Product Information
Registration Status: ActiveSIN14891P
VIEKIRA PAK TABLET is approved to be sold in Singapore with effective from 2015-02-11. It is marketed by ABBVIE PTE LTD, with the registration number of SIN14891P.
This product contains Dasabuvir 250mg,Ombitasvir 12.5mg,Paritaprevir 75mg, and Ritonavir 50mg in the form of TABLET, FILM-COATED. It is approved for ORAL use.
This product is manufactured by Fournier Laboratories Ireland Limited (ombitasvir/paritaprevir/ritonavir tablet) in UNITED STATES,AbbVie Ireland NL B.V. (dasabuvir tablet) in IRELAND, andAbbVie Inc. (Primary and Secondary Packager) in GERMANY.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Product Reference
Important Note: For generic product, the SPC/PIL provided may not be brand specific.
{{/items}} {{^items}}Description
Dasabuvir is a direct acting antiviral medication used as part of combination therapy to treat chronic Hepatitis C, an infectious liver disease caused by infection with Hepatitis C Virus (HCV). HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients [L852]. Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) such as Dasabuvir. Dasabuvir is a non-nucleoside NS5B inhibitor which binds to the palm domain of NS5B and induces a conformational change which renders the polymerase unable to elongate viral RNA [FDA Label]. The binding sites for non-nucleoside NS5B inhibitors are poorly conserved across HCV genotypes leading to the restriction of Dasabuvir's use to genotype 1 only. In a joint recommendation published in 2016, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) recommend Dasabuvir as first line therapy in combination with [DB09296], [DB09297], and [DB00503] for genotype 1b and with [DB00811] for genotype 1a of Hepatitis C [L852]. Dasabuvir, [DB09296], [DB09297], [DB00503], and [DB00811] are used with the intent to cure, or achieve a sustained virologic response (SVR), after 12 weeks of therapy. SVR and eradication of HCV infection is associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of Hepatocellular Carcinoma, and reduced all-cause mortality [A19626]. Dasabuvir is available as a fixed dose combination product with [DB09296], [DB09297], and [DB00503] (tradename Viekira Pak) used for the treatment of chronic Hepatitis C. Approved in December 2014 by the FDA, Viekira Pak is indicated for the treatment of HCV genotype 1a with [DB00811] or genotype 1b without [DB00811] [FDA Label]. When combined together, Dasabuvir [DB09296], [DB09297], and [DB00503] as the combination product Viekira Pak have been shown to achieve a SVR of 100% for genotype 1b and 89% or 95% for genotype 1a after 12 weeks or 24 weeks of treatment including [DB00811].
Indication
Dasabuvir, in combination with [DB09296], [DB09297], and [DB00503] (as Viekira Pak) is indicated for the treatment of patients with HCV genotype 1a with [DB00811] or genotype 1b without [DB00811] including those with compensated cirrhosis [FDA Label].
Mechanism of Action
Dasabuvir is a non-nucleoside inhibitor of the HCV RNA-dependent RNA polymerase encoded by the NS5B gene, which is essential for replication of the viral genome [FDA Label]. Based on drug resistance mapping studies of HCV genotypes 1a and 1b, dasabuvir targets the palm domain of the NS5B polymerase, and is therefore referred to as a non-nucleoside NS5B-palm polymerase inhibitor. The EC50 values of dasabuvir against genotype 1a-H77 and 1b-Con1 strains in HCV replicon cell culture assays were 7.7 nM and 1.8 nM, respectively. By binding to NS5b outside of the active site of the enzyme, dasabuvir induces a conformational change thereby preventing further elongation of the nascent viral genome [A19593, FDA Label]. A limitation of binding outside of the active site is that these binding sites are poorly preserved across the viral genotypes. This results in a limited potential for cross-genotypic activity and increased potential for development of resistance. Dasabuvir is therefore limited to treating genotypes 1a and 1b, and must be used in combination with other antiviral products.
