Transcript Slide 0

Hepatitis C: Updates in Therapeutics
Presented by
Whitney Jandreau, PharmD
PGY1 Pharmacy Practice Resident
VA Maine Healthcare System
April 2, 2016
The author of this presentation has the following to
disclose concerning possible financial or personal
relationships with commercial entities that may have a
direct or indirect interest in the subject matter of this
presentation.
Whitney Jandreau: Nothing to disclose
Objectives
1. Examine recent trends in the diagnosis and management of
hepatitis C virus (HCV) infection.
2. Identify risk factor-based screening strategies to improves
rates of detection and treatment of HCV infection.
3. Construct an individualized management plan for both
treatment-naïve and treatment-experienced patients with
HCV infection.
4. Develop a monitoring and assessment plan for patients with
HCV infection who are initiated on various
pharmacotherapies.
5. Describe strategies for optimized care of HCV patients who
VETERANSare
ADMINISTRATION
PATIENT
CARE SERVICESHIV/HCV coinfected, or cirrhotic.
post-liver
transplant,
2
Introduction
OVERVIEW OF HEPATITIS C VIRUS (HCV)
VETERANS ADMINISTRATION PATIENT CARE SERVICES
Introduction to HCV
• Hepatitis C is a viral liver infection and the most
common blood-borne infection in the United States
• The virus lacks a proofreading polymerase – the
resulting mutations allow the virus to evade the
immune system
VETERANS ADMINISTRATION PATIENT CARE SERVICES
Viral Genotypes
VETERANS ADMINISTRATION PATIENT CARE SERVICES
Negro, F. & Alberti, A. Liver Transpl. 31 (Suppl. 2), 1–3 (2011) and Center for Disease Analysis
Pathophysiology
ISG: interferon-stimulated genes
VETERANS ADMINISTRATION PATIENT CARE SERVICES
IFN: interferon
HCV: hepatitis C virus
CHC: chronic hepatitis C
6
Assessment of Fibrosis/Cirrhosis
METAVIR Score
FIB-4 Index
*Histologic*
APRI
Child-Turcotte-Pugh Score
*Non-invasive*
*Non-invasive*
*Non-invasive*
(age x AST)/(plt x [sqr ALT])
(AST to platelet ratio index)
Points assigned for clinical
parameters: ascites, T bili, alb,
PT/INR, hepatic encephalopathy.
F0: no fibrosis
F1: portal fibrosis without
septa
F2: portal fibrosis with
septa
F3: portal fibrosis with
numerous septa without
cirrhosis
HCV:
<1.45 = METAVIR F0-F1
>3.25 = METAVIR F3-F4
NASH:
<1.30 = METAVIR F0-F1
>2.67 = METAVIR F3-F4
F4: cirrhosis
Intensity of
necroinflammatory
lesions is graded A0 (no
activity) to A3 (severe).
≤0.3: unlikely cirrhosis or
significant fibrosis
>0.3 and ≤0.5: unlikely
cirrhosis, significant fibrosis
possible
>0.5 and ≤1.5: significant
fibrosis or cirrhosis possible
7 to 9: B (significant functional
compromise; 60% 2-yr survival)
10 to 15: C (decompensated;
35% 2-yr survival)
>1.5 and ≤2: likely significant
fibrosis, cirrhosis possible
>2: likely cirrhosis
VETERANS ADMINISTRATION PATIENT CARE SERVICES
Prepared by Whitney Jandreau, PharmD
5 to 6: A (well-compensated;
85% 2-yr survival)
7
Viral Transmission
• Primarily through large or repeated percutaneous exposure
to infectious blood
– Injection drug use
– Receipt of blood, blood products, or organs
– Needlestick injuries
– Birth to an HCV-infected mother
• Infrequently through
– Sexual contact
– Sharing personal items (e.g. razors)
– Other invasive healthcare procedures
VETERANS ADMINISTRATION PATIENT CARE SERVICES
8
Burden of Disease
• Chronic HCV carries
significant morbidity and
mortality as the primary
reason for:
– Liver transplant
and the leading cause of:
– End-stage liver disease
– Liver-related death
– Hepatocellular carcinoma
(HCC)
VETERANS ADMINISTRATION PATIENT CARE SERVICES
Infographic: CDC
Examine recent trends in the diagnosis and
management of hepatitis C virus (HCV)
infection.
OBJECTIVE 1
VETERANS ADMINISTRATION PATIENT CARE SERVICES
Diagnosis
HCV Antibody
Nonreactive
Reactive
HCV RNA
STOP
Follow-up testing for
those with continued
risk factors. HCV RNA
testing may be
considered for
immunocompromised
patients.
Not Detected
Detected
No current HCV
infection*
Current HCV
infection
AdaptedVETERANS
from CentersADMINISTRATION
for Disease Control andPATIENT
Prevention,
2013SERVICES
CARE
*Additional testing as appropriate. Repeat RNA testing if the person is suspected to have had HCV exposure
within the past 6 months or has clinical evidence of HCV disease.
Link to Care
Barriers to Treatment
Less
than
20% of HCV-infected
receive
treatment.
About
50%
of HCV-infected
personspersons
are unaware
they
are infected.
Lack of Appropriate Screening
Patient-related Barriers
•
•
•
•
•
Lack of knowledge of risk factors
Asymptomatic; physical exam and
routine labs not remarkable
VETERANS ADMINISTRATION PATIENT CARE SERVICES
Contraindications to treatment
Lack of acceptance of treatment
Lack of access to treatment
Overcoming Barriers
• Education
− Healthcare providers
− Patients
• A multidisciplinary approach to
care increases the proportion of
patients with psychiatric or
substance abuse comorbidities
who begin treatment. This
approach ensures that the most
appropriate course is chosen.
VETERANS ADMINISTRATION PATIENT CARE SERVICES
Patient-related Barriers to
Treatment Initiation
● Contraindications to treatment
Medical or psychiatric comorbidities
● Lack of acceptance of treatment
Asymptomatic nature of disease
Competing priorities
Perceived low treatment efficacy
Perceived long treatment duration
Adverse effects
● Lack of access to treatment
Cost
Distance to specialist
Overcoming Barriers
• Current pharmacologic therapies
provide better side effect profiles,
shorter durations, and very high cure
rates. These make healthcare
providers more capable than ever of
maximizing the individuals screened,
treated, and cured.
• Telemedicine and knowledge
networks have successfully overcome
geographic barriers to treatment
centers as well as to specialists.
VETERANS ADMINISTRATION PATIENT CARE SERVICES
Patient-related Barriers to
Treatment Initiation
● Contraindications to treatment
Medical or psychiatric comorbidities
● Lack of acceptance of treatment
Asymptomatic nature of disease
Competing priorities
Perceived low treatment efficacy
Perceived long treatment duration
Adverse effects
● Lack of access to treatment
Cost
Distance to specialist
AASLD/IDSA Guidance on Hepatitis C
COMPREHENSIVE & DYNAMIC GUIDELINE
Supported by membership-based societies and not by
pharmaceutical companies or other commercial interests.
