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Grazoprevir Combined with Elbasvir or Other 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
Grazoprevir (GZR) inhibits the HCV NS3/4A protease, which cleaves the HCV polyprotein at specific sites during viral replication. Early studies showed in vitro activity against HCV genotypes 1a, 1b, 2a, 2b, and 3a, including common NS3 resistance mutations such as R155K and A156T. Cross-resistance to mutations elicited by NS5A inhibitors (Y93H) or NS5B nucleoside inhibitors (S282T) was not observed. The compound showed potent antiviral activity in replicon assays and 4–5 log reductions in HCV RNA when tested in chronically infected chimpanzees (Summa et al., 2012). Elbasvir (EBR) inhibits another important therapeutic target, the HCV NS5A protein, which does not have an enzymatic function but is thought to be involved in viral assembly. The compound showed activity against HCV replicons of genotypes 1a, 2a, 2b, 3a, and 4a as well as key mutations, such as Y93H (Coburn et al., 2013). These drugs have been combined as a fixed-dose combination of GZR 100 mg and EBR 50 mg for clinical use as a once-daily, all-oral, interferon-free regimen.
Health-related quality of life in people receiving opioid agonist treatment and treatment for hepatitis C virus infection
Published in Journal of Addictive Diseases, 2023
Olav Dalgard, Alain H. Litwin, Oren Shibolet, Jason Grebely, Ronald Nahass, Frederick L. Altice, Brian Conway, Edward J. Gane, Anne F. Luetkemeyer, Cheng-Yuan Peng, David Iser, Isaias Noel Gendrano, Michelle M. Kelly, Barbara A. Haber, Heather Platt, Amy Puenpatom
Elbasvir/grazoprevir is a fixed-dose combination treatment for patients with HCV genotype 1 and 4 infection.6–10 COSTAR was a phase 3 clinical trial that evaluated the efficacy and safety of elbasvir/grazoprevir for 12 weeks in participants with HCV infection who were stable for ≥3 months on opioid agonist therapy. In this placebo-controlled trial, a sustained virologic response (SVR) at 12 weeks (SVR12) after completion of therapy was achieved by 96% of participants (274 of 286 participants in the modified full analysis set [FAS] population) receiving elbasvir/grazoprevir, with an associated safety profile that was generally similar to placebo.11 As this was a placebo-controlled double-blind trial that included people who injected drugs, including those who were using drugs during the study, this provides an unique opportunity to assess the effect of HCV on HRQOL in this population.
Fostemsavir for the treatment of HIV
Published in Expert Review of Anti-infective Therapy, 2021
Nikhil Seval, Cynthia Frank, Michael Kozal
Fostemsavir is primarily metabolized via esterases with lesser contribution via the CYP3A4 enzyme and other p450 pathways. Hence, drug metabolism can be affected by CYP modulating medications but this effect is minimized due to primary esterase degradation. Coadministration with strong CYP inducers (i.e. rifampin, carbamazepine, phenytoin, St Johns Wort, etc.) and the HCV direct-acting antiviral elbasvir/grazoprevir is not recommended. Pharmacokinetic interaction studies revealed no dose adjustment required when coadministered with protease inhibitors, boosters, or moderately CYP inducing NNRTIs. The drug may increase the dose of statins via interaction with the OATP metabolism pathway and careful dose titration is recommended. Doses of estrogen-based therapies should not contain more than 30 µg of ethinyl estradiol per day when co-administered, as temsavir has been shown to increase concentrations; caution should be paid particularly for those with underlying risk factors for thromboembolic events. Fostemsavir absorption is not affected by food or acid-blocking medications such as proton pump inhibitors.
Direct acting antivirals for the treatment of hepatitis C in ethnic minority populations
Published in Expert Opinion on Pharmacotherapy, 2018
The approval of the regimen of elbasvir/grazoprevir for HCV treatment was monumental as it was the first regimen that was safe and efficacious in the setting of underlying renal disease [29]. Individuals with HCV have significantly greater relative risk of having and/or developing CKD compared with uninfected individuals [30]. This is particularly important given the disproportionate burden of end stage renal disease and associated mortality in racial ethnic minority populations [31]. Grazoprevir and elbasvir are potent HCV-specific inhibitors of the NS3/4A protease (grazoprevir) and the NS5A protein (elbasvir) (see Table 1). They received Federal Drug Administration (FDA) approval based on the results of the C-EDGE trial [32]. This trial was a randomized, blinded, placebo-controlled trial to evaluate the safety and efficacy of this combination in the management of treatment naïve cirrhotic and non-cirrhotic patients with HCV. Patients were treated with 12 weeks of therapy. This study was relatively more diverse than earlier clinical trials in HCV, and was comprised of 60% Whites, 19% Black, and 17% Asian [32]. Subgroup analyses revealed that race did not alter SVR rates within this trial. Whites had a SVR of 94.2% (180/191), Blacks had an SVR of 96.6% (57/59), and Asians had an SVR of 94.4% (51/54) [32]. While there is no specific reference to Hispanics/Latinons inthis analysis, there were 12 individuals considered ‘other’ and they achieved an SVR of 91.7% (11/12). There were no reported racial/ethnic differences in safety or adverse events.