Future Treatments for Chronic Hepatitis C Patients
Jeffery D. Evans, Pharm.D.
Michael C. Nguyen, Pharm.D. Candidate
University of Louisiana at Monroe, School of Pharmacy
The authors report no financial conflicts with any products discussed in this paper.
Introduction /Current therapy
limitations
The use of the two medication regimen of pegylated
interferon and ribavirin had been the standard of
care for Hepatits C virus (HCV) for more than 15
years prior to the introduction of new oral agents.
The combination of pegylated interferon and
ribavirin provided a fifty percent sustained viral
response (SVR.)1 However in the last few years
two newer agents, telaprevir and boceprevir, have
been released that allow for triple therapy and have
increased the success rate to between 63 – 75%
with many patients receiving a shortened treatment
period. In late 2013 two other agents, sofosbuvir
and simeprevir, were approved for use in the United
States.2
With the additional new medications though,
side effects seen in dual therapy have become
more common3. Anemia, neutropenia, and
thrombocytopenia all increase in frequency in
patients on triple therapy. Non-hematologic side
effects such as metallic taste and rashes also
increased in patients taking the triple therapy.
Though dropouts from the trials were few due to the
added adverse effects, additional treatments, such
as erythropoietin in trials with boceprevir, had to
be provided. With the increase in medications, the
number of drug-drug interactions also increase.4
Though rates of successful treatment have increased,
the need for better tolerated and more effective
medications is present. Healthcare costs for patients
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that fail therapy may be thirteen times higher
compared to patients with SVR.5
The intent of this review is to research the current
HCV medications in the research pipeline and
prepare the practitioner for the issues that may be
present when they are released.
Methods
A search of MEDLINE through PubMed was made
with the initial search term of ‘Hepatitis C’ and
‘treatment.’ From the 500+ responses, a second
search for ‘novel’ and ‘adverse effect’ was completed
to identify new agents and potential adverse
effects from current therapies. All articles had to be
published within the last 15 years and published in
English to be considered
NS3/4A Serine Protease Inhibitors
Two of the newer agents used for HCV treatment are
part of a new class of anti-viral that target one of the
proteases that the virus produces.6 As the protease
is responsible for cleaving parts of the virus to ensure
its viability, inhibiting the enzyme will terminate
the ability of an infected cell to produce new virus.
Already among this new class, a first and second
generation of the class has already appeared. One
issue within the first generation of the class is a cross
reactivity of resistance to these agents with HCV
variants being able to be resistant to other agents in
the class.