Hepatitis C Medication

Updated: Mar 28, 2016
  • Author: Vinod K Dhawan, MD, FACP, FRCPC, FIDSA; Chief Editor: BS Anand, MD  more...
  • Print
Medication

Medication Summary

The addition of HCV protease and polymerase inhibitors with or without PED IFN alfa and ribavirin has become the new standard of care for the treatment of chronic HCV infection. Regimens that use these new agents significantly improve sustained virologic response rates in patients with genotype 1 HCV infection and, often, they also allow shorter treatment durations.

Sofosbuvir is an oral NS5B polymerase inhibitor that was FDA-approved for HCV genotypes 1, 2, 3, and 4. The combination of ledipasvir/sofosbuvir is the first oral regimen without INF and ribavirin approved by the FDA for HCV.

Daclatasvir (Daklinza), an NS5A inhibitor, was FDA approved in July 2015 for use with sofosbuvir for chronic HCV genotype 3 infection in treatment-naive or treatment-experienced patients. [97]

Ombitasvir/paritaprevir/ritonavir and dasabuvir (Viekira Pak) is another IFN-free combination regimen that has been FDA approved. It is indicated for treatment of chronic HCV genotype 1 infection, including patients with compensated cirrhosis. This combination regimen also may be used for patients with HCV/HIV-1 coinfection. Ombitasvir/paritaprevir/ritonavir and dasabuvir is used in combination with ribavirin in certain patient populations (ie, those with genotype 1a, with or without cirrhosis; those with genotype 1b, with cirrhosis).

The combination product ombitasvir/paritaprevir/ritonavir (Technivie) was FDA approved in July 2015. [96] It is indicated for treatment of genotype 4 chronic HCV infection without cirrhosis in patients who were either treatment naïve or did not achieve a virologic response with prior treatment with pegylated interferon/ribavirin (pegIFN/RBV). It is recommended to be used in combination with ribavirin, although it may be considered for treatment-naïve patients who cannot take or tolerate ribavirin. [96]

Next:

HCV Protease Inhibitors

Class Summary

These agents interfere with HCV replication by inhibiting a key viral enzyme, NS3/4A serine protease.

Simeprevir (Olysio)

Simeprevir inhibits HCV NS3/4A protease needed for proteolytic cleavage of the HCV-encoded polyprotein into mature forms. It is indicated for the treatment of chronic hepatitis C genotypes 1 and 4 infection in combination with peginterferon alfa and ribavirin. For genotype 1a, it may be prescribed as an all-oral regimen in combination with sofosbuvir.

Previous
Next:

HCV Polymerase Inhibitors

Class Summary

HCV NS5B polymerase plays an essential role in HCV replication.

Sofosbuvir (Sovaldi)

Sofosbuvir is a NS5B polymerase inhibitor that results in suppression of HCV replication and interrupts HCV life cycle. It is indicated for treatment of CHC infection genotypes 1, 2, 3, and 4 as part of a combination antiviral regimen, including those with hepatocellular carcinoma meeting Milan criteria (awaiting liver transplantation) to prevent HCV recurrence and those with HCV/HIV-1 co-infection.

Previous
Next:

HCV NS5A Inhibitors

Class Summary

NS5A is integral for HCV RNA viral replication.

Daclatasvir (Daklinza)

Daclatasvir inhibits NS5A, a nonstructural protein encoded by HCV. It binds to the N-terminus within domain 1 of NS5A, which may cause structural distortions that interfere with NS5A functions, and thereby inhibits both viral RNA replication and virion assembly. It is indicated for use with sofosbuvir for chronic HCV genotypes 1 and 3 infection. Depending on the genotype and other variables (eg, presence of cirrhosis, post liver transplantation), the regimen may also include ribavirin.

Previous
Next:

Combination Products

Class Summary

Several combination products have been approved and additional ones are being investigated to provide all oral regimens with high degrees of efficacy.

Ledipasvir/sofosbuvir (Harvoni)

Ledipasvir inhibits HCV NS5A protein, which is required for viral replication. Sofosbuvir is an inhibitor of HCV NS5B RNA-dependent polymerase. The oral combination is indicated for treatment of adults with chronic hepatitis C infection with genotype 1, 4, 5, or 6. Duration of therapy ranges from 8 to 24 weeks and depends on if the patient is treatment-naïve or experienced, and if cirrhosis is evident.

