Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Posaconazole: Difference between pages

{{Short description|Pharmaceutical drug}}

{{Use dmy dates|date=November 2022}}

| Watchedfields = changed

| verifiedrevid = 464210822

| width = 200

| width2 = 200

| tradename = Noxafil, Posanol, others

| DailyMedID = Posaconazole

| licence_EU = yes

| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Posaconazole (Noxafil) Use During Pregnancy | website=Drugs.com | date=23 April 2019 | url=https://www.drugs.com/pregnancy/posaconazole.html | access-date=30 January 2020 | archive-date=30 January 2020 | archive-url=https://web.archive.org/web/20200130064302/https://www.drugs.com/pregnancy/posaconazole.html | url-status=live }}</ref>

| pregnancy_category=

| routes_of_administration = [[Oral administration|By mouth]], [[Intravenous therapy|intravenous]]

| ATC_prefix = J02

| ATC_suffix = AC04

<!-- Legal status -->

| legal_AU = S4

| legal_AU_comment = <ref>{{cite web | title=Posaconazole suspension ARX/Posaconazole TIH/APX-Posaconazole (Arrow Pharma Pty Ltd) | website=Therapeutic Goods Administration (TGA) | date=16 February 2023 | url=https://www.tga.gov.au/resources/prescription-medicines-registrations/posaconazole-suspension-arxposaconazole-tihapx-posaconazole-arrow-pharma-pty-ltd | access-date=29 April 2023 | archive-date=18 March 2023 | archive-url=https://web.archive.org/web/20230318023605/https://www.tga.gov.au/resources/prescription-medicines-registrations/posaconazole-suspension-arxposaconazole-tihapx-posaconazole-arrow-pharma-pty-ltd | url-status=live }}</ref>

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

| legal_BR_comment =

| legal_CA = Rx-only

| legal_CA_comment = <ref>{{cite web | title=Posanol Product information | website=Health Canada | date=25 April 2012 | url=https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=77877 | access-date=3 July 2022 | archive-date=16 May 2021 | archive-url=https://web.archive.org/web/20210516213116/https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=77877 | url-status=live }}</ref>

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

| legal_DE_comment =

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

| legal_NZ_comment =

| legal_UK = POM

| legal_UK_comment = <ref>{{cite web | title=Noxafil 100 mg Gastro-resistant Tablets - Summary of Product Characteristics (SmPC) | website=(emc) | date=10 January 2022 | url=https://www.medicines.org.uk/emc/product/5388/smpc | access-date=3 July 2022 | archive-date=24 February 2022 | archive-url=https://web.archive.org/web/20220224234448/https://www.medicines.org.uk/emc/product/5388/smpc | url-status=live }}</ref>

| legal_US_comment = <ref name="Noxafil FDA label" />

| legal_EU = Rx-only

| legal_EU_comment = <ref name="Noxafil EPAR">{{cite web | title=Noxafil EPAR | website=European Medicines Agency | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/noxafil | access-date=3 July 2022 | archive-date=19 October 2021 | archive-url=https://web.archive.org/web/20211019032440/https://www.ema.europa.eu/en/medicines/human/EPAR/noxafil | url-status=live }}</ref>

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

| legal_UN_comment =

| legal_status = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->

| bioavailability = Low (8 to 47% Oral)

| metabolism = [[Liver]] ([[glucuronidation]])

| excretion = Fecal (71–77%) and [[Kidney]] (13–14%)

| ChEBI_Ref = {{ebicite|changed|EBI}}

| ChEBI = 64355

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

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

| ChEMBL = 1397

| synonyms =

<!--Chemical data-->

| IUPAC_name = 4-[4-[4-[4-<nowiki/>{{Square bracket open|2}}(3''R'',5''R'')-5-(2,4-difluorophenyl)tetrahydro-5-(1''H''-1,2,4-triazol-1-ylmethyl)-3-furanyl]methoxy]phenyl]-1-piperazinyl{{Square bracket close}}phenyl{{Square bracket close}}-2-[(1''S'',2''S'')-1-ethyl-2- hydroxypropyl]-2,4-dihydro-3''H''-1,2,4-triazol-3-one

| C=37 | H=42 | F=2 | N=8 | O=4

| SMILES = O=C1N(/N=C\N1c2ccc(cc2)N7CCN(c6ccc(OCC3C[C@@](OC3)(c4ccc(F)cc4F)Cn5ncnc5)cc6)CC7)[C@@H](CC)[C@@H](O)C

