Posaconazole
{{Short description|Pharmaceutical drug}}
{{Use dmy dates|date=November 2022}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 464210822
| image = Posaconazole.svg
| width = 200
| image2 = Posaconazole3d.png
| width2 = 200
| tradename = Noxafil, Posanol, others
| Drugs.com = {{drugs.com|monograph|posaconazole}}
| MedlinePlus = a607036
| DailyMedID = Posaconazole
| licence_EU = yes
| licence_US = Posaconazole
| pregnancy_AU = B3
| pregnancy_category=
| routes_of_administration = By mouth, intravenous
| ATC_prefix = J02
| ATC_suffix = AC04
| legal_AU = S4
| legal_BR =
| legal_BR_comment =
| legal_CA = Rx-only
| legal_DE =
| legal_DE_comment =
| legal_NZ =
| legal_NZ_comment =
| legal_UK = POM
| legal_US = Rx-only
| legal_EU = Rx-only
| legal_UN =
| legal_UN_comment =
| legal_status =
| bioavailability = Low (8 to 47% Oral)
| protein_bound = 98 to 99%
| metabolism = Liver (glucuronidation)
| elimination_half-life = 16 to 31 hours
| excretion = Fecal (71–77%) and Kidney (13–14%)
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 171228-49-2
| PubChem = 147912
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 64355
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01263
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 130409
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 6TK1G07BHZ
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D02555
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 1397
| synonyms =
| IUPAC_name = 4-[4-[4-[4-
| 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
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C37H42F2N8O4/c1-3-35(26(2)48)47-36(49)46(25-42-47)31-7-5-29(6-8-31)43-14-16-44(17-15-43)30-9-11-32(12-10-30)50-20-27-19-37(51-21-27,22-45-24-40-23-41-45)33-13-4-28(38)18-34(33)39/h4-13,18,23-27,35,48H,3,14-17,19-22H2,1-2H3/t26-,27?,35-,37-/m0/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = RAGOYPUPXAKGKH-AGDNISCASA-N
}}
Posaconazole, sold under the brand name Noxafil among others, is a triazole antifungal medication.{{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 }}{{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}}
It was approved for medical use in the European Union in October 2005, and in the United States in September 2006.{{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 }} It is available as a generic medication.{{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 }}{{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 }}
Medical uses
Posaconazole is used to treat invasive Aspergillus and Candida infections. It is also used for the treatment of oropharyngeal candidiasis (OPC), including OPC refractory to other drugs such as itraconazole and fluconazole.{{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 }}
Clinical evidence of efficacy in treatment of invasive disease caused by Fusarium species (fusariosis) is limited.{{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 }}
It appears to be helpful in a mouse model of naegleriasis{{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 }} and kills Acanthamoeba castellanii cysts in vitro.{{cite journal |vauthors=Iovieno A, Miller D, Ledee DR, Alfonso EC |title=Cysticidal activity of antifungals against different genotypes of Acanthamoeba |journal=Antimicrob Agents Chemother |volume=58 |issue=9 |pages=5626–8 |date=September 2014 |pmid=25001304 |pmc=4135811 |doi=10.1128/AAC.02635-14}}
It has been used to treat mucormycosis (black fungus disease) caused by Rhizopus mold. {{cite journal |vauthors=Fatemizadeh R, Rodman E, Demmler-Harrison GJ, Dinu D |title=Rhizopus Infection in a Preterm Infant: A Novel Use of Posaconazole |journal=Pediatr Infect Dis J |volume=39 |issue=4 |pages=310–312 |date=April 2020 |pmid=32084112 |doi=10.1097/INF.0000000000002554 |url=}}
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 14α-demethylase and accumulation of methylated sterol precursors. Posaconazole is significantly more potent at inhibiting 14-alpha demethylase than itraconazole.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}}{{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 }}
==Microbiology==
Posaconazole is active against the following microorganisms:{{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 }}
- Candida spp.
- Aspergillus spp.
- Zygomycetes spp. {{Clarify|date=April 2025}}
=Pharmacokinetics=
Posaconazole is absorbed within three to five hours. It is predominantly eliminated through the liver, and has a 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.
References
{{Reflist}}
External links
- {{Commonscatinline}}
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Category:27-Hydroxylase inhibitors
Category:Lanosterol 14α-demethylase inhibitors
Category:Drugs developed by Merck & Co.
Category:Phenylethanolamine ethers