Ombitasvir/paritaprevir/ritonavir & dasabuvir (Viekira Pak)

This product is indicated for treatment of chronic HCV genotype 1 infection, including patients with compensated cirrhosis; may be used for patients with HCV/HIV-1 coinfection. It is used in combination with ribavirin in certain patient populations (ie, genotype 1a, with or without cirrhosis; genotype 1b, with cirrhosis). Ombitasvir inhibits HCV NS5A, which is required for viral replication. Paritaprevir is a NS3/4A serine protease inhibitor. NS3/4A protease is needed for proteolytic cleavage of the HCV-encoded polyprotein into mature forms. Ritonavir is a protease inhibitor that is used as a "boosting agent" to increase paritaprevir serum levels. Dasabuvir is a nonnucleoside NS5B RNA-dependent polymerase inhibitor. It's inhibition, in turn, suppresses viral replication.

Ombitasvir/paritaprevir/ritonavir (Technivie)

Ombitasvir/paritaprevir/ritonavir is indicated in combination with ribavirin for genotype 4 chronic HCV infection without cirrhosis. Ombitasvir inhibits HCV NS5A, which is required for viral replication. Paritaprevir is a NS3/4A serine protease inhibitor. NS3/4A protease is needed for proteolytic cleavage of the HCV-encoded polyprotein into mature forms. Ritonavir is a protease inhibitor that is used as a "boosting agent" to increase paritaprevir serum levels.

Elbasvir/grazoprevir (Zepatier)

Elbasvir is an inhibitor of HCV NS5A, which is essential for viral RNA replication and virion assembly. Grazoprevir is an inhibitor of HCV NS3/4A protease, which is necessary for the proteolytic cleavage of the HCV-encoded polyprotein (into mature forms of the NS3, NS4A, NS4B, NS5A, and NS5B proteins) and is essential for viral replication. It is indicated with or without ribavirin for treatment of adults with chronic HCV genotypes 1 or 4 infection.

Previous
Next:

Interferons and ribavirin

Class Summary

Interferons are naturally produced proteins with antiviral, antitumoral, and immunomodulatory actions. Interferons alfa, beta, and gamma may be given topically, systemically, and intralesionally. Interferons are immunomodulators that may shorten the clinical course, prevent complications, prevent latent and/or subsequent recurrences, decrease transmission, and eliminate established latency.

Interferon alfa-2b (Intron-A)

IFN alfa-2b is a protein product manufactured by recombinant DNA technology. The adult dosage is 3 million units subcutaneously (SC) 3 times weekly. Modulation of host immune response by IFN may play an important role in the treatment of viral diseases.

Peginterferon alfa-2b (PEG-Intron, Sylatron)

PEG-IFN consists of IFN alfa-2b attached to a single 12-kd PEG chain. It is excreted by the kidneys. PEG-IFN has sustained absorption, a slower rate of clearance, and a longer half-life than unmodified IFN, which permits more convenient once-weekly dosing and significantly improves quality of life for patients. The adult dose is 1.5 mcg/kg SC.

Pegylated interferon alfa-2a (Pegasys)

PEG-IFN alfa-2a consists of IFN alfa-2a attached to a 40-kd branched PEG molecule. It is predominantly metabolized by the liver. The adult dosage is 180 mcg/kg SC once weekly.

Ribavirin (Rebetol, Virazole, Copegus, Moderiba, Ribasphere)

Ribavirin is an antiviral nucleoside analogue. Its chemical name is D-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide. Given alone, ribavirin has little effect on the course of hepatitis C. Given with IFN, it significantly augments the rate of sustained virologic response. The adult dosage is 10.6 mg/kg orally once daily or in 2 divided doses.

Previous
Next:

Thrombopoietin-Receptor Agonists

Class Summary

These agents directly stimulate bone marrow platelet production to provide stable platelet counts to allow therapy with interferons.

Eltrombopag (Promacta)

Oral thrombopoietin (TPO) receptor agonist. Interacts with transmembrane domain of human TPO receptor and induces megakaryocyte proliferation and differentiation from bone marrow progenitor cells. Indicated for treatment of thrombocytopenia in patients with chronic hepatitis C to allow the initiation and maintenance of interferon-based therapy.

Previous