'''Posaconazole''', sold under the brand name '''Noxafil''' among others, is a [[triazole]] [[antifungal medication]].<ref name="pmid18035188">{{cite journal | vauthors = Schiller DS, Fung HB | title = Posaconazole: an extended-spectrum triazole antifungal agent | journal = Clinical Therapeutics | volume = 29 | issue = 9 | pages = 1862–86 | date = September 2007 | pmid = 18035188 | doi = 10.1016/j.clinthera.2007.09.015 }}</ref><ref name="pmid18713852">{{cite journal | vauthors = Rachwalski EJ, Wieczorkiewicz JT, Scheetz MH | title = Posaconazole: an oral triazole with an extended spectrum of activity | journal = The Annals of Pharmacotherapy | volume = 42 | issue = 10 | pages = 1429–38 | date = October 2008 | pmid = 18713852 | doi = 10.1345/aph.1L005 | url = http://www.theannals.com/cgi/pmidlookup?view=long&pmid=18713852 | access-date = 11 December 2008 | s2cid = 21777822 }}{{dead link|date=August 2020|bot=medic}}{{cbignore|bot=medic}}</ref>

It was approved for medical use in the United States in September 2006,<ref name="Noxafil FDA label" /><ref>{{cite web | title=Drug Approval Package: Noxafil (Posaconazole) NDA #022003 | website=U.S. [[Food and Drug Administration]] (FDA) | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/022003s000_NoxafilTOC.cfm | date=9 November 2006 | access-date=15 August 2020 | archive-date=3 April 2021 | archive-url=https://web.archive.org/web/20210403042324/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/022003s000_NoxafilTOC.cfm | url-status=live }}</ref> and is available as a [[generic medication]].<ref>{{cite web | title=Posaconazole: 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=212411 | access-date=15 August 2020 | archive-date=20 October 2020 | archive-url=https://web.archive.org/web/20201020140140/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=212411 | url-status=live }}</ref><ref>{{cite web | title=First Generic Drug Approvals | website=U.S. Food and Drug Administration | date=17 October 2022 | url=https://www.fda.gov/drugs/drug-and-biologic-approval-and-ind-activity-reports/first-generic-drug-approvals | access-date=28 November 2022 | archive-date=26 January 2021 | archive-url=https://web.archive.org/web/20210126083800/http://www.fda.gov/drugs/drug-and-biologic-approval-and-ind-activity-reports/first-generic-drug-approvals | url-status=live }}</ref>

==Medical uses==

Posaconazole is used to treat invasive ''[[Aspergillus]]'' and ''[[Candida (fungus)|Candida]]'' infections.<ref name="Noxafil FDA label" /> It is also used for the treatment of [[Oral candidiasis|oropharyngeal candidiasis]] (OPC), including OPC refractory to [[itraconazole]] and/or [[fluconazole]] therapy.<ref name="Noxafil FDA label">{{cite web | title=Noxafil- posaconazole suspension Noxafil- posaconazole tablet, coated Noxafil- posaconazole solution | website=DailyMed | date=20 March 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b073b082-7b57-4423-8c06-4fd4263d6f84 | access-date=15 August 2020 | archive-date=26 February 2021 | archive-url=https://web.archive.org/web/20210226164143/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b073b082-7b57-4423-8c06-4fd4263d6f84 | url-status=live }}</ref>

It is also used to treat invasive infections by ''Candida'', ''[[Mucor]]'', and ''Aspergillus'' species in severely immunocompromised patients.<ref name="pmid14657086">{{cite journal | vauthors = Li X, Brown N, Chau AS, López-Ribot JL, Ruesga MT, Quindos G, Mendrick CA, Hare RS, Loebenberg D, DiDomenico B, McNicholas PM | display-authors = 6 | title = Changes in susceptibility to posaconazole in clinical isolates of Candida albicans | journal = The Journal of Antimicrobial Chemotherapy | volume = 53 | issue = 1 | pages = 74–80 | date = January 2004 | pmid = 14657086 | doi = 10.1093/jac/dkh027 | doi-access = free }}</ref><ref name="pmid17143808">{{cite journal | vauthors = Walsh TJ, Raad I, Patterson TF, Chandrasekar P, Donowitz GR, Graybill R, Greene RE, Hachem R, Hadley S, Herbrecht R, Langston A, Louie A, Ribaud P, Segal BH, Stevens DA, van Burik JA, White CS, Corcoran G, Gogate J, Krishna G, Pedicone L, Hardalo C, Perfect JR | display-authors = 6 | title = Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: an externally controlled trial | journal = Clinical Infectious Diseases | volume = 44 | issue = 1 | pages = 2–12 | date = January 2007 | pmid = 17143808 | doi = 10.1086/508774 | doi-access = free | jstor = 4485188 }} {{Subscription required|via=[[JSTOR]]}}</ref>