VETERANS ADMINISTRATION PATIENT CARE SERVICES
15
Identify risk factor-based screening
strategies to improves rates of
detection and treatment of HCV infection.
OBJECTIVE 2
VETERANS ADMINISTRATION PATIENT CARE SERVICES
Recommendations for One-time HCV Testing
AASLD/IDSA HCV Guidance
• One-time HCV testing is
recommended for all
persons born between 1945
and 1965, without prior
ascertainment of risk.
– 51 to 71 years old in 2016
• Risk behaviors
– Injection-drug use (current or
ever, including those who
injected once)
– Intranasal illicit drug use
VETERANS ADMINISTRATION PATIENT CARE SERVICES
Infographic: Axium Healthcare Pharmacy
Recommendations for One-time HCV Testing
AASLD/IDSA HCV Guidance
• Risk exposures
– Long-term hemodialysis (ever)
– Getting a tattoo in an unregulated setting
– Healthcare, emergency medical, and public safety workers after needlesticks,
sharps, or mucosal exposures to HCV-infected blood
– Children born to HCV-infected women
– Prior recipients of transfusions or organ transplants, including persons who:
• Received a transfusion of blood or blood components, or underwent an organ transplant before July
1992
• Received clotting factor concentrates produced before 1987
– Persons who were ever incarcerated
• Other
– HIV infection
– Unexplained chronic liver disease and/or chronic hepatitis including elevated
alanine aminotransferase levels
– Solid
organ donors
(deceased
and living)
VETERANS
ADMINISTRATION
PATIENT
CARE SERVICES
Recommendations for HCV Testing those
with Ongoing Risk Factors
AASLD/IDSA HCV Guidance
• Annual HCV testing is recommended for persons who inject
drugs and for HIV-seropositive men who have unprotected sex
with men.
• Periodic testing should be offered to other persons with ongoing
risk factors for exposure to HCV.
VETERANS ADMINISTRATION PATIENT CARE SERVICES
Construct an individualized management
plan for both treatment-naïve and treatmentexperienced patients with HCV infection.
OBJECTIVE 3
Develop a monitoring and assessment plan
for patients with HCV infection who are
initiated on various pharmacotherapies.
OBJECTIVE 4
VETERANS ADMINISTRATION PATIENT CARE SERVICES
When and in Whom To Initiate Treatment
AASLD/IDSA
All patients with chronic HCV infection should be treated when
(s)he is ready and the necessary resources are available.
Exception: those with short life expectancies that cannot be remediated by treating
HCV, by transplantation, or by other directed therapy.
VETERANS ADMINISTRATION PATIENT CARE SERVICES
21
Goal of Treatment
AASLD/IDSA
Reduce all-cause mortality and liver-related health adverse
consequences by achievement of virologic cure as evidenced by
a sustained virologic response (SVR).
VETERANS ADMINISTRATION PATIENT CARE SERVICES
22
Pre-treatment Assessments
Renal &
Hepatic
Function
HCV
Genotype
& Viral
Load
CBC & INR
(& TSH if IFN
therapy)
VETERANS
IFN:
interferonADMINISTRATION PATIENT CARE SERVICES
23
HCV Pharmacotherapy Timeline
Daclatasvir
(Daklinza™)
Boceprevir
(Victrelis®)
Telaprevir
(Incivek®)
Interferon (IFN)
Pegylated
IFN + RBV
taken with
Pegylated IFN
+ RBV
50 – 75%
Ombitasvir/
paritaprevir/
ritonavir/
(Technivie™)
Sofosbuvir
(Sovaldi®)
Simeprevir
(Olysio®)
taken in
combination
or with RBV 
Pegylated IFN
85 – 93%
40 – 50%
6 – 26%
Ledipasvir/
sofosbuvir
(Harvoni®)
Elbasvir/
grazoprevir
(Zepatier™)
Ombitasvir/
paritaprevir/
ritonavir/
dasabuvir
(Viekira Pak™)
Sofosbuvir/
velpatasvir
(under FDA review)
94 – 100%
90 – 100%
1991
2002
2011
VETERANS ADMINISTRATION PATIENT CARE SERVICES
2013
2014
2015
2016
24
HCV Pharmacotherapy Timeline
Daclatasvir
(Daklinza™)
NS3/4A PI
NS5B polymerase inhibitor
Ombitasvir/
paritaprevir/
ritonavir/
(Technivie™)
NS5A replication inhibitor
Non-specific agent
Non-Nuc NS5B inhibitor
Pharmacokinetic enhancer
Boceprevir
(Victrelis®)
Telaprevir
(Incivek®)
Interferon (IFN)
Pegylated
IFN + RBV
taken with
Pegylated IFN
+ RBV
50 – 75%
Sofosbuvir
(Sovaldi®)
Simeprevir
(Olysio®)
taken in
combination
or with RBV 
Pegylated IFN
85 – 93%
40 – 50%
6 – 26%
Ledipasvir/
sofosbuvir
(Harvoni®)
Elbasvir/
grazoprevir
(Zepatier™)
Ombitasvir/
paritaprevir/
ritonavir/
dasabuvir
(Viekira Pak™)
Sofosbuvir/
velpatasvir
(under FDA review)
94 – 100%
90 – 100%
1991
2002
2011
VETERANS ADMINISTRATION PATIENT CARE SERVICES
2013
2014
2015
2016
25
Targeted Drug Therapies
VETERANS ADMINISTRATION PATIENT CARE SERVICES
26
Monitoring Virologic Response
Sustained Virologic Response (SVR)
• The continued
absence of
detectable HCV RNA
at least 12 weeks
after therapy
completion
• Virologic CURE
Assessment of HCV Viral Load
Baseline
Treatment Week 4
End of Treatment
(EOT)
EOT + 12 weeks
VETERANS ADMINISTRATION PATIENT CARE SERVICES
27
Summary of Recommendations for Patients
Who are Initiating Therapy for HCV Infection
TREATMENT-NAÏVE
VETERANS ADMINISTRATION PATIENT CARE SERVICES
Recommendations for Initial Treatment
AASLD/IDSA
Zepatier™ [elbasvir 50 mg/grazoprevir 100 mg] x 12 weeks if no baseline high foldchange NS5A resistance-associated variants for elbasvir are detected (no cirrhosis
or compensated cirrhosis).
Harvoni® [LDV 90 mg/SOF 400 mg] daily x 12 weeks (no cirrhosis or compensated
cirrhosis).
Genotype 1a
Viekira Pak™ [paritaprevir 150 mg/ritonavir 100 mg/ombitasvir 25 mg daily +
dasabuvir 250 mg BID] + RBV (weight based) BID x 12 weeks (no cirrhosis).
