Dasabuvir

Last updated
Dasabuvir
Dasabuvir.svg
Clinical data
Trade names Exviera, Viekira Pak, Viekira XR
Other namesABT-333
AHFS/Drugs.com Viekira Pak Monograph
Dasabuvir UK Drug Information
MedlinePlus a616040
License data
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • US: ℞-only co-packaged with ombitasvir/paritaprevir/ritonavir (Viekira Pak) [1]
  • EU:Rx-only [2]
Identifiers
  • N-{6-[5-(2,4-Dioxo-3,4-dihydro-1(2H)-pyrimidinyl)-2-methoxy-3-(2-methyl-2-propanyl)phenyl]-2-naphthyl}methanesulfonamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard 100.232.246 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C26H27N3O5S
Molar mass 493.58 g·mol−1
3D model (JSmol)
  • CC(C)(C)c1cc(cc(c1OC)c2ccc3cc(ccc3c2)NS(=O)(=O)C)n4ccc(=O)[nH]c4=O
  • InChI=1S/C26H27N3O5S/c1-26(2,3)22-15-20(29-11-10-23(30)27-25(29)31)14-21(24(22)34-4)18-7-6-17-13-19(28-35(5,32)33)9-8-16(17)12-18/h6-15,28H,1-5H3,(H,27,30,31)
  • Key:NBRBXGKOEOGLOI-UHFFFAOYSA-N

Dasabuvir, sold under the brand name Exviera, is an antiviral medication for the treatment of hepatitis C. [3] It is often used together with the combination medication ombitasvir/paritaprevir/ritonavir specifically for hepatitis C virus (HCV) type 1. [3] Ribavirin may also additionally be used. [1] [2] These combinations result in a cure in more than 90% of people. [4] It is taken by mouth. [3]

Contents

Common side effects include trouble sleeping, nausea, itchiness, and feeling tired. [4] It is not recommended in those with liver failure but appears okay in people with kidney disease. [3] While there is no evidence of harm if used during pregnancy, it has not been well studied. [3] It should not be used with birth control pills that contain ethinylestradiol. [4] Dasabuvir is in the HCV NS5B polymerase inhibitor class of medication. [3]

Dasabuvir was approved for medical use in 2014. [5] It is on the World Health Organization's List of Essential Medicines. [6] In the United States, it is approved by the Food and Drug Administration (FDA) only for use in combination with ombitasvir/paritaprevir/ritonavir. [3] As of 2015, the ability to get these medications in many areas of the world is poor. [7]

Medical uses

Dasabuvir is used in the treatment of chronic Hepatitis C infection. It is used in the following HCV subtypes: genotype 1a, genotype 1b, genotype 1 of unknown subtype, and genotype 1 mixed infection without cirrhosis or with compensated cirrhosis. [8]

In the European Union, dasabuvir (Exviera) is always used in combination with another medicine, ombitasvir/paritaprevir/ritonavir (Viekirax) for the treatment of hepatitis C virus genotypes 1a and 1b. [2] Some people taking dasabuvir are also treated with another antiviral medicine, ribavirin, in addition to ombitasvir/paritaprevir/ritonavir. [2]

In the United States, dasabuvir is co-packaged with ombitasvir/paritaprevir/ritonavir (Viekira Pak) and the combination is indicated for the treatment of adults with chronic hepatitis C virus genotype 1b without cirrhosis or with compensated cirrhosis. [1] The co-packaged dasabuvir and ombitasvir/paritaprevir/ritonavir is used in combination with ribavirin for the treatment of adults with chronic hepatitis C virus genotype 1a without cirrhosis or with compensated cirrhosis. [1]

Contraindications

People should not be taking dasabuvir if they meet any of the following criteria:

In October 2015, the U.S. Food and Drug Administration (FDA) required the manufacturer to add a warning to the drug label that hepatitis C treatments Viekira Pak and Technivie can cause serious liver injury mostly in people with underlying advanced liver disease. [9]