Pharmacokinetics
- Absorption
- Dasabuvir reaches peak plasma concentration 4 hours after administration [FDA Label]. The absolute bioavailability of Dasabuvir is 70%.
- Distribution
- Dasabuvir has a volume of distribution at steady state of 149 liters [FDA Label].
- Metabolism
- Dasabuvir is predominantly metabolized by CYP2C8, and to a lesser extent by CYP3A [FDA Label].
- Elimination
Clearance
Clearance of Dasabuvir has not been determined.
Toxicity
The most common adverse effects of Viekira Pak either in combination with or without [DB00811] were pruritus, nausea, insomnia, and asthenia [FDA Label].
Active Ingredient/Synonyms
Sodium 3-(3-tert-butyl-4-methoxy-5-{6 [(methylsulfonyl)amino]naphthalene-2-yl}phenyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-ide hydrate (1:1:1) | N-{6-[3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyphenyl]naphthalen-2-yl}methanesulfonamide | Dasabuvir |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.
Description
Ombitasvir is a direct acting antiviral medication used as part of combination therapy to treat chronic Hepatitis C, an infectious liver disease caused by infection with Hepatitis C Virus (HCV). HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients [L852]. Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) such as Ombitasvir. Ombitasvir is an inhibitor of NS5A, a protein essential for viral replication and virion assembly [FDA Label]. The barrier for develoment of resistance to NS5A inhibitors is lower than that of NS5B inhibitors, another class of DAAs [A19593]. In a joint recommendation published in 2016, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) recommend Ombitasvir as a first line therapy option when used in combination with other antivirals for genotypes 1a, 1b, and 4 [L852]. Depending on the genotype, Ombitasvir is often used in combination with other antivirals such as [DB09183], [DB09297], [DB00503], and [DB00811] with the intent to cure, or achieve a sustained virologic response (SVR), after 12 weeks of daily therapy. SVR and eradication of HCV infection is associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of Hepatocellular Carcinoma, and reduced all-cause mortality [A19626]. Treatment with direct acting antivirals such as Ombitasvir is associated with very minimal side effects, with the most common being headache and fatigue [FDA Label]. Lack of significant side effects and short duration of therapy is a considerable advantage over older interferon-based regimens, which were limited by infusion site reactions, reduced blood count, and neuropsychiatric effects [A19635]. Ombutasvir first came on the market as a fixed-dose combination product with [DB09183], [DB09297], and [DB00503] as the FDA-approved product Viekira Pak. First approved in December 2014, Viekira Pak is indicated for the treatment of HCV genotype 1b without cirrhosis or with compensated cirrhosis, and when combined with Ribavirin for the treatment of HCV genotype 1a without cirrhosis or with compensated cirrhosis. Ombutasvir is also available as a fixed-dose combination product with [DB09297] and [DB00503] as the FDA- and Health Canada-approved product Technivie. First approved in July 2015, Technivie is indicated in combination with Ribavirin for the treatment of patients with genotype 4 chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis. In Canada, Ombutasvir is also available as a fixed-dose combination product with [DB09183], [DB09297], and [DB00503] as the Health Canada-approved, commercially available product Holkira Pak. First approved in January 2015, Holkira Pak is indicated for the treatment of HCV genotype 1b with or without cirrhosis, and when combined with [DB00811] for the treatment of HCV genotype 1a with or without cirrhosis.
Indication
When used in combination with [DB09297] and [DB00503] (as the fixed dose product Technivie), Ombitasvir is indicated in combination with [DB00811] for the treatment of patients with genotype 4 chronic hepatitis C virus (HCV) infection without cirrhosis [L866]. When used in combination with [DB09297], [DB00503], and [DB09183] (as the fixed dose product Viekira Pak), Ombitasvir is indicated for the treatment of HCV genotype 1b and ,when combined with [DB00811], for the treatment of HCV genotype 1a [FDA Label]
Mechanism of Action
Ombitasvir is an inhibitor of the HCV non-structural protein 5A. While the precise role of this protein is unknown, it is essential to viral replication and virion assembly [FDA Label]. Potential modes of action of NS5A inhibitors like Elbasvir include blocking signaling interactions, redistribution of NS5A from the endoplasmic reticulum to the surface of lipid droplets, and modification of the HCV replication complex [A19593].