Sovaldi™ [SOF 400 mg] + Olysio™ [SMV 150 mg] daily  RBV (weight-based) BID x
12 weeks (no cirrhosis).
Daklinza® [daclatasvir 60mg*] daily + Sovaldi™ [SOF 400 mg] x 12 weeks (no
cirrhosis).
VETERANS ADMINISTRATION PATIENT CARE SERVICES
LDV: ledipasvir
RBV: ribavirin
BID: twice daily
SOF: sofosbuvir
SMV: simeprevir
*Dose adjusted when used concomitantly with CYP 450 3A4 inducers/inhibitors.
29
Recommendations for Initial Treatment
AASLD/IDSA
Zepatier™ [elbasvir 50 mg/grazoprevir 100 mg] x 12 weeks (no cirrhosis or
compensated cirrhosis).
Harvoni® [LDV 90 mg/SOF 400 mg] daily x 12 weeks (no cirrhosis or compensated
cirrhosis).
Genotype 1b
Viekira Pak™ [paritaprevir 150 mg/ritonavir 100 mg/ombitasvir 25 mg daily +
dasabuvir 250 mg BID] + RBV (weight based) BID x 12 weeks (no cirrhosis or
compensated cirrhosis).
Sovaldi™ [SOF 400 mg] + Olysio™ [SMV 150 mg] daily  RBV (weight-based) BID x
12 weeks (no cirrhosis).
Daklinza® [daclatasvir 60mg*] daily + Sovaldi™ [SOF 400 mg] x 12 weeks (no
cirrhosis).
VETERANS ADMINISTRATION PATIENT CARE SERVICES
LDV: ledipasvir
RBV: ribavirin
BID: twice daily
SOF: sofosbuvir
SMV: simeprevir
*Dose adjusted when used concomitantly with CYP 450 3A4 inducers/inhibitors.
30
Recommendations for Initial Treatment
AASLD/IDSA
Sovaldi™ [SOF 400 mg] + RBV (weight-based) BID x 12 weeks (no cirrhosis) OR x
16-24 weeks (compensated cirrhosis).
Genotype 2
Genotype 3
Daklinza® [daclatasvir 60mg*] daily + Sovaldi™ [SOF 400 mg] x 12 weeks (no
cirrhosis) OR x 16-24 weeks (compensated cirrhosis).
Daklinza® [daclatasvir 60mg*] daily + Sovaldi™ [SOF 400 mg] x 12 weeks (no
cirrhosis) OR Daklinza® [daclatasvir 60mg*] daily + Sovaldi™ [SOF 400 mg]  RBV
(weight-based) BID x 24 weeks (compensated cirrhosis).
Sovaldi™ [SOF 400 mg] + PegIFN SC weekly + RBV (weight-based) BID x 12 weeks
(no cirrhosis or compensated cirrhosis).
VETERANS ADMINISTRATION PATIENT CARE SERVICES
RBV: ribavirin
BID: twice daily
PegIFN: pegylated interferon
SC: subcutaneously
SMV: simeprevir
*Dose adjusted when used concomitantly with CYP 450 3A4 inducers/inhibitors.
31
Recommendations for Initial Treatment
AASLD/IDSA
Zepatier™ [elbasvir 50 mg/grazoprevir 100 mg] x 12 weeks (no cirrhosis or
compensated cirrhosis).
Genotype 4
Harvoni® [LDV 90 mg/SOF 400 mg] daily x 12 weeks (no cirrhosis or compensated
cirrhosis).
Technivie™ [paritaprevir 150 mg/ritonavir 100 mg/ombitasvir 25 mg daily] + RBV
(weight based) BID x 12 weeks (no cirrhosis or compensated cirrhosis).
Genotypes 5/6
Harvoni® [LDV 90 mg/SOF 400 mg] daily x 12 weeks (regardless of cirrhosis status).
VETERANS ADMINISTRATION PATIENT CARE SERVICES
LDV: ledipasvir
RBV: ribavirin
BID: twice daily
SOF: sofosbuvir
SMV: simeprevir
*Dose adjusted when used concomitantly with CYP 450 3A4 inducers/inhibitors.
32
Summary of Recommendations for Patients in
Whom Previous Treatment Has Failed
TREATMENT-EXPERIENCED
VETERANS ADMINISTRATION PATIENT CARE SERVICES
Considerations for Treatment-Experienced
Patients with HCV Infection
• The retreatment regimen selection for persons in whom prior
therapy has failed is dependent on:
– Failed agents
– Genotype
– Cirrhosis status
• General approach
– Different agents (mechanisms of action)
– May add ribavirin
– May extend treatment duration
Included in this presentation are recommendations for
pegylated interferon (PegIFN) and ribavirin (RBV) treatment failures ONLY
VETERANS ADMINISTRATION PATIENT CARE SERVICES
34
Recommendations for Retreatment after
PegIFN/RBV Treatment Failure
AASLD/IDSA
Zepatier™ [elbasvir 50 mg/grazoprevir 100 mg] x 12 weeks if no baseline high foldchange NS5A resistance-associated variants for elbasvir are detected (no cirrhosis
or compensated cirrhosis).
Harvoni® [LDV 90 mg/SOF 400 mg] daily x 12 weeks (no cirrhosis). Harvoni® [LDV
90 mg/SOF 400 mg] daily x 24 weeks OR x Harvoni® [LDV 90 mg/SOF 400 mg] daily
12 weeks + RBV (weight based) BID (compensated cirrhosis).
Genotype 1a
Viekira Pak™ [paritaprevir 150 mg/ritonavir 100 mg/ombitasvir 25 mg daily +
dasabuvir 250 mg BID] + RBV (weight based) BID x 12 weeks (no cirrhosis).
Sovaldi™ [SOF 400 mg] + Olysio™ [SMV 150 mg] daily x 12 weeks (no cirrhosis).
Daklinza® [daclatasvir 60mg*] daily + Sovaldi™ [SOF 400 mg] x 12 weeks (no
cirrhosis).
VETERANS ADMINISTRATION PATIENT CARE SERVICES
LDV: ledipasvir
RBV: ribavirin
BID: twice daily
PegIFN: pegylated interferon
SOF: sofosbuvir
SMV: simeprevir
*Dose adjusted when used concomitantly with CYP 450 3A4 inducers/inhibitors.
35
Recommendations for Retreatment after
PegIFN/RBV Treatment Failure
AASLD/IDSA
Zepatier™ [elbasvir 50 mg/grazoprevir 100 mg] x 12 weeks (no cirrhosis or
compensated cirrhosis).
Harvoni® [LDV 90 mg/SOF 400 mg] daily x 12 weeks (no cirrhosis). Harvoni® [LDV
90 mg/SOF 400 mg] daily x 24 weeks OR x Harvoni® [LDV 90 mg/SOF 400 mg] daily
12 weeks + RBV (weight based) BID (compensated cirrhosis).
