Viekirax and Exviera are two new medications used to
treat hepatitis C. Viekirax is a
combination pill containing paritaprevir and ombitasvir with a booster dose of
ritonavir. Exviera or dasabuvir is a
separate pill usually taken with Viekirax.
Viekirax and Exviera were approved in Europe in January
2015 for treatment of adults with genotype 1 chronic hepatitis C. Most people
should take these medications with ribavirin. Viekirax without Exviera was
also approved for people with genotype 4 hepatitis C. In Europe, Viekirax and Exviera are available for separate prescription, but in some
countries they are packaged together (Viekira
Pak in the US and Australia, Holkira
Pak in Canada).
The Viekirax
and Exviera regimen offers a new
interferon-free option for many people with hepatitis C. Successful treatment
reduces the risk of long-term complications of hepatitis C such as liver cancer
or needing a liver transplant.
How do Viekirax and Exviera work?
Viekirax
contains two direct-acting antiviral drugs that target different steps of the
hepatitis C virus (HCV) lifecycle. Paritaprevir is an HCV protease inhibitor, meaning
it blocks the protease enzyme which the virus needs to reproduce. It is
combined with a small dose of ritonavir to boost its level in the blood. Ombitasvir is an HCV NS5A replication complex
inhibitor that interferes with another important HCV protein. Exviera or dasabuvir is a non-nucleoside
HCV polymerase inhibitor that blocks a third viral enzyme. Targeting multiple steps of the HCV lifecycle makes the combination more effective and
makes it harder for the virus to develop drug resistance.
Who can
use Viekirax and Exviera?
Viekirax and Exviera are indicated for use by adults
with chronic hepatitis C, meaning infection lasting more than six months. Viekirax plus Exviera, taken with or without ribavirin, were approved for people
with HCV genotype 1. Genotype 1 is the most common type in Europe. Viekirax without Exviera was approved for use with ribavirin for people with HCV genotype
4.
Viekirax and Exviera can be used by people being
treated for hepatitis C for the first time (known as 'treatment-naive') and for
retreatment of people who were not cured with previous interferon-based therapy
(known as 'treatment-experienced').
Viekirax and Exviera have been tested in people with
HIV and HCV co-infection. Response rates and side effects are similar to those
of HIV-negative people, but some of the drugs in this combination can interact
with antiretroviral medications for HIV. People with HIV and HCV co-infection
who want to take this regimen should do so under the care of a doctor who has
experience treating both infections.
Viekirax and Exviera can be used by people with all
stages of compensated liver disease including cirrhosis. However, it works
better for people with less advanced liver damage. This combination must not
be used by people with advanced or decompensated cirrhosis or severe liver function
impairment, but it can be used by people who have recurring HCV infection after
a liver transplant.
Viekirax and Exviera can be used by people using
opioid substitution therapy, such as methadone or buprenorphine, to manage drug
addiction.
How are Viekirax and Exviera taken?
Viekirax
is taken as two tablets once daily (in the morning) with food. Exviera is taken as a one tablet twice daily
(in the morning and evening) with food. Most people will also need to take
ribavirin pills twice daily, with doses based on body weight. Recommended
combinations and length of treatment will depend on a person's HCV genotype and
amount of liver damage. Genotype 1 includes two subtypes, 1a and 1b, with 1a
being harder to treat.
| |
Combined
with:
|
Length
of treatment
|
|
Genotype
1b
without
cirrhosis
|
Viekirax + Exviera
|
12 weeks
|
|
Genotype
1b with
compensated
cirrhosis
|
Viekirax + Exviera
|
12 weeks
|
|
Genotype
1a
without
cirrhosis
|
Viekirax + Exviera + ribavirin
|
12 weeks
|
|
Genotype
1a with
compensated
cirrhosis
|
Viekirax + Exviera + ribavirin
|
24 weeks
|
|
Genotype
4
without
cirrhosis
|
Viekirax +
ribavirin
|
12 weeks
|
|
Genotype
4 with
compensated
cirrhosis
|
Viekirax +
ribavirin
|
24 weeks
|
All people without liver cirrhosis can be treated for
12 weeks, but those with genotype 1a or 4 who have compensated cirrhosis should
extend treatment to 24 weeks. People with genotype 1b and no cirrhosis do not
need ribavirin. Exviera does not work
against genotype 4, so people with this genotype should take Viekirax with ribavirin alone.
Recommendations for people with HIV and HCV co-infection
are the same as for HIV-negative people. However, Viekirax should not be used with certain antiretroviral
medications. Viekirax contains
ritonavir and should not be combined with additional ritonavir used to boost
HIV protease inhibitors. People with HIV and HCV co-infection who are not on
antiretroviral therapy should not use Viekirax
because the ritonavir could cause HIV drug resistance.
