Drugs Information:
Paritaprevir
Basic Information
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| ID | DDInter1395 | |
| Drug Type | small molecule | |
| Molecular Formula | C40H43N7O7S | |
| Molecular Weight | 765.890 | |
| CAS Number | 1216941-48-8 | |
| Description | Paritaprevir is a direct acting antiviral medication used as part of combination therapy to treat chronic Hepatitis C, an infectious liver disease caused by infection with Hepatitis C Virus (HCV). HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients [L852]. Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) such as paritaprevir. As a newer generation and directly acting HCV antiviral, paritaprevir products have better Sustained Virological Response (SVR) rates, higher barriers to resistance, fewer side effects, and a reduced pill burden compared to older agents such as [DB08873], [DB05521], [DB00008], [DB00022], and [DB00811]. By combining multiple antiretroviral medications into fixed dose products, the viral lifecycle can be targeted at multiple stages while simultaneously reducing the risk of developing resistant viral strains [A19593]. Within Canada and the United States, paritaprevir is currently available in three fixed dose products: Viekira Pak (FDA), Technivie (FDA and Health Canada), and Holkira Pak (Health Canada). More specifically, paritaprevir prevents viral replication by inhibiting the NS3/4A serine protease of Hepatitis C Virus (HCV) [FDA Label]. Following viral replication of HCV genetic material and translation into a single polypeptide, Nonstructural Protein 3 (NS3) and its activating cofactor Nonstructural Protein 4A (NS4A) are responsible for cleaving genetic material into the following structural and nonstructural proteins required for assembly into mature virus: NS3, NS4A, NS4B, NS5A, and NS5B [A19643]. By inhibiting viral protease NS3/4A, paritaprevir therefore prevents viral replication and function. In a joint recommendation published in 2016, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) recommend Paritaprevir as a first line therapy option when used in combination with other antivirals for genotypes 1a, 1b, and 4[L852]. Depending on the genotype, Paritaprevir is often used in combination with other antivirals such as [DB09296], [DB09183], [DB00503], and [DB00811], with the intent to cure, or achieve a sustained virologic response (SVR), after 12 weeks of daily therapy. SVR and eradication of HCV infection is associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of Hepatocellular Carcinoma, and reduced all-cause mortality [A19626]. Treatment with direct acting antivirals such as paritaprevir is associated with very minimal side effects, with the most common being headache and fatigue [FDA Label]. Lack of significant side effects and short duration of therapy is a considerable advantage over older interferon-based regimens, which were limited by infusion site reactions, reduced blood count, and neuropsychiatric effects [A19635]. Paritaprevir first came on the market as a fixed-dose combination product with [DB09296], [DB09183], and [DB00503] as the FDA-approved product Viekira Pak. First approved in December 2014, Viekira Pak is indicated for the treatment of HCV genotype 1b without cirrhosis or with compensated cirrhosis, and when combined with [DB00811] for the treatment of HCV genotype 1a without cirrhosis or with compensated cirrhosis. Paritaprevir is also available as a fixed-dose combination product with [DB09296] and [DB00503] as the FDA- and Health Canada-approved product Technivie. First approved in July 2015, Technivie is indicated in combination with [DB00811] for the treatment of patients with genotype 4 chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis. In Canada, paritaprevir is also available as a fixed-dose combination product with [DB09296], [DB09183], and [DB00503] as the Health Canada-approved, commercially available product Holkira Pak. First approved in January 2015, Holkira Pak is indicated for the treatment of HCV genotype 1b with or without cirrhosis, and when combined with [DB00811] for the treatment of HCV genotype 1a with or without cirrhosis. | |
| ATC Classification | J05AP53 J05AP52 | |
| IUPAC Name | (1S,4R,6S,7Z,14S,18R)-N-(cyclopropanesulfonyl)-14-(5-methylpyrazine-2-amido)-2,15-dioxo-18-(phenanthridin-6-yloxy)-3,16-diazatricyclo[14.3.0.0^{4,6}]nonadec-7-ene-4-carboxamide | |
| InChI | UAUIUKWPKRJZJV-QPLHLKROSA-N | |
| Canonical SMILES | [H][C@@]12C[C@]1(NC(=O)[C@]1([H])C[C@H](CN1C(=O)[C@H](CCCCC\C=C/2)NC(=O)C1=CN=C(C)C=N1)OC1=NC2=C(C=CC=C2)C2=C1C=CC=C2)C(=O)NS(=O)(=O)C1CC1 | |
| Useful Links | DrugBank ChEBI PubChem Substance KEGG Drug ChemSpider PharmGKB Wikipedia ChEMBL ZINC | |
Interactions with
Paritaprevir
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