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{{Short description|Chemical compound}}
{{Short description|Chemical compound}}
{{Use dmy dates|date=September 2024}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Drugbox
{{Drugbox
| Watchedfields = changed
| Watchedfields = changed
| verifiedrevid = 461740624
| verifiedrevid = 461740624
⚫
| IUPAC_name = (''RS'')-1-(2-(2,4-Dichlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl)-1''H''-imidazole
| image = Miconazole.svg
| image = Miconazole.svg
| width = 200px
| width = 200
| alt =
| image2 = Miconazole ball-and-stick.png
| image2 = Miconazole ball-and-stick.png
| width2 = 200px
| width2 = 200
| alt2 =
| chirality = [[Racemic mixture]]
| chirality = [[Racemic mixture]]


<!--Clinical data-->
<!--Clinical data-->
| tradename = Desenex, Monistat, others
| tradename = Monistat, others
| Drugs.com = {{drugs.com|monograph|miconazole-nitrate}}
| Drugs.com = {{drugs.com|monograph|miconazole}}
| MedlinePlus = a601203
| MedlinePlus = a601203
| DailyMedID = Miconazole
| pregnancy_AU =
| pregnancy_AU =
| pregnancy_AU_comment =
| pregnancy_AU_comment =
| pregnancy_US = N
⚫
| pregnancy_category =
| pregnancy_US_comment= <ref name="Drugs.com pregnancy">{{cite web | title=Miconazole topical Use During Pregnancy | website=Drugs.com | date=3 September 2019 | url=https://www.drugs.com/pregnancy/miconazole-topical.html | access-date=20 August 2020}}</ref>
⚫
| routes_of_administration = [[Topical administration|Topical]], [[Vaginal administration|vaginal]], [[sublabial administration|sublabial]]
⚫
| pregnancy_category =
⚫
| ATC_prefix = A01
⚫
| ATC_suffix = AB09
⚫
| ATC_supplemental = {{ATC|A07|AC01}} {{ATC|D01|AC02}} {{ATC|G01|AF04}} {{ATC|J02|AB01}} {{ATC|S02|AA13}}

| legal_AU = S2
| legal_AU = S2
⚫
| legal_AU_comment = Schedule 2 for topical formulations, schedule 3 for vaginal use and for oral [[candidiasis]], otherwise schedule 4{{cn|date=June 2023}}
| legal_CA =
| legal_CA =
| legal_UK = POM
| legal_UK = POM
| legal_US = OTC
| legal_US = OTC
| legal_US_comment = /&nbsp;Rx-only<ref name="Oravig FDA label">{{cite web | title=Oravig- miconazole tablet | website=DailyMed | date=1 January 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=dc2427ff-e566-4b48-b289-9e51c011250a | access-date=20 June 2023 | archive-date=14 August 2022 | archive-url=https://web.archive.org/web/20220814225102/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=dc2427ff-e566-4b48-b289-9e51c011250a | url-status=live }}</ref>
| legal_US_comment = /&nbsp;Rx-only
⚫
| legal_AU_comment = Schedule 2 for topical formulations, schedule 3 for vaginal use and for oral [[candidiasis]], otherwise schedule 4
⚫
| routes_of_administration = [[Topical]], [[vaginal]], [[sublabial administration|sublabial]]


<!--Pharmacokinetic data-->
<!--Pharmacokinetic data-->
Line 32: Line 38:
| metabolism = [[CYP3A4]]
| metabolism = [[CYP3A4]]
| elimination_half-life = 20–25 hrs
| elimination_half-life = 20–25 hrs
| excretion = Mainly faeces
| excretion = Mainly feces


<!--Identifiers-->
<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 22916-47-8
| CAS_number = 22916-47-8
⚫
| ATC_prefix = A01
⚫
| ATC_suffix = AB09
⚫
| ATC_supplemental = {{ATC|A07|AC01}} {{ATC|D01|AC02}} {{ATC|G01|AF04}} {{ATC|J02|AB01}} {{ATC|S02|AA13}}
| PubChem = 4189
| PubChem = 4189
| IUPHAR_ligand = 2449
| IUPHAR_ligand = 2449
Line 57: Line 60:


<!--Chemical data-->
<!--Chemical data-->
⚫
| IUPAC_name = (''RS'')-1-(2-(2,4-Dichlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl)-1''H''-imidazole
| C=18 | H=14 | Cl=4 | N=2 | O=1
| C=18 | H=14 | Cl=4 | N=2 | O=1
| SMILES = Clc1cc(Cl)ccc1C(Cn2ccnc2)OCc3ccc(Cl)cc3Cl
| SMILES = Clc1cc(Cl)ccc1C(Cn2ccnc2)OCc3ccc(Cl)cc3Cl
Line 64: Line 68:
| StdInChIKey = BYBLEWFAAKGYCD-UHFFFAOYSA-N
| StdInChIKey = BYBLEWFAAKGYCD-UHFFFAOYSA-N
}}
}}

<!-- Definition and medical uses -->
<!-- Definition and medical uses -->
'''Miconazole''', sold under the brand name '''Monistat''' among others, is an [[antifungal medication]] used to treat [[ring worm]], [[pityriasis versicolor]], and [[candidiasis|yeast infections]] of the skin or vagina.<ref name=AHFS2016/> It is used for ring worm of the [[tinea corporis|body]], [[jock itch|groin]] (jock itch), and [[athlete's foot|feet]] (athlete's foot).<ref name=AHFS2016/> It is applied to the skin or vagina as a cream or ointment.<ref name=AHFS2016>{{cite web|title=Miconazole Nitrate|url=https://www.drugs.com/monograph/miconazole-nitrate.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161221013013/https://www.drugs.com/monograph/miconazole-nitrate.html|archive-date=21 December 2016}}</ref>
'''Miconazole''', sold under the brand name '''Monistat''' among others, is an [[antifungal medication]] used to treat [[ring worm]], [[pityriasis versicolor]], and [[candidiasis|yeast infections]] of the skin or vagina.<ref name=AHFS2016/> It is used for ring worm of the [[tinea corporis|body]], [[jock itch|groin]] (jock itch), and [[athlete's foot|feet]] (athlete's foot).<ref name=AHFS2016/> It is applied to the skin or vagina as a cream or ointment.<ref name=AHFS2016>{{cite web|title=Miconazole Nitrate|url=https://www.drugs.com/monograph/miconazole-nitrate.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161221013013/https://www.drugs.com/monograph/miconazole-nitrate.html|archive-date=21 December 2016}}</ref><ref>{{cite web | title=Miconazole Monograph for Professionals | website=Drugs.com | date=22 July 2022 | url=https://www.drugs.com/monograph/miconazole.html | access-date=20 June 2023 | archive-date=21 September 2022 | archive-url=https://web.archive.org/web/20220921191831/https://www.drugs.com/monograph/miconazole.html | url-status=live }}</ref>


<!-- Side effects and mechanism -->
<!-- Side effects and mechanism -->
Line 71: Line 76:


<!-- History and culture -->
<!-- History and culture -->
Miconazole was patented in 1968 and approved for medical use in 1971.<ref name=Fis2006>{{cite book| vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery|date=2006|publisher=John Wiley & Sons|isbn=9783527607495|page=502|url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA502|language=en|url-status=live|archive-url=https://web.archive.org/web/20161220144314/https://books.google.ca/books?id=FjKfqkaKkAAC&pg=PA502|archive-date=2016-12-20}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref>
Miconazole was patented in 1968 and approved for medical use in 1971.<ref name=Fis2006>{{cite book| vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery|date=2006|publisher=John Wiley & Sons|isbn=9783527607495|page=502|url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA502|url-status=live|archive-url=https://web.archive.org/web/20161220144314/https://books.google.ca/books?id=FjKfqkaKkAAC&pg=PA502|archive-date=2016-12-20}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO23rd">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}</ref> It is available as a [[generic medication]].<ref name=AHFS2016/>