Clinical evidence for its utility in treatment of invasive disease caused by ''[[Fusarium]]'' species ([[fusariosis]]) is limited.<ref>{{cite journal | vauthors = Raad II, Hachem RY, Herbrecht R, Graybill JR, Hare R, Corcoran G, Kontoyiannis DP | title = Posaconazole as salvage treatment for invasive fusariosis in patients with underlying hematologic malignancy and other conditions | journal = Clinical Infectious Diseases | volume = 42 | issue = 10 | pages = 1398–403 | date = May 2006 | pmid = 16619151 | doi = 10.1086/503425 | doi-access = free }}</ref>

It appears to be helpful in a [[mouse model]] of [[naegleriasis]].<ref name="ColonRice2019">{{cite journal | vauthors = Colon BL, Rice CA, Guy RK, Kyle DE | title = Phenotypic Screens Reveal Posaconazole as a Rapidly Acting Amebicidal Combination Partner for Treatment of Primary Amoebic Meningoencephalitis | journal = The Journal of Infectious Diseases | volume = 219 | issue = 7 | pages = 1095–1103 | date = March 2019 | pmid = 30358879 | pmc = 6420171 | doi = 10.1093/infdis/jiy622 }}</ref>

==Pharmacology ==

===Pharmacodynamics===

Posaconazole works by disrupting the close packing of acyl chains of [[phospholipids]], impairing the functions of certain membrane-bound enzyme systems such as ATPase and enzymes of the electron transport system, thus inhibiting growth of the fungi. It does this by blocking the synthesis of [[ergosterol]] by inhibiting of the enzyme [[Lanosterol 14 alpha-demethylase|lanosterol 14α-demethylase]] and accumulation of methylated sterol precursors. Posaconazole is significantly more potent at inhibiting 14-alpha demethylase than [[itraconazole]].<ref name="Noxafil FDA label" /><ref name="Goodman & Gilman">Brunton L, Lazo J, Parker K. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th ed. San Francisco: McGraw-Hill; 2006. {{ISBN|978-0-07-142280-2}}</ref><ref name="ClinicalPharm">{{cite web |title = Clinical Pharmacology Posaconazole |url = http://www.clinicalpharmacology-ip.com/Forms/Monograph/monograph.aspx?cpnum=2811&sec=monmech |access-date = 18 February 2010 |archive-date = 30 August 2021 |archive-url = https://web.archive.org/web/20210830002750/https://dpm.demdex.net/id?d_visid_ver=5.2.0&d_fieldgroup=MC&d_rtbd=json&d_ver=2&d_verify=1&d_orgid=4D6368F454EC41940A4C98A6%40AdobeOrg&d_nsid=0&ts=1630283270255 |url-status = live }}</ref>

====Microbiology====

Posaconazole is active against the following microorganisms:<ref name="Goodman & Gilman" /><ref name="Ashley_2017">{{cite book | vauthors = Ashley ED, Perfect JR | chapter = Pharmacology of azoles | title = UpToDate | veditors = Kauffman CA | publisher = UpToDate | location = Waltham, MA | date = October 2017 | url=http://www.utdol.com/online/content/topic.do?topicKey=antibiot/9969&selectedTitle=4%7E38&source=_result#H9|url-status=dead|archive-url=https://archive.today/20130209004024/http://www.utdol.com/online/content/topic.do?topicKey=antibiot/9969&selectedTitle=4~38&source=_result%23H9|archive-date=9 February 2013|access-date=18 February 2010 }}</ref>

* ''[[Candida (genus)|Candida]]'' spp.

* ''[[Aspergillus]] '' spp.

* ''[[Zygomycetes]]'' spp.

===Pharmacokinetics===

Posaconazole is absorbed within three to five hours. It is predominantly eliminated through the liver, and has a [[Biological half-life|half-life]] of about 35 hours. Oral administration of posaconazole taken with a high-fat meal exceeds 90% [[bioavailability]] and increases the concentration by four times compared to fasting state.<ref name="Noxafil FDA label" /><ref name="Ashley_2017" />

== References ==

{{Reflist}}

==External links==

* {{Commonscatinline}}

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