Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir Tablets for Hepatitis C Virus Genotype 1 Infection

• Published in: Annals of Pharmacotherapy 2015-05, Vol.49 (5), p.566-581
• Main Authors: Klibanov, Olga M., Gale, Stormi E., Santevecchi, Barbara
• Format: Article
• Language: English
• Subjects: Anilides - therapeutic use; Antiviral Agents - therapeutic use; Carbamates - therapeutic use; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Drug Combinations; Drug Resistance, Viral; Drug Therapy, Combination; Genotype; Hepacivirus - genetics; Hepatitis C, Chronic - drug therapy; Humans; Liver Cirrhosis - drug therapy; Macrocyclic Compounds - therapeutic use; Ribavirin - therapeutic use; Ritonavir - therapeutic use; Sulfonamides - therapeutic use; Tablets; Uracil - analogs & derivatives; Uracil - therapeutic use
• ISSN: 1060-0280; 1542-6270
• DOI: 10.1177/1060028015570729

Objective: To review the data with ombitasvir/paritaprevir/ritonavir and dasabuvir for the treatment of chronic hepatitis C virus (HCV) genotype 1 infection. Data Sources: Phase I, II, and III trials and review articles were identified through MEDLINE (1996-January 2015) and PubMed (1996-January 2015), conference abstracts, and US national clinical trials registry, using the keywords NS3/4A protease inhibitor, NS5A inhibitor, NS5B polymerase inhibitor, ABT-450, ABT-267, ABT-333, paritaprevir, ombitasvir, and dasabuvir. Study Selection and Data Extraction: Preclinical, phase I, II, and III studies describing pharmacology, pharmacokinetics, efficacy, safety, and tolerability were identified. Data Synthesis: Noncirrhotic patients with HCV genotype 1b experienced sustained virological response 12 weeks after completion of therapy (SVR12) rates of 96% to 100% when ombitasvir/paritaprevir/ritonavir and dasabuvir were administered for 12 weeks, regardless of inclusion of ribavirin. SVR12 rates of 95% to 97% were seen in noncirrhotic patients with HCV genotype 1a infection who received ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin for 12 weeks. Patients with Child-Pugh Class A cirrhosis also experienced high SVR12 rates (91.8%) when ombitasvir/paritaprevir/ritonavir and dasabuvir were administered with ribavirin for 12 weeks. Cirrhotic patients with HCV genotype 1a and a history of prior null response to peginterferon/ribavirin have higher SVR12 rates when ombitasvir/paritaprevir/ritonavir and dasabuvir and ribavirin are administered for 24 instead of 12 weeks (94.2% vs 88.6%). Adverse events are typically mild, most commonly consisting of fatigue, headache, nausea, and diarrhea. Conclusion: The regimen consisting of ombitasvir/paritaprevir/ritonavir and dasabuvir is highly efficacious in the treatment of HCV genotype 1 infection, with minimal adverse events. It is expected to play an important role in the armamentarium of novel agents that have a high chance of curing HCV infection.