Liver transplant recipients with HCV genotype 1 should
use Viekirax and Exviera plus ribavirin for 24 weeks. Ribavirin doses may need to be
lowered to reduce side effects.
Viekirax and Exviera are not approved for people with
HCV genotypes 2, 3, 5 or 6.
How
effective are Viekirax and Exviera?
Viekirax
and Exviera work better for
some people than for others. Several factors predict how well someone will
respond, including HCV genotype, extent of liver damage and previous treatment
history.
People with advanced liver disease do not respond as
well as those with mild or moderate liver fibrosis. People who are new to
treatment have a better chance of being cured than those who did not respond to
prior treatment. These factors may be overcome by longer treatment or by adding
ribavirin, which helps prevent relapse.
Other factors that traditionally predict poor response
to interferon-based therapy do not make as much difference with interferon-free
treatment.
Viekirax and Exviera treatment response
The safety and effectiveness of Viekirax and Exviera (also
known as the '3D' regimen) were tested in more than 2300 people with chronic hepatitis
C in six large international clinical trials.
Overall, 90% to 100% of study participants with HCV
genotype 1 were curedusing Viekirax plus Exviera, with or without ribavirin, for 12 or 24 weeks. People with
sustained virological response, who still have undetectable HCV viral load 12
weeks after finishing treatment (known as 'SVR12'), are considered cured.
The SAPPHIRE-I and -II trials showed that Viekirax plus Exviera with ribavirin for 12 weeks cured 96% of previously
untreated and treatment-experienced people with HCV genotype 1 without
cirrhosis, including a majority with harder-to-treat subtype 1a.
The PEARL-II and -III studies compared 12 weeks of Viekirax plus Exviera with or without ribavirin for treatment-naive and treatment
experienced people with easier-to-treat genotype 1b without cirrhosis, while
PEARL-IV looked at previously untreated people with genotype 1a. Everyone with genotype
1b was cured with Viekirax plus Exviera without ribavirin. For those
with genotype 1a cure rates were 90% without ribavirin and 97% with ribavirin.
The TURQUOISE-II trial showed that Viekirax plus Exviera with ribavirin for 12 weeks cured 99% of previously
untreated and treatment-experienced people with genotype 1b who had compensated
cirrhosis with mild liver function impairment. Among people with genotype 1a,
the cure rate was 95% with 24 weeks of treatment. Side effects were similar to
those seen in people without cirrhosis.
The smaller TURQUOISE-I study showed that Viekirax plus Exviera with ribavirin for 12 or 24 weeks cured 92% of people with
HIV and HCV co-infection (mostly with HCV subtype 1a). The CORAL-I study saw a
cure rate of 97% for genotype 1 liver transplant recipients who took Viekirax plus Exviera with ribavirin for 24 weeks. The cure rate was also 97% in
a small study of people on opioid substitution therapy.
Viekirax plus
ribavirin without Exviera (also known
as the '2D' regimen) cured 100% of treatment-naive and treatment-experienced
people with HCV genotype 4 in the PEARL-I study, but the response rate fell to
91% without ribavirin.
The effectiveness of Viekirax and Exviera in
'real world' use may be somewhat lower than cure rates seen in clinical trials,
in part because patients may be sicker or have other conditions that make
treatment more complicated.
What are
the side effects of Viekirax and Exviera?
The drugs in
Viekirax and Exviera are
generally safe and well tolerated. The most common side effects seen in
clinical trials were fatigue,
nausea, insomnia, weakness and itching. Ribavirin can cause side effects
including anaemia (low haemoglobin level). Participants in the SAPPHIRE trials who took Viekirax and Exviera with ribavirin were no more
likely to stop treatment due to side effects than those taking inactive placebo
pills.
Viekirax
and Exviera have not yet been tested
in pregnant or breastfeeding women. Ribavirin can cause birth defects,
so it should not be used by pregnant women, women planning to become pregnant,
or their male partners.
Do Viekirax and Exviera interact with other drugs?
The drugs in Viekirax
and Exviera can interact with other
drugs that are processed by the same enzymes in the liver or intestines. These
include some antiretroviral drugs for HIV, contraceptive pills, allergy
medications, antibiotics, TB medications, statins and other heart drugs,
psychiatric medications and herbal products containing St John's wort.
Sometimes drug doses can be adjusted to overcome these interactions, but some medications
should not be used together with Viekirax
and Exviera. Information about
specific drug interactions is available online at www.hep-druginteractions.org.
How can
I get Viekirax and Exviera?
Viekirax
and Exviera are available by
prescription in European Union countries to treat people with hepatitis C genotypes
1 or 4, subject to national approval. When to start treatment will depend on a
number of factors, including severity of liver damage (as determined by FibroScan or a liver biopsy). Ask your
GP or liver specialist if Viekirax and
Exviera may be a good option for you.
Factsheet reviewed April 2022.