Pseudoephedrine/loratadine and Ombitasvir/paritaprevir/ritonavir: Difference between pages

{{Short description|Pharmaceutical drug}}

{{Use dmy dates|date=December 2019}}

{{Drugbox

| verifiedrevid = 439439973

<!--Combo data-->

| type = combo

| component1 = Ombitasvir

| class1 = [[Antiviral drug|Antiviral]] ([[NS5A]] inhibitor)

| component2 = Paritaprevir

| class2 = Antiviral ([[NS3 (HCV)|NS3]] inhibitor)

| component3 = Ritonavir

| class3 = [[Pharmacokinetics|PK]] enhancer ([[CYP3A4]], [[CYP2D6]] inhibitor)

<!--Clinical data-->

| tradename = Viekira Pak (with [[dasabuvir]]), Technivie, Viekirax, others

| Drugs.com = {{drugs.com|monograph|ombitasvir-paritaprevir-and-ritonavir}}

| MedlinePlus = a615036

| licence_CA = Technivie

| licence_EU = yes

| DailyMedID = Technivie

| licence_US = Technivie

| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->

| pregnancy_AU_comment =

| pregnancy_category =

| routes_of_administration = [[Oral administration|By mouth]]

| class =

| ATCvet =

| ATC_prefix = J05

| ATC_suffix = AP53

| ATC_supplemental =

<!-- Legal data -->

| legal_AU = S4

| legal_AU_comment = <ref>{{cite web | title=Prescription medicines: registration of new chemical entities in Australia, 2015 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/prescription-medicines-registration-new-chemical-entities-australia-2015 | access-date=10 April 2023}}</ref>

| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F-->

| legal_BR_comment =

| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->

| legal_DE = <!-- Anlage I, II, III -->

| legal_NZ = <!-- Class A, B, C -->

| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->

| legal_US = Rx-only

| legal_EU = Rx-only

| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV-->

| legal_status = <!-- Free text -->

<!-- Pharmacokinetic data -->

| bioavailability =

| protein_bound =

| metabolism =

| metabolites =

| onset =

| elimination_half-life =

| duration_of_action =

| excretion =

<!--Identifiers-->

| CAS_number = 1799419-19-4

| PubChemSubstance = 254741706

| IUPHAR_ligand =

| ChemSpiderID = none

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D10745

| ChEBI = 90919

| ChEMBL =

| NIAID_ChemDB =

| PDB_ligand =

| synonyms =

<!-- Chemical and physical data -->

{{Drugbox

| drug_name = Dasabuvir/ombitasvir/paritaprevir/ritonavir

<!--Combo data-->

| type = combo

| component1 = Dasabuvir

| class1 = [[Antiviral drug|Antiviral]]

| component2 = Ombitasvir

| class2 = [[Antiviral drug|Antiviral]] ([[NS5A]] inhibitor)

| component3 = Paritaprevir

| class3 = Antiviral ([[NS3 (HCV)|NS3]] inhibitor)

| component4 = Ritonavir

| class4 = [[Pharmacokinetics|PK]] enhancer ([[CYP3A4]], [[CYP2D6]] inhibitor)

<!--Clinical data-->

| tradename = Viekira Pak, Viekira XR, Holkira Pak, others

| Drugs.com = {{drugs.com|monograph|ombitasvir-paritaprevir-ritonavir-and-dasabuvir}}

| MedlinePlus = a614057

| licence_CA = Holkira Pak

| DailyMedID = Viekira

| licence_US = Viekira Pak

| pregnancy_US = N

| routes_of_administration = [[By mouth]]

<!-- Legal data -->

| legal_US = Rx-only

<!--Identifiers-->

| ATC_prefix = J05

| ATC_suffix = AP52

| KEGG = D10582

| ChemSpiderID = none

| PubChem = 254741544

| ChEBI = 85177

<!--Chemical data-->

}}

<!-- Definition and medical uses -->

'''Ombitasvir/paritaprevir/ritonavir''', sold under the brand name '''Technivie''' among others, is a medication used to treat [[hepatitis C]].<ref name=AHFS2016Vi/> It is a [[fixed-dose combination]] of [[ombitasvir]], [[paritaprevir]], and [[ritonavir]].<ref name=AHFS2016Vi/> Specifically it is used together with [[dasabuvir]] or [[ribavirin]] for cases caused by [[hepatitis C virus genotype]] 1 or 4.<ref name=AHFS2016Vi/><ref name=UK2015>{{cite web|title=Viekirax 12.5 mg/75 mg/50 mg film-coated tablets - Summary of Product Characteristics (SPC) - (eMC)|url=https://www.medicines.org.uk/emc/medicine/29784|website=www.medicines.org.uk|access-date=31 December 2016|date=15 January 2015|url-status=live|archive-url=https://web.archive.org/web/20170101002825/https://www.medicines.org.uk/emc/medicine/29784|archive-date=1 January 2017}}</ref> Cure rates are around 95%.<ref name=UK2015/> It is taken [[Oral administration|by mouth]].<ref name=AHFS2016Vi/>

