Drug-Drug Interactions in Children and Adolescents Receiving Ledipasvir/Sofosbuvir for the Treatment of Hepatitis C Virus Infection

Clin Drug Investig. 2019 Sep;39(9):857-864. doi: 10.1007/s40261-019-00805-5.

Abstract

Background and objective: Drug-drug interactions need to be considered to optimize the pharmacotherapeutic outcome of direct-acting antivirals. The aim of this study was to report on possible drug-drug interactions between ledipasvir/sofosbuvir and other medications received by children and adolescents with hepatitis C virus, in addition to suggested management for these drug-drug interactions.

Methods: Hepatitis C virus-infected children and adolescents, 12-17 years of age and/or weighing ≥ 35 kg, who presented to the Pediatric Hepatology Unit at Cairo University Pediatric Hospitals for ledipasvir/sofosbuvir treatment were included. Medication history was taken including long-term medications for chronic conditions and on-demand medications for inter-current illnesses. Medications were reviewed by the Kasr Alainy Drug Information Center to identify possible drug-drug interactions with prescribed ledipasvir/sofosbuvir and their management. HEP Drug Interactions provided by the University of Liverpool, Lexicomp®, and Medscape were the utilized references. Each drug-drug interaction was assigned a risk rating of A, B, C, D, or X.

Results: Sixty hepatitis C virus-infected children and adolescents assigned to receive ledipasvir/sofosbuvir were enrolled. Thirty percent of patients had associated chronic co-morbid conditions. The overall number of medications received was 48; 39 were prescribed as long-term medications with a median of 3 (interquartile range 4.24) medications per patient. Proton pump inhibitors, antacids, histamine H2 receptor antagonists, sodium bicarbonate, and colchicine were reported to be associated with a drug-drug interaction risk D necessitating therapy modification, which occurred prior to administration.

Conclusions: Early identification and prompt response to drug-drug interactions with the aid of pharmacists optimize the pharmacotherapeutic outcome and eliminate possible morbidities when using direct-acting antivirals in children and adolescents with hepatitis C virus.

MeSH terms

  • Adolescent
  • Antiviral Agents / therapeutic use*
  • Benzimidazoles / therapeutic use*
  • Child
  • Drug Interactions
  • Female
  • Fluorenes / therapeutic use*
  • Hepatitis C / drug therapy
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Male
  • Risk Assessment
  • Sofosbuvir
  • Treatment Outcome
  • Uridine Monophosphate / analogs & derivatives*
  • Uridine Monophosphate / therapeutic use

Substances

  • Antiviral Agents
  • Benzimidazoles
  • Fluorenes
  • ledipasvir, sofosbuvir drug combination
  • Uridine Monophosphate
  • Sofosbuvir