From Wikipedia, the free encyclopedia
Pharmaceutical drug
Posaconazole
Trade names Noxafil, Posanol, others
AHFS /
Drugs.com
Monograph
MedlinePlus
a607036
License data
Pregnancy category
Routes of administration
By mouth ,
intravenous
ATC code
Legal status
Bioavailability Low (8 to 47% Oral)
Protein binding 98 to 99%
Metabolism
Liver (
glucuronidation )
Elimination half-life 16 to 31 hours
Excretion Fecal (71–77%) and
Kidney (13–14%)
4-[4-[4-[4-[[(3R ,5R )-5-(2,4-difluorophenyl)tetrahydro-5-(1H -1,2,4-triazol-1-ylmethyl)-3-furanyl]methoxy]phenyl]-1-piperazinyl]phenyl]-2-[(1S ,2S )-1-ethyl-2- hydroxypropyl]-2,4-dihydro-3H -1,2,4-triazol-3-one
CAS Number
PubChem
CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (
EPA )
ECHA InfoCard
100.208.201
Formula C 37 H 42 F 2 N 8 O 4
Molar mass 700.792 g·mol−1 3D model (
JSmol )
O=C1N(/N=C\N1c2ccc(cc2)N7CCN(c6ccc(OCC3C[C@@](OC3)(c4ccc(F)cc4F)Cn5ncnc5)cc6)CC7)[C@@H](CC)[C@@H](O)C
InChI=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
Y Key:RAGOYPUPXAKGKH-AGDNISCASA-N
Y
N Y
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(verify)
Posaconazole , sold under the brand name Noxafil among others, is a
triazole
antifungal medication .
[7]
[8]
It was approved for medical use in the United States in September 2006,
[5]
[9] and is available as a
generic medication .
[10]
[11]
Medical uses
Posaconazole is used to treat invasive
Aspergillus and
Candida infections.
[5] It is also used for the treatment of
oropharyngeal candidiasis (OPC), including OPC refractory to
itraconazole and/or
fluconazole therapy.
[5]
It is also used to treat invasive infections by Candida ,
Mucor , and Aspergillus species in severely immunocompromised patients.
[12]
[13]
Clinical evidence for its utility in treatment of invasive disease caused by
Fusarium species (
fusariosis ) is limited.
[14]
It appears to be helpful in a
mouse model of
naegleriasis .
[15]
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 .
[5]
[16]
[17]
Microbiology
Posaconazole is active against the following microorganisms:
[16]
[18]
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.
[5]
[18]
References
^
"Posaconazole (Noxafil) Use During Pregnancy" . Drugs.com . 23 April 2019.
Archived from the original on 30 January 2020. Retrieved 30 January 2020 .
^
"Posaconazole suspension ARX/Posaconazole TIH/APX-Posaconazole (Arrow Pharma Pty Ltd)" . Therapeutic Goods Administration (TGA) . 16 February 2023.
Archived from the original on 18 March 2023. Retrieved 29 April 2023 .
^
"Posanol Product information" . Health Canada . 25 April 2012.
Archived from the original on 16 May 2021. Retrieved 3 July 2022 .
^
"Noxafil 100 mg Gastro-resistant Tablets - Summary of Product Characteristics (SmPC)" . (emc) . 10 January 2022.
Archived from the original on 24 February 2022. Retrieved 3 July 2022 .
^
a
b
c
d
e
f
"Noxafil- posaconazole suspension Noxafil- posaconazole tablet, coated Noxafil- posaconazole solution" . DailyMed . 20 March 2020.
Archived from the original on 26 February 2021. Retrieved 15 August 2020 .
^
"Noxafil EPAR" . European Medicines Agency . 17 September 2018.
Archived from the original on 19 October 2021. Retrieved 3 July 2022 .
^ Schiller DS, Fung HB (September 2007). "Posaconazole: an extended-spectrum triazole antifungal agent". Clinical Therapeutics . 29 (9): 1862–86.
doi :
10.1016/j.clinthera.2007.09.015 .
PMID
18035188 .
^ Rachwalski EJ, Wieczorkiewicz JT, Scheetz MH (October 2008).
"Posaconazole: an oral triazole with an extended spectrum of activity" . The Annals of Pharmacotherapy . 42 (10): 1429–38.
doi :
10.1345/aph.1L005 .
PMID
18713852 .
S2CID
21777822 . Retrieved 11 December 2008 . [
dead link ]
^
"Drug Approval Package: Noxafil (Posaconazole) NDA #022003" . U.S.
Food and Drug Administration (FDA) . 9 November 2006.
Archived from the original on 3 April 2021. Retrieved 15 August 2020 .
^
"Posaconazole: FDA-Approved Drugs" . U.S.
Food and Drug Administration (FDA) .
Archived from the original on 20 October 2020. Retrieved 15 August 2020 .
^
"First Generic Drug Approvals" . U.S. Food and Drug Administration . 17 October 2022.
Archived from the original on 26 January 2021. Retrieved 28 November 2022 .
^ Li X, Brown N, Chau AS, López-Ribot JL, Ruesga MT, Quindos G, et al. (January 2004).
"Changes in susceptibility to posaconazole in clinical isolates of Candida albicans" . The Journal of Antimicrobial Chemotherapy . 53 (1): 74–80.
doi :
10.1093/jac/dkh027 .
PMID
14657086 .
^ Walsh TJ, Raad I, Patterson TF, Chandrasekar P, Donowitz GR, Graybill R, et al. (January 2007).
"Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: an externally controlled trial" . Clinical Infectious Diseases . 44 (1): 2–12.
doi :
10.1086/508774 .
JSTOR
4485188 .
PMID
17143808 . – via
JSTOR (subscription required)
^ Raad II, Hachem RY, Herbrecht R, Graybill JR, Hare R, Corcoran G, Kontoyiannis DP (May 2006).
"Posaconazole as salvage treatment for invasive fusariosis in patients with underlying hematologic malignancy and other conditions" . Clinical Infectious Diseases . 42 (10): 1398–403.
doi :
10.1086/503425 .
PMID
16619151 .
^ Colon BL, Rice CA, Guy RK, Kyle DE (March 2019).
"Phenotypic Screens Reveal Posaconazole as a Rapidly Acting Amebicidal Combination Partner for Treatment of Primary Amoebic Meningoencephalitis" . The Journal of Infectious Diseases . 219 (7): 1095–1103.
doi :
10.1093/infdis/jiy622 .
PMC
6420171 .
PMID
30358879 .
^
a
b 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
^
"Clinical Pharmacology Posaconazole" .
Archived from the original on 30 August 2021. Retrieved 18 February 2010 .
^
a
b Ashley ED, Perfect JR (October 2017). "Pharmacology of azoles". In Kauffman CA (ed.).
UpToDate . Waltham, MA: UpToDate. Archived from
the original on 9 February 2013. Retrieved 18 February 2010 .
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