Identification

Name
Paritaprevir
Accession Number
DB09297
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 8. 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 Boceprevir, Telaprevir, Peginterferon alfa-2a, Peginterferon alfa-2b, and Ribavirin. 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 7. 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) 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 6. 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 48. Depending on the genotype, Paritaprevir is often used in combination with other antivirals such as Ombitasvir, Dasabuvir, Ritonavir, and Ribavirin, 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 4. Treatment with direct acting antivirals such as paritaprevir is associated with very minimal side effects, with the most common being headache and fatigue 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 5.

Paritaprevir first came on the market as a fixed-dose combination product with Ombitasvir, Dasabuvir, and Ritonavir 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.

Paritaprevir is also available as a fixed-dose combination product with Ombitasvir and Ritonavir 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, paritaprevir is also available as a fixed-dose combination product with Ombitasvir, Dasabuvir, and Ritonavir 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.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 765.89
Monoisotopic: 765.294467927
Chemical Formula
C40H43N7O7S
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
  • Paritaprevir
  • Veruprevir
External IDs
  • ABT 450
  • ABT-450
  • ABT450

Pharmacology

Indication

When used within the fixed-dose combination product with Ombitasvir, Dasabuvir, and Ritonavir 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 Ribavirin for the treatment of HCV genotype 1a without cirrhosis or with compensated cirrhosis.

When used within the fixed-dose combination product with Ombitasvir and Ritonavir as the FDA- and Health Canada-approved product Technivie, paritaprevir 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.

When used within the fixed-dose combination product with Ombitasvir, Dasabuvir, and Ritonavir 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 Ribavirin for the treatment of HCV genotype 1a with or without cirrhosis.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

At concentrations approximately 6 and 1.8 times the therapeutic concentrations of paritaprevir and ombitasvir, the combination did not prolong QTc to any clinically relevant extent Label.

Mechanism of action

Paritaprevir is a potent inhibitor of the NS3/4A serine protease of Hepatitis C Virus (HCV) 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.

TargetActionsOrganism
ANS3/4A protein
inhibitor
Hepatitis C Virus
Absorption

Tmax of approximately 4 to 5 hours with a maximum concentration (Cmax) of 194 ng/mL Label.

Volume of distribution

Volume of distribution at steady state is approximately 103 L Label.

Protein binding

97 to 98.6% bound to human plasma proteins Label.

Metabolism

Paritaprevir is predominantly metabolized by CYP3A4 and to a lesser extent by CYP3A5 Label.

Route of elimination

Following a single dose administration of 14C-paritaprevir co-dosed with 100 mg of ritonavir, approximately 88% of the radioactivity was recovered in feces with limited radioactivity (8.8%) in urine; unchanged paritaprevir accounted for 1.1% of the radioactivity in the feces and 0.05% in the urine Label.

Half-life

5.5 hr Label

Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity
Not Available
Affected organisms
  • Hepatitis C Virus
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirThe metabolism of Abacavir can be decreased when combined with Paritaprevir.
AbametapirThe serum concentration of Paritaprevir can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Paritaprevir can be increased when combined with Abatacept.
AbemaciclibParitaprevir may decrease the excretion rate of Abemaciclib which could result in a higher serum level.
AcalabrutinibThe metabolism of Paritaprevir can be decreased when combined with Acalabrutinib.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Paritaprevir.
AcetylcysteineThe excretion of Paritaprevir can be decreased when combined with Acetylcysteine.
AdalimumabThe metabolism of Paritaprevir can be increased when combined with Adalimumab.
Adenovirus type 7 vaccine liveThe therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Paritaprevir.
AfatinibParitaprevir may decrease the excretion rate of Afatinib which could result in a higher serum level.
Additional Data Available
  • Extended Description
    Extended Description
    Available for Purchase

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity
    Available for Purchase

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level
    Available for Purchase

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action
    Available for Purchase

