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| {{Drugbox | | __NOTOC__ |
| | drug_name = Simeprevir
| | {{Simeprevir}} |
| | IUPAC_name =
| | {{CMG}} |
| | image = Simeprevir.svg
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| | width = 200
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| | alt =
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| | caption =
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| <!-- Clinical data -->
| | ==Overview== |
| | tradename = Olysio
| | [[Medivir]] and [[Johnson & Johnson]]'s pharmaceutical division [[Janssen Pharmaceutica]]. In the United States, simeprevir is approved by the [[Food and Drug Administration]] for use in combination with[[peginterferon-alfa]] and [[ribavirin]].<ref>{{cite web | url = http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm376449.htm | title = FDA approves new treatment for hepatitis C virus | publisher = [[Food and Drug Administration]] | date = Nov 22, 2013}}</ref> Simeprevir has been approved in Japan for the treatment of chronic hepatitis C infection, genotype 1.<ref>{{cite web | url = http://online.wsj.com/article/PR-CO-20130927-900120.html| title = Medivir: Simeprevir has been approved in Japan for the treatment of genotype 1 chronic hepatitis C infection | date = September 27, 2013 |publisher = The Wall Street Journal}}</ref> |
| | Drugs.com =
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| | MedlinePlus =
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| | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | |
| | pregnancy_US = <!-- A / B / C / D / X --> | |
| | pregnancy_category= | |
| | legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled--> | |
| | legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
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| | legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM --> | |
| | legal_US = Rx-only | |
| | legal_status = | |
| | routes_of_administration = | |
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| <!-- Pharmacokinetic data --> | | ==Category== |
| | bioavailability =
| | Antiviral |
| | protein_bound =
| | ==US Brand Names== |
| | metabolism =
| | OLYSIO<sup>®</sup> |
| | elimination_half-life =
| | ==FDA Package Insert== |
| | excretion =
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| <!-- Identifiers -->
| | ''' [[Simeprevir description|Description]]''' |
| | CAS_number = 923604-59-5 | | '''| [[Simeprevir clinical pharmacology|Clinical Pharmacology]]''' |
| | PubChem = 56928193 | | '''| [[Simeprevir microbiology|Microbiology]]''' |
| | ChemSpiderID = 23331536 | | '''| [[Simeprevir indications and usage|Indications and Usage]]''' |
| | ATCvet = | | '''| [[Simeprevir contraindications|Contraindications]]''' |
| | ATC_prefix = <!-- 'none' if uncategorised --> | | '''| [[Simeprevir warnings and precautions|Warnings and Precautions]]''' |
| | ATC_suffix = | | '''| [[Simeprevir adverse reactions|Adverse Reactions]]''' |
| | DrugBank = | | '''| [[Simeprevir drug interactions|Drug Interactions]]''' |
| | synonyms = TMC435; TMC435350 | | '''| [[Simeprevir overdosage|Overdosage]]''' |
| | '''| [[Simeprevir clinical studies|Clinical Studies]]''' |
| | '''| [[Simeprevir dosage and administration|Dosage and Administration]]''' |
| | '''| [[Simeprevir how supplied|How Supplied]]''' |
| | '''| [[Simeprevir labels and packages|Labels and Packages]]''' |
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| <!-- Chemical data -->
| | ==Mechanism of Action== |
| | C=38|H=47|N=5|O=7|S=2
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| | molecular_weight = 749.94 g/mol
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| | smiles = Cc1c(ccc2c1nc(cc2O[C@@H]3C[C@@H]4[C@@H](C3)C(=O)N(CCCC/C=C\[C@@H]5C[C@]5(NC4=O)C(=O)NS(=O)(=O)C6CC6)C)c7nc(cs7)C(C)C)OC
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| | InChI = 1/C38H47N5O7S2/c1-21(2)30-20-51-35(40-30)29-18-32(26-13-14-31(49-5)22(3)33(26)39-29)50-24-16-27-28(17-24)36(45)43(4)15-9-7-6-8-10-23-19-38(23,41-34(27)44)37(46)42-52(47,48)25-11-12-25/h8,10,13-14,18,20-21,23-25,27-28H,6-7,9,11-12,15-17,19H2,1-5H3,(H,41,44)(H,42,46)/b10-8-/t23-,24-,27-,28-,38-/m1/s1