==Medical uses==
==Medical uses==
Miconazole is mainly used externally for the treatment of [[ringworm]] including [[jock itch]] and [[athlete's foot]]. Internal application is used for [[Oral candidiasis|oral]] or [[Candidiasis|vaginal thrush]] ([[yeast infection]]). This oral gel may also be used for the lip disorder [[angular cheilitis]] and other associated systems.
Miconazole is used externally for the treatment of [[ringworm]], [[jock itch]], and [[athlete's foot]].<ref name=AHFS2016/> Internal application is used for [[oral candidiasis]] or [[Candidiasis|vaginal thrush]] ([[yeast infection]]).<ref name=AHFS2016/>
In the UK, miconazole may be used to treat [[neonatal]] oral thrush, while the alternative [[nystatin]] is only licensed for patients over the age of one month, but drug interactions are possible.


==Side effects==
==Side effects==
Miconazole is generally well tolerated. The oral gel can cause dry mouth, [[nausea]] and an unpleasant taste in about 1–10% of people. [[Anaphylactic reaction]]s are rare. The drug prolongs the [[QT interval]].<ref name="AC" /><ref name="AC-gel" />
Miconazole is generally well tolerated. The oral gel can cause dry mouth, [[nausea]] and an unpleasant taste in about 1–10% of people. [[Anaphylactic reaction]]s are rare. The drug prolongs the [[QT interval]].<ref name="AC" /><ref name="AC-gel" />


==Interactions==
== Interactions ==
The substance is partly absorbed in the intestinal tract when used orally, as with the oral gel, and possibly when used vaginally.<ref name="BNF">[[British National Formulary]] '45' March 2003</ref> This can lead to increased concentrations of drugs that are metabolized by the liver enzymes [[CYP3A4]] and [[CYP2C9]], because miconazole inhibits these enzymes. Such interactions occur for example with [[anticoagulant]]s of the [[warfarin]] type, [[phenytoin]], some newer [[atypical antipsychotic]]s, [[ciclosporin]], and most [[statin]]s used to treat [[hypercholesterolemia]].<ref name="AC-gel" />
Miconazole is partly absorbed in the intestinal tract when used orally, as with the oral gel, and possibly when used vaginally.<ref name="BNF">[[British National Formulary]] '45' March 2003</ref> This can lead to increased concentrations of drugs that are metabolized by the liver enzymes [[CYP3A4]] and [[CYP2C9]], because miconazole inhibits these enzymes. Such interactions occur for example with [[anticoagulant]]s of the [[warfarin]] type, [[phenytoin]], some newer [[atypical antipsychotic]]s, [[ciclosporin]], and most [[statin]]s used to treat [[hypercholesterolemia]].<ref name="AC-gel" /> These interactions are not relevant for miconazole that is applied to the skin.<ref name="AC-gel" />

These interactions are not relevant for miconazole that is applied to the skin.<ref name="AC-gel" />