Genotype 1b
Viekira Pak™ [paritaprevir 150 mg/ritonavir 100 mg/ombitasvir 25 mg daily +
dasabuvir 250 mg BID] + RBV (weight based) BID x 12 weeks (no cirrhosis or
compensated cirrhosis).
Sovaldi™ [SOF 400 mg] + Olysio™ [SMV 150 mg] daily x 12 weeks (no cirrhosis).
Daklinza® [daclatasvir 60mg*] daily + Sovaldi™ [SOF 400 mg] x 12 weeks (no
cirrhosis).
VETERANS ADMINISTRATION PATIENT CARE SERVICES
LDV: ledipasvir
RBV: ribavirin
BID: twice daily
PegIFN: pegylated interferon
SOF: sofosbuvir
SMV: simeprevir
*Dose adjusted when used concomitantly with CYP 450 3A4 inducers/inhibitors.
36
Recommendations for Retreatment after
PegIFN/RBV Treatment Failure
AASLD/IDSA
Sovaldi™ [SOF 400 mg] + RBV (weight-based) BID x 12 weeks (no cirrhosis) OR x
16-24 weeks (compensated cirrhosis).
Genotype 2
Genotype 3
Daklinza® [daclatasvir 60mg*] daily + Sovaldi™ [SOF 400 mg] x 12 weeks (no
cirrhosis) OR x 16-24 weeks (compensated cirrhosis).
Daklinza® [daclatasvir 60mg*] daily + Sovaldi™ [SOF 400 mg] x 12 weeks (no
cirrhosis) OR Daklinza® [daclatasvir 60mg*] daily + Sovaldi™ [SOF 400 mg] + RBV
(weight-based) BID x 24 weeks (compensated cirrhosis).
Sovaldi™ [SOF 400 mg] + PegIFN SC weekly + RBV (weight-based) BID x 12 weeks
(no cirrhosis or compensated cirrhosis).
VETERANS ADMINISTRATION PATIENT CARE SERVICES
LDV: ledipasvir
RBV: ribavirin
BID: twice daily
PegIFN: pegylated interferon
SOF: sofosbuvir
SMV: simeprevir
*Dose adjusted when used concomitantly with CYP 450 3A4 inducers/inhibitors.
37
Recommendations for Retreatment after
PegIFN/RBV Treatment Failure
AASLD/IDSA
Technivie™ [paritaprevir 150 mg/ritonavir 100 mg/ombitasvir 25 mg daily] + RBV
(weight based) BID x 12 weeks (no cirrhosis or compensated cirrhosis).
Genotype 4
Zepatier™ [elbasvir 50 mg/grazoprevir 100 mg]  RBV (weight-based) BID x 12-16
weeks (no cirrhosis or compensated cirrhosis).
Harvoni® [LDV 90 mg/SOF 400 mg] daily x 12 weeks (no cirrhosis) or 24 weeks
(compensated cirrhosis) OR Harvoni® [LDV 90 mg/SOF 400 mg] daily + RBV
(weight-based) BID x 12 weeks (compensated cirrhosis).
Genotypes 5/6
Harvoni® [LDV 90 mg/SOF 400 mg] daily x 12 weeks (regardless of cirrhosis status).
VETERANS ADMINISTRATION PATIENT CARE SERVICES
LDV: ledipasvir
RBV: ribavirin
BID: twice daily
PegIFN: pegylated interferon
SOF: sofosbuvir
SMV: simeprevir
*Dose adjusted when used concomitantly with CYP 450 3A4 inducers/inhibitors.
38
Direct Acting Antivirals for HCV Infection
APPROVED IN 2014 TO 2016
VETERANS ADMINISTRATION PATIENT CARE SERVICES
39
• Place in Therapy
– Genotypes 1 & 4
• Mechanism of Action
– Elbasvir
– Grazoprevir
NS5A replication inhibitor
NS3/4A PI
• Significant DDIs
– CYP3A Inducers, OATP1B1/3 Inhibitors
• Warning
– ALT elevations
• Monitoring
– Hepatic labs prior to therapy, at treatment week 8, and as clinically indicated;
CBC periodically
VETERANS ADMINISTRATION PATIENT CARE SERVICES
40
• Directions for Use
– One tablet once daily
• Common Side Effects
– Fatigue, headache, nausea, anemia
• Additional Testing
– NS5A resistance testing in HCV genotype 1a prior to
therapy
• Resistance associated variants (RAVs) found in 10% to 15% of
genotype 1-infected patients without prior exposure to NS5A
inhibitors
• If baseline RAVs are present, treatment extension to 16 weeks
with the addition of weight-based RBV (1000 mg [<75 kg] to
1200 mg [≥75 kg]) is recommended
VETERANS ADMINISTRATION PATIENT CARE SERVICES
41
• Place in Therapy
– Genotypes 1, 2, 3
• Mechanism of Action
– Daclatasvir
NS5A replication inhibitor
• Significant DDIs
– Strong CYP3A Inhibitors
• Dose adjustment: 30 mg once daily
– Moderate CYP3A Inducers
• Dose adjustment: 90 mg once daily
– Strong CYP3A Inducers: concomitant use is contraindicated
VETERANS ADMINISTRATION PATIENT CARE SERVICES
42
• Warnings
– Bradycardia (in combination with sofosbuvir and
amiodarone)
– Do not use as monotherapy
• Monitoring
– Liver enzymes and serum creatinine at baseline and
when clinically indicated
• Directions for Use
– 60 mg once daily with concomitant sofosbuvir
• Common Side Effects (STUDIED IN COMBINATION
WITH SOFOSBUVIR)
– Fatigue, headache, nausea, diarrhea
VETERANS ADMINISTRATION PATIENT CARE SERVICES
43
technivie™
ombitasvir, paritaprevir and ritonavir tablets
12.5mg/75mg/50mg
• Place in Therapy
– Genotype 4
• Mechanism of Action
– Ombitasvir
– Paritaprevir
– Ritonavir
NS5A replication inhibitor
NS3/4A PI
Pharmacokinetic enhancer
• Significant DDIs
– CYP3A Inducers
– Ethinyl estradiol-containing products
contraindicated
• Warnings
– Hepatic failure or liver decompensation in
patients with underlying cirrhosis,
VETERANS hypersensitivity
ADMINISTRATION PATIENT
CARE(including
SERVICES angioedema)
reaction
44
technivie™
ombitasvir, paritaprevir and ritonavir tablets
12.5mg/75mg/50mg
• Directions for Use
– Two tablets once daily with a meal
– In combination with RBV
• Common Side Effects
– Weakness, fatigue, insomnia, nausea, increased serum ALT, anemia
• Serious Side Effects
– Jaundice, dark urine, loss of appetite, vomiting
• Monitoring
– Hepatic function; consider discontinuation of therapy if ALT persists >10x
ULN or if ALT is elevated with additional s/sx of hepatic inflammation
• Contraception Counseling
– RBV may cause birth defects and/or fetal death; two forms of appropriate
birth control required during treatment and for 6 months after
VETERANS ADMINISTRATION PATIENT CARE SERVICES
completion.
