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{{Drugbox
__NOTOC__
| IUPAC_name        =
{{Telaprevir}}
| image            = Telaprevir.svg
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{{CMG}}; '''Assistant Editor-In-Chief:''' Nina Axiotakis [mailto:naxiotak@oberlin.edu]


==Overview==
==Overview==
'''Telaprevir''' ([[International Nonproprietary Name|INN]]) is a [[protease inhibitor (pharmacology)|protease inhibitor]] being studied as a treatment for [[hepatitis C]].
'''Telaprevir''' ([[International Nonproprietary Name|INN]]) is a [[protease inhibitor (pharmacology)|protease inhibitor]] being studied as a treatment for [[hepatitis C]].


Telaprevir is currently being marketed as Incivek. It has completed its phase III trials (ADVANCE;  A New Direction in HCV Care: A Study of Treatment-naïve Hepatitis C Patients with Telaprevir) in previously untreated patients with genotype 1, the most common strain in North American and Europe It is an orally bioavailable inhibitor of the nonstructural 3/4A (NS3/4A) HCV serine protease. <ref> Poordad F (February 2011). "Big Changes Are Coming in Hepatitis C ". Curr Gastroenterol Rep. 13 (1): 72-7. PMCID: PMC3026711. doi:  10.1007/s11894-010-0153-9. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3026711/?tool=pubmed></ref> <ref>McHutchison JG, Everson GT, Gordon SC, Jacobson IM,  Sulkowski M, Kauffman R, McNair L, Alam J, Muir AJ. (April 2009). "Telaprevir with Peginterferon and Ribavirin for Chronic HCV Genotype 1 Infection". N Engl J Med. 360 (18): 1827-38. <http://www.nejm.org/doi/full/10.1056/nejmoa0806104#t=citedby></ref> It was approved by the FDA on May 23rd, 2011 as a hepatitis C virus protease inhibitor, making it the second direct-acting antiviral HCV drug therapy to be approved behind boceprevir. <ref>Klein R, Struble K. (May 2011). "Approval of Incivek (telaprevir), a direct acting antiviral drug (DAA) to treat hepatitis C (HCV)". U.S. Food and Drug Administration. < http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/ucm256328.htm></ref> Telaprevir is most successful in patients who have not yet been previously treated for the condition.<sup>2</sup>
Telaprevir is currently being marketed as Incivek. It has completed its phase III trials (ADVANCE;  A New Direction in HCV Care: A Study of Treatment-naïve Hepatitis C Patients with Telaprevir) in previously untreated patients with genotype 1, the most common strain in North American and Europe It is an orally bioavailable inhibitor of the nonstructural 3/4A (NS3/4A) HCV serine protease. <ref> Poordad F (February 2011). "Big Changes Are Coming in Hepatitis C ". Curr Gastroenterol Rep. 13 (1): 72-7. PMCID: PMC3026711. doi:  10.1007/s11894-010-0153-9.<http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3026711/?tool=pubmed></ref> <ref>McHutchison JG, Everson GT, Gordon SC, Jacobson IM,  Sulkowski M, Kauffman R, McNair L, Alam J, Muir AJ. (April 2009). "Telaprevir with Peginterferon and Ribavirin for Chronic HCV Genotype 1 Infection". N Engl J Med. 360 (18): 1827-38. <http://www.nejm.org/doi/full/10.1056/nejmoa0806104#t=citedby></ref> It was approved by the FDA on May 23rd, 2011 as a hepatitis C virus protease inhibitor, making it the second direct-acting antiviral HCV drug therapy to be approved behind boceprevir. <ref>Klein R, Struble K. (May 2011). "Approval of Incivek (telaprevir), a direct acting antiviral drug (DAA) to treat hepatitis C (HCV)". U.S. Food and Drug Administration. <http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/ucm256328.htm></ref> Telaprevir is most successful in patients who have not yet been previously treated for the condition.<sup>2</sup>