==Contraindications==
==Contraindications==
Line 96: Line 97:
==Pharmacology==
==Pharmacology==
===Mechanism of action===
===Mechanism of action===
Miconazole inhibits the fungal enzyme [[14α-sterol demethylase]], resulting in a reduced production of ergosterol.<ref>{{cite journal | vauthors = Becher R, Wirsel SG | title = Fungal cytochrome P450 sterol 14α-demethylase (CYP51) and azole resistance in plant and human pathogens | journal = Applied Microbiology and Biotechnology | volume = 95 | issue = 4 | pages = 825–40 | date = August 2012 | pmid = 22684327 | doi = 10.1007/s00253-012-4195-9 | s2cid = 17688962 }}</ref> In addition to its antifungal actions, miconazole, similarly to [[ketoconazole]], is known to act as an [[receptor antagonist|antagonist]] of the [[glucocorticoid receptor]].<ref name="pmid16608920">{{cite journal | vauthors = Duret C, Daujat-Chavanieu M, Pascussi JM, Pichard-Garcia L, Balaguer P, Fabre JM, Vilarem MJ, Maurel P, Gerbal-Chaloin S | display-authors = 6 | title = Ketoconazole and miconazole are antagonists of the human glucocorticoid receptor: consequences on the expression and function of the constitutive androstane receptor and the pregnane X receptor | journal = Molecular Pharmacology | volume = 70 | issue = 1 | pages = 329–39 | date = July 2006 | pmid = 16608920 | doi = 10.1124/mol.105.022046 | url = http://www.hal.inserm.fr/inserm-00086861 | s2cid = 21455699 }}</ref>
Miconazole inhibits the fungal enzyme [[14α-sterol demethylase]], resulting in a reduced production of ergosterol.<ref>{{cite journal | vauthors = Becher R, Wirsel SG | title = Fungal cytochrome P450 sterol 14α-demethylase (CYP51) and azole resistance in plant and human pathogens | journal = Applied Microbiology and Biotechnology | volume = 95 | issue = 4 | pages = 825–840 | date = August 2012 | pmid = 22684327 | doi = 10.1007/s00253-012-4195-9 | s2cid = 17688962 }}</ref> In addition to its antifungal actions, miconazole, similarly to [[ketoconazole]], is known to act as an [[receptor antagonist|antagonist]] of the [[glucocorticoid receptor]].<ref name="pmid16608920">{{cite journal | vauthors = Duret C, Daujat-Chavanieu M, Pascussi JM, Pichard-Garcia L, Balaguer P, Fabre JM, Vilarem MJ, Maurel P, Gerbal-Chaloin S | display-authors = 6 | title = Ketoconazole and miconazole are antagonists of the human glucocorticoid receptor: consequences on the expression and function of the constitutive androstane receptor and the pregnane X receptor | journal = Molecular Pharmacology | volume = 70 | issue = 1 | pages = 329–339 | date = July 2006 | pmid = 16608920 | doi = 10.1124/mol.105.022046 | s2cid = 21455699 }}</ref>


===Pharmacokinetics===
===Pharmacokinetics===
Line 102: Line 103:


==Chemistry==
==Chemistry==
The solubilities of miconazole nitrate powder are 0.03% in water, 0.76% in ethanol and up to 4% in acetic acid.<ref>[http://www.google.com/patents/US5461068 United States Patent 5461068] {{webarchive|url=https://web.archive.org/web/20140910102525/http://www.google.com/patents/US5461068 |date=2014-09-10 }}</ref> Miconazole crystallises as colourless prisms in the [[Monoclinic crystal system|monoclinic]] space group P2<sub>1</sub>/c.<ref>{{Cite journal |last1=Kaspiaruk |first1=H. |last2=Chęcińska |first2=L. |date=2022-06-01 |title=A comparison of three crystalline forms of miconazole: solvent-free, ethanol monosolvate and hemihydrate |url=https://journals.iucr.org/c/issues/2022/06/00/vp3025/ |journal=Acta Crystallographica Section C: Structural Chemistry |language=en |volume=78 |issue=6 |pages=343–350 |doi=10.1107/S2053229622004909 |pmid=35662134 |s2cid=248839249 |issn=2053-2296}}</ref>
The solubilities of miconazole nitrate powder are 0.03% in water, 0.76% in ethanol and up to 4% in acetic acid.<ref>{{cite patent | inventor = Thaler I, Strauss R | country = US | number = 5461068 | title = Imidazole derivative tincture and method of manufacture | assign1 = Current Assignee Corwood Laboratories Inc | assign2 = Bausch Health Companies Inc | gdate = 24 October 1995 | postscript = . }}</ref> Miconazole crystallises as colourless prisms in the [[Monoclinic crystal system|monoclinic]] space group P2<sub>1</sub>/c.<ref>{{cite journal | vauthors = Kaspiaruk H, Chęcińska L | title = A comparison of three crystalline forms of miconazole: solvent-free, ethanol monosolvate and hemihydrate | journal = Acta Crystallographica Section C | volume = 78 | issue = Pt 6 | pages = 343–350 | date = June 2022 | pmid = 35662134 | doi = 10.1107/S2053229622004909 | s2cid = 248839249 }}</ref>


