Hospital Pharmacy - April 2018 - 77

Levien and Baker
in patients with moderate hepatic impairment, and use is contraindicated in patients with severe hepatic impairment.1
Clinically significant differences in the pharmacokinetics
of either agent were not observed based on age (18 to 88
years), gender, race/ethnicity, or body weight.1,6

Comparative Efficacy
Indication: Infection With Hepatitis C Virus
Genotypes 1 Through 6 Without Cirrhosis or
With Compensated Cirrhosis
Guidelines
Guidelines: HCV guidance: Recommendations for testing, managing, and treating hepatitis C
Reference: American Association for the Study of Liver
Diseases/Infectious Diseases Society of America/
International Antiviral Society-USA (AASLD/IDSA/
IAS-USA)7
Comments: The recommended therapies for treating
HCV infections (genotypes 1 through 6) are listed below
according to HCV genotype, cirrhosis status, and prior
treatment exposure. Glecaprevir/pibrentasvir has not yet
been incorporated into these guidelines.
Treatment-naive.
Genotype 1a
** Without cirrhosis: Elbasvir/grazoprevir; glecaprevir/
pibrentasvir; ledipasvir/sofosbuvir; or sofosbuvir/velpatasvir. Alternative regimens are paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD) with ribavirin;
simeprevir plus sofosbuvir; daclatasvir plus sofosbuvir; or elbasvir/grazoprevir with ribavirin.
** With compensated cirrhosis: Elbasvir/grazoprevir;
glecaprevir/pibrentasvir; ledipasvir/sofosbuvir; or
sofosbuvir/velpatasvir. Alternative regimen is elbasvir/grazoprevir with ribavirin.
Genotype 1b
** Without cirrhosis: Elbasvir/grazoprevir; glecaprevir/
pibrentasvir; ledipasvir/sofosbuvir; or sofosbuvir/velpatasvir. Alternative regimens are PrOD; simeprevir
plus sofosbuvir; or daclatasvir plus sofosbuvir.
** With compensated cirrhosis: Elbasvir/grazoprevir;
glecaprevir/pibrentasvir; ledipasvir/sofosbuvir; or
sofosbuvir/velpatasvir. Alternative regimen is PrOD.
Genotype 2
** With or without compensated cirrhosis: Glecaprevir/
pibrentasvir or sofosbuvir/velpatasvir. Alternative
regimen is daclatasvir plus sofosbuvir.

Genotype 3
** Without cirrhosis: Glecaprevir/pibrentasvir or sofosbuvir/velpatasvir. Alternative regimen is daclatasvir
plus sofosbuvir.
** With compensated cirrhosis: Glecaprevir/pibrentasvir
or sofosbuvir/velpatasvir. Alternative regimens are
sofosbuvir/velpatasvir/voxilaprevir or daclatasvir
plus sofosbuvir with or without ribavirin.
Genotype 4
** With or without compensated cirrhosis: Glecaprevir/
pibrentasvir; sofosbuvir/velpatasvir; elbasvir/grazoprevir; or ledipasvir/sofosbuvir. Alternative regimen
is paritaprevir/ritonavir/ombitasvir with ribavirin.
Genotype 5 or 6
** With or without compensated cirrhosis: Glecaprevir/
pibrentasvir; sofosbuvir/velpatasvir; or ledipasvir/
sofosbuvir.
Treatment-experienced
** Recommendations are dependent on what agents were
previously used. Some drug regimens include the
addition of ribavirin and/or peginterferon, and/or
require a longer duration of therapy.
Studies
Drug: Glecaprevir/Pibrentasvir versus Sofosbuvir plus
Daclatasvir
Reference: Foster GR, et al, 2017 (ENDURANCE-3 trial)8
Study Design: Phase 3, randomized, open-label, multicenter study
Study Funding: AbbVie
Patients: 505 treatment-naive patients with HCV genotype 3 infection without cirrhosis. Approximately half of
the sample was male (52%).
Intervention: Patients were randomized (2:1) to receive
glecaprevir 300 mg/pibrentasvir 120 mg once daily or
sofosbuvir 400 mg plus daclatasvir 60 mg once daily for
12 weeks. Subsequently, an additional treatment arm in
which patients received glecaprevir 300 mg/pibrentasvir
120 mg once daily for 8 weeks was added.

Results
Primary End Point(s)
** Sustained virologic response at posttreatment week 12
(SVR12) was achieved in 222 of 233 patients (95%;
95% confidence interval [CI], 93%-98%) treated with
glecaprevir/pibrentasvir for 12 weeks, in 111 of 115
(97%; 95% CI, 91%-9%) treated with sofosbuvir plus
daclatasvir for 12 weeks, and in 149 of 157 (95%; 95%

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