Victrelis (Boceprevir) and Incivek (Telaprevir) first generation protease inhibitors to treat hepatitis C.
Mar 19 2015
Boceprevir Expected to be Discontinued by December 2015
Merck expects to discontinue the manufacturing and distribution of its inhibitor boceprevir for the treatment of hepatitis C virus by December, according to a company spokesperson.
Hepatitis C Infection Treatment Will Be Discontinued
The Food and Drug Administration (FDA) is informing that Victrelis (boceprevir; Merck) 200mg capsules will be discontinued.
**On Aug 12 2014 Vertex to stop selling hepatitis C drug Incivek
Nov 2 2014
Triple Therapy for Hepatitis C Infection: Bacterial Infection Risk Rises, Changes
Studies showed that HCV-infected patients who have comorbid HCV-related cirrhosis who receive double therapy (interferon and ribavirin) are at elevated risk of bacterial infections. Recent guidelines recommend adding a protease inhibitor (telaprevir or boceprevir, called triple therapy) to the interferon and ribavirin regimen to increase the likelihood of sustained virologic response. A team of European researchers, curious about how infection rates might be affected, set out to compare infection rates between treatments. Their study appeared in the October 2014 issue of the Journal of Hepatology.
Vertex to stop selling hepatitis C drug Incivek
15 hepatitis C patients die of drug’s side effects
Fifteen hepatitis C patients who were prescribed a drug manufactured by Mitsubishi Tanabe Pharma Corp. have died after developing serious side effects such as liver failure and whole-body dermatitis, according to the drug company and other sources.
Incidence and Management of Rash in Telaprevir-Treated Patients: Lessons for Simeprevir?
Telaprevir-induced rash is a common, therapy-limiting adverse drug event (ADE) for patients with hepatitis c virus (HCV) infection. Given the similarity between telaprevir and simeprevir, real-world management of rash during treatment with an NS3/4A protease inhibitor and its implications are important.
Safety and Efficacy of Telaprevir for Advanced HCV
Gut, July 3, 2014
In compensated patients with advanced fibrosis due to hepatitis C genotype 1, how effective is triple therapy with telaprevir?
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New! Hepatitis C treatment factsheets – telaprevir, boceprevir and sofosbuvir
How Long Should HCV Treatment Last? Study Suggests Answers Are Complex
In previous studies, a more invasive procedure – core needle biopsy – was used to sample the liver in HCV infection. In the current study, fine needle aspiration was used; this method is better tolerated by patients and allows for repeated sampling at more time points than core needle biopsy.
“Fine needle aspiration enables us to sample the liver repeatedly during the course of treatment, to better understand what’s happening with the virus, how these drugs work and how to tailor therapy to the patient,” Talal explained...
How I Manage HCV Patients for Whom First-Generation Protease Inhibitors Failed
Successes and Failures With Protease Inhibitors
Virologic characterization of genotype 4 hepatitis C virus variants in patients treated with telaprevir
The complete article is available as a provisional PDF
Boceprevir Combo Helpful in Compensated HCV Cirrhosis In well-compensated cirrhotic patients with HCV-1, peginterferon/ribavirin along with boceprevir appears to have a generally favorable benefit-risk profile, according to pooled data from phase 3 studies.
Efficacy and Safety of Telaprevir Triple Therapy for HCV
Journal of Viral Hepatitis, May 12, 2014
May 6 2014
DDW-Telaprevir showed greater SVR, cost-effectiveness than boceprevir among HCV patients
Patients with severe telaprevir-related skin eruption can continue treatment
Patients with grade 3 widespread morbilliform eruption associated with telaprevir can continue their triple therapy as long as they are closely monitored, according to researchers from Massachusetts General Hospital.
Triple therapy decreased SVR12 in mildly decompensated patients
Patients with a Child-Turcotte-Pugh scores greater than 6 who underwent protease inhibitor triple therapy experienced decreases in sustained virologic response at 12 weeks, according to data in a new study.
Researchers conducted a multicenter study of 160 adults with genotype 1 hepatitis C virus (HCV) infection with cirrhosis; 69% were treated with pegylated interferon ribavirin (PEG-IFN/RBV) plus telaprevir, and 31% were treated with PEG-IFN/RBV plus boceprevir. Researchers compared patients with Child-Turcotte-Pugh (CTP) values of 5 with those with values of 6 or greater.
April 5 2014
Skin Adverse Events During Dual and Triple Therapy for HCV-Related Cirrhosis
We report the case of a 64 year old man with HCV genotype 1 who discontinued telaprevir therapy for eczematiform lesions (grade 3) with improvement of the rash within seven days of telaprevir withdrawal. The patient continued PEG-IFN and RBV treatment, and, after a skin lesion-free period, showed repeated episodes of skin lesions different than those occurred during triple therapy both for type and location.
