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Drug‐Drug Interactions of Tacrolimus or Cyclosporine With Glecaprevir and Pibrentasvir in Healthy Subjects
Author(s) -
Kosloski Matthew P.,
Zhao Weihan,
Li Hong,
Pugatch David,
Asatryan Armen,
Kort Jens,
Mensa Federico J.,
Liu Wei
Publication year - 2019
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.671
Subject(s) - tacrolimus , medicine , pharmacology , gastroenterology , adverse effect , area under the curve , transplantation
A fixed‐dose combination of glecaprevir and pibrentasvir is approved for treatment of chronic infection with hepatitis C virus (HCV) genotypes 1‐6. Three phase 1 open‐label studies were conducted in healthy volunteers to evaluate the potential for clinically relevant drug‐drug interactions of the glecaprevir 300‐mg and pibrentasvir 120‐mg combination with the immunosuppressants tacrolimus (1 mg) or cyclosporine (100 and 400 mg). Glecaprevir and pibrentasvir exposure was unaffected by tacrolimus, whereas the tacrolimus area under the curve (AUC) value was 45% higher with glecaprevir and pibrentasvir. Cyclosporine 100 mg had a limited effect on glecaprevir or pibrentasvir exposure (≤37% AUC increase), but cyclosporine 400 mg increased exposure of both glecaprevir and pibrentasvir (410% and 93% AUC increase, respectively). Cyclosporine concentration was unaffected by glecaprevir and pibrentasvir at either cyclosporine dose (≤14% AUC change). Adverse events were all grade 1 (mild), with the most common nausea and flushing attributed to cyclosporine. Findings from these studies supported evaluation of glecaprevir/pibrentasvir in HCV‐infected kidney and liver transplant recipients receiving tacrolimus without additional dose adjustment or receiving cyclosporine up to 100 mg per day.