Velpatasvir: Difference between revisions

Velpatasvir
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Revision as of 11:59, 9 February 2025

Antiviral medication used to treat hepatitis C

Velpatasvir is an antiviral drug used in combination with sofosbuvir to treat hepatitis C virus (HCV) infection. It is a direct-acting antiviral agent that works by inhibiting the NS5A protein, which is essential for viral replication.

Medical uses

Velpatasvir is used in combination with sofosbuvir as a fixed-dose combination tablet for the treatment of chronic hepatitis C virus infection in adults. This combination is effective against all six major genotypes of HCV, making it a pan-genotypic treatment option. The standard treatment duration is 12 weeks, but it may vary depending on the presence of cirrhosis or previous treatment history.

Mechanism of action

Velpatasvir is an inhibitor of the NS5A protein, a non-structural protein of the hepatitis C virus. NS5A is involved in viral replication and assembly, and its inhibition disrupts these processes, leading to a reduction in viral load. When used with sofosbuvir, which inhibits the NS5B polymerase, the combination effectively halts the replication of the virus.

Side effects

Common side effects of the velpatasvir and sofosbuvir combination include headache, fatigue, and nausea. Serious side effects are rare but may include bradycardia when used with amiodarone. Patients are advised to consult their healthcare provider if they experience any unusual symptoms.

Pharmacokinetics

Velpatasvir is well absorbed orally, with peak plasma concentrations occurring approximately 3 hours after dosing. It is highly protein-bound and is metabolized in the liver. The drug is primarily excreted in the feces, with a small amount eliminated in the urine.

History

Velpatasvir was developed by Gilead Sciences and was approved by the U.S. Food and Drug Administration (FDA) in 2016 as part of the fixed-dose combination with sofosbuvir, marketed under the brand name Epclusa. It was the first pan-genotypic treatment approved for hepatitis C.

Research

Ongoing research is exploring the use of velpatasvir in combination with other antiviral agents to improve treatment outcomes and reduce treatment duration. Studies are also investigating its efficacy in special populations, such as those with HIV co-infection or renal impairment.

