Hospital Pharmacy - April 2018 - 75

746417
research-article2017

HPXXXX10.1177/0018578717746417Hospital PharmacyLevien and Baker

Formulary Drug Reviews

Formulary Drug Reviews: Glecaprevir/
Pibrentasvir

Hospital Pharmacy
2018, Vol. 53(2) 75-84
© The Author(s) 2017
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https://doi.org/10.1177/0018578717746417
DOI: 10.1177/0018578717746417
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Terri L. Levien1 and Danial E. Baker1

Abstract
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Generic Name: Glecaprevir/Pibrentasvir
Proprietary Name: Mavyret (AbbVie)
Approval Rating: 1P
Therapeutic Class: Hepatitis C Virus Direct-Acting
Antivirals
Similar Drugs: Sofosbuvir/Velpatasvir (Epclusa)
Sound- or Look-Alike Names: Grazoprevir

Indications
Glecaprevir/pibrentasvir is Food and Drug Administration
(FDA) approved for the treatment of patients with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5, or 6 infection without
cirrhosis or with compensated cirrhosis (Child-Pugh A), and for
the treatment of patients with HCV genotype 1 infection who
have been previously treated with a regimen containing an HCV
NS5A inhibitor or an NS3/4A protease inhibitor, but not both.1
Indications for available pangenotypic, fixed-dose combination products are compared in Table 1.1-3

Clinical Pharmacology
Glecaprevir is an HCV NS3/4A protease inhibitor. In assays,
glecaprevir inhibited proteolytic activity of recombinant
NS3/4A enzymes from clinical isolates of HCV genotypes
1a, 1b, 2a, 2b, 3a, 4a, 5a, and 6a.1 Pibrentasvir is an HCV
NS5A inhibitor that has demonstrated activity against laboratory and clinical isolates from subtypes 1a, 1b, 2a, 2b, 3a,
4a, 4b, 4d, 5a, 6a, 6e, and 6p.1
In cell culture, resistance has been observed with some
amino acid substitutions known to reduce antiviral susceptibility, and some combinations of amino acid substitutions were
associated with greater reductions in susceptibility. In clinical trials, virologic failure was observed in small numbers of patients
with HCV genotype 1, 2, or 3 infection; 2 treatment-naive

patients with genotype 1 infection and 18 treatment-naive
patients with HCV genotype 3 infection developed treatmentemergent amino acid substitutions in NS3 and/or NS5A.
Treatment-emergent substitutions were also observed in several treatment-experienced patients who experienced virologic
failure while receiving glecaprevir/pibrentasvir. Not all patients
with virologic failure demonstrated treatment-emergent substitutions.1 Baseline HCV polymorphisms in genotypes 1, 2, 4, 5,
and 6 had no impact on treatment outcome; a lower response
rate was observed in patients with genotype 3 HCV infection
and baseline NS5A A30K polymorphism.1 Pibrentasvir has
been observed to retain some activity against some common
resistance-conferring substitutions in HCV genotypes 1, 2, 3, 4,
5, or 6 that have been identified for other NS5A inhibitors,
including those at key amino acid positions 28, 30, 31, or 93.
Genotype 3a Y93H, which confers 200-fold or greater resistance to other NS5A inhibitors, conferred a 2.3-fold change in
susceptibility to pibrentasvir.4

Pharmacokinetics
Following oral administration of the individual components
of glecaprevir/pibrentasvir in healthy subjects, peak glecaprevir and pibrentasvir concentrations are both reached in 5
hours. Relative to fasting, administration with a moderate- to
high-fat meal raises glecaprevir exposure by 83% to 163%
and raises pibrentasvir exposure by 40% to 53%. Following
administration of combination glecaprevir/pibrentasvir in
1

Washington State University, Spokane, WA, USA

Corresponding Author:
Terri L. Levien, Clinical Professor, Department of Pharmacotherapy,
College of Pharmacy, Washington State University Spokane,
PO Box 1495, Spokane, WA 99210-1495, USA.
Email: levient@wsu.edu
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