==Other uses==
==Other uses==
Miconazole is also used in [[Ektachrome]] film developing in the final rinse of the [[Kodak]] [[E-6 process]] and similar Fuji CR-56 process, replacing [[formaldehyde]]. [[Fujifilm|Fuji Hunt]] also includes miconazole as a final rinse additive in their formulation of the C-41RA rapid access color negative developing process.
Miconazole is also used in [[Ektachrome]] film developing in the final rinse of the [[Kodak]] [[E-6 process]] and similar Fuji CR-56 process,{{cn|date=June 2023}} replacing [[formaldehyde]].<ref>{{cite web | title=Kodak Chemicals: Process E-6 Publication: Z-119 | website=Kodak | date=8 October 1999 | url=http://www.kodak.com/global/en/service/Zmanuals/z119.shtml | archive-url=https://web.archive.org/web/20070715005022/http://www.kodak.com/global/en/service/Zmanuals/z119.shtml | archive-date=15 July 2007 | url-status=dead | access-date=20 June 2023}}</ref><ref>{{cite web | title=Kodak Chemicals: Q-LAB Process Control Handbook: Publication Z-6 | website=Kodak | date=1 November 2004 | url=http://www.kodak.com/global/en/service/Zmanuals/z6.shtml | archive-url=https://web.archive.org/web/20070207080023/http://www.kodak.com/global/en/service/Zmanuals/z6.shtml | archive-date=7 February 2007 | url-status=dead | access-date=20 June 2023}}</ref> [[Fujifilm|Fuji Hunt]] also includes miconazole as a final rinse additive in their formulation of the C-41RA rapid access color negative developing process.{{cn|date=December 2022}}


==Brands and formulations==
==Brands and formulations==
[[File:Miconazol.jpg|thumb|160px|Vaginal miconazole 20 mg/g - Brazil]]
[[File:Miconazol.jpg|thumb|160px|Vaginal miconazole 20 mg/g - Brazil]]


Oral treatment: (brand names Daktarin in UK, Fungimin Oral Gel in Bangladesh):
Oral treatment: (brand names Daktarin in UK, Fungimin Oral Gel in Bangladesh):{{cn|date=December 2022}}


⚫
In 2010, the US Food and Drug Administration approved Oravig (miconazole) buccal tablets for the local treatment of oropharyngeal candidiasis, more commonly known as thrush, in adults and children age 16 and older.<ref name="Oravig FDA label" />
* Oral gel 24&nbsp;mg/ml (20&nbsp;mg/g)
* Oravig 50&nbsp;mg once daily [[buccal administration|buccal]] tablet:


External skin treatment (brand names Desenex and Zeasorb in US and Canada, Micatin, Monistat-Derm, Daktarin in India, UK, Australia, Belgium and the Philippines, Daktar in Norway, Fungidal in Bangladesh, Decocort in Malaysia){{cn|date=December 2022}} (Note that Desenex originally contained not miconazole, but rather the fungistatic agents, [[undecylenic acid]] and zinc undecylenate, which were in the foot powder developed by the US government for troops during WWII.<ref>{{Cite web |title=History |url=https://achh.army.mil/history/book-wwii-communicablediseasesv5-chapter7/ |access-date=2024-03-03 |website=achh.army.mil |language=en |archive-date=2024-03-03 |archive-url=https://web.archive.org/web/20240303214812/https://achh.army.mil/history/book-wwii-communicablediseasesv5-chapter7/ |url-status=live }}</ref>)
⚫
In 2010, the U.S. Food and Drug Administration approved Oravig (miconazole) buccal tablets once daily for the local treatment of oropharyngeal candidiasis, more commonly known as thrush, in adults and children age 16 and older. Oravig is the only local, oral prescription formulation of miconazole approved for this use in the U.S.{{Citation needed|date=May 2012}}


⚫
Vaginal treatment (brand names Miconazex, Monistat, Femizol or Gyno-Daktarin in UK):{{cn|date=December 2022}}
External skin treatment (brand names Desenex and Zeasorb in US and Canada, Micatin, Monistat-Derm, Daktarin in India, UK, Australia, Belgium and the Philippines, Daktar in Norway, Fungidal in Bangladesh, Decocort in Malaysia)
{{clear}}