Related pages

References

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-{{intro}}
+{{Short description|Antiviral medication used to treat hepatitis C}}
-Velpatasvir is an NS5A inhibitor which is used together with sofosbuvir in the treatment of hepatitis C infection of all six major genotypes. It is an oral nucleoside analogue and potent inhibitor of the hepatitis C virus (HCV) RNA polymerase that is used in combination with other antiviral agents to treat chronic hepatitis C.
+{{Drugbox
+| verifiedfields = changed
+| verifiedrevid = 477002123
+| image = Velpatasvir.svg
+| width = 200px
+}}
-{{livtox}}
+'''Velpatasvir''' is an [[antiviral drug]] used in combination with [[sofosbuvir]] to treat [[hepatitis C]] virus (HCV) infection. It is a [[direct-acting antiviral]] agent that works by inhibiting the [[NS5A protein]], which is essential for viral replication.
-Elevations in serum enzyme levels during sofosbuvir therapy are uncommon, and it has not been implicated convincingly in cases of clinically apparent [[liver injury]] with [[jaundice]]. Nevertheless, and for unknown reasons, successful antiviral therapy of hepatitis C with sofosbuvir and other direct acting agents in patients with cirrhosis is occasionally complicated by hepatic decompensation; furthermore, treatment can cause reactivation of hepatitis B in susceptible patients coinfected with the hepatitis B virus (HBV).
-{{moa}}
+==Medical uses==
-Sofosbuvir (soe fos' bue vir) is an orally available nucleotide analogue that has potent activity against the RNA-dependent RNA polymerase of the hepatitis C virus (HCV). Sofosbuvir is a monophosphorylated uracil derivative whose single phosphate is protected by an alaninate cap that allows for the absorption and uptake of the molecule by hepatocytes where it is hydrolyzed to sofosbuvir monophosphate. Intracellular host kinases then convert it to the active triphosphate moiety. In multiple clinical trials, sofosbuvir has been shown to cause a rapid and marked decline in serum HCV RNA levels and, in combination with other antiviral agents and with more prolonged therapy, to result in sustained clearance of HCV (sustained virological response: SVR) in a high proportion of patients.
+Velpatasvir is used in combination with sofosbuvir as a fixed-dose combination tablet for the treatment of chronic hepatitis C virus infection in adults. This combination is effective against all six major genotypes of HCV, making it a [[pan-genotypic]] treatment option. The standard treatment duration is 12 weeks, but it may vary depending on the presence of [[cirrhosis]] or previous treatment history.
-{{fda}}
+==Mechanism of action==
-{{PAGENAME}} was approved for use in the United States in 2013 to be used in combination with ribavirin or with both peginterferon and ribavirin in patients with chronic hepatitis C, genotypes 1, 2, 3 or 4. Sofosbuvir is available in tablets of 400 mg under the brand name Solvaldi, the recommended dose being 400 mg once daily in combination with either ribavirin alone (1000 or 1200 mg daily for 12 weeks for genotype 2 and 24 weeks for genotype 3) or in combination with both ribavirin and peginterferon for 12 weeks for patients with genotype 1.
+Velpatasvir is an inhibitor of the NS5A protein, a non-structural protein of the hepatitis C virus. NS5A is involved in viral replication and assembly, and its inhibition disrupts these processes, leading to a reduction in viral load. When used with sofosbuvir, which inhibits the NS5B polymerase, the combination effectively halts the replication of the virus.
-Subsequently, a fixed combination of sofosbuvir (400 mg) and the HCV NS5A replication complex inhibitor ledipasvir (le dip' as vir: 90 mg) was approved for use in patients with chronic hepatitis C, genotype 1 in 2014 and for genotype 4 in 2015. This combination is available as a fixed dose, single tablet under the brand name [[Harvoni]] and the recommended dose is one tablet daily for 12 weeks, which can be shortened to 8 weeks in selected patients.
+==Side effects==
+Common side effects of the velpatasvir and sofosbuvir combination include headache, fatigue, and nausea. Serious side effects are rare but may include bradycardia when used with [[amiodarone]]. Patients are advised to consult their healthcare provider if they experience any unusual symptoms.
-In addition, sofosbuvir combined with NS5A inhibitors with broader activity against HCV genotypes, daclatasvir [dak lat' as vir: 2015] and velpatasvir [vel pat' as vir: 2016], has been shown to be effective in treating almost all HCV genotypes with sustained response rates of 95% or greater in response to 12 weeks of treatment in genotypes 1, 2, 4, 5 and 6. In 2016, the fixed combination of sofosbuvir (400 mg) and velpatasvir (100 mg) was approved for use in patients with all 6 genotypes of hepatitis C. This combination is available as a fixed dose, single tablet under the brand name Epclusa. The recommended dose is one tablet daily for 12 weeks. For patients with decompensated cirrhosis (Childs-Pugh Class B or C), ribavirin (1000 to 1200 mg in two divided doses daily) should be added to Epclusa for 12 weeks. Finally, the combination of sofosbuvir with an HCV specific NS3/4 protease inhibitor (such as simeprevir [2014]) was also shown to be highly effective in patients with genotype 1 infection generally in 12 week courses.
+==Pharmacokinetics==
+Velpatasvir is well absorbed orally, with peak plasma concentrations occurring approximately 3 hours after dosing. It is highly protein-bound and is metabolized in the liver. The drug is primarily excreted in the feces, with a small amount eliminated in the urine.
-For patients who fail to respond to a two or three drug combination of direct acting antiviral agents, combinations of potent agents active against the three major HCV poiypeptide products have been developed and have shown excellent activity in these refractory patients. The first such regimen was a single tablet formulation of sofosbuvir (400 mg), velpatasvir (100 mg) and a potent, broad spectrum (pangenomic) HCV protease inhibitor, voxilaprevir (100 mg).
+==History==
+Velpatasvir was developed by [[Gilead Sciences]] and was approved by the [[U.S. Food and Drug Administration]] (FDA) in 2016 as part of the fixed-dose combination with sofosbuvir, marketed under the brand name [[Epclusa]]. It was the first pan-genotypic treatment approved for hepatitis C.
-{{fda}}
+==Research==
-This combination {{PAGENAME}} was FDA approved for use in the United States in 2017 and is available under the brand name Vosevi. The recommended dosing regimen is 1 tablet daily for 12 weeks. This regimen is not recommended for patients with decompensated cirrhosis (Childs-Pugh Class B or C).
+Ongoing research is exploring the use of velpatasvir in combination with other antiviral agents to improve treatment outcomes and reduce treatment duration. Studies are also investigating its efficacy in special populations, such as those with [[HIV]] co-infection or [[renal impairment]].
-As such, sofosbuvir transformed the therapy of chronic hepatitis C and became the most commonly used HCV-specific antiviral agent, replacing peginterferon and combinations of peginterferon, ribavirin and protease inhibitors. Sofosbuvir has few side effects and in placebo controlled trials adverse events occurred at a similar rate with sofosbuvir as placebo.
+==Related pages==
+* [[Hepatitis C]]
+* [[Sofosbuvir]]
+* [[Direct-acting antiviral]]
-{{se}}
+==References==
-Side effects may include [[headache]], [[dizziness]], [[nausea]] and [[diarrhea]]. Rare, but potentially severe adverse events include marked bradycardia when sofosbuvir is given with amiodarone.
+{{Reflist}}
-{{hepatitis c drugs}}
-{{coststubd}}
+[[Category:Antiviral drugs]]
+[[Category:Hepatitis C]]
+[[Category:Gilead Sciences]]