<!-- Side effects and mechanism -->

It is generally well tolerated.<ref name=WHO2015Use>{{cite book | vauthors = ((World Health Organization)) | year = 2015 | title = 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) | publisher = World Health Organization | location = Geneva | author-link = World Health Organization | hdl = 10665/189763 | id = WHO technical report series;994 | hdl-access=free | isbn = 9789241209946 | issn = 0512-3054 | pages = 70–4}}</ref> Common side effects include nausea, itchiness, rash, and trouble sleeping.<ref name=AHFS2016Vi/> Other side effects include [[allergic reactions]] and reactivation of [[hepatitis B]] among those previously infected.<ref name=AHFS2016Vi/> Use is not recommended in those with significant [[liver problems]].<ref name=AHFS2016Vi/> While there is no evidence of harm with use during [[pregnancy]], this use has not been well studied.<ref name=AHFS2016Vi/> Each of the medications works by a different mechanism.<ref name=UK2015/> The ritonavir is present to decrease the breakdown of paritaprevir.<ref name=AHFS2016Vi>{{cite web|title=Ombitasvir, Paritaprevir, and Ritonavir with Dasabuvir Sodium|url=https://www.drugs.com/monograph/ombitasvir-paritaprevir-and-ritonavir-with-dasabuvir-sodium.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20170101003220/https://www.drugs.com/monograph/ombitasvir-paritaprevir-and-ritonavir-with-dasabuvir-sodium.html|archive-date=1 January 2017}}</ref>

<!-- History and culture -->

Ombitasvir/paritaprevir/ritonavir with dasabuvir was approved for medical use in the United States in 2014, and without dasabuvir in 2015.<ref name=UW2016Vi>{{cite web|title=Ombitasvir-Paritaprevir-Ritonavir and Dasabuvir (Viekira Pak) - Treatment - Hepatitis C Online|url=http://www.hepatitisc.uw.edu/page/treatment/drugs/3d|website=www.hepatitisc.uw.edu|access-date=31 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161101211226/http://www.hepatitisc.uw.edu/page/treatment/drugs/3d|archive-date=1 November 2016}}</ref><ref name=AHFS2016Te>{{cite web|title=Ombitasvir, Paritaprevir, and Ritonavir|url=https://www.drugs.com/monograph/ombitasvir-paritaprevir-and-ritonavir.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20170101003129/https://www.drugs.com/monograph/ombitasvir-paritaprevir-and-ritonavir.html|archive-date=1 January 2017}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref>

{{TOC limit|3}}

==Medical uses==

Ombitasvir/paritaprevir/ritonavir is used together with [[dasabuvir]] or [[ribavirin]] for cases caused by [[hepatitis C virus genotype]] 1 or 4.<ref name=AHFS2016Vi/><ref name=UK2015/> Cure rates are around 95%.<ref name=UK2015/>

== Contraindications ==

* People with moderate to severe liver impairment{{cn|date=January 2023}}

* Concurrent use of moderate to strong inducers of [[CYP3A]] and strong inducers of [[CYP2C8]] reduce efficacy<ref name=":0">{{Cite web|title = Safety Information - Viekira Pak (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets), Copackaged for Oral Use|url = https://www.fda.gov/safety/medwatch/safetyinformation/ucm458365.htm|website = www.fda.gov|access-date = 2015-11-30|first = Office of the|last = Commissioner|url-status = live|archive-url = https://web.archive.org/web/20161117150645/https://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm458365.htm|archive-date = 2016-11-17}}</ref>

== 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 [[Alanine aminotransferase|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 (medicine)|baseline]].<ref name=":0" />

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.<ref>{{cite web | title=Direct-acting antivirals indicated for treatment of hepatitis C (interferon-free) | website=[[European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/referrals/direct-acting-antivirals-indicated-treatment-hepatitis-c-interferon-free | access-date=4 February 2020}}</ref>

==Society and culture==

It is manufactured by [[Abbvie]]. In the United States ombitasvir/paritaprevir/ritonavir together with dasabuvir is sold as Viekira Pak.<ref>Viekira Pak {{Drugs.com|parent|viekira-pak}} on [[Drugs.com]].</ref> Technivie consists of only ombitasvir/paritaprevir/ritonavir tablets.<ref>{{cite web | title=Technivie (ombitasvir, paritaprevir and ritonavir) tablets, for oral useInitial U.S. Approval: 2015 | website=DailyMed | date=22 January 2020 | url=https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=463754 | access-date=26 April 2020}}</ref> Technivie was discontinued in the US market in 2020.<ref>{{cite web | title=Technivie: FDA-Approved Drugs | website=U.S. [[Food and Drug Administration]] (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=207931 | access-date=25 April 2020}}</ref>