In Japan, Mochida Healthcare, a subsidiary of [[Mochida Pharmaceutical]], produces a line of body soaps and shampoo under the brand name Collage (コラージュ) that contain miconazole nitrate as their main ingredient.<ref>{{Cite web|title=Mochida Pharmaceutical Co., list of product ingredients|url=https://hc.mochida.co.jp/products/ingredients/list.html|access-date=2024-08-21|website=hc.mochida.co.jp|language=jp}}</ref>
* Topical cream: 2-5%
* Combination: [[hydrocortisone/miconazole]] cream with 1% and 2%, respectively (Daktacort in UK, Daktodor in Greece)
* Dusting powder: 2% powder with chlorhexidine hydrochloride (mycoDust)


⚫
== References ==
⚫
Vaginal treatment (brand names Miconazex, Monistat, Femizol or Gyno-Daktarin in UK):

* Pessaries: 200 or 100&nbsp;mg
* Vaginal cream: 2% (7-day treatment), 4% (3-day treatment)
* Combination: 2% cream with either 100 or 200&nbsp;mg

⚫
==References==
{{reflist}}
{{reflist}}

==External links==
* [https://web.archive.org/web/20070715005022/http://www.kodak.com/global/en/service/Zmanuals/z119.shtml Kodak process E6] [[Ektachrome]] (color transparency) processing manual Z-119
* [https://web.archive.org/web/20070207080023/http://www.kodak.com/global/en/service/Zmanuals/z6.shtml Kodak process E6 Q-LAB] processing manual Z-6 (more details than processing manual Z119 above)
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/miconazole | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Miconazole }}


{{Stomatological preparations}}
{{Stomatological preparations}}
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{{Otologicals}}
{{Otologicals}}
{{Glucocorticoid receptor modulators}}
{{Glucocorticoid receptor modulators}}
{{Portal bar|Medicine}}
{{Portal bar | Medicine}}
{{Authority control}}


[[Category:21-Hydroxylase inhibitors]]
[[Category:21-Hydroxylase inhibitors]]

Revision as of 06:25, 24 September 2024

Miconazole
Clinical data
Trade namesMonistat, others
AHFS/Drugs.comMonograph
MedlinePlusa601203
License data
Routes of
administration		Topical, vaginal, sublabial
ATC code
Legal status
Legal status
  • AU: S2 (Pharmacy medicine) Schedule 2 for topical formulations, schedule 3 for vaginal use and for oral candidiasis, otherwise schedule 4[citation needed]
  • UK: POM (Prescription only)
  • US: OTC / Rx-only[1]
Pharmacokinetic data
Bioavailability<1% after application to the skin
Protein binding88.2%
MetabolismCYP3A4
Elimination half-life20–25 hrs
ExcretionMainly feces
Identifiers
  • (RS)-1-(2-(2,4-Dichlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl)-1H-imidazole
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.041.188 Edit this at Wikidata
Chemical and physical data
FormulaC18H14Cl4N2O
Molar mass416.12 g·mol−1
3D model (JSmol)
ChiralityRacemic mixture
  • Clc1cc(Cl)ccc1C(Cn2ccnc2)OCc3ccc(Cl)cc3Cl
  • InChI=1S/C18H14Cl4N2O/c19-13-2-1-12(16(21)7-13)10-25-18(9-24-6-5-23-11-24)15-4-3-14(20)8-17(15)22/h1-8,11,18H,9-10H2 checkY
  • Key:BYBLEWFAAKGYCD-UHFFFAOYSA-N checkY
  (verify)

Miconazole, sold under the brand name Monistat among others, is an antifungal medication used to treat ring worm, pityriasis versicolor, and yeast infections of the skin or vagina.[2] It is used for ring worm of the body, groin (jock itch), and feet (athlete's foot).[2] It is applied to the skin or vagina as a cream or ointment.[2][3]

