DDInter548 DDInter1395
A synthetic nonsteroidal estrogen used in the treatment of menopausal and postmenopausal disorders. It was also used formerly as a growth promoter in animals. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), diethylstilbestrol has been listed as a known carcinogen. (Merck, 11th ed) The FDA withdrew its approval for the use of all oral and parenteral drug products containing 25 milligrams or more of diethylstilbestrol per unit dose.
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 . 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 , , , , and . 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 . 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 . 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. Depending on the genotype, Paritaprevir is often used in combination with other antivirals such as , , , and , 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 . 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 . Paritaprevir first came on the market as a fixed-dose combination product with , , and 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 for the treatment of HCV genotype 1a without cirrhosis or with compensated cirrhosis. Paritaprevir is also available as a fixed-dose combination product with and as the FDA- and Health Canada-approved product Technivie. First approved in July 2015, Technivie is indicated in combination with 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 , , and 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 for the treatment of HCV genotype 1a with or without cirrhosis.
Diethylstilbestrol {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Esomeprazole
Esomeprazole {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Paritaprevir
Diethylstilbestrol (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Esomeprazole (Compound) and Esomeprazole may cause a moderate interaction that could exacerbate diseases when taken with Paritaprevir