Title: Pharmacokinetic evaluation of sofosbuvir/velpatasvir for the treatment of chronic hepatitis C in pediatrics aged 3 and older
Source: Expert Opinion on Drug Metabolism & Toxicology 2023, Dec 7. [E-publication]
Date of publication: December 2023
Publication type: Review article
Abstract: Introduction: The World Health Organization proposed targets to eliminate hepatitis C virus (HCV) by 2030, aiming to treat ≥ 80% of people with HCV infection, decreasing new chronic infections by 90% and liver-related mortality by 65%. While children/adolescents represent a minority of cases, the true burden is underestimated, with the majority of disease transmission attributed to vertical transmission. Advances in drug development have resulted in simplified treatments, formulated as single-tablet regimens, that are well-tolerated, effective, and pangenotypic. Sofosbuvir/velpatasvir, a combined nucleotide analog NS5B polymerase inhibitor and NS5A inhibitor, respectively, is approved for HCV treatment for individuals ≥3 years, supported by safety data for pediatric populations with lower-dose, novel formulations.
Areas covered: This review discusses chemistry, pharmacokinetics, pharmacodynamics, dosing, efficacy and safety of sofosbuvir/velpatasvir for HCV treatment, highlighting pediatric data. Literature review included publications/conference abstracts from PubMed, Google, and Google Scholar. Information from key clinical trials/regulatory approvals were reviewed. An expert opinion is provided.
Expert opinion: Sofosbuvir/velpatasvir is a safe, effective therapy for treatment of pangenotypic chronic HCV infection with limited cases of virologic relapse and adverse events among pediatric populations 3 years of age and older. However, tolerability among children 6 years and younger could be improved by alternative formulations (such as liquids, long-acting formulations) or routes of administration, if not, shorter treatment durations. Beyond its role for HCV treatment, an aspirational role of direct-acting antivirals (DAAs) that should be explored is for prevention of infection in exposed and at-risk pediatric populations.
