Ombitasvir/paritaprevir/ritonavir

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Ombitasvir/paritaprevir/ritonavir
Combination of
Ombitasvir Antiviral (NS5A inhibitor)
Paritaprevir Antiviral (NS3 inhibitor)
Ritonavir PK enhancer (CYP3A4, CYP2D6 inhibitor)
Clinical data
Trade names Viekira Pak (with dasabuvir), Technivie, Viekirax, others
AHFS/Drugs.com Monograph
MedlinePlus a615036
License data
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
Identifiers
CAS Number
PubChem SID
ChemSpider
  • none
KEGG
ChEBI
   (verify)
Dasabuvir/ombitasvir/paritaprevir/ritonavir
Combination of
Dasabuvir Antiviral
Ombitasvir Antiviral (NS5A inhibitor)
Paritaprevir Antiviral (NS3 inhibitor)
Ritonavir PK enhancer (CYP3A4, CYP2D6 inhibitor)
Clinical data
Trade names Viekira Pak, Viekira XR, Holkira Pak, others
AHFS/Drugs.com Monograph
MedlinePlus a614057
License data
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
Identifiers
PubChem CID
ChemSpider
  • none
KEGG
ChEBI

Ombitasvir/paritaprevir/ritonavir, sold under the brand name Technivie among others, is a medication used to treat hepatitis C. [2] It is a fixed-dose combination of ombitasvir, paritaprevir, and ritonavir. [2] Specifically it is used together with dasabuvir or ribavirin for cases caused by hepatitis C virus genotype 1 or 4. [2] [3] Cure rates are around 95%. [3] It is taken by mouth. [2]

Contents

It is generally well tolerated. [4] Common side effects include nausea, itchiness, rash, and trouble sleeping. [2] Other side effects include allergic reactions and reactivation of hepatitis B among those previously infected. [2] Use is not recommended in those with significant liver problems. [2] While there is no evidence of harm with use during pregnancy, this use has not been well studied. [2] Each of the medications works by a different mechanism. [3] The ritonavir is present to decrease the breakdown of paritaprevir. [2]

Ombitasvir/paritaprevir/ritonavir with dasabuvir was approved for medical use in the United States in 2014, and without dasabuvir in 2015. [5] [6] It is on the World Health Organization's List of Essential Medicines. [7]

Medical uses

Ombitasvir/paritaprevir/ritonavir is used together with dasabuvir or ribavirin for cases caused by hepatitis C virus genotype 1 or 4. [2] [3] Cure rates are around 95%. [3]

Contraindications

Side effects

Post-market surveillance reports show hepatic decompensation and hepatic failure associated with Viekira Pak use. It is likely that most patients who experienced this had advanced cirrhosis prior to treatment initiation. Hepatic decompensation is described by rising bilirubin without ALT elevations alongside clinical symptoms such as ascites and hepatic encephalopathy. Patients should be monitored for signs of hepatic decompensation and bilirubin levels should be tested in the first four weeks of treatment and compared to baseline. [8]

Ombitasvir/paritaprevir/ritonavir 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 ombitasvir/paritaprevir/ritonavir for hepatitis C in order to minimize the risk of hepatitis B reactivation. [9]

Society and culture

It is manufactured by Abbvie. In the United States ombitasvir/paritaprevir/ritonavir together with dasabuvir is sold as Viekira Pak. [10] Technivie consists of only ombitasvir/paritaprevir/ritonavir tablets. [11] Technivie was discontinued in the US market in 2020. [12]

Approval

United States

Ombitasvir/paritaprevir/ritonavir together with dasabuvir was approved in its first review cycle by the FDA in December 2014. [13] The Center for Drug Evaluation and Research (CDER) designated the product for Fast Track because it had potential to treat unmet medical need. This track allows the CDER to view certain information ahead of a completed NDA to cut down the time to approval. Additionally, it was designated Breakthrough Therapy for its substantial improvement in the primary endpoint SVR12 and given Priority Review under the Prescription Drug User Fee Act allowing the review to be completed in six months rather than the standard ten months. [14]

Europe

In Europe, ombitasvir/paritaprevir/ritonavir is approved under the trade name Viekirax for combination therapy together with dasabuvir, with or without ribavirin. [15] [16]