Pharmacokinetics
- Absorption
- Ombitasvir reaches peak plasma concentration 5 hours after administration [FDA Label]. It has an absolute bioavailability of 48%. Taking ombitasvir with high or normal fat meals increases exposure by 1.76 or 1.82 fold respectively.
- Distribution
- Ombitasvir has a volume of distribution at steady state of 173 liters [FDA Label].
- Metabolism
- Ombitasvir is mainly metabolized by amide hydrolysis followed by CYP2C8-mediated oxidative metabolism [FDA Label].
- Elimination
Clearance
Clearance of Ombitasvir has not been determined.
Toxicity
The most common adverse effects of Viekira Pak either in combination with or without [DB00811] were pruritus, nausea, insomnia, and asthenia [FDA Label]. The most common adverse effects of Technivie with or without [DB00811] were asthenia, fatigue, nausea, insomnia and pruritus [L866].
Active Ingredient/Synonyms
dimethyl ([(2S,5S)-1-(4-tert-butylphenyl)pyrrolidine-2,5-diyl]bis{(4,1-phenylene)carbamoyl(2S)pyrrolidine-2,1-diyl[(2S)-3-methyl-1-oxobutane-1,2-diyl]})biscarbamate | Ombitasvir |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.
Description
Paritaprevir is a direct acting antiviral medication used as part of combination therapy to treat chronic Hepatitis C, an infectious liver disease caused by infection with Hepatitis C Virus (HCV). HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients [L852]. Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) such as paritaprevir. As a newer generation and directly acting HCV antiviral, paritaprevir products have better Sustained Virological Response (SVR) rates, higher barriers to resistance, fewer side effects, and a reduced pill burden compared to older agents such as [DB08873], [DB05521], [DB00008], [DB00022], and [DB00811]. By combining multiple antiretroviral medications into fixed dose products, the viral lifecycle can be targeted at multiple stages while simultaneously reducing the risk of developing resistant viral strains [A19593]. Within Canada and the United States, paritaprevir is currently available in three fixed dose products: Viekira Pak (FDA), Technivie (FDA and Health Canada), and Holkira Pak (Health Canada). More specifically, paritaprevir prevents viral replication by inhibiting the NS3/4A serine protease of Hepatitis C Virus (HCV) [FDA Label]. Following viral replication of HCV genetic material and translation into a single polypeptide, Nonstructural Protein 3 (NS3) and its activating cofactor Nonstructural Protein 4A (NS4A) are responsible for cleaving genetic material into the following structural and nonstructural proteins required for assembly into mature virus: NS3, NS4A, NS4B, NS5A, and NS5B [A19643]. By inhibiting viral protease NS3/4A, paritaprevir therefore prevents viral replication and function. In a joint recommendation published in 2016, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) recommend Paritaprevir as a first line therapy option when used in combination with other antivirals for genotypes 1a, 1b, and 4[L852]. Depending on the genotype, Paritaprevir is often used in combination with other antivirals such as [DB09296], [DB09183], [DB00503], and [DB00811], with the intent to cure, or achieve a sustained virologic response (SVR), after 12 weeks of daily therapy. SVR and eradication of HCV infection is associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of Hepatocellular Carcinoma, and reduced all-cause mortality [A19626]. Treatment with direct acting antivirals such as paritaprevir is associated with very minimal side effects, with the most common being headache and fatigue [FDA Label]. Lack of significant side effects and short duration of therapy is a considerable advantage over older interferon-based regimens, which were limited by infusion site reactions, reduced blood count, and neuropsychiatric effects [A19635]. Paritaprevir first came on the market as a fixed-dose combination product with [DB09296], [DB09183], and [DB00503] as the FDA-approved product Viekira Pak. First approved in December 2014, Viekira Pak is indicated for the treatment of HCV genotype 1b without cirrhosis or with compensated cirrhosis, and when combined with [DB00811] for the treatment of HCV genotype 1a without cirrhosis or with compensated cirrhosis. Paritaprevir is also available as a fixed-dose combination product with [DB09296] and [DB00503] as the FDA- and Health Canada-approved product Technivie. First approved in July 2015, Technivie is indicated in combination with [DB00811] for the treatment of patients with genotype 4 chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis. In Canada, paritaprevir is also available as a fixed-dose combination product with [DB09296], [DB09183], and [DB00503] as the Health Canada-approved, commercially available product Holkira Pak. First approved in January 2015, Holkira Pak is indicated for the treatment of HCV genotype 1b with or without cirrhosis, and when combined with [DB00811] for the treatment of HCV genotype 1a with or without cirrhosis.
