Exviera

Exviera Uses, Dosage, Side Effects, Food Interaction and all others data.

Exviera 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 Exviera. Exviera is a non-nucleoside NS5B inhibitor which binds to the palm domain of NS5B and induces a conformational change which renders the polymerase unable to elongate viral RNA . The binding sites for non-nucleoside NS5B inhibitors are poorly conserved across HCV genotypes leading to the restriction of Exviera's use to genotype 1 only.

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 Exviera as first line therapy in combination with Ombitasvir, Paritaprevir, and Ritonavir for genotype 1b and with Ribavirin for genotype 1a of Hepatitis C . Exviera, Ombitasvir, Paritaprevir, Ritonavir, and Ribavirin are used with the intent to cure, or achieve a sustained virologic response (SVR), after 12 weeks of 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 .

Exviera is available as a fixed dose combination product with Ombitasvir, Paritaprevir, and Ritonavir (tradename Viekira Pak) used for the treatment of chronic Hepatitis C. Approved in December 2014 by the FDA, Viekira Pak is indicated for the treatment of HCV genotype 1a with Ribavirin or genotype 1b without Ribavirin . When combined together, Exviera Ombitasvir, Paritaprevir, and Ritonavir as the combination product Viekira Pak have been shown to achieve a SVR of 100% for genotype 1b and 89% or 95% for genotype 1a after 12 weeks or 24 weeks of treatment including Ribavirin.

Exviera
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Exviera
Generic	Dasabuvir
Dasabuvir Other Names	Dasabuvir
Type
Formula	C₂₆H₂₇N₃O₅S
Weight	Average: 493.58 Monoisotopic: 493.167142155
Protein binding	Dasabuvir is greater than 99.5% bound to human plasma proteins .
Groups	Approved
Therapeutic Class
Manufacturer
Available Country
Last Updated:	September 19, 2023 at 7:00 am

Uses

Exviera is a direct-acting antiviral agent used to treat specific hepatitis C virus (HCV) infections in combination with other antiviral agents.

Exviera, in combination with Ombitasvir, Paritaprevir, and Ritonavir (as Viekira Pak) is indicated for the treatment of patients with HCV genotype 1a with Ribavirin or genotype 1b without Ribavirin including those with compensated cirrhosis .

Exviera is also used to associated treatment for these conditions: Chronic hepatitis C genotype 1a, Chronic hepatitis C genotype 1b

How Exviera works

Exviera is a non-nucleoside inhibitor of the HCV RNA-dependent RNA polymerase encoded by the NS5B gene, which is essential for replication of the viral genome . Based on drug resistance mapping studies of HCV genotypes 1a and 1b, dasabuvir targets the palm domain of the NS5B polymerase, and is therefore referred to as a non-nucleoside NS5B-palm polymerase inhibitor. The EC50 values of dasabuvir against genotype 1a-H77 and 1b-Con1 strains in HCV replicon cell culture assays were 7.7 nM and 1.8 nM, respectively.

By binding to NS5b outside of the active site of the enzyme, dasabuvir induces a conformational change thereby preventing further elongation of the nascent viral genome . A limitation of binding outside of the active site is that these binding sites are poorly preserved across the viral genotypes. This results in a limited potential for cross-genotypic activity and increased potential for development of resistance. Exviera is therefore limited to treating genotypes 1a and 1b, and must be used in combination with other antiviral products.

Toxicity

The most common adverse effects of Viekira Pak either in combination with or without Ribavirin were pruritus, nausea, insomnia, and asthenia .

Food Interaction

Avoid St. John's Wort. This herb induces the CYP3A metabolism of dasabuvir and may reduce its serum concentration. St. John's Wort is contraindicated for use with Viekira Pak.
Take at the same time every day.
Take with food.

Volume of Distribution

Exviera has a volume of distribution at steady state of 149 liters .

Elimination Route

Exviera reaches peak plasma concentration 4 hours after administration . The absolute bioavailability of Exviera is 70%.

Half Life

The half-life of elimination of dasabuvir is 5.5 to 6 hours .

Clearance

Clearance of Exviera has not been determined.

Elimination Route

Exviera is mainly excreted in the feces (94.4%) with very little excreted in the urine (2%) . 26.2% and 0.03% of the drug excreted in the feces and urine respectively was present as the parent compound suggesting metabolism as the major elimination pathway.