45
• Place in Therapy
– Genotype 1
• Mechanism of Action
–
–
–
–
Ombitasvir
Paritaprevir
Ritonavir
Dasabuvir
NS5A replication inhibitor
NS3/4A PI
Pharmacokinetic enhancer
Non-Nuc NS5B inhibitor
• Significant DDIs
– CYP3A Inducers
– Ethinyl estradiol-containing products
contraindicated
• Warning/Monitoring
– Hepatic failure (underlying
cirrhosis)/hepatic function
VETERANS ADMINISTRATION PATIENT CARE SERVICES
46
• Directions for Use
– Daily dose packs
– Take with food
• Common Side Effects
– Fatigue, nausea, pruritis, insomnia
• Serious Side Effects
– Jaundice, dark urine, loss of appetite, vomiting
• Missed Dose Instructions
– Ombitasvir/paritaprevir/ritonavir: if it has been more than 12 hours since
the missed dose, skip the missed dose and resume normal dosing
schedule
– Dasabuvir: if it has been more than 6 hours since your missed dose, skip
the missed dose and resume normal dosing schedule
VETERANS
ADMINISTRATION
CARE
– Do
not double PATIENT
the dose
of SERVICES
either tablet
47
• Place in Therapy
– Genotypes 1, 4, 5, 6
• Mechanism of Action
– Ledipasvir
– Sofosbuvir
NS5A replication inhibitor
NS5B polymerase inhibitor
• Significant DDIs
– Antacids (acid-dependent absorption)
• Warning
– Administration with amiodarone is not
recommended due to risk of serious (possibly
fatal) bradycardia
• Monitoring
– Bilirubin,
liver enzymes,
SCr
at baseline
VETERANS
ADMINISTRATION
PATIENT CARE
SERVICES
periodically when clinically indicated
and
48
• Directions for Use
– One tablet, once a day
• Common Side Effects
– Fatigue, headache
• Use of Antacids & Reflux Medications
– Antacids (Tums, Rolaids, Maalox, Mylanta, Alka-Seltzer)
• TAKE ANTACID 4 HOURS BEFORE OR 4 HOURS AFTER HARVONI®
– H2 Receptor Antagonists
• TAKE AT THE SAME TIME AS HARVONI® OR 12 HOURS APART
• Dose not to exceed famotidine 40 mg BID = cimetidine 800 mg BID = ranitidine 150 mg BID
– Proton Pump Inhibitors
• TAKE AT THE SAME TIME AS HARVONI® ON AN EMPTY STOMACH
• Dose not to exceed omeprazole 20 mg = lansoprazole 30 mg = esomeprazole 20 mg to 40 mg =
pantoprazole 40 mg = dexlansoprazole 60 mg
VETERANS ADMINISTRATION PATIENT CARE SERVICES
49
Other Pharmacotherapies for HCV
INCLUDED FOR REFERENCE
VETERANS ADMINISTRATION PATIENT CARE SERVICES
50
Ribasphere®
ribavirin
MECHANISM OF
ACTION
WARNINGS & MONITORING
PATIENT COUNSELING
HIGHLIGHTS
Inhibits replication of RNA
and DNA viruses; inhibits
influenza virus RNA
polymerase activity and
inhibits the initiation and
elongation of RNA fragments
resulting in inhibition of viral
protein synthesis.
US Boxed Warnings, Associated Monitoring
Appropriate use (oral): Ribavirin
monotherapy is not effective for the
treatment of chronic hepatitis C virus.
• Weight-based dosing given in two divided
doses daily.
• Ribavirin may cause birth defects and/or
death of the exposed fetus. Use 2 forms of
contraception to avoid pregnancy (in female
patients and female partners of male
patients) during and for 6 months after
therapy.
• This drug can cause hemolytic anemia which
can cause significant fatigue, make heart
disease worse, and lead to heart attacks. Tell
your doctor if you have ever had heart
problems. Do not take this drug if you have
ever had very bad heart disease or heart
problems that are not being treated. Call your
doctor right away if you have chest pain while
taking this drug.
• This drug is typically dosed twice daily.
• Take a missed dose as soon as you think
about it. If it is close to the time for your next
dose, skip the missed dose and resume your
regular dosing schedule. Do not double doses.
Used to treat HCV genotypes
1-4.
Hemolytic anemia (oral): The primary clinical
toxicity of ribavirin is hemolytic anemia,
which may result in worsening of cardiac
disease and lead to fatal and nonfatal
myocardial infarctions. Anemia usually
occurs within 1 to 2 weeks of therapy
initiation
Pregnancy (oral): Significant teratogenic
and/or embryocidal effects. Ribavirin has a
multiple-dose half-life of 12 days, and may
persist in nonplasma compartments for as
long as 6 months. Therefore, ribavirin
therapy is contraindicated in women who are
pregnant and in the male partners of women
who are pregnant. At least 2 reliable forms of
effective contraception must be used during
treatment and for 6 months posttreatment.
VETERANS ADMINISTRATION PATIENT CARE SERVICES
Contraindicated if CrCl < 50 mL/min.
51
Sovaldi®
sofosbuvir
MECHANISM OF
ACTION
After being metabolized to its
active form, sofosbuvir
inhibits HCV NS5B RNAdependent RNA polymerase,
essential for viral replication,
and acts as a chain
terminator.
Used to treat HCV genotypes
1-4.
WARNINGS & MONITORING
Warnings
Administration with amiodarone in
combination with another direct-acting
antiviral (e.g. simeprevir) is not
recommended due to risk of serious, even
life-threatening, symptomatic bradycardia.
Do not use as monotherapy; use only in
combination with ribavirin (with or without
PEG-IFN depending upon the clinical
indication).
Monitoring
Bilirubin, liver enzymes, and serum
creatinine at baseline and periodically when
indicated. If used in combination with
amiodarone and another direct acting
antihepaciviral (or in patients who
discontinued amiodarone just prior to
initiating sofosbuvir in combination with a
direct acting antihepaciviral), inpatient
cardiac monitoring for the first 48 hours of
coadministration, then outpatient or selfof heart
rate daily through at
VETERANS ADMINISTRATION monitoring
PATIENT CARE
SERVICES
least the first 2 weeks of treatment.
PATIENT COUNSELING
HIGHLIGHTS
• May be taken with or without food.
• There are multiple significant drug-drug
interactions for this drug. Consult a healthcare
professional prior to new drug use (including
over-the-counter and herbal drugs).
• RBV counseling points (if used in
combination with RBV).
• Side effects may include itching, headache,
insomnia, or feeling tired or weak.
• Take a missed dose as soon as possible on
the same day or resume regular dosing
schedule on the next day.