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Avoid St. John's Wort.
  • Take with food.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Paritaprevir dihydrateHRQ5901O781456607-71-8AWGQIDLXYMGEEH-RHSIAEQTSA-N
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Holkira PakParitaprevir (75 mg) + Dasabuvir (250 mg) + Ombitasvir (12.5 mg) + Ritonavir (50 mg)Kit; TabletOralAbbvie2015-01-062018-08-15Canada flag
TechnivieParitaprevir dihydrate (75 mg/1) + Ombitasvir heminonahydrate (12.5 mg/1) + Ritonavir (50 mg/1)TabletOralAbbVie Inc.2015-07-242019-03-14US flag
TechnivieParitaprevir (75 mg) + Ombitasvir (12.5 mg) + Ritonavir (50 mg)TabletOralAbbvie2015-11-242018-07-30Canada flag
Viekira PakParitaprevir dihydrate (75 mg/1) + Dasabuvir sodium monohydrate (250 mg/1) + Ombitasvir heminonahydrate (12.5 mg/1) + Ritonavir (50 mg/1)Kit; TabletOralAbbVie Inc.2014-12-19Not applicableUS flag
Viekira XRParitaprevir dihydrate (50 mg/1) + Dasabuvir sodium monohydrate (200 mg/1) + Ombitasvir heminonahydrate (8.33 mg/1) + Ritonavir (33.33 mg/1)Kit; TabletOralAbbVie Inc.2016-07-222019-01-17US flag

Categories

ATC Codes
J05AP53 — Ombitasvir, paritaprevir and ritonavirJ05AP52 — Dasabuvir, ombitasvir, paritaprevir and ritonavir
Drug Categories
Classification
Not classified

Chemical Identifiers

UNII
OU2YM37K86
CAS number
1216941-48-8
InChI Key
UAUIUKWPKRJZJV-QPLHLKROSA-N
InChI
InChI=1S/C40H43N7O7S/c1-24-21-42-33(22-41-24)35(48)43-32-16-6-4-2-3-5-11-25-20-40(25,39(51)46-55(52,53)27-17-18-27)45-36(49)34-19-26(23-47(34)38(32)50)54-37-30-14-8-7-12-28(30)29-13-9-10-15-31(29)44-37/h5,7-15,21-22,25-27,32,34H,2-4,6,16-20,23H2,1H3,(H,43,48)(H,45,49)(H,46,51)/b11-5-/t25-,26-,32+,34+,40-/m1/s1
IUPAC Name
(1S,4R,6S,7Z,14S,18R)-N-(cyclopropanesulfonyl)-14-(5-methylpyrazine-2-amido)-2,15-dioxo-18-(phenanthridin-6-yloxy)-3,16-diazatricyclo[14.3.0.0^{4,6}]nonadec-7-ene-4-carboxamide
SMILES
[H][[email protected]@]12C[[email protected]]1(NC(=O)[[email protected]]1([H])C[[email protected]](CN1C(=O)[[email protected]](CCCCC\C=C/2)NC(=O)C1=CN=C(C)C=N1)OC1=NC2=C(C=CC=C2)C2=C1C=CC=C2)C(=O)NS(=O)(=O)C1CC1

