tetano
Editor, Senior Moderator
J Infect Chemother
. 2021 May 24;S1341-321X(21)00138-0.
doi: 10.1016/j.jiac.2021.05.009. Online ahead of print.
Open-label study of the safety, pharmacokinetics, and effectiveness of a 2 mg/kg dose of baloxavir marboxil 2% granules in children <20 kg with influenza
Takuhiro Sonoyama[SUP] 1 [/SUP], Hiroki Sakaguchi[SUP] 2 [/SUP], Hiroki Koshimichi[SUP] 3 [/SUP], Takeshi Noshi[SUP] 4 [/SUP], Kenji Tsuchiya[SUP] 5 [/SUP], Takeki Uehara[SUP] 6 [/SUP]
Affiliations
Abstract
Introduction: Baloxavir marboxil is an oral anti-influenza drug with demonstrated safety and efficacy in pediatric patients when a 2% granules formulation is administered at 1 mg/kg. This study assessed safety, effectiveness, and pharmacokinetics of a higher dose (2 mg/kg) of baloxavir marboxil 2% granules in pediatric patients weighing <20 kg.
Methods: This multicenter, open-label, noncontrolled study was conducted at 15 sites in Japan (January 2019-March 2020; JapicCTI-194577). Patients aged <12 years with confirmed influenza received a single oral dose of baloxavir marboxil at 2 mg/kg if body weight was <10 kg or 20 mg if ≥ 10 to <20 kg. Safety, pharmacokinetics, effectiveness (time to illness alleviation [TTIA] of influenza; time to resolution of fever; virus titer), and polymerase acidic protein (PA) substituted viruses were assessed over 22 days.
Results: 45 patients, all aged ≤6 years, were enrolled. Adverse events were reported in 24 (53.3%) patients, most commonly nasopharyngitis, diarrhea, and upper respiratory tract infection. Median (95% confidence interval [CI]) TTIA was 37.8 (27.5-46.7) hours; median (95% CI) time to resolution of fever was 22.0 (20.2-28.6) hours. A >4 log decrease in mean viral titer occurred at day 2 and a subsequent temporary 1-2 log increase in patients with influenza A(H3N2) and B. Treatment-emergent PA/I38X-substituted virus was detected in 16/39 (41.0%) patients, but no prolonged TTIA or time to resolution of fever was associated with its presence.
Conclusions: Baloxavir granules administered at 2 mg/kg in children <20 kg were well tolerated, with symptom alleviation similar to 1 mg/kg.
Keywords: Baloxavir; Child; Human; Influenza; Pharmacokinetics.
. 2021 May 24;S1341-321X(21)00138-0.
doi: 10.1016/j.jiac.2021.05.009. Online ahead of print.
Open-label study of the safety, pharmacokinetics, and effectiveness of a 2 mg/kg dose of baloxavir marboxil 2% granules in children <20 kg with influenza
Takuhiro Sonoyama[SUP] 1 [/SUP], Hiroki Sakaguchi[SUP] 2 [/SUP], Hiroki Koshimichi[SUP] 3 [/SUP], Takeshi Noshi[SUP] 4 [/SUP], Kenji Tsuchiya[SUP] 5 [/SUP], Takeki Uehara[SUP] 6 [/SUP]
Affiliations
- PMID: 34045119
- DOI: 10.1016/j.jiac.2021.05.009
Abstract
Introduction: Baloxavir marboxil is an oral anti-influenza drug with demonstrated safety and efficacy in pediatric patients when a 2% granules formulation is administered at 1 mg/kg. This study assessed safety, effectiveness, and pharmacokinetics of a higher dose (2 mg/kg) of baloxavir marboxil 2% granules in pediatric patients weighing <20 kg.
Methods: This multicenter, open-label, noncontrolled study was conducted at 15 sites in Japan (January 2019-March 2020; JapicCTI-194577). Patients aged <12 years with confirmed influenza received a single oral dose of baloxavir marboxil at 2 mg/kg if body weight was <10 kg or 20 mg if ≥ 10 to <20 kg. Safety, pharmacokinetics, effectiveness (time to illness alleviation [TTIA] of influenza; time to resolution of fever; virus titer), and polymerase acidic protein (PA) substituted viruses were assessed over 22 days.
Results: 45 patients, all aged ≤6 years, were enrolled. Adverse events were reported in 24 (53.3%) patients, most commonly nasopharyngitis, diarrhea, and upper respiratory tract infection. Median (95% confidence interval [CI]) TTIA was 37.8 (27.5-46.7) hours; median (95% CI) time to resolution of fever was 22.0 (20.2-28.6) hours. A >4 log decrease in mean viral titer occurred at day 2 and a subsequent temporary 1-2 log increase in patients with influenza A(H3N2) and B. Treatment-emergent PA/I38X-substituted virus was detected in 16/39 (41.0%) patients, but no prolonged TTIA or time to resolution of fever was associated with its presence.
Conclusions: Baloxavir granules administered at 2 mg/kg in children <20 kg were well tolerated, with symptom alleviation similar to 1 mg/kg.
Keywords: Baloxavir; Child; Human; Influenza; Pharmacokinetics.