===Approval===

====United States====

Ombitasvir/paritaprevir/ritonavir together with dasabuvir was approved in its first review cycle by the FDA in December 2014.<ref>{{Cite web|title = Press Announcements - FDA approves Viekira Pak to treat hepatitis C|url = https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427530.htm|website = www.fda.gov|access-date = 2015-11-30|url-status = live|archive-url = https://web.archive.org/web/20151031114612/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427530.htm|archive-date = 2015-10-31}}</ref> The [[Center for Drug Evaluation and Research]] (CDER) designated the product for [[FDA Fast Track Development Program|Fast Track]] because it had potential to treat unmet medical need. This track allows the CDER to view certain information ahead of a completed [[New drug application|NDA]] to cut down the time to approval. Additionally, it was designated [[Breakthrough therapy|Breakthrough Therapy]] for its substantial improvement in the primary endpoint SVR₁₂ and given [[Priority review voucher|Priority Review]] under the [[Prescription Drug User Fee Act]] allowing the review to be completed in six months rather than the standard ten months.<ref>{{Cite news|url = https://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DrugInnovation/UCM430299.pdf|title = Novel New Drugs 2014 Summary|date = January 2015 |access-date = November 30, 2015|publisher = U.S. [[Food and Drug Administration]] (FDA)|url-status = live|archive-url = https://web.archive.org/web/20160115144615/https://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DrugInnovation/UCM430299.pdf|archive-date = January 15, 2016}}</ref>

====Europe====

In Europe, ombitasvir/paritaprevir/ritonavir is approved under the trade name Viekirax for combination therapy together with dasabuvir, with or without [[ribavirin]].<ref name="Austria-Codex">{{cite book|title=Austria-Codex|editor=Haberfeld|publisher=Österreichischer Apothekerverlag|location=Vienna|language=de}}</ref><ref>{{cite web | title=Viekirax EPAR | website=[[European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/viekirax | access-date=26 April 2020}}</ref>

== Research ==

=== Sapphire I ===

Sapphire I was a 12-week placebo-controlled, randomized, double-blind trial which had a primary endpoint of cure ([[Sustained viral response|SVR₁₂]]) rate in non-cirrhotic patients with [[Hepatitis C|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.<ref name=":1">{{Cite web|url = https://www.abbvie.com/content/dam/abbviecorp/us/desktop/contentrooms/downloads/ClinicalTrialsFactsheet_ViekiraPak_US.pdf|title = Hepatitis C clinical trials program overview|access-date = November 27, 2015|publisher = Abbvie|url-status = live|archive-url = https://web.archive.org/web/20150907180710/http://www.abbvie.com/content/dam/abbviecorp/us/desktop/contentrooms/downloads/ClinicalTrialsFactsheet_ViekiraPak_US.pdf|archive-date = September 7, 2015}}</ref>

=== 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.<ref name=":1" />

=== 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.<ref name=":1" />

=== 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<ref name=":1" />

=== 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.<ref name=":1" />

=== 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.<ref name=":1" />

{{reflist}}

==External links==

* {{cite web| url = https://druginfo.nlm.nih.gov/drugportal/name/ombitasvir%20mixture%20with%20paritaprevir%20and%20ritonavir | publisher = U.S. National Library of Medicine| work = Drug Information Portal| title = Ombitasvir mixture with paritaprevir and ritonavir }}

* {{cite web| url = https://druginfo.nlm.nih.gov/drugportal/name/dasabuvir%20combination%20with%20ombitasvir,%20paritaprevir%20and%20ritonavir | publisher = U.S. National Library of Medicine| work = Drug Information Portal| title = Dasabuvir combination with ombitasvir, paritaprevir and ritonavir }}

* {{cite web | title=FDA Drug Safety Communication: FDA warns of serious liver injury risk with hepatitis C treatments Viekira Pak and Technivie | website=U.S. [[Food and Drug Administration]] (FDA) | date=24 August 2016 | url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-serious-liver-injury-risk-hepatitis-c-treatments-viekira-pak }}

* {{cite web | title=FDA Drug Safety Communication: FDA warns about the risk of hepatitis B reactivating in some patients treated with direct-acting antivirals for hepatitis C | website=U.S. [[Food and Drug Administration]] (FDA) | date=4 October 2016 | url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-about-risk-hepatitis-b-reactivating-some-patients-treated }}

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