Research

Sapphire I

Sapphire I was a 12-week placebo-controlled, randomized, double-blind trial which had a primary endpoint of cure (SVR12) rate in non-cirrhotic patients with HCV GT1a and GT1b - who were new to HCV treatment - and were given Viekira Pak and ribavirin (RBV). Sapphire I reported a 96% cure rate. [17]

Sapphire II

Sapphire II was a 12-week placebo-controlled, randomized, double-blind trial which had a primary endpoint of cure (SVR12) rate in non-cirrhotic patients with HCV GT1a and GT1b - who had previously received treatment - and were given Viekira Pak and (RBV). SAPPHIRE II reported a 96% cure rate. [17]

Pearl II

Pearl II was a 12-week open-label, randomized trial which had a primary endpoint of cure (SVR12) rate in non-cirrhotic patients with HCV GT1b - who had previously received treatment - and were given either Viekira Pak and (RBV) or Viekira Pak alone. Pearl II reported a 100% cure rate. [17]

Pearl III

Pearl III was a 12-week placebo-controlled, randomized, double-blind trial which had a primary endpoint of cure (SVR12) rate in non-cirrhotic patients with HCV GT1b - who were new to HCV treatment - and were given Viekira Pak and (RBV) or Viekira Pak and a RBV placebo. Pearl III reported a 100% cure rate [17]

Pearl IV

Pearl IV was a 12-week placebo-controlled, randomized, double-blind trial which had a primary endpoint of cure (SVR12) rate in non-cirrhotic patients with HCV GT1b - who were new to HCV treatment - and were given Viekira Pak and (RBV) or Viekira Pak and a RBV placebo. The primary difference between Pearl III and PEARL IV was that PEARL IV had a 1:2 allocation ratio meaning twice as many participants were given Viekira Pak and RBV placebo compared to Viekira Pack and RBV. Pearl IV had a 97% cure rate. [17]

Turquoise II

Turquoise II was an open-label, randomized trial which had a primary endpoint of cure (SVR12) rate in patients with compensated cirrhosis and either HCV GT1a or GT1b and both treatment arms were given Viekira Pak and (RBV). The two treatment arms differed by length of treatment: subjects were randomly assigned to receive treatment for either 12 or 24 weeks. The results were stratified based on whether or not subjects had previously received pegIFN/RBV treatment. This is the only phase III trial which has been completed with Viekira Pak and cirrhotic patients with HCV. TURQUOISE II reported a 95% cure rate for the 24-week arm and 99% cure rate for the 12-week arm. Subjects with genotype 1a had higher cure rates in the 24-week arm than the 12-week arm. [17]

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 period, people often have mild or no symptoms. Early symptoms can include fever, dark urine, abdominal pain, and yellow tinged skin. The virus persists in the liver, becoming chronic, in about 70% 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.

<span class="mw-page-title-main">Ritonavir</span> Antiretroviral medication

Ritonavir, sold under the brand name Norvir, is an antiretroviral medication used along with other medications to treat HIV/AIDS. This combination treatment is known as highly active antiretroviral therapy (HAART). Ritonavir is a protease inhibitor and is used with other protease inhibitors. It may also be used in combination with other medications to treat hepatitis C and COVID-19. It is taken by mouth. Tablets of ritonavir are not bioequivalent to capsules, as the tablets may result in higher peak plasma concentrations.

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

Dronedarone, sold under the brand name Multaq, is a class III antiarrhythmic medication developed by Sanofi-Aventis. It was approved by the FDA on July 2, 2009. Besides being indicated in arrhythmias, it was recommended as an alternative to amiodarone for the treatment of atrial fibrillation and atrial flutter in people whose hearts have either returned to normal rhythm or who undergo drug therapy or electric shock treatment i.e. direct current cardioversion (DCCV) to maintain normal rhythm. It is a class III antiarrhythmic drug. In the United States, the FDA approved label includes a claim for reducing hospitalization, but not for reducing mortality, as a reduction in mortality was not demonstrated in the clinical development program. A trial of the drug in heart failure was stopped as an interim analysis showed a possible increase in heart failure deaths, in patients with moderate to severe CHF.

