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Investigational Antiviral Drugs
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
John Mills, Suzanne M. Crowe, Marianne Martinello
Glecaprevir (ABT-493) is a potent second-generation pangenotypic HCV protease inhibitor, co-formulated with pibrentasvir (ABT-530). In phase II studies, very high sustained virologic response 12 weeks posttreatment (SVR1)2 (97–100%) was achieved with 8–12 weeks of glecaprevir–pibrentasvir 300/120 mg daily in HCV genotypes (GT) 1–6, including participants with GT-3 and compensated cirrhosis. High SVR12 (91%) was also achieved in direct-acting antiviral (DAA) experienced HCV GT-1 noncirrhotic participants with 12 weeks of glecaprevir–pibrentasvir 300/120mg daily plus ribavirin. Glecaprevir–pibrentasvir appears to be safe and well tolerated; the most commonly reported adverse events were fatigue (18%), headache (17%), nausea (13%), and diarrhea (10%). The combined oral formulation and dose will be glecaprevir–pibrentasvir 100/40 mg, three tablets daily (Kwo et al., 2016a; Kwo et al., 2016b; Lawitz et al., 2015; Poordad et al., 2016a; Poordad et al., 2016b).
Hepatitis C
Published in Vincenzo Berghella, Maternal-Fetal Evidence Based Guidelines, 2022
Rebecca Pierce-Williams, Neil Silverman, Raja Dhanekula, Jonathan M. Fenkel, Danielle Tholey
Historically, treatment regimens for HCV consisted of pegylated interferon (PEG-IFN), ribavirin, and protease inhibitors. In 2011, the first direct-acting antiviral agents (DAAs) were introduced (telaprevir and boceprevir) and since then progressive generations of DAAs have proved to be superior with regard to effectiveness, patient tolerance, and duration of therapy. The three classes of DAAs include NS3/4A protease inhibitors, NS5B nucleoside analog polymerase inhibitors, and nonstructural (NS5A) protein inhibitors [60]. First-line therapy now consists of a short course (8–12 weeks) of DAAs. For any genotype, in a treatment-naïve patient without cirrhosis, the preferred therapy is either 8 weeks of glecaprevir/pibrentasvir, or 12 weeks of sofosbuvir/velpatasvir. If cirrhosis is present, genotypes 1 thru 6 can be treated with glecaprevir/pibentasvir for 8 weeks. Combination sofosbuvir/velpatasvir for 12 weeks can be used in genotypes 1, 2, 4, 5, or 6 in this group. Genotype 1, the most common in the United States, can also be treated with 12 weeks of ledipasvir/sofosbuvir [5]. Genotype 3 remains a challenging genotype, with increased rates of HCC, and current guidance recommends treatment with sofosbuvir, ribavirin, and PEG-IFN for 12 weeks, or sofosbuvir plus ribavirin for 24 weeks [62]. These combinations have very few and generally mild side effects including headache, nausea, fatigue, and insomnia, and has not been shown to be associated with an increased risk of serious adverse events [63–65]. Many therapies and combinations exist, and the AASLD/IDSA “HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C” can be referenced for additional information [5].
Direct antiviral agents (DAAs) and their use in pregnant women with hepatitis C (HCV)
Published in Expert Review of Anti-infective Therapy, 2022
Sandra Abdul Massih, Ahizechukwu C. Eke
are both potent, pan-genotypic (HCV genotypes 1–6) combination of a NS3/4A protease inhibitor (GLE) and an NS5A inhibitor (PIB) [40]. Glecaprevir/Pibrentasvir is manufactured as a fixed-dose combination of 100 mg/40 mg tablet of GLE and PIB, respectively, and is dosed in a single administration per day (three tablets) [40]. This fixed-drug combination was FDA approved in 2019 for treatment of HCV, as this drug combination was noted to be effective against HCV genotypes 1–6 [40]. As a combination of a NS3/4A protease inhibitor and an NS5A inhibitor, GLE/PIB inhibits the viral replication and virion assembly [40]. Glecaprevir/Pibrentasvir is absorbed well orally when dosed with meals, with an 83–163% increase in absorption for GLE following a meal, compared with only 40–53% increase for PIB. The oral bioavailability of GLE/PIB is approximately 90% in humans, with a protein-binding of >97% [40]. Following an oral dose of GLE/PIB, drug concentrations are widely distributed, with the highest concentrations found in the liver. The Tmax is approximately 5 hours, with an elimination half-life of 6 and 13 hours for GLE and PIB, respectively. This might be related to the fact that, while both are primarily eliminated through the biliary-fecal route (with minimal renal excretion), GLE is secondarily metabolized by CYP3A4/5, while PIB is not [40].
Direct-acting antiviral treatment of acute hepatitis C virus infections
Published in Expert Review of Anti-infective Therapy, 2018
Suresh Misra, Douglas T. Dieterich, Behnam Saberi, Tatyana Kushner
There is an interesting clinical trial underway using glecaprevir plus pibrentasavir for the treatment of AHCV infections for 6 weeks versus 12 weeks (Table 3). This DAA led to SVR rates of > 98% in all genotypes of chronic hepatitis C without cirrhosis despite baseline patient or viral characteristics [92]. This medication if proven effective in AHCV may obviate preliminary work up and streamline treatment for AHCV patients whom are difficult to engage in care and for this reason at risk for progressive liver disease. As this medication is the cheapest on the market it will likely drive market prices down further. These potential developments could facilitate treatment of AHCV further and ultimately help in our goal of eradicating hepatitis C.
Chronic hepatitis C: Diagnosis and treatment made easy
Published in European Journal of General Practice, 2022
Naim Abu-Freha, Binil Mathew Jacob, Ali Elhoashla, Zaid Afawi, Talab Abu-Hammad, Foad Elsana, Sergey Paz, Ohad Etzion
Glecaprevir and pibrentasvir are used as a pan-genotypic treatment for HCV and contain 100 mg glecaprevir and 40 mg pibrentasvir, to be taken as three tablets, once daily with food. The treatment duration is eight weeks for naïve non-cirrhotic or compensated, cirrhotic patients; however, 12 weeks treatment is recommended for experienced patients with compensated cirrhosis (Child-Pugh A). Special consideration is essential for genotype 3, whereas 8 weeks treatment for naïve non-cirrhotic patients and 12 weeks for experienced non-cirrhotic patients is recommended, patients with genotype 3 and compensated cirrhosis should be treated for 8–12, whereas for compensated experienced patients with cirrhosis, 16 weeks are recommended [18].