Currently, it is reported by the World Health Organization that 170-180 million people worldwide suffer from the hepatitis C virus (HCV ) and it is considered to be a serious global health crisis. <ref>Walker EP,  (May 2011). "Boceprevir Wins FDA Approval to Treat Hepatitis C". MedPage Today. <http://www.medpagetoday.com/InfectiousDisease/Hepatitis/26469></ref> <ref>Njoroge FG, Chen KX, Shih NY, Piwinski JJ (January 2008). "Challenges in modern drug discovery: a case study of boceprevir, an HCV protease inhibitor for the treatment of hepatitis C virus infection". Acc. Chem. Res. 41 (1): 50–9.</ref> <ref>Susser S, Welsch C, Wang Y, Zettler M, Domingues FS, Karey U, Hughes E, Ralston R, Tong X, Herrmann E, Zeuzem S, Sarrazin C. (December 2009). "Characterization of resistance to the protease inhibitor boceprevir in hepatitis C virus–infected patients". Hepatology. 50 (6): 1709-18. DOI: 10.1002/hep.23192 <http://onlinelibrary.wiley.com/doi/10.1002/hep.23192/full></ref> It is the most common blood born infection worldwide.<sup>5</sup> Of this population, at least 130 million patients are estimated to be chronic HCV carriers who are at severe risk of developing liver cirrhosis and liver cancer.<sup>4</sup>, <sup>6</sup> The HCV RNA genome serves as a template for viral replication and as a viral messenger RNA for viral production. It is translated into a polyprotein that is cleaved by proteases, and then viral assembly occurs.<sup>4</sup>
Currently, it is reported by the World Health Organization that 170-180 million people worldwide suffer from the hepatitis C virus (HCV ) and it is considered to be a serious global health crisis. <ref>Walker EP,  (May 2011). "Boceprevir Wins FDA Approval to Treat Hepatitis C". MedPage Today.<http://www.medpagetoday.com/InfectiousDisease/Hepatitis/26469></ref> <ref>Njoroge FG, Chen KX, Shih NY, Piwinski JJ (January 2008). "Challenges in modern drug discovery: a case study of boceprevir, an HCV protease inhibitor for the treatment of hepatitis C virus infection". Acc. Chem. Res. 41 (1): 50–9.</ref> <ref>Susser S, Welsch C, Wang Y, Zettler M, Domingues FS, Karey U, Hughes E, Ralston R, Tong X, Herrmann E, Zeuzem S, Sarrazin C. (December 2009). "Characterization of resistance to the protease inhibitor boceprevir in hepatitis C virus–infected patients". Hepatology. 50 (6): 1709-18. DOI: 10.1002/hep.23192 <http://onlinelibrary.wiley.com/doi/10.1002/hep.23192/full></ref> It is the most common blood born infection worldwide.<sup>5</sup> Of this population, at least 130 million patients are estimated to be chronic HCV carriers who are at severe risk of developing liver cirrhosis and liver cancer.<sup>4</sup>, <sup>6</sup> The HCV RNA genome serves as a template for viral replication and as a viral messenger RNA for viral production. It is translated into a polyprotein that is cleaved by proteases, and then viral assembly occurs.<sup>4</sup>