Indication
When used within the fixed-dose combination product with [DB09296], [DB09183], and [DB00503] as the FDA-approved product Viekira Pak, paritaprevir is indicated for the treatment of HCV genotype 1b without cirrhosis or with compensated cirrhosis, and when combined with [DB00811] for the treatment of HCV genotype 1a without cirrhosis or with compensated cirrhosis. When used within the fixed-dose combination product with [DB09296] and [DB00503] as the FDA- and Health Canada-approved product Technivie, paritaprevir is indicated in combination with [DB00811] for the treatment of patients with genotype 4 chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis. When used within the fixed-dose combination product with [DB09296], [DB09183], and [DB00503] as the Health Canada-approved, commercially available product Holkira Pak, paritaprevir is indicated for the treatment of HCV genotype 1b with or without cirrhosis, and when combined with [DB00811] for the treatment of HCV genotype 1a with or without cirrhosis.
Mechanism of Action
Paritaprevir is a potent inhibitor of the NS3/4A serine protease of Hepatitis C Virus (HCV) [FDA Label]. Following viral replication of HCV genetic material and translation into a single polypeptide, Nonstructural Protein 3 (NS3) and its activating cofactor Nonstructural Protein 4A (NS4A) are responsible for cleaving it into the following structural and nonstructural proteins required for assembly into mature virus: NS3, NS4A, NS4B, NS5A, and NS5B. By inhibiting viral protease NS3/4A, paritaprevir therefore prevents viral replication and function.
Pharmacokinetics
- Absorption
- Tmax of approximately 4 to 5 hours with a maximum concentration (Cmax) of 194 ng/mL [FDA Label].
- Distribution
- Volume of distribution at steady state is approximately 103 L [FDA Label].
- Metabolism
- Paritaprevir is predominantly metabolized by CYP3A4 and to a lesser extent by CYP3A5 [FDA Label].
- Elimination
Active Ingredient/Synonyms
(2R,6S,12Z,13aR,14aR,16aS)-N-(cyclopropanesulfonyl)-6-[(5-methylpyrazine-2-carbonyl)amino]-5,16-dioxo-2-[(phenanthridin-6-yl)oxy]-1,2,3,6,7,8,9,10,11,13a,14,15,16,16a-tetradecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a(5H)-carboxamide | Veruprevir | Paritaprevir |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.