FDA update to Victrelis (boceprevir) label to include a new virologic futility rule
On February 24, 2014, FDA approved an update to the Victrelis (boceprevir) label to include a new virologic futility rule.
Specifically Section 2, Dosage and Administration, Table 1 was revised to state:
If a patient has HCV-RNA results greater than or equal to 1000 IU/mL at treatment week 8, then discontinue three-medicine regimen.
This statement is also reflected in subsection 2.4
Discontinuation of Dosing Based on Treatment Futility:
Discontinuation of therapy is recommended in all patients with 1) HCV-RNA levels of greater than or equal to 1000 IU per mL at TW8 (treatment week 8); or 2) HCV-RNA levels of greater than or equal to 100 IU per mL at TW12 (treatment week 12); or 3) confirmed detectable HCV-RNA levels at TW24 (treatment week 24).
You can view the complete revised Victrelis label and Medication Guide at Drugs@FDA.
Telaprevir-Based Triple Therapy for HIV/HCV Coinfection
Hepatitis - FDA Label update for Victrelis (boceprevir)
he Victrelis (boceprevir) label has been updated to include the following information under Section 5 Warnings and Precautions: 5.4 Pancytopenia (Use with Ribavirin and Peginterferon Alfa)
*Pancytopenia is a medical condition in which there is a reduction in the number of red and white blood cells, as well as platelets.
Serious cases of pancytopenia have been reported postmarketing in patients receiving VICTRELIS in combination with peginterferon alfa and ribavirin. Complete blood counts (with white blood cell differential counts) should be obtained at pretreatment, and at Treatment Weeks 2, 4, 8, and 12, and should be monitored closely at other time points, as clinically appropriate.
Refer to the Package Inserts for ribavirin and peginterferon alfa for guidelines for discontinuation of therapy based on laboratory parameters.
Additionally section 6.2 Postmarketing Experience was updated to include agranulocytosis, pancytopenia, thrombocytopenia, pneumonia and sepsis.
Triple therapy resulted in reduced fibrosis among patients with HCV
Manousou P. Gut. 2014;doi:10.1136/gutjnl-2013-305606.
Liver transplant patients with recurrent hepatitis C virus displayed less fibrotic progression when treated with tacrolimus, azathioprine and steroids compared with those patients receiving tacrolimus monotherapy in a recent study.
Researchers in the UK and Ireland evaluated 97 consecutive patients who had undergone liver transplantation and were randomly assigned to tacrolimus monotherapy (n=49) or triple therapy with tacrolimus, azathioprine and methylprednisolone (n=48) for 6 months. Patients received 0.1 mg/kg tacrolimus daily or 20 mg prednisolone daily, tapered to stop by 6 months; 0.1 mg/kg tacrolimus daily and 1 mg/kg azathioprine daily.
Ishak stage and collagen proportionate area (CPA) assessed fibrosis progression in annual liver biopsies for a median follow-up of 8 years. Nineteen monotherapy patients reached at least Ishak stage 4 in a median of 32 months, while 11 triple therapy patients reached the same level in a median of 49 months (P=.009). At the last biopsy CPA was 12% and 8% for monotherapy and triple therapy patients, respectively (P=.004).
Among 33 biopsies performed in the monotherapy cohort, 11 patients reached HVPG levels of at least 10 mm HG, considered clinically significant portal hypertension, while four of 31 patients receiving triple therapy who received biopsies attained a similar threshold.
Nine monotherapy and four triple therapy patients were decompensated. Using Cox regression analysis, only monotherapy was significantly associated with decompensation (OR=3.23; 95% CI, 1.01-10.3).
Researchers reported that 14 tacrolimus-only patients died and five required retransplantation compared with seven and four who received triple therapy.
“Long-term immunosuppression with tacrolimus, azathioprine and short-term prednisolone in HCV cirrhosis recipients resulted in slower progression to severe fibrosis … less portal hypertension and decompensation, compared with tacrolimus alone,” the researchers concluded.
Disclosure: Researchers Andrew K. Burroughs, FRCP, FMedSci, and Amar P. Dhillon, MD, (FRCPath), have an unrestricted education grant from Pfizer.
Source - Healio
Treatment of Chronic HCV Infection With Telaprevir
BMC Gastroenterology, January 29, 2014
Victrelis (boceprevir) label changes update contraindications and drug interactions
FDA approved changes to the Victrelis (boceprevir) package insert to expand the list of contraindicated medications and update the Drug Interaction section. Doxazosin, silodosin and tamsulosin, alpha 1-adrenoreceptor antagonists, were added to the section 4 Contraindications due to the potential for alpha 1-adrenoreceptor antagonist-associated adverse events such as hypotension and priapism. In section 7 Drug Interactions the calcium channel blockers, amlodipine, dilitiazem, nisoldipine and verapamil were added.