The previously leading treatment therapy, a regimen of pegylated interferon and ribavirin, was only effective in about 38% - 46% of patients.2 <ref>Asselah T, Marcellin P. (January 2011). "New direct-acting antivirals' combination for the treatment of chronic hepatitis C". Liver International. 31 (s1): 68-77. DOI: 10.1111/j.1478-3231.2010.02411.x <http://onlinelibrary.wiley.com/doi/10.1111/j.1478-3231.2010.02411.x/abstract></ref> <ref>Kwo PY, Vinayek R. (November 2011). "The Therapeutic Approaches for Hepatitis C Virus: Protease Inhibitors and Polymerase Inhibitors". Gut Liver. 5 (4): 406-17. doi:  10.5009/gnl.2011.5.4.406  PMCID: PMC3240782 <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3240782/?tool=pubmed></ref> It was administered for 24 weeks in patients with genotypes 2 or 3, or for 48 weeks in patients with genotype 1, the most common strain in Europe and North America.<sup>2</sup> Fortunately, the recently FDA approved telaprevir is a significant and improved development in the successful treatment of HCV. Telaprevir is a polymerase-inhibiting direct-acting antiviral (DAA) agent that is to be administered to the patients in combination with peginterferon and ribavirin.1 DAA drug agents work to attack the virus directly; they work by different mechanisms of action than previous treatments which indirectly fought the virus by trying to boost the immune system.<sup>4</sup>, <ref>Adiwijaya BS, Kieffer TL, Henshaw J, Eisenhauer K,  Kimko H, Alam JJ, Kauffman RS, Garg V. (January 2012). "A Viral Dynamic Model for Treatment Regimens with Direct-acting Antivirals for Chronic Hepatitis C Infection". PLoS Comput Biol. 8 (1): 1-11. PMCID: PMC3252270 doi:  10.1371/journal.pcbi.1002339 <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3252270/?tool=pubmed></ref> The introduction of this drug has broadened treatment options for patients suffering HCV considerably with the main goal of treatment being the achievement of a sustained virologic response (SVR), defined as an undetectable serum HCV RNA level 24 weeks after cessation of therapy.<sup>2</sup> The achievement of SVR means that the virus has been eradicated and will further complications such as cirrhosis and hepatocellular carcinoma (HCC) are prevented.<sup>1</sup>, <sup>4</sup>
The previously leading treatment therapy, a regimen of pegylated interferon and ribavirin, was only effective in about 38% - 46% of patients.2<ref>Asselah T, Marcellin P. (January 2011). "New direct-acting antivirals' combination for the treatment of chronic hepatitis C". Liver International. 31 (s1): 68-77. DOI: 10.1111/j.1478-3231.2010.02411.x <http://onlinelibrary.wiley.com/doi/10.1111/j.1478-3231.2010.02411.x/abstract></ref> <ref>Kwo PY, Vinayek R. (November 2011). "The Therapeutic Approaches for Hepatitis C Virus: Protease Inhibitors and Polymerase Inhibitors". Gut Liver. 5 (4): 406-17. doi:  10.5009/gnl.2011.5.4.406  PMCID: PMC3240782 <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3240782/?tool=pubmed></ref> It was administered for 24 weeks in patients with genotypes 2 or 3, or for 48 weeks in patients with genotype 1, the most common strain in Europe and North America.<sup>2</sup> Fortunately, the recently FDA approved telaprevir is a significant and improved development in the successful treatment of HCV. Telaprevir is a polymerase-inhibiting direct-acting antiviral (DAA) agent that is to be administered to the patients in combination with peginterferon and ribavirin.1 DAA drug agents work to attack the virus directly; they work by different mechanisms of action than previous treatments which indirectly fought the virus by trying to boost the immune system.<sup>4</sup>, <ref>Adiwijaya BS, Kieffer TL, Henshaw J, Eisenhauer K,  Kimko H, Alam JJ, Kauffman RS, Garg V. (January 2012). "A Viral Dynamic Model for Treatment Regimens with Direct-acting Antivirals for Chronic Hepatitis C Infection". PLoS Comput Biol. 8 (1): 1-11. PMCID: PMC3252270 doi:  10.1371/journal.pcbi.1002339 <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3252270/?tool=pubmed></ref> The introduction of this drug has broadened treatment options for patients suffering HCV considerably with the main goal of treatment being the achievement of a sustained virologic response (SVR), defined as an undetectable serum HCV RNA level 24 weeks after cessation of therapy.<sup>2</sup> The achievement of SVR means that the virus has been eradicated and will further complications such as cirrhosis and hepatocellular carcinoma (HCC) are prevented.<sup>1</sup>,<sup>4</sup>


Serine protease inhibitors such as telaprevir used in the treatment of HCV for post-translational processing and the inhibition viral replication. It is most successful when given in combination with peginterferon and ribavirin at achieving sustained virologic responses in most patients who have genotype 1. However, when used as monotherapy, without the combination of the other standard drugs, the body quickly develops resistance.<sup>6</sup>
Serine protease inhibitors such as telaprevir used in the treatment of HCV for post-translational processing and the inhibition viral replication. It is most successful when given in combination with peginterferon and ribavirin at achieving sustained virologic responses in most patients who have genotype 1. However, when used as monotherapy, without the combination of the other standard drugs, the body quickly develops resistance.<sup>6</sup>
==Category==
Antiviral
==US Brand Names==
INCIVEK<sup>®</sup>


===Clinical Trials===
==FDA Package Insert==
 
Incivek’s approval was based upon safety and efficacy data in approximately 2,250 adult subjects who had been previously untreated (ADVANCE and ILLUMINATE) or who had failed previous peginterferon and ribavirin therapy (REALIZE) in clinical studies.<sup>3</sup>


Trial evidence shows that that the addition of telaprevir to peginterferon and ribavirin combination therapy could nearly double the rate of successful SVR outcomes in patients who have HCV genotype 1.1 Data has shown a that a population of null responders to previous therapy attempts, particularly those with cirrhosis, did not achieve an SVR on telaprevir and telaprevir resistance-associated substitutions emerged on treatment with INCIVEK combination treatment.<sup>3</sup>
'''  [[Telaprevir description|Description]]'''
 
'''| [[Telaprevir clinical pharmacology|Clinical Pharmacology]]'''
The efficacy of Incivek has not yet been established for patients who previously failed a treatment regimen that included Incivek or another protease inhibitor.<sup>3</sup>
'''| [[Telaprevir microbiology|Microbiology]]'''
 