52
Olysio®
simeprevir
MECHANISM OF
ACTION
Inhibits HCV NS3/4A
protease, a protease that is
essential for viral replication.
It is considered a direct-acting
antiviral treatment for HCV,
also called a specifically
targeted antiviral therapy for
HCV (STAT-C).
Used to treat HCV genotype
1.
WARNINGS & MONITORING
Warnings
Serious symptomatic bradycardia when
co‐administered with sofosbuvir and
amiodarone.
Hepatic decompensation and failure have
been reported, most cases in patients with
advanced and/or decompensated cirrhosis.
Sulfa allergy: Contains a sulfonamide moiety.
In patients with a history of sulfa allergy, the
risk of reaction cannot be excluded.
Photosensitivity, rash.
Women of reproductive potential should use
effective contraception during therapy.
Child-Pugh class B or C: Use is not
recommended. Use with peginterferon and
ribavirin is contraindicated.
Monitoring
Bilirubin, liver enzymes, and uric acid at
baseline and periodically when clinically
VETERANS ADMINISTRATION indicated.
PATIENT CARE SERVICES
PATIENT COUNSELING
HIGHLIGHTS
• Take capsule (150 mg once daily) with food
to increase the amount of drug absorbed.
Swallow the capsule whole.
• This drug will make you more sensitive to the
sun. Avoid excessive exposure to sunlight or
sunlamps. Use sunscreen and wear protective
clothing.
• Side effects may include itching, headache,
nausea, or feeling tired or weak.
• If you experience rash, report this to your
provider immediately.
• There are multiple significant drug-drug
interactions for this drug. Consult a healthcare
professional prior to new drug use (including
over-the-counter and herbal drugs).
• Take a missed dose as soon as possible, but
if next dose is in less than 12 hours, skip the
missed dose.
• RBV counseling points (if used in
combination with RBV).
53
Pegasys®
peginterferon alfa-2
MECHANISM OF
ACTION
WARNINGS & MONITORING
PATIENT COUNSELING
HIGHLIGHTS
Interferons interact with cells
through high affinity cell
surface receptors. Interferons
inhibit cellular growth, alter
the state of cellular
differentiation, interfere with
oncogene expression, alter
cell surface antigen
expression, increase
phagocytic activity of
macrophages, and augment
cytotoxicity of lymphocytes
for target cells.
US Boxed Warning
Peginterferon alfa-2a may cause or aggravate
fatal or life-threatening neuropsychiatric,
autoimmune, ischemic, and infectious
disorders.
• Weekly subcutaneous injection that can be
given in the abdomen or thighs.
• Suicidal or homicidal ideation, depression,
hallucinations, psychoses, and relapse of drug
addiction have happened during treatment
and within 6 months after the last dose.
• Hypotension, tachycardia, chest pain or
pressure, trouble breathing, and heart attacks
have happened while taking alpha interferons.
• RBV counseling points (if used in
combination with RBV).
• If a dose is missed or up to 2 days late,
patient should take dose as soon as possible. If
the missed dose is more than 2 days late,
patient should contact healthcare professional.
Used to treat HCV genotypes
1-4.
Monitoring
Periodic CBC (including hemoglobin, WBC,
and platelets) and chemistries (including liver
function tests and uric acid); TSH measured
every 12 weeks.
In combination with RBV, pregnancy tests
should continue monthly up to 6 months
after discontinuation of therapy.
Evaluate for depression and other psychiatric
symptoms; baseline eye exams and
periodically in patients with baseline
disorders; baseline echocardiogram in
patients with cardiac disease.
Child-Pugh Classes B & C.
VETERANS ADMINISTRATION Contraindicated
PATIENT CARE inSERVICES
54
Describe strategies for optimized care of HCV
patients who are post-liver transplant,
HIV/HCV coinfected, or cirrhotic.
OBJECTIVE 5
VETERANS ADMINISTRATION PATIENT CARE SERVICES
Post-Liver Transplantation
• HCV infection occurs universally in those with viremia at the
time of transplantation
– Histologic features present within 6 months for most
• Consider DDIs with transplantation medications
VETERANS ADMINISTRATION PATIENT CARE SERVICES
56
HIV/HCV Coinfection
• HIV/HCV-coinfection increases risk of
– Liver-related morbidity and mortality
– Non-hepatic organ dysfunction
– Overall mortality
• Treatment requires continued awareness of complex drug
interactions between HCV and HIV medications
VETERANS ADMINISTRATION PATIENT CARE SERVICES
57
Decompensated Cirrhosis
• Achievement of SVR significantly decreases hepatic
decompensation events, HCC, and liver-related mortality
• Referral to experienced specialist is recommended
VETERANS ADMINISTRATION PATIENT CARE SERVICES
58
In Summary
• Increased awareness of risk factors and implementation of
risk-factor based screening can improve rates of detection of
hepatitis C virus
• The treatment options and recommendations for HCV
infection are rapidly evolving
• New agents and progressive practice models have overcome
several barriers to HCV treatment…
… But barriers remain
Hepatitis
VETERANS ADMINISTRATION PATIENT CARE SERVICES
59
Questions?
VETERANS ADMINISTRATION PATIENT CARE SERVICES
References
•
•
•
•
•
•
•
•
•
•
•
Searson G , Engelson E, Carriero D, et al. Treatment of chronic hepatitis C virus infection in the United States: some
remaining obstacles. Liver Int. 2014;34:668-671.
Lemoine M, Thursz M. Hepatitis C, a global issue: access to care and new therapeutic and preventive approaches in
resource-contained areas. Semin Liver Dis. 2014;34:89-97.
Saifu H, Asch S, Bidwell M et al. Evaluation of HIV and hepatitis C telemedicine clinics. Am J Manag Care.
2012;18(4):207-212.
Groessl E, Sklar M, Cheung R, et al. Increasing antiviral treatment through integrated hepatitis C care: a randomized
multicenter trial. Contemp Clin Trials. 2013;35:97-107.
Chopra S. Epidemiology and transmission of hepatitis C virus infection. UpToDate. March 1, 2015.
Chopra S & Pockros P. Overview of the management of chronic hepatitis C virus infection. UpToDate. March 30, 2015.
American Association for the Study of Liver Diseases. Hepatology 2004; 39:1147.
Chronic Hepatitis C Virus (HCV) Infection: Treatment Considerations. Department of Veterans Affairs National Hepatitis
C Resource Center Program and the Office of Public Health, March 2014; revised February 17, 2015.
Recommendations for Testing, Managing, and Treating Hepatitis C. Joint panel from the American Association of the
Study of Liver Diseases and the Infectious Diseases Society of America. December 2014.
Viral Hepatitis – Hepatitis C Information. Centers for Disease Control and Prevention. www.cdc.gov/hepatitis/HCV.
Accessed September 17, 2015.