Adverse effects

The FDA approved combination of dasabuvir used with ombitasvir, paritaprevir, and ritonavir in the product Viekira Pak can cause a number of adverse effects. When Viekira Pak was used without ribavirin, nausea, severe itching, and insomnia occurred in more than 5% of the subjects. [1] Less commonly, patients experienced increases in liver enzymes, such as AST and ALT, to greater than five times the upper limit of normal (occurred in 1% of patients). [1] Usually this was asymptomatic. However, this is notable because females who are taking ethinylestradiol are at an increased risk for this side effect (25%). [1]

Dasabuvir could cause hepatitis B re-activation in people co-infected with hepatitis B and C viruses. The European Medicines Agency recommended screening all people for hepatitis B before starting dasabuvir for hepatitis C in order to minimize the risk of hepatitis B reactivation. [10]

Mechanism of action

Dasabuvir works by inhibiting the action of NS5B palm polymerase, effectively terminating RNA polymerization and stopping the replication of the HCV's genome. [11] By blocking NS5B polymerase, the virus can no longer multiply and infect new cells. [4]

History

The U.S. FDA approved regimen of ombitasvir-paritaprevir-ritonavir and dasabuvir on December 19, 2014, to be used in the treatment of genotype 1 chronic hepatitis C infection in adults, which includes those with compensated cirrhosis. [12]

Administration and storage

The two tablets of ombitasvir, paritaprevir, ritonavir will be taken in the morning and the one dasabuvir tablet taken twice a day in the morning and in the evening with a meal. [1]

The combination pack is packaged in a monthly package for 28 days of treatment. [1]

Related Research Articles

<span class="mw-page-title-main">Hepatitis C</span> Human viral infection

Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, abdominal pain, and yellow tinged skin occurs. The virus persists in the liver in about 75% to 85% of those initially infected. Early on, chronic infection typically has no symptoms. Over many years however, it often leads to liver disease and occasionally cirrhosis. In some cases, those with cirrhosis will develop serious complications such as liver failure, liver cancer, or dilated blood vessels in the esophagus and stomach.

Pegylated interferon alfa-2b is a drug used to treat melanoma, as an adjuvant therapy to surgery. Also used to treat hepatitis C, it is no longer recommended due to poor efficacy and adverse side-effects. Subcutaneous injection is the preferred delivery method.

<span class="mw-page-title-main">Boceprevir</span> Chemical compound

Boceprevir is a protease inhibitor used to treat hepatitis caused by hepatitis C virus (HCV) genotype 1. It binds to the HCV nonstructural protein 3 active site.

<span class="mw-page-title-main">Telaprevir</span>

Telaprevir (VX-950), marketed under the brand names Incivek and Incivo, is a pharmaceutical drug for the treatment of hepatitis C co-developed by Vertex Pharmaceuticals and Johnson & Johnson. It is a member of a class of antiviral drugs known as protease inhibitors. Specifically, telaprevir inhibits the hepatitis C viral enzyme NS3/4A serine protease. Telaprevir is only indicated for use against hepatitis C genotype 1 viral infections and has not been proven to be safe or effective when used for other genotypes of the virus. The standard therapy of pegylated interferon and ribavirin is less effective than telaprevir in those with genotype 1.

<span class="mw-page-title-main">Sofosbuvir</span> Chemical compound

Sofosbuvir, sold under the brand name Sovaldi among others, is a medication used to treat hepatitis C. It is taken by mouth.

<span class="mw-page-title-main">Daclatasvir</span> Chemical compound

Daclatasvir, sold under the brand name Daklinza, is an antiviral medication used in combination with other medications to treat hepatitis C (HCV). The other medications used in combination include sofosbuvir, ribavirin, and interferon, vary depending on the virus type and whether the person has cirrhosis. It is taken by mouth.

<span class="mw-page-title-main">Simeprevir</span> Chemical compound

Simeprevir, sold under the trade names Olysio among others, is a medication used in combination with other medications for the treatment of hepatitis C. It is specifically used for hepatitis C genotype 1 and 4. Medications it is used with include sofosbuvir or ribavirin and peginterferon-alfa. Cure rates are in 80s to 90s percent. It may be used in those who also have HIV/AIDS. It is taken by mouth once daily for typically 12 weeks.

