Ombitasvir/paritaprevir/ritonavir

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
AHFS/Drugs.com Monograph
License data
Pregnancy
category
  • US: B (No risk in non-human studies)
    Routes of
    administration    		 by mouth
    ATC code
    Legal status
    Legal status
    Identifiers
    ChemSpider
    • none
    KEGG
      (verify)

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

    It is generally well tolerated.[3] Common side effects include nausea, itchiness, rash, and trouble sleeping.[1] Other side effects include allergic reactions and reactivation of hepatitis B among those previously infected.[1] Use is not recommended in those with significant liver problems.[1] While there is no evidence of harm with use during pregnancy, this use has not been well studied.[1] Each of the medications works by a different mechanism.[2] The ritonavir is present to decrease the breakdown of paritaprevir.[1]

    Ombitasvir/paritaprevir/ritonavir with dasabuvir was approved for medical use in the United States in 2014 and without dasabuvir in 2015.[4][5] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[6] The cost in the United Kingdom is 32,199.99 pounds for 12 weeks of treatment.[7] The wholesale cost for 12 weeks in the United States is 76,653.00 USD while the combination with dasabuvir cost 83,319.00.[4][8]

    Medical uses

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

    Contraindications

    • People with moderate to severe liver impairment
    • Concurrent use of moderate to strong inducers of CYP3A and strong inducers of CYP2C8 reduce efficacy[9]

    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.[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]

    Approval

    United States

    Ombitasvir/paritaprevir/ritonavir together with dasabuvir was approved in its first review cycle by the FDA in December 2014.[12] 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.[13]

    Europe

    In Europe, ombitasvir/paritaprevir/ritonavir is approved under the trade name Viekirax for combination therapy together with dasabuvir, with or without ribavirin.[14]

    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.[15]

    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.[15]

    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.[15]

    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[15]

    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.[15]

    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. It should be noted that subjects with genotype 1a had higher cure rates in the 24-week arm than the 12-week arm.[15]

    References

    1. 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.
    2. 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.
    3. ↑ 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) (PDF). WHO. 2015. p. 71. ISBN 9789240694941. Archived (PDF) from the original on 20 December 2016. Retrieved 8 December 2016.
    4. 1 2 "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.
    5. ↑ "Ombitasvir, Paritaprevir, and Ritonavir". The American Society of Health-System Pharmacists. Archived from the original on 1 January 2017. Retrieved 8 December 2016.
    6. ↑ "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Archived (PDF) from the original on 13 December 2016. Retrieved 8 December 2016.
    7. ↑ "Viekirax® : British National Formulary". NICE. NICE. Retrieved 31 December 2016.
    8. ↑ "Ombitasvir-Paritaprevir-Ritonavir (Technivie) - Treatment - Hepatitis C Online". www.hepatitisc.uw.edu. Archived from the original on 24 December 2016. Retrieved 31 December 2016.
    9. 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 2016-11-17. Retrieved 2015-11-30.
    10. ↑ Viekira Pak viekira-pak on Drugs.com.
    11. ↑ "TECHNIVIE™ (ombitasvir, paritaprevir and ritonavir) Tablets, for Oral Use. Full Prescribing Information" (PDF). AbbVie Inc., North Chicago, IL 60064. Archived (PDF) from the original on 7 August 2015. Retrieved 28 July 2015.
    12. ↑ "Press Announcements - FDA approves Viekira Pak to treat hepatitis C". www.fda.gov. Archived from the original on 2015-10-31. Retrieved 2015-11-30.
    13. ↑ "Novel New Drugs 2014 Summary" (PDF). periodical. U.S. Food and Drug Administration - Center for Drug Evaluation and Research. January 2015. Archived (PDF) from the original on January 15, 2016. Retrieved November 30, 2015.
    14. ↑ Haberfeld (ed.). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
    15. 1 2 3 4 5 6 "Hepatitis C clinical trials program overview" (PDF). Abbvie. Archived (PDF) from the original on September 7, 2015. Retrieved November 27, 2015.
    This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.