Posaconazole

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Posaconazole
Posaconazole.svg
Posaconazole3d.png
Clinical data
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
Legal status
Pharmacokinetic data
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%)
Identifiers
  • 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 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C37H42F2N8O4
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 Yes check.svgY
  • Key:RAGOYPUPXAKGKH-AGDNISCASA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Posaconazole, sold under the brand name Noxafil among others, is a triazole antifungal medication. [7] [8]

Contents

It was approved for medical use in the European Union in October 2005, [6] and in the United States in September 2006. [5] [9] It 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]

Related Research Articles

<span class="mw-page-title-main">Antifungal</span> Pharmaceutical fungicide or fungistatic used to treat and prevent mycosis

An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as cryptococcal meningitis, and others. Such drugs are usually obtained by a doctor's prescription, but a few are available over the counter (OTC). The evolution of antifungal resistance is a growing threat to health globally.

<span class="mw-page-title-main">Itraconazole</span> Medication used to treat fungal infections

Itraconazole, sometimes abbreviated ITZ, is an antifungal medication used to treat a number of fungal infections. This includes aspergillosis, blastomycosis, coccidioidomycosis, histoplasmosis, and paracoccidioidomycosis. It may be given by mouth or intravenously.

<span class="mw-page-title-main">Simvastatin</span> Lipid-lowering medication

Simvastatin, sold under the brand name Zocor among others, is a statin, a type of lipid-lowering medication. It is used along with exercise, diet, and weight loss to decrease elevated lipid levels. It is also used to decrease the risk of heart problems in those at high risk. It is taken by mouth.

<span class="mw-page-title-main">Ketoconazole</span> Antifungal chemical compound

Ketoconazole, sold under the brand name Nizoral among others, is an antiandrogen, antifungal, and antiglucocorticoid medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous candidiasis, pityriasis versicolor, dandruff, and seborrheic dermatitis. Taken by mouth it is a less preferred option and only recommended for severe infections when other agents cannot be used. Other uses include treatment of excessive male-patterned hair growth in women and Cushing's syndrome.

<span class="mw-page-title-main">Fluconazole</span> Antifungal medication

Fluconazole is an antifungal medication used for a number of fungal infections. This includes candidiasis, blastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and tinea versicolor. It is also used to prevent candidiasis in those who are at high risk such as following organ transplantation, low birth weight babies, and those with low blood neutrophil counts. It is given either by mouth or by injection into a vein.

<i>Coccidioides immitis</i> Species of fungus

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<span class="mw-page-title-main">Caspofungin</span> Antifungal medication

Caspofungin is a lipopeptide antifungal drug from Merck & Co., Inc.. It is a member of a class of antifungals termed the echinocandins. It works by inhibiting the enzyme (1→3)-β-D-glucan synthase and thereby disturbing the integrity of the fungal cell wall.

<span class="mw-page-title-main">Terconazole</span> Chemical compound

Terconazole is an antifungal drug used to treat vaginal yeast infection. It comes as a lotion or a suppository and disrupts the biosynthesis of fats in a yeast cell. It has a relatively broad spectrum compared to azole compounds but not triazole compounds. Testing shows that it is a suitable compound for prophylaxis for those that suffer from chronic vulvovaginal candidiasis.

<span class="mw-page-title-main">Anidulafungin</span> Antifungal medication

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<span class="mw-page-title-main">Aspergillosis</span> Medical condition

Aspergillosis is a fungal infection of usually the lungs, caused by the genus Aspergillus, a common mould that is breathed in frequently from the air, but does not usually affect most people. It generally occurs in people with lung diseases such as asthma, cystic fibrosis or tuberculosis, or those who are immunocompromised such as those who have had a stem cell or organ transplant or those who take medications such as steroids and some cancer treatments which suppress the immune system. Rarely, it can affect skin.

<span class="mw-page-title-main">Echinocandin</span> Group of chemical compounds

Echinocandins are a class of antifungal drugs that inhibit the synthesis of β-glucan in the fungal cell wall via noncompetitive inhibition of the enzyme 1,3-β glucan synthase. The class has been dubbed the "penicillin of antifungals," along with the related papulacandins, as their mechanism of action resembles that of penicillin in bacteria. β-glucans are carbohydrate polymers that are cross-linked with other fungal cell wall components, the fungal equivalent to bacterial peptidoglycan. Caspofungin, micafungin, and anidulafungin are semisynthetic echinocandin derivatives with limited clinical use due to their solubility, antifungal spectrum, and pharmacokinetic properties.

<span class="mw-page-title-main">Micafungin</span> Chemical compound

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<span class="mw-page-title-main">Sterol 14-demethylase</span> Class of enzymes

In enzymology, a sterol 14-demethylase (EC 1.14.13.70) is an enzyme of the cytochrome P450 (CYP) superfamily. It is any member of the CYP51 family. It catalyzes a chemical reaction such as:

<span class="mw-page-title-main">Isavuconazonium</span> Chemical compound

Isavuconazonium, sold under the brand name Cresemba, is a systemic antifungal medication of the triazole class which is used to treat invasive aspergillosis and mucormycosis. It is used as the sulfate. It is taken by mouth or given via injection into a vein.

<span class="mw-page-title-main">Ravuconazole</span> Chemical compound

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<span class="mw-page-title-main">Efinaconazole</span> Chemical compound

Efinaconazole, sold under the brand name Jublia among others, is a triazole antifungal medication. It is approved for use in the United States, Canada, and Japan as a 10% topical solution for the treatment of onychomycosis. Efinaconazole acts as a 14α-demethylase inhibitor.

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References

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  2. "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.
  3. "Posanol Product information". Health Canada. 25 April 2012. Archived from the original on 16 May 2021. Retrieved 3 July 2022.
  4. "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.
  5. 1 2 3 4 5 6 "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.
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  8. 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 ]
  9. "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.
  10. "Posaconazole: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Archived from the original on 20 October 2020. Retrieved 15 August 2020.
  11. "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.
  12. 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.{{cite journal}}: CS1 maint: overridden setting (link)
  13. 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.{{cite journal}}: CS1 maint: overridden setting (link)(registration required)
  14. Raad II, Hachem RY, Herbrecht R, Graybill JR, Hare R, Corcoran G, et al. (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.
  15. 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.
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