'''| [[Telaprevir indications and usage|Indications and Usage]]'''
Treatment-Naïve Adults: Study 108 (ADVANCE)
'''| [[Telaprevir contraindications|Contraindications]]'''
 
'''| [[Telaprevir warnings and precautions|Warnings and Precautions]]'''
*SVR rates were higher (absolute difference of at least 22%) for the T12/PR group than for the Pbo/PR48 group across subgroups by sex, age, race, ethnicity, body mass index, HCV genotype subtype, baseline HCV-RNA (less than 800,000, greater than or equal to 800,000 IU/mL), and extent of liver fibrosis.<sup>3</sup>
'''| [[Telaprevir adverse reactions|Adverse Reactions]]'''
 
'''| [[Telaprevir drug interactions|Drug Interactions]]'''
Treatment-Naïve Adults: Study 111 (ILLUMINATE)
'''| [[Telaprevir overdosage|Overdosage]]'''
 
'''| [[Telaprevir clinical studies|Clinical Studies]]'''
*The SVR rate for all subjects enrolled in the trial was 74%. A total of 352 (65%) subjects achieved eRVR and of those 322 (60%) were randomized to 24 weeks (T12/PR24, n=162) or 48 weeks (T12/PR48, n=160) of treatment. The SVR rates were similar at 92% (T12/PR24) and 90% (T12/PR48), respectively. Again, small numbers of subjects were enrolled in some key subgroups.<sup>3</sup>
'''| [[Telaprevir dosage and administration|Dosage and Administration]]'''
 
'''| [[Telaprevir how supplied|How Supplied]]'''
Previously Treated Adults: Study C216 (REALIZE)
'''| [[Telaprevir labels and packages|Labels and Packages]]'''
 
*The study enrolled prior relapsers (subjects with HCV-RNA undetectable at end of treatment with a pegylated interferon-based regimen, but HCV RNA detectable within 24 weeks of treatment follow-up) and prior non responders (subjects who did not have undetectable HCV-RNA levels during or at the end of a prior course of at least 12 weeks of treatment).3
*Among prior relapsers, 76% (218/286) achieved an eRVR and of those 95% (208/218) achieved an SVR. In an earlier, dose-finding clinical trial, 78% (52/67) of prior relapsers achieved an eRVR and were treated with 24 weeks of peginterferon alfa and ribavirin (T12/PR24); of those 94% (49/52) achieved an SVR.<sup>3</sup>
 
===Administration===
 
Previous treatment regimens resulted in SVR less than 50% of the time, were difficult to tolerate, and requires injection. Newer treatment regimens involving telaprevir are more effective, less toxic, and are easier to administer. Incivek must be administered in combination with peginterferon and ribavirin and must not be given as mono-therapy. In many patients, the treatment period can be successfully reduced from 48 weeks to 24 weeks on the this telaprevir-based regimen while still maintaining an SVR.<sup>2</sup>
 
The recommended dosage of Incivek is tablets is 750 mg (two 375-mg tablets) taken orally 3 times a day (7-9 hours apart) with food.<sup>3</sup> It is not recommended that foods be low in fat. Specific doses are peginterferon and ribavirin are included on their respective prescribing information. The recommended duration of treatment is 12 weeks in combination with the other two drugs, with HCV-RNA levels being monitored at week 4 and week 12 to determine combination treatment duration and assess for treatment futility.<sup>3</sup> Treatment-naïve patients with cirrhosis of the liver who have HCV-RNA levels that are undetectable at weeks 4 and 12 under Incivek combination treatment may benefit from an additional 36 weeks of peginterferon and ribavirin for 48 weeks of treatment total. Patients with inadequate viral response are not likely to achieve sustained virologic response and may develop treatment-emergent resistance substitution.<sup>3</sup> The discontinuation of treatment is highly recommended in patients with HCV-RNA levels that are greater than or equal to 1000 IU/mL at treatment week 4 or week 12, or in patients with detectable HCV-RNA levels that have been confirmed at week 24 of treatment.<sup>3</sup>
 
===Contraindications and Complications===
 
Pregnant women and men whose female partners are pregnant compose the contraindications because of the risks for birth defects and fetal death associated with the consumption of ribavirin.<sup>3</sup> Patients should be required to have a negative pregnancy test prior to their start on therapy and for six months following the treatment period.
 