<span class="mw-page-title-main">Ledipasvir</span> Hepatitis C drug

Ledipasvir is a drug for the treatment of hepatitis C that was developed by Gilead Sciences. After completing Phase III clinical trials, on February 10, 2014, Gilead filed for U.S. approval of a ledipasvir/sofosbuvir fixed-dose combination tablet for genotype 1 hepatitis C. The ledipasvir/sofosbuvir combination is a direct-acting antiviral agent that interferes with HCV replication and can be used to treat patients with genotypes 1a or 1b without PEG-interferon or ribavirin.

<span class="mw-page-title-main">NS5B (Hepacivirus)</span>

Nonstructural protein 5B (NS5B) is a viral protein found in the hepatitis C virus (HCV). It is an RNA-dependent RNA polymerase, having the key function of replicating HCV's viral RNA by using the viral positive RNA strand as a template to catalyze the polymerization of ribonucleoside triphosphates (rNTP) during RNA replication. Several crystal structures of NS5B polymerase in several crystalline forms have been determined based on the same consensus sequence BK. The structure can be represented by a right hand shape with fingers, palm, and thumb. The encircled active site, unique to NS5B, is contained within the palm structure of the protein. Recent studies on NS5B protein genotype 1b strain J4's (HC-J4) structure indicate a presence of an active site where possible control of nucleotide binding occurs and initiation of de-novo RNA synthesis. De-novo adds necessary primers for initiation of RNA replication.

<span class="mw-page-title-main">Paritaprevir</span> Chemical compound

Paritaprevir is an acylsulfonamide inhibitor of the NS3-4A serine protease manufactured by Abbott Laboratories that shows promising results as a treatment of hepatitis C. When given in combination with ritonavir and ribavirin for 12 weeks, the rate of sustained virologic response at 24 weeks after treatment has been estimated to be 95% for those with hepatitis C virus genotype 1. Resistance to treatment with paritaprevir is uncommon, because it targets the binding site, but has been seen to arise due to mutations at positions 155 and 168 in NS3.

<span class="mw-page-title-main">Ombitasvir</span> Chemical compound

Ombitasvir is an antiviral drug for the treatment of hepatitis C virus (HCV) infection by AbbVie. In the United States, it is approved by the Food and Drug Administration for use in combination with paritaprevir, ritonavir and dasabuvir in the product Viekira Pak for the treatment of HCV genotype 1, and with paritaprevir and ritonavir in the product Technivie for the treatment of HCV genotype 4.

<span class="mw-page-title-main">Ledipasvir/sofosbuvir</span> Medication used to treat hepatitis C

Ledipasvir/sofosbuvir, sold under the trade name Harvoni among others, is a medication used to treat hepatitis C. It is a fixed-dose combination of ledipasvir and sofosbuvir. Cure rates are 94% to 99% in people infected with hepatitis C virus (HCV) genotype 1. Some evidence also supports use in HCV genotype 3 and 4. It is taken daily by mouth for 8–24 weeks.

Ombitasvir/paritaprevir/ritonavir, sold under the brand name Technivie among others, is a medication used to treat hepatitis C. It is a fixed-dose combination of ombitasvir, paritaprevir, and ritonavir. Specifically it is used together with dasabuvir or ribavirin for cases caused by hepatitis C virus genotype 1 or 4. Cure rates are around 95%. It is taken by mouth.

<span class="mw-page-title-main">Beclabuvir</span>

Beclabuvir is an antiviral drug for the treatment of hepatitis C virus (HCV) infection that has been studied in clinical trials. In February 2017, Bristol-Myers Squibb began sponsoring a post-marketing trial of beclabuvir, in combination with asunaprevir and daclatasvir, to study the combination's safety profile with regard to liver function. From February 2014 to November 2016, a phase II clinical trial was conducted on the combination of asunaprevir/daclatasvir/beclabuvir on patients infected with both HIV and HCV. Furthermore, a recent meta-analysis of six published six clinical trials showed high response rates in HCV genotype 1-infected patients treated with daclatasvir, asunaprevir, and beclabuvir irrespective of ribavirin use, prior interferon-based therapy, or restriction on noncirrhotic patients, IL28B genotype, or baseline resistance-associated variants

<span class="mw-page-title-main">Grazoprevir</span>

Grazoprevir is a drug approved for the treatment of hepatitis C. It was developed by Merck and completed Phase III trials, used in combination with the NS5A replication complex inhibitor elbasvir under the trade name Zepatier, either with or without ribavirin.