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| | InChIKey = JTZZSQYMACOLNN-VDWJNHBNBI
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| | StdInChI = 1S/C38H47N5O7S2/c1-21(2)30-20-51-35(40-30)29-18-32(26-13-14-31(49-5)22(3)33(26)39-29)50-24-16-27-28(17-24)36(45)43(4)15-9-7-6-8-10-23-19-38(23,41-34(27)44)37(46)42-52(47,48)25-11-12-25/h8,10,13-14,18,20-21,23-25,27-28H,6-7,9,11-12,15-17,19H2,1-5H3,(H,41,44)(H,42,46)/b10-8-/t23-,24-,27-,28-,38-/m1/s1
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| | StdInChIKey = JTZZSQYMACOLNN-VDWJNHBNSA-N
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| }}
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| '''Simeprevir''' (formerly '''TMC435'''; trade name '''Olysio''') is a drug for the treatment and cure of [[hepatitis C]].<ref>[http://www.nature.com/news/united-states-to-approve-potent-oral-drugs-for-hepatitis-c-1.14059 News: United States to approve potent oral drugs for hepatitis C,] Sara Reardon, Nature, 30 October 2013</ref> It was [[drug development|developed]] by [[Medivir]] and [[Johnson & Johnson]]'s pharmaceutical division [[Janssen Pharmaceutica]]. In the United States, simeprevir is approved by the [[Food and Drug Administration]] for use in combination with [[peginterferon-alfa]] and [[ribavirin]].<ref>{{cite web | url = http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm376449.htm | title = FDA approves new treatment for hepatitis C virus | publisher = [[Food and Drug Administration]] | date = Nov 22, 2013}}</ref> Simeprevir has been approved in Japan for the treatment of chronic hepatitis C infection, genotype 1.<ref>{{cite web | url = http://online.wsj.com/article/PR-CO-20130927-900120.html | title = Medivir: Simeprevir has been approved in Japan for the treatment of genotype 1 chronic hepatitis C infection | date = September 27, 2013 | publisher = The Wall Street Journal}}</ref>
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| ==Mechanism of action== | |
| Simeprevir is a [[hepatitis C virus]] [[protease inhibitor (pharmacology)|protease inhibitor]].<ref>{{cite journal | pmid = 19171797 | year = 2009 | last1 = Lin | first1 = TI | last2 = Lenz | first2 = O | last3 = Fanning | first3 = G | last4 = Verbinnen | first4 = T | last5 = Delouvroy | first5 = F | last6 = Scholliers | first6 = A | last7 = Vermeiren | first7 = K | last8 = Rosenquist | first8 = A | last9 = Edlund | first9 = M | title = In vitro activity and preclinical profile of TMC435350, a potent hepatitis C virus protease inhibitor | volume = 53 | issue = 4 | pages = 1377–85 | doi = 10.1128/AAC.01058-08 | pmc = 2663092 | journal = Antimicrobial agents and chemotherapy | last10 = Samuelsson | first10 = B. | last11 = Vrang | first11 = L. | last12 = De Kock | first12 = H. | last13 = Wigerinck | first13 = P. | last14 = Raboisson | first14 = P. | last15 = Simmen | first15 = K.}}</ref>
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| Simeprevir is a NS3/4A protease inhibitor, thus preventing viral maturation through inhibition of protein synthesis. Simeprevir is administered as one capsule once daily with pegylated interferon and ribavirin for the treatment of genotype 1 or genotype 4 chronic hepatitis C in adult patients with compensated liver disease (including cirrhosis), with or without HIV-1 co-infection, who are treatment naive or who have failed previous interferon therapy.<ref>{{cite journal | doi = 10.1016/j.jhep.2011.02.023 | title = EASL Clinical Practice Guidelines: Management of hepatitis C virus infection | year = 2011 | journal = Journal of Hepatology | volume = 55 | issue = 2 | pages = 245–64 | pmid = 21371579 | author1 = European Association for the Study of the Liver}}</ref><ref>{{cite journal | author = Zein NN | title = Clinical Significance of Hepatitis C Virus Genotypes | journal = Clin. Microbiol. Rev. | year = 2000 | volume = 13 | issue = 2 | pages = 223–235 | doi = 10.1128/CMR.13.2.223-235.2000 | pmid = 10755999 | pmc = 100152}}</ref> Genotype 1 is the most prevalent form of hepatitis C virus (HCV) worldwide.