Martin M, McNicholl I. Advances in hepatitis C therapy. In: Murphy JE, Lee MW, eds. Pharmacotherapy Self-Assessment
Program, 2015 Book 1. Infectious Diseases. Lenexa, KS: American College of Clinical Pharmacy, 2015:167-191.
VETERANS ADMINISTRATION PATIENT CARE SERVICES
Post-Questions for Pharmacy Technicians
VETERANS ADMINISTRATION PATIENT CARE SERVICES
Post-Questions for Pharmacy Technicians
1. Which of the following is a TRUE statement
about hepatitis C virus (HCV) diagnosis and
treatment?
a. About 75 percent of persons infected with
HCV receive treatment.
b. Chronic HCV infection can be diagnosed
based on routine physical examination
and labs.
c.
All cases of acute HCV infection progress
to chronic disease.
Answer: D
Targeted Objective: Examine recent trends in
the diagnosis and management of hepatitis C
virus (HCV).
Option A: less than 20% of HCV-infected persons receive
treatment.
Option B: Diagnosis of HCV requires an antibody blood
test and confirmatory RNA testing.
Option C: Up to 30% of people acutely infected with
HCV will clear the virus on their own.
d. Diagnosis of HCV infection relies upon
appropriate identification of risk factors.
VETERANS ADMINISTRATION PATIENT CARE SERVICES
63
Post-Questions for Pharmacy Technicians
2. Which one of the following U.S. patients is
MOST at risk for the transmission of hepatitis
C virus (HCV)?
a. An infant born at 38 weeks gestation to a
25 year-old mother infected with HCV.
b. A 19-year-old woman who uses
intravenous heroin.
c.
A 32-year-old man who has sex with men.
d. A 50-year-old woman who received a
kidney transplant in 2001.
VETERANS ADMINISTRATION PATIENT CARE SERVICES
Answer: B
Targeted Objective: Identify risk factor-based
screening strategies to improves rates of
detection and treatment of HCV.
According to AASLD/IDSA 2016, the most important risk
for HCV infection is injection drug use, accounting for at
least 60% of acute HCV infections in the United States.
Considerations for other options:
Option A: represents a risk exposure that is less likely to
transmit HCV compared to IV drug use.
Option C: sexual transmission of HCV is inefficient
except among HIV-infected men who have unprotected
sex with men.
Option D: routine screening of donated blood and
organs began in 1992.
64
Post-Questions for Pharmacy Technicians
3. Annual hepatitis C virus (HCV) testing is
recommended for which of the following
selections?
a. Injection drug users.
b. Persons born between 1945 and 1965.
c.
Answer: A
Targeted Objective: Identify risk factor-based
screening strategies to improves rates of
detection and treatment of HCV.
Per AASLD/IDSA 2016, annual HCV testing is
recommended for persons who inject drugs and for HIVseropositive men who have unprotected sex with men.
Persons who are HIV-positive.
d. Healthcare workers.
VETERANS ADMINISTRATION PATIENT CARE SERVICES
65
Post-Questions for Pharmacists
VETERANS ADMINISTRATION PATIENT CARE SERVICES
Post-Questions for Pharmacists
1. Which one of the following U.S. patients is
MOST at risk for the transmission of hepatitis
C virus (HCV)?
a. An infant born at 38 weeks gestation to a
25 year-old mother infected with HCV.
b. A 19-year-old woman who uses
intravenous heroin.
c.
A 32-year-old man who has sex with men.
d. A 50-year-old woman who received a
kidney transplant in 2001.
VETERANS ADMINISTRATION PATIENT CARE SERVICES
Answer: B
Targeted Objective: Identify risk factor-based
screening strategies to improves rates of
detection and treatment of HCV.
According to AASLD/IDSA 2016, the most important risk
for HCV infection is injection drug use, accounting for at
least 60% of acute HCV infections in the United States.
Considerations for other options:
Option A: represents a risk exposure that is less likely to
transmit HCV compared to IV drug use.
Option C: sexual transmission of HCV is inefficient
except among HIV-infected men who have unprotected
sex with men.
Option D: routine screening of donated blood and
organs began in 1992.
67
Post-Questions for Pharmacists
2. A 62-year-old treatment-naïve non-cirrhotic man with
HCV genotype 1a presents for initial evaluation of HCV.
His HCV viral load is 12.4 million. The patient’s
medication list includes amlodipine 5 mg daily, sildenafil
100 mg as needed for erectile dysfunction, atorvastatin
40 mg daily, and omeprazole 20 mg daily before
breakfast. Which of the following regimens would be
best to recommend for this patient?
a.
b.
c.
Daily fixed-dose combination of ledipasvir 90
mg/sofosbuvir 400 mg for 12 weeks.
Daily fixed-dose combination of paritaprevir 150
mg/ritonavir 100 mg/ombitasvir 25 mg plus weightbased ribavirin for 12 weeks.
Daily combination of sofosbuvir 400 mg with
weight-based ribavirin for 24 weeks.
Three-times-daily boceprevir 800 mg with weightbased ribavirin
for 12 weeks.
VETERANS
ADMINISTRATION
PATIENT CARE SERVICES
Answer: A
Targeted Objective: Construct an
individualized management plan for both
treatment-naïve and treatment-experienced
patients with HCV infection.
Option B is not correct because the use of Viekira Pak™
is contraindicated with sildenafil. Sildenafil therapy
would need to be held during HCV treatment.
Option C is not correct because sofosbuvir with RBV is a
regimen that is not recommended for GT1 treatmentnaïve patients due to relatively low efficacy compared
to newer agents.
Option D is not correct because boceprevir-based
regimens are no longer recommended for treatment of
HCV due to relatively low efficacy compared to newer
agents. Boceprevir is no longer manufactured.
d.
68
Post-Questions for Pharmacists
3. A 40-year-old treatment-experienced woman
with HCV genotype 4 has compensated cirrhosis
and is 3 months post-liver transplantation. Which
of the following regimens would be best to
recommend for this patient?
a.
b.
c.
d.
Twice-daily telaprevir 1125 mg with weightbased ribavirin and pegylated interferon for
24 weeks.
Daily fixed-dose combination of ledipasvir 90
mg/sofosbuvir 400 mg for 24 weeks.
Daily daclatasvir 60mg plus sofosbuvir 400
mg with low initial dose of ribavirin (600 mg,
titrated as tolerated) for 12 weeks.
Daily fixed-dose combination of elbasvir
50mg/grazoprevir 100 mg for 12 weeks.
VETERANS ADMINISTRATION PATIENT CARE SERVICES
Answer: C
Targeted Objective: Describe strategies for
optimized care of HCV patients who are
post-transplant, HIV co-infected, or cirrhotic.
Option A is not correct because telaprevir-based
regimens are no longer recommended for treatment of
HCV due to relatively low efficacy compared to newer
agents. Telaprevir is no longer manufactured.
Option B is not correct because Harvoni® monotherapy
is not recommended in this patient population; it would
be correct if it were in combination with weight-based
RBV.