Comparative Effectiveness of the Hepatitis C Virus Protease Inhibitors Boceprevir and Telaprevir in a Large U.S. Cohort
Sustained virological response was more likely with telaprevir-based regimens compared with boceprevir-based regimens in routine medical practice, after accounting for patient differences. Early discontinuation and haematological events, however, were similar.
Jan 9 2014
How to Prepare for Hep C Triple Therapy
In Preparing for Hep C Triple Therapy you need understanding of treatment side effects and how to deal with them effectively. Learn helpful tools and tips that have worked for other Hep C patients in their treatment experience.We continue today with part 2, Physical preparation. See part 1 in How to Prepare for Hep C Triple Therapy. See continued articles on Preparing; Emotionally, Mentally, Spiritually and Financially.
Depression: Hep C Treatment Side Effect and Help to Get Through It, part 1
Adverse events with telaprevir in half of California HIV/HCV group
Author: Mark Mascolini 08 January 2014 Half of 24 patients coinfected with HIV and hepatitis C virus had serious adverse events when taking the HCV protease inhibitor telaprevir with pegylated interferon and ribavirin.
Telaprevir was one of the first HCV protease inhibitors licensed for use against infection with genotype 1 HCV, but its impact in people with HIV is still being assessed. Prescribing information warns about serious skin reactions, anemia, fatigue, vomiting, and other possible complications with telaprevir. Its use is contraindicated with strong CYP3A inhibitors and inducers, which include many antiretrovirals.
This retrospective cohort study involved HIV/HCV-coinfected people treated with telaprevir plus pegylated interferon and ribavirin at the University of California, San Diego HIV clinic. Among 24 consecutive patients, serious adverse events developed in 12 (50%). Seven patients (29%) had to stop HCV therapy because of adverse events, “despite an intensive multidisciplinary monitoring approach.” The authors suggest that “careful consideration of the risks and benefits of telaprevir-based therapy should be undertaken, given prospects for interferon-sparing therapy in the near future.
” The United States Food and Drug Administration has licensed three other direct-acting HCV antivirals: boceprevir, sofosbuvir, and simeprevir Source: Edward R. Cachay, David L. Wyles, Francesca J. Torriani, Craig Ballard, Bradford Colwell, Jennifer C. Lin, Lucas Hill, William C. Mathews. High incidence of serious adverse events in HIV-infected patients treated with a telaprevir-based hepatitis C virus treatment regimen. AIDS. 2013; 27: 2893-2897. For the study abstract (Downloading the complete article requires a subscription to AIDS or an online payment; the abstract is free.)
Effect of fibrosis on adverse events in patients with hepatitis C treated with telaprevir (pages 209–216)
K. Bichoupan, J. M. Schwartz, V. Martel-Laferriere, E. R. Giannattasio, K. Marfo, J. A. Odin, L. U. Liu, T. D. Schiano, P. Perumalswami, M. Bansal, P. J. Gaglio, H. Kalia, D. T. Dieterich, A. D. Branch and J. F. Reinus
Adverse events were common, but were not significantly related to the presence of advanced fibrosis or cirrhosis. More critical monitoring in older and female patients with low platelets throughout treatment may reduce adverse event-related discontinuations.
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How to optimize current therapy of HCV genotype 1 infection with boceprevir
Marc Bourlière, Xavier Adhoute, Astrid Wendt, Christelle Ansaldi, Valérie Oules and Paul Castellani
Article first published online: 23 DEC 2013 | DOI: 10.1111/liv.12390
Treatment with first generation protease inhibitors (PIs) is a milestone in the history of HCV therapy. Triple therapy with boceprevir (BOC) improves sustained virological response (SVR) by 30% in treatment naïve genotype 1 patients and by 50–60% in relapsers, 40–45% in partial responders and 25% in null responders compared with the Pegylated Interferon (PEG-IFN) and ribavirin regimen. To optimize BOC treatment, screening and access to treatment must be improved in genotype 1 patients. To select the ideal candidate for immediate treatment with triple therapy, an individual risk/benefit ratio must be assessed. Recent data have shown that patients with compensated cirrhosis and more advanced disease may also benefit from this regimen. Moreover, in HCV patients with extrahepatic manifestations, patients with HCV recurrence after liver transplantation and HIV-HCV co-infected patients, immediate treatment with triple therapy should be discussed. There is growing evidence that triple therapy with BOC is cost-effective in genotype 1 patients. Finally, the treatment design of BOC must be optimized in relation to baseline characteristics, so that optimal stopping rules can be followed, Drug-drug interactions (DDIs) can be prevented and AEs can be accurately prevented and managed.
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