<span class="mw-page-title-main">Elbasvir</span> Chemical compound

Elbasvir is a drug approved by the FDA in January 2016 for the treatment of hepatitis C. It was developed by Merck and completed Phase III trials, used in combination with the NS3/4A protease inhibitor grazoprevir under the trade name Zepatier, either with or without ribavirin.

Elbasvir/grazoprevir is a fixed-dose combination for the treatment of hepatitis C, containing elbasvir and grazoprevir. It is used to treat chronic hepatitis C virus (HCV) genotypes 1 or 4 infection in both treatment-naïve and treatment-experienced patients.

<span class="mw-page-title-main">Narlaprevir</span>

Narlaprevir, is an inhibitor of NS3/4A serine protease, intended for the treatment of chronic hepatitis C caused by genotype 1 virus in combination with other antiviral drugs.

Sofosbuvir/velpatasvir, sold under the brand name Epclusa among others, is a fixed-dose combination medication for the treatment of hepatitis C in adults. It combines sofosbuvir and velpatasvir. It is more than 90% effective for hepatitis C genotypes one through six. It also works for hepatitis C in those who also have cirrhosis or HIV/AIDS. It is taken by mouth.

Glecaprevir/pibrentasvir (G/P), sold under the brand names Mavyret and Maviret, is a fixed-dose combination medication used to treat hepatitis C. It contains glecaprevir and pibrentasvir. It works against all six types of hepatitis C. At twelve weeks following treatment between 81% and 100% of people have no evidence of hepatitis C. It is taken once a day by mouth with food.

References

  1. 1 2 3 4 5 6 7 8 9 "Viekira Pak- dasabuvir and ombitasvir and paritaprevir and ritonavir kit". DailyMed. 12 December 2019. Retrieved 13 October 2020.
  2. 1 2 3 4 "Exviera EPAR". European Medicines Agency (EMA). Retrieved 13 October 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  3. 1 2 3 4 5 6 7 "Viekira Pak". The American Society of Health-System Pharmacists. Archived from the original on 20 December 2016. Retrieved 8 December 2016.
  4. 1 2 3 4 5 6 7 8 9 "European Medicines Agency - Find medicine - Exviera". www.ema.europa.eu. 24 May 2016. Archived from the original on 10 November 2016. Retrieved 2016-11-09.
  5. ↑ Časar, Zdenko (2016). Synthesis of Heterocycles in Contemporary Medicinal Chemistry. Springer. p. 92. ISBN   9783319399171. Archived from the original on 2016-12-20.
  6. ↑ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl: 10665/325771 . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  7. ↑ World Health Organization (2015). The selection and use of essential medicines. Twentieth report of the WHO Expert Committee 2015 (including 19th WHO Model List of Essential Medicines and 5th WHO Model List of Essential Medicines for Children). World Health Organization. p. 73. hdl: 10665/189763 . ISBN   9789241209946. ISSN   0512-3054. WHO technical report series;994.
  8. ↑ Commissioner, Office of the. "Safety Information - Viekira Pak (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets), Copackaged for Oral Use". www.fda.gov. Archived from the original on 2016-11-17. Retrieved 2016-11-17.
  9. ↑ "FDA Drug Safety Communication: FDA warns of serious liver injury risk with hepatitis C treatments Viekira Pak and Technivie". U.S. Food and Drug Administration (FDA). 24 August 2016. Retrieved 13 October 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  10. ↑ "Direct-acting antivirals indicated for treatment of hepatitis C (interferon-free)". European Medicines Agency (EMA). 17 September 2018. Retrieved 4 February 2020.
  11. ↑ "The DrugBank database". www.drugbank.ca/drugs/DB09183. Archived from the original on 2016-11-11. Retrieved 2016-10-28.
  12. ↑ "Ombitasvir-Paritaprevir-Ritonavir and Dasabuvir (Viekira Pak) - Treatment - Hepatitis C Online". www.hepatitisc.uw.edu. Archived from the original on 2016-11-01. Retrieved 2016-11-09.
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