===Side Effects===
 
Skin rashes developed in 56% of patients taking Incivek combination treatment. Severe rash (e.g., a generalized rash or rash with vesicles or bullae or ulcerations other than SJS) was reported in 4% of patients, compared to less than 1% receiving only peginterferon and ribavirin. Serious skin reactions including Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) and Stevens-Johnson Syndrome (SJS) were reported in less than 1% of subjects who received Incivek combination treatment, compared to none who received peginterferon and ribavirin alone. All patients who experienced skin disorders recovered from it, but management required hospitalization.<sup>2</sup>
 
Side effects corresponding to peginterferon and ribavirin combination treatment include anemia, and the addition of Incivek to the therapy combination has been associated with an additional increase in hemoglobin concentrations. Hemoglobin values less than or equal to 10 g/dL were observed in 36% of subjects who received Incivek treatment with peginterferon and ribavirin compared to 17% of subjects who received peginterferon and ribavirin alone.<sup>2</sup>
 
Other commonly reported adverse drug reactions include fatigue, pruritus, nausea, diarrhea, vomiting, hemorrhoids, anorectal discomfort, dysgeusia and anal pruritis. 14% of patients receiving Incivek discontinued the therapy because of adverse drug reactions in one study.<sup>3</sup>


==Mechanism of Action==
Telaprevir is an inhibitor of the HCV NS3/4A serine protease, necessary for the proteolytic cleavage of the HCV encoded polyprotein into mature forms of the NS4A, NS4B, NS5A and NS5B proteins and essential for viral replication. In a biochemical assay, telaprevir inhibited the proteolytic activity of the recombinant HCV NS3 protease domain with an IC50 value of 10 nM.


==References==
==References==
{{Reflist|2}}


{{reflist|2}}
[[Category:Antiviral]]
 
[[Category:Wikinfect]]
 
==See Also==
* [[Boceprevir]], a similar agent for the treatment of hepatitis C
 
 
{{Antivirals}}
 
[[Category:Protease inhibitors]]
[[Category:Drugs]]
 
{{WikiDoc Help Menu}}
{{WS}}

Latest revision as of 01:44, 8 January 2014

Telaprevir
INCIVEK® FDA Package Insert
Description
Clinical Pharmacology
Microbiology
Indications and Usage
Contraindications
Warnings and Precautions
Adverse Reactions
Drug Interactions
Overdosage
Dosage and Administration
How Supplied
Labels and Packages

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sheng Shi, M.D. [2]

Overview

Telaprevir (INN) is a protease inhibitor being studied as a treatment for hepatitis C.

Telaprevir is currently being marketed as Incivek. It has completed its phase III trials (ADVANCE; A New Direction in HCV Care: A Study of Treatment-naïve Hepatitis C Patients with Telaprevir) in previously untreated patients with genotype 1, the most common strain in North American and Europe It is an orally bioavailable inhibitor of the nonstructural 3/4A (NS3/4A) HCV serine protease. [1] [2] It was approved by the FDA on May 23rd, 2011 as a hepatitis C virus protease inhibitor, making it the second direct-acting antiviral HCV drug therapy to be approved behind boceprevir. [3] Telaprevir is most successful in patients who have not yet been previously treated for the condition.2

Currently, it is reported by the World Health Organization that 170-180 million people worldwide suffer from the hepatitis C virus (HCV ) and it is considered to be a serious global health crisis. [4] [5] [6] It is the most common blood born infection worldwide.5 Of this population, at least 130 million patients are estimated to be chronic HCV carriers who are at severe risk of developing liver cirrhosis and liver cancer.4, 6 The HCV RNA genome serves as a template for viral replication and as a viral messenger RNA for viral production. It is translated into a polyprotein that is cleaved by proteases, and then viral assembly occurs.4

The previously leading treatment therapy, a regimen of pegylated interferon and ribavirin, was only effective in about 38% - 46% of patients.2[7] [8] It was administered for 24 weeks in patients with genotypes 2 or 3, or for 48 weeks in patients with genotype 1, the most common strain in Europe and North America.2 Fortunately, the recently FDA approved telaprevir is a significant and improved development in the successful treatment of HCV. Telaprevir is a polymerase-inhibiting direct-acting antiviral (DAA) agent that is to be administered to the patients in combination with peginterferon and ribavirin.1 DAA drug agents work to attack the virus directly; they work by different mechanisms of action than previous treatments which indirectly fought the virus by trying to boost the immune system.4, [9] The introduction of this drug has broadened treatment options for patients suffering HCV considerably with the main goal of treatment being the achievement of a sustained virologic response (SVR), defined as an undetectable serum HCV RNA level 24 weeks after cessation of therapy.2 The achievement of SVR means that the virus has been eradicated and will further complications such as cirrhosis and hepatocellular carcinoma (HCC) are prevented.1,4