<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> Chemical compound

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">Simeprevir</span> Chemical compound

Simeprevir, sold under the brand name 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">Hepatitis C virus nonstructural protein 5B</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">Dasabuvir</span> Chemical compound

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

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

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

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">Gamal Esmat</span>

Gamal Esmat is a professor at Endemic Medicine and Hepatogastroenterology Department, Cairo University. He was vice president of Cairo University for Graduate Studies and Research.

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<span class="mw-page-title-main">Sofosbuvir/daclatasvir</span> Combination drug

Daclatasvir/sofosbuvir is a two-drug combination for the treatment of hepatitis C. It is given as a single daily pill containing daclatasvir, a viral NS5A inhibitor, and sofosbuvir, a nucleotide inhibitor of the viral RNA polymerase NS5B.

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

Danoprevir (INN) is an orally available 15-membered macrocyclic peptidomimetic inhibitor of NS3/4A HCV protease. It contains acylsulfonamide, fluoroisoindole and tert-butyl carbamate moieties. Danoprevir is a clinical candidate based on its favorable potency profile against multiple HCV genotypes 1–6 and key mutants (GT1b, IC50 = 0.2–0.4 nM; replicon GT1b, EC50 = 1.6 nM). Danoprevir has been evaluated in an open-label, single arm clinical trial in combination with ritonavir for treating COVID-19 and favourably compared to lopinavir/ritonavir in a second trial.

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. ↑ "Prescription medicines: registration of new chemical entities in Australia, 2015". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 10 April 2023.
  2. 1 2 3 4 5 6 7 8 9 10 "Ombitasvir, Paritaprevir, and Ritonavir with Dasabuvir Sodium". The American Society of Health-System Pharmacists. Archived from the original on 1 January 2017. Retrieved 8 December 2016.
  3. 1 2 3 4 5 "Viekirax 12.5 mg/75 mg/50 mg film-coated tablets - Summary of Product Characteristics (SPC) - (eMC)". www.medicines.org.uk. 15 January 2015. Archived from the original on 1 January 2017. Retrieved 31 December 2016.
  4. ↑ 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). Geneva: World Health Organization. pp. 70–4. hdl: 10665/189763 . ISBN   9789241209946. ISSN   0512-3054. WHO technical report series;994.
  5. ↑ "Ombitasvir-Paritaprevir-Ritonavir and Dasabuvir (Viekira Pak) - Treatment - Hepatitis C Online". www.hepatitisc.uw.edu. Archived from the original on 1 November 2016. Retrieved 31 December 2016.
  6. ↑ "Ombitasvir, Paritaprevir, and Ritonavir". The American Society of Health-System Pharmacists. Archived from the original on 1 January 2017. Retrieved 8 December 2016.
  7. ↑ 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.
  8. 1 2 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 17 November 2016. Retrieved 30 November 2015.
  9. ↑ "Direct-acting antivirals indicated for treatment of hepatitis C (interferon-free)". European Medicines Agency (EMA). 17 September 2018. Retrieved 4 February 2020.
  10. ↑ Viekira Pak viekira-pak on Drugs.com.
  11. ↑ "Technivie (ombitasvir, paritaprevir and ritonavir) tablets, for oral useInitial U.S. Approval: 2015". DailyMed. 22 January 2020. Retrieved 26 April 2020.
  12. ↑ "Technivie: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 25 April 2020.
  13. ↑ "Press Announcements - FDA approves Viekira Pak to treat hepatitis C". www.fda.gov. Archived from the original on 31 October 2015. Retrieved 30 November 2015.
  14. ↑ "Novel New Drugs 2014 Summary" (PDF). U.S. Food and Drug Administration (FDA). January 2015. Archived (PDF) from the original on 15 January 2016. Retrieved 30 November 2015.
  15. ↑ Haberfeld (ed.). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
  16. ↑ "Viekirax EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 26 April 2020.
  17. 1 2 3 4 5 6 "Hepatitis C clinical trials program overview" (PDF). Abbvie. Archived (PDF) from the original on 7 September 2015. Retrieved 27 November 2015.
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