Option D is not correct because the use of Zepatier™
has not been studied in liver transplant recipients. The
impact of Zepatier™ on the efficacy of
immunosuppressive therapy is unknown.
69
Slides for Reference
VETERANS ADMINISTRATION PATIENT CARE SERVICES
Expanding Access to Hepatitis C Care for Rural Maine Veterans Using
Pharmacist-Driven Education
Whitney Jandreau, PharmD Rachel Mayer, PharmD Sarah Smith, PharmD, BCACP
Gina Puglisi, PharmD Tomasz Jodlowski, PharmD, BCPS (AQ-ID), AAHIVP
VA Maine Healthcare System, Augusta, Maine
Background
• HCV infection is the most common
blood borne infection in the United
States, with a prevalence estimated
above 3 million
• Current pharmacologic options
against HCV are safe and highly
efficacious
• 75% of HCV-infected persons are
unaware of the infection and less than
20% receive treatment
• In a primarily rural location,
geographical barriers prevent access
to care, including disease screening
Objectives
• Increase HCV screening and utilization
of CVT to link rural Veterans t to
treatment
Data Collection
• Number of rural patients screened for
HCV prior to, then after, intervention
• Number of rural patients with HCV
connected to gastroenterology team of
specialists for medical care
Abbreviations: HCV, hepatitis C virus; CVT, clinical video telehealth; CBOC, Community Based Outpatient Clinic; VAMEHCS, Veterans Affairs Maine Healthcare System
Recommendations for Medical Management
and Monitoring in Acute HCV Infection
AASLD/IDSA
VETERANS ADMINISTRATION PATIENT CARE SERVICES
72
Recommended Treatment for Patients with
Acute HCV Infection
AASLD/IDSA
VETERANS ADMINISTRATION PATIENT CARE SERVICES
73
Recommendations for Follow-up of Initial
Testing
AASLD/IDSA HCV Guidance
• An anti-HCV test is recommended for HCV testing, and if the
result is positive, current infection should be confirmed by a
sensitive HCV RNA test.
• Among persons at risk of reinfection after previous spontaneous
or treatment-related viral clearance, initial HCV-RNA testing is
recommended because an anti-HCV test is expected to be
positive.
• Quantitative HCV-RNA testing is recommended prior to the
initiation of antiviral therapy to document the baseline level of
viremia (i.e., baseline viral load).
• Testing for HCV genotype is recommended to guide selection of
the most
appropriate
antiviral
VETERANS
ADMINISTRATION
PATIENT CARE
SERVICES regimen.
FDA: 2016 Updates
• 02/12/2016
– On February 12, 2016, the FDA approved changes to the Harvoni (ledipasvir
and sofosbuvir) fixed-dose combination label to expand the patient population
to include those with chronic hepatitis C virus genotype 1, infection who are
liver transplant recipients, genotype 4 infection who are liver transplant
recipients without cirrhosis, or with compensated cirrhosis, and genotype 1
infection with decompensated cirrhosis. The major changes to the label are
the following.
• 03/01/2016
– The OLYSIO (simeprevir) label was updated to include pharmacokinetic, safety
and efficacy data in treatment-naïve adult patients of East Asian ancestry with
chronic hepatitis C virus genotype 1 infection. Patients of East Asian ancestry
exhibit higher simeprevir plasma exposures but no dosage adjustment is
required based on race.
VETERANS ADMINISTRATION PATIENT CARE SERVICES
FDA
75
FDA: 2015 Updates
• 03/24/2015
– FDA Drug Safety Communication: Harvoni and Sovaldi
• The U.S. Food and Drug Administration (FDA) is warning that serious slowing of the heart rate
can occur when the antiarrhythmic drug amiodarone is taken together with either the hepatitis
C drug Harvoni (ledipasvir/sofosbuvir) or with Sovaldi (sofosbuvir) taken in combination with
another direct acting antiviral for the treatment of hepatitis C infection. We are adding
information about serious slowing of the heart rate, known as symptomatic bradycardia, to the
Harvoni and Sovaldi labels. We are recommending that health care professionals should not
prescribe either Harvoni or Sovaldi combined with another direct acting antiviral, such as the
investigational drug daclatasvir or Olysio (simeprevir), with amiodarone. Patients should not
stop taking any of their medicines without first talking to their health care professionals.
• 04/15/2015
– FDA approved changes to Olysio package insert
VETERANS ADMINISTRATION PATIENT CARE SERVICES
FDA
76
FDA: 2015 Updates
• 10/22/2015
– FDA Drug Safety Communication: Viekira Pak and Technivie
• The U.S. Food and Drug Administration (FDA) is warning that hepatitis C treatments Viekira Pak
and Technivie can cause serious liver injury mostly in patients with underlying advanced liver
disease. As a result, new information about this safety risk was added to the Viekira Pak and
Technivie labels.
• 11/13/2015
– Harvoni label updated
• The HARVONI (ledipasvir/sofosbuvir) labeling was updated to: (1) expand the indication to the
treatment of chronic hepatitis C virus (HCV) genotype 4, 5 and 6 infection, (2) include dosage
recommendations for HCV/HIV-1 co-infection and (3) state HARVONI + ribavirin for 12 weeks
can be considered in treatment-experienced genotype 1 patients with cirrhosis who are eligible
for ribavirin. Additionally the label was updated with drug-drug interaction information.
VETERANS ADMINISTRATION PATIENT CARE SERVICES
FDA
77
CTP
VETERANS ADMINISTRATION PATIENT CARE SERVICES
78
ALT
AST
BOC
CBC
CTP
DAA
ESRD
FDA
GFR
HBsAg
HBV
HCC
IDU
INR
MELD
MSM
NAT
NIH
OATP
P-gp
PrOD
RAV
RBC
RBV
RGT
RVR
sAg
SMV
alanine aminotransferase
aspartate aminotransferase
boceprevir
complete blood cell (eg, complete blood cell count)
Child Turcotte Pugh
direct-acting antiviral
end-stage renal disease
Food and Drug Administration
glomerular filtration rate
hepatitis B virus surface antigen
hepatitis B virus
hepatocellular carcinoma
injection drug use or user
international normalized ratio
model for end-stage liver disease
men who have sex with men
nucleic acid testing
National Institutes of Health
organic anion-transporting polypeptide
p-glycoprotein
paritaprevir/ritonavir/ombitasvir plus dasabuvir
resistance-associated variant
red blood cell (eg, red blood cell count)
ribavirin
response-guided therapy
rapid virologic response
surface antigen
simeprevir; used for the treatment of those with genotype 1 of hepatitis C virus (HCV) who have compensated liver disease, including
cirrhosis
SOF
sofosbuvir; a nucleoside analogue used in combination with other drugs for the treatment of HCV infection
SVR12 (or sustained virologic response at 12 weeks (or at 24 weeks, or at 48 weeks, etc)
24 or 48,
etc)
Select Abbreviations