References

General References
  1. Klibanov OM, Gale SE, Santevecchi B: Ombitasvir/paritaprevir/ritonavir and dasabuvir tablets for hepatitis C virus genotype 1 infection. Ann Pharmacother. 2015 May;49(5):566-81. doi: 10.1177/1060028015570729. Epub 2015 Feb 13. [PubMed:25680759]
  2. Hull MW, Yoshida EM, Montaner JS: Update on Current Evidence for Hepatitis C Therapeutic Options in HCV Mono-infected Patients. Curr Infect Dis Rep. 2016 Jul;18(7):22. doi: 10.1007/s11908-016-0527-8. [PubMed:27357277]
  3. Lam JT, Salazar L: New combination antiviral for the treatment of hepatitis C. Am J Health Syst Pharm. 2016 Jul 15;73(14):1042-50. doi: 10.2146/ajhp150163. Epub 2016 May 23. [PubMed:27217519]
  4. Myers RP, Shah H, Burak KW, Cooper C, Feld JJ: An update on the management of chronic hepatitis C: 2015 Consensus guidelines from the Canadian Association for the Study of the Liver. Can J Gastroenterol Hepatol. 2015 Jan-Feb;29(1):19-34. Epub 2015 Jan 13. [PubMed:25585348]
  5. Dusheiko G: Side effects of alpha interferon in chronic hepatitis C. Hepatology. 1997 Sep;26(3 Suppl 1):112S-121S. [PubMed:9305675]
  6. Moradpour D, Penin F: Hepatitis C virus proteins: from structure to function. Curr Top Microbiol Immunol. 2013;369:113-42. doi: 10.1007/978-3-642-27340-7_5. [PubMed:23463199]
  7. Bagaglio S, Uberti-Foppa C, Morsica G: Resistance Mechanisms in Hepatitis C Virus: implications for Direct-Acting Antiviral Use. Drugs. 2017 May 12. doi: 10.1007/s40265-017-0753-x. [PubMed:28497432]
  8. American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance. http://hcvguidelines.org. Accessed June 12, 2017. [Link]
KEGG Drug
D10580
PubChem Compound
68498031
PubChem Substance
310265189
ChemSpider
32700634
RxNav
1597373
ChEBI
85188
ChEMBL
CHEMBL3391662
ZINC
ZINC000197964623
PharmGKB
PA166163410
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Paritaprevir
FDA label
Download (6.48 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentChronic Hepatitis C Virus (HCV) Infection1
4Active Not RecruitingTreatmentChronic Hepatitis C Virus (HCV) Infection / Chronic Kidney Disease (CKD)1
4Active Not RecruitingTreatmentHepatitis C Virus (HCV) Infection1
4CompletedPreventionHepatitis C Viral Infection1
4CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection1
4CompletedTreatmentEnd Stage Renal Disease (ESRD) / HCV Coinfection1
4CompletedTreatmentHCV Coinfection1
4CompletedTreatmentHepatitis C Viral Infection1
4CompletedTreatmentHepatitis Viruses1
4Unknown StatusTreatmentAntiviral Drug Adverse Reaction1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
TabletOral
Kit; tabletOral
Tablet, film coatedOral12.5 MG
Tablet, coatedOral12.5 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US6703403Yes2004-03-092016-12-26US flag
US6037157Yes2000-03-142016-12-26US flag
US7364752Yes2008-04-292021-05-10US flag
US7148359Yes2006-12-122020-01-19US flag
US8268349Yes2012-09-182025-02-25US flag
US8399015Yes2013-03-192025-02-25US flag
US9139536No2015-09-222028-11-09US flag
US8685984No2014-04-012032-09-04US flag
US8466159No2013-06-182032-09-04US flag
US8642538No2014-02-042029-09-10US flag
US8501238No2013-08-062028-09-17US flag
US8680106No2014-03-252032-09-04US flag
US8492386No2013-07-232032-09-04US flag
US8188104No2012-05-292029-05-17US flag
US9006387No2015-04-142030-06-10US flag
US9044480No2015-06-022031-04-10US flag
US8686026No2014-04-012031-06-09US flag
US8420596Yes2013-04-162031-10-10US flag
US8691938No2014-04-082032-04-13US flag
US9629841No2017-04-252033-10-18US flag
US9333204No2016-05-102035-01-02US flag
US9744170No2017-08-292035-01-02US flag
US10105365No2018-10-232035-01-02US flag
US10201584No2019-02-122032-05-17US flag
US10201542No2019-02-122033-10-18US flag
US10201541No2019-02-122032-05-17US flag
Additional Data Available
  • Filed On
    Filed On
    Available for Purchase

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00778 mg/mLALOGPS
logP3.5ALOGPS
logP2.49ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)3.8ChemAxon
pKa (Strongest Basic)2.64ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area189.65 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity200.98 m3·mol-1ChemAxon
Polarizability78.72 Å3ChemAxon
Number of Rings8ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

Kind
Protein
Organism
Hepatitis C Virus
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serine-type peptidase activity
Specific Function
Not Available
Gene Name
NS3/4A
Uniprot ID
B0B3C9
Uniprot Name
Genome polyprotein
Molecular Weight
72789.28 Da
References
  1. Lam JT, Salazar L: New combination antiviral for the treatment of hepatitis C. Am J Health Syst Pharm. 2016 Jul 15;73(14):1042-50. doi: 10.2146/ajhp150163. Epub 2016 May 23. [PubMed:27217519]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Shen J, Serby M, Reed A, Lee AJ, Zhang X, Marsh K, Khatri A, Menon R, Kavetskaia O, Fischer V: Metabolism and Disposition of the Hepatitis C Protease Inhibitor Paritaprevir in Humans. Drug Metab Dispos. 2016 Aug;44(8):1164-73. doi: 10.1124/dmd.115.067488. Epub 2016 May 13. [PubMed:27179127]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Shen J, Serby M, Reed A, Lee AJ, Zhang X, Marsh K, Khatri A, Menon R, Kavetskaia O, Fischer V: Metabolism and Disposition of the Hepatitis C Protease Inhibitor Paritaprevir in Humans. Drug Metab Dispos. 2016 Aug;44(8):1164-73. doi: 10.1124/dmd.115.067488. Epub 2016 May 13. [PubMed:27179127]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. Alam N, Angeli MG, Greenblatt DJ: Mechanism of in-vitro inhibition of UGT1A1 by paritaprevir. J Pharm Pharmacol. 2017 Dec;69(12):1794-1801. doi: 10.1111/jphp.12821. Epub 2017 Oct 9. [PubMed:28990653]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da

Drug created on October 30, 2015 10:02 / Updated on June 12, 2020 11:42

Pbdb medl 1