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Effective and Safe Daclatasvir Drug Exposures Predicted in Children Using Adult Formulations

Tim R Cressey1,2,3, Maggie Abbassi4, Marc Lallemant1,5

  • 1From the AMS-PHPT Research Collaboration, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand.

The Pediatric Infectious Disease Journal
|July 29, 2021
PubMed

Insights

Daclatasvir (DCV) 30 mg once daily is predicted to be safe and effective for children aged 14 to <35 kg with chronic hepatitis C virus (HCV) infection. This finding could expand global access to HCV treatment for pediatric populations.

Area of Science:

  • Pharmacokinetics and pharmacodynamics of antiviral agents
  • Pediatric infectious diseases
  • Hepatitis C virus (HCV) treatment

Background:

  • Sofosbuvir/daclatasvir (SOF/DCV) is a preferred direct-acting antiviral for chronic hepatitis C virus (HCV) in adults.
  • Limited data exist on daclatasvir (DCV) use in pediatric populations.
  • Population pharmacokinetic (PK) analysis is crucial for predicting drug exposure in children.

Purpose of the Study:

  • To predict daclatasvir (DCV) exposure in children using available adult formulations.
  • To evaluate the safety and efficacy of SOF/DCV in pediatric patients with HCV.
  • To inform optimal dosing strategies for pediatric HCV treatment.

Main Methods:

  • Population pharmacokinetic (PK) analysis of DCV concentration data from HCV-infected adolescents.
  • Monte Carlo simulations to predict DCV exposure in virtual children aged 10 to <35 kg.
  • Comparison of predicted pediatric DCV exposures with established adult ranges.

Main Results:

  • Adolescents receiving 60 mg DCV showed specific PK parameters (AUC, Cmax, Cmin).
  • Predicted DCV exposures in children receiving 30 mg were compared to adults.
  • Increased proportion of children with exposures above adult range for lower weight groups and higher doses.

Conclusions:

  • Daclatasvir (DCV) 30 mg once daily is predicted to achieve effective and safe exposures in children 14 to <35 kg, potentially down to 10 kg.
  • Clinical validation of these findings is recommended.
  • Utilizing low-cost adult DCV formulations with approved pediatric SOF doses can enhance global HCV treatment access for children.
Abstract

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