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 tablets), Technivie, Viekirax |
| AHFS/Drugs.com | entry |
| Pregnancy category |
|
| Legal status |
|
| Routes of administration | Oral |
| Identifiers | |
| ATC code | J05AX67 |
| (verify) | |
A combination product of three antiviral drugs ombitasvir, paritaprevir and ritonavir is used with the drug dasabuvir in the treatment of hepatitis C Virus Genotype 1a or 1b (HCV GT1a or GT1b). Both are manufactured by Abbvie.
In the US, Viekira Pak is a product containing ombitasvir/paritaprevir/ritonavir combination tablets and dasabuvir tablets.[1] Technivie consists only of ombitasvir/paritaprevir/ritonavir tablets.[2]
In Europe, ombitasvir/paritaprevir/ritonavir is approved under the trade name Viekirax for combination therapy together with dasabuvir (trade name Exviera), with or without ribavirin.[3]
Contraindications
- Patients with moderate to severe hepatic impairment
- Concurrent use of moderate to strong inducers of CYP3A and strong inducers of CYP2C8 reduce efficacy[4]
Warnings
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.[4]
Clinical trials
Phase III
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.[5]
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.[5]
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.[5]
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[5]
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.[5]
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.[5]
FDA approval
Viekira Pak was approved in its first review cycle by the FDA in December 2014.[6] 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.[7]
References
- ↑ Viekira Pak entry on Drugs.com.
- ↑ "TECHNIVIE™ (ombitasvir, paritaprevir and ritonavir) Tablets, for Oral Use. Full Prescribing Information" (PDF). AbbVie Inc., North Chicago, IL 60064. Retrieved 28 July 2015.
- ↑ Haberfeld (ed.). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
- 1 2 Commissioner, Office of the. "Safety Information - Viekira Pak (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets), Copackaged for Oral Use". www.fda.gov. Retrieved 2015-11-30.
- 1 2 3 4 5 6 "Hepatitis C clinical trials program overview" (PDF). Abbvie. Retrieved November 27, 2015.
- ↑ "Press Announcements - FDA approves Viekira Pak to treat hepatitis C". www.fda.gov. Retrieved 2015-11-30.
- ↑ "Novel New Drugs 2014 Summary" (PDF). periodical (U.S. Food and Drug Administration - Center for Drug Evaluation and Research). January 2015. Retrieved November 30, 2015.
External links
| ||||||||||||||||||||||||||||||||||||||||||