (DOI-9) and stopped on DOI-20 after two consecutive undetectable EBOV plasma viral loads. Despite the high doses used, favipiravir was well tolerated, without adverse events clearly related to the drug. The patient fully recovered and was discharged on DOI-34.
Conclusions
The contribution of favipiravir to disease resolution is difficult to ascertain because the use of other therapies (convalescent plasma and supportive treatment) and the spontaneous evolution of the disease, which can all be related to the cure of our patient. However, considering the time to treatment initiation, the severity of the disease, and the high viral load, contribution of favipiravir to the outcome of our patient must be considered and support its role as experimental therapy.