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| ==Clinical study==
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| Simeprevir has been tested in combination regimens with [[pegylated interferon alfa-2a]] and [[ribavirin]],<ref>{{cite web | url = http://www.hivandhepatitis.com/hepatitis-c/hepatitis-c-topics/hcv-treatment/3926-phase-3-studies-show-simeprevir-plus-interferonribavirin-cures-most-patients-in-24-weeks | title = Phase 3 Studies Show Simeprevir plus Interferon/Ribavirin Cures Most Patients in 24 Weeks | publisher = hivandhepatitis.com | date = December 27, 2012}}</ref> and in interferon-free regimens with other direct-acting antiviral agents including [[daclatasvir]]<ref>[http://www.medivir.se/v4/en/ir_media/pressrelease.cfm?year=2012&releaseid=659101 Medivir announces TMC435 in an expanded clinical collaboration]. Medivir. 18 April 2012.</ref> and [[sofosbuvir]] <ref>[http://www.medivir.se/v4/en/ir_media/pressrelease.cfm Results from a phase IIa study evaluating Simeprevir and Sofosbuvir in prior null responder Hepatitis C patients have been presented at CROI. 6 March 2013.]</ref>
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| Results from three phase 3 randomized, double-blind, placebo controlled clinical trials (C208, C216, and HPC3007) in patients with chronic HCV GT1 were favourable and resulted in FDA supporting the approval of Simeprevir for Hepatitis C genotype 1.<ref>http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AntiviralDrugsAdvisoryCommittee/UCM371623.pdf</ref> Interestingly, members of the FDA commented following a presentation by Johnson & Johnson (24 October 2013) that post-marketing studies in racial and ethnic minorities, patients co-infected with HIV, and other underrepresented populations is needed.
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| In the pooled analysis, 2% of those in the simeprevir group had serious adverse events, versus 3% of those in the control group during the initial 12 weeks. A total of 3 patients (0.4%) in the simeprevir group had significant adverse events, which were determined to be related to simeprevir by the study investigator; 1 patient experienced major depression and 2 patients experienced photosensitivity reactions. A total of 4 deaths occurred in the treatment groups, and they were judged to be unrelated to treatment. Other common adverse events were rash (218 [28%] treatment groups; 79 [20%] control groups), influenza like illness (203 [26%] treatment groups; 84 [21%] control groups), pruritis (168 [22%] treatment groups; 58 [15%] control groups), and nausea (173 [22%] treatment groups; 70 [18%] control groups). For all (new) medications, adverse events or suspected adverse events should be made known to a relevant medical practitioner and health professionals are advised to report this to local authorities to promote surveillance and potential recognition of these negative effects.
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| ==References== | | ==References== |
| {{reflist}} | | {{Reflist|2}} |
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| [[Category:Anti-RNA virus drugs]] | | [[Category:Antiviral]] |
| [[Category:Cyclopropanes]] | | [[Category:Wikinfect]] |
| [[Category:Macrocycles]]
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| [[Category:Thiazoles]]
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| [[Category:Sulfonamides]]
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| [[Category:Protease inhibitors]]
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| [[Category:Quinolines]]
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| [[Category:Hepatitis C]]
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