Serine protease inhibitors such as telaprevir used in the treatment of HCV for post-translational processing and the inhibition viral replication. It is most successful when given in combination with peginterferon and ribavirin at achieving sustained virologic responses in most patients who have genotype 1. However, when used as monotherapy, without the combination of the other standard drugs, the body quickly develops resistance.6

Category

Antiviral

US Brand Names

INCIVEK®

FDA Package Insert

Description | Clinical Pharmacology | Microbiology | Indications and Usage | Contraindications | Warnings and Precautions | Adverse Reactions | Drug Interactions | Overdosage | Clinical Studies | Dosage and Administration | How Supplied | Labels and Packages

Mechanism of Action

Telaprevir is an inhibitor of the HCV NS3/4A serine protease, necessary for the proteolytic cleavage of the HCV encoded polyprotein into mature forms of the NS4A, NS4B, NS5A and NS5B proteins and essential for viral replication. In a biochemical assay, telaprevir inhibited the proteolytic activity of the recombinant HCV NS3 protease domain with an IC50 value of 10 nM.

References

  1. ↑ Poordad F (February 2011). "Big Changes Are Coming in Hepatitis C ". Curr Gastroenterol Rep. 13 (1): 72-7. PMCID: PMC3026711. doi: 10.1007/s11894-010-0153-9.<http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3026711/?tool=pubmed>
  2. ↑ McHutchison JG, Everson GT, Gordon SC, Jacobson IM, Sulkowski M, Kauffman R, McNair L, Alam J, Muir AJ. (April 2009). "Telaprevir with Peginterferon and Ribavirin for Chronic HCV Genotype 1 Infection". N Engl J Med. 360 (18): 1827-38. <http://www.nejm.org/doi/full/10.1056/nejmoa0806104#t=citedby>
  3. ↑ Klein R, Struble K. (May 2011). "Approval of Incivek (telaprevir), a direct acting antiviral drug (DAA) to treat hepatitis C (HCV)". U.S. Food and Drug Administration. <http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/ucm256328.htm>
  4. ↑ Walker EP, (May 2011). "Boceprevir Wins FDA Approval to Treat Hepatitis C". MedPage Today.<http://www.medpagetoday.com/InfectiousDisease/Hepatitis/26469>
  5. ↑ Njoroge FG, Chen KX, Shih NY, Piwinski JJ (January 2008). "Challenges in modern drug discovery: a case study of boceprevir, an HCV protease inhibitor for the treatment of hepatitis C virus infection". Acc. Chem. Res. 41 (1): 50–9.
  6. ↑ Susser S, Welsch C, Wang Y, Zettler M, Domingues FS, Karey U, Hughes E, Ralston R, Tong X, Herrmann E, Zeuzem S, Sarrazin C. (December 2009). "Characterization of resistance to the protease inhibitor boceprevir in hepatitis C virus–infected patients". Hepatology. 50 (6): 1709-18. DOI: 10.1002/hep.23192 <http://onlinelibrary.wiley.com/doi/10.1002/hep.23192/full>
  7. ↑ Asselah T, Marcellin P. (January 2011). "New direct-acting antivirals' combination for the treatment of chronic hepatitis C". Liver International. 31 (s1): 68-77. DOI: 10.1111/j.1478-3231.2010.02411.x <http://onlinelibrary.wiley.com/doi/10.1111/j.1478-3231.2010.02411.x/abstract>
  8. ↑ Kwo PY, Vinayek R. (November 2011). "The Therapeutic Approaches for Hepatitis C Virus: Protease Inhibitors and Polymerase Inhibitors". Gut Liver. 5 (4): 406-17. doi: 10.5009/gnl.2011.5.4.406 PMCID: PMC3240782 <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3240782/?tool=pubmed>
  9. ↑ Adiwijaya BS, Kieffer TL, Henshaw J, Eisenhauer K, Kimko H, Alam JJ, Kauffman RS, Garg V. (January 2012). "A Viral Dynamic Model for Treatment Regimens with Direct-acting Antivirals for Chronic Hepatitis C Infection". PLoS Comput Biol. 8 (1): 1-11. PMCID: PMC3252270 doi: 10.1371/journal.pcbi.1002339 <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3252270/?tool=pubmed>
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