Description
Ritonavir is an HIV protease inhibitor that interferes with the reproductive cycle of HIV. Although it was initially developed as an independent antiviral agent, it has been shown to possess advantageous properties in combination regimens with low-dose ritonavir and other protease inhibitors. It is now more commonly used as a booster of other protease inhibitors and is available in both liquid formulation and as capsules. While ritonavir is not an active antiviral agent against hepatitis C virus (HCV) infection, it is added in combination therapies indicated for treatment of HCV infections as a booster. Ritonavir is a potent CYP3A inhibitor that increases peak and trough plasma drug concentrations of other protease inhibitors such as [DB09297] and overall drug exposure. American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) guidelines recommend ritonavir-boosted combination therapies as a first-line therapy for HCV Genotype 1a/b and 4 treatment-naïve patients with or without cirrhosis. Ritonavir is found in a fixed-dose combination product with [DB09296], [DB09183], and [DB09297] as the FDA-approved product Viekira Pak. First approved in December 2014, Viekira Pak is indicated for the treatment of HCV genotype 1b without cirrhosis or with compensated cirrhosis, and when combined with Ribavirin for the treatment of HCV genotype 1a without cirrhosis or with compensated cirrhosis. Ritonavir is also available as a fixed-dose combination product with [DB09296] and [DB09297] as the FDA- and Health Canada-approved product Technivie. First approved in July 2015, Technivie is indicated in combination with Ribavirin for the treatment of patients with genotype 4 chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis. In Canada, ritonavir is also available as a fixed-dose combination product with [DB09296], [DB09183], and [DB09297] as the Health Canada-approved, commercially available product Holkira Pak. First approved in January 2015, Holkira Pak is indicated for the treatment of HCV genotype 1b with or without cirrhosis, and when combined with Ribavirin for the treatment of HCV genotype 1a with or without cirrhosis. Inclusion of ritonavir can can select for HIV-1 protease inhibitor resistance-associated substitutions. Any HCV/HIV-1 co-infected patients treated with ritonavir-containing combination therapies should also be on a suppressive antiretroviral drug regimen to reduce the risk of HIV-1 protease inhibitor drug resistance.
Indication
Indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection.
Mechanism of Action
Ritonavic inhibits the HIV viral proteinase enzyme that normally cleaves the structural and replicative proteins that arise from major HIV genes, such as *gag* and *pol*. *Gag* encodes proteins involved in the core and the nucleocapsid, while *pol* encodes the the HIV reverse transcriptase, ribonuclease H, integrase, and protease [A19647]. The *pol*-encoded proteins are initially translated in the form of a larger precursoe polypeptide, *gag-pol*, and needs to be cleaved by HIV protease to form other complement proteins [A19647]. Ritonavir prevents the cleavage of the *gag-pol* polyprotein, which results in noninfectious, immature viral particles. Ritonavir is a potent inhibitor of cytochrome P450 CYP3A4 isoenzyme present both in the intestinal tract and liver [A19647]. It is a type II ligand that perfectly fits into the CYP3A4 active site cavity and irreversibly binds to the heme iron via the thiazole nitrogen, which decreases the redox potential of the protein and precludes its reduction with the redox partner, cytochrome P450 reductase [A19648]. Ritonavir may also play a role in limiting cellular transport and efflux of other protease inhibitors via the P-glycoprotein and MRP efflux channels [A19647].
Pharmacokinetics
- Absorption
- The absolute bioavailability of ritonavir has not been determined.
- Distribution
- Metabolism
- Ritonavir circulates in the plasma predominantly as unchanged drug. Five metabolites have been identified. The isopropylthiazole oxidation metabolite (M-2) is the major metabolite in low plasma concentrations and retains similar antiviral activity to unchanged ritonavir. The cytochrome P450 enzymes CYP3A and CYP2D6 are primarily involved in the metabolism of ritonavir.
- Elimination
Toxicity
Human experience of acute overdose with ritonavir is limited. One patient in clinical trials took ritonavir 1500 mg/day for two days. The patient reported paresthesias which resolved after the dose was decreased. A post-marketing case of renal failure with eosinophilia has been reported with ritonavir overdose. The approximate lethal dose was found to be greater than 20 times the related human dose in rats and 10 times the related human dose in mice. Oral LD value in rats is >2500 mg/kg. Adverse effects of ritonavir may arise from drug-drug interactions. Other effects include hepatotoxicity, pancreatitis, and allergic reactions/hypersensitivity.
Active Ingredient/Synonyms
Ritonavir | Ritonavirum | Ritonavir |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.