Common side effects include itchiness or irritation of the area in which it was applied.[2] Use in pregnancy is believed to be safe for the baby.[4] Miconazole is in the imidazole family of medications.[2] It works by decreasing the ability of fungi to make ergosterol, an important part of their cell membrane.[2]

Miconazole was patented in 1968 and approved for medical use in 1971.[5] It is on the World Health Organization's List of Essential Medicines.[6] It is available as a generic medication.[2]

Medical uses

Miconazole is used externally for the treatment of ringworm, jock itch, and athlete's foot.[2] Internal application is used for oral candidiasis or vaginal thrush (yeast infection).[2]

Side effects

Miconazole is generally well tolerated. The oral gel can cause dry mouth, nausea and an unpleasant taste in about 1–10% of people. Anaphylactic reactions are rare. The drug prolongs the QT interval.[7][8]

Interactions

Miconazole is partly absorbed in the intestinal tract when used orally, as with the oral gel, and possibly when used vaginally.[9] This can lead to increased concentrations of drugs that are metabolized by the liver enzymes CYP3A4 and CYP2C9, because miconazole inhibits these enzymes. Such interactions occur for example with anticoagulants of the warfarin type, phenytoin, some newer atypical antipsychotics, ciclosporin, and most statins used to treat hypercholesterolemia.[8] These interactions are not relevant for miconazole that is applied to the skin.[8]

Contraindications

Miconazole is contraindicated for people who use certain drugs that are metabolized by CYP3A4, for the reasons mentioned above:[8]

Pharmacology

Mechanism of action

Miconazole inhibits the fungal enzyme 14α-sterol demethylase, resulting in a reduced production of ergosterol.[10] In addition to its antifungal actions, miconazole, similarly to ketoconazole, is known to act as an antagonist of the glucocorticoid receptor.[11]

Pharmacokinetics

After application to the skin, miconazole can be measured in the skin for up to four days, but less than 1% is absorbed into the bloodstream. When applied to the oral mucosa (and possibly also for vaginal use[9]), it is significantly absorbed. In the bloodstream, 88.2% are bound to plasma proteins and 10.6% to blood cells. The substance is partly metabolized via the liver enzyme CYP3A4 and mainly eliminated via the faeces.[7][8]

Chemistry

The solubilities of miconazole nitrate powder are 0.03% in water, 0.76% in ethanol and up to 4% in acetic acid.[12] Miconazole crystallises as colourless prisms in the monoclinic space group P21/c.[13]

Other uses

Miconazole is also used in Ektachrome film developing in the final rinse of the Kodak E-6 process and similar Fuji CR-56 process,[citation needed] replacing formaldehyde.[14][15] Fuji Hunt also includes miconazole as a final rinse additive in their formulation of the C-41RA rapid access color negative developing process.[citation needed]

Brands and formulations

Vaginal miconazole 20 mg/g - Brazil

Oral treatment: (brand names Daktarin in UK, Fungimin Oral Gel in Bangladesh):[citation needed]

In 2010, the US Food and Drug Administration approved Oravig (miconazole) buccal tablets for the local treatment of oropharyngeal candidiasis, more commonly known as thrush, in adults and children age 16 and older.[1]

External skin treatment (brand names Desenex and Zeasorb in US and Canada, Micatin, Monistat-Derm, Daktarin in India, UK, Australia, Belgium and the Philippines, Daktar in Norway, Fungidal in Bangladesh, Decocort in Malaysia)[citation needed] (Note that Desenex originally contained not miconazole, but rather the fungistatic agents, undecylenic acid and zinc undecylenate, which were in the foot powder developed by the US government for troops during WWII.[16])

Vaginal treatment (brand names Miconazex, Monistat, Femizol or Gyno-Daktarin in UK):[citation needed]

In Japan, Mochida Healthcare, a subsidiary of Mochida Pharmaceutical, produces a line of body soaps and shampoo under the brand name Collage (コラージュ) that contain miconazole nitrate as their main ingredient.[17]

References

  1. ^ a b "Oravig- miconazole tablet". DailyMed. 1 January 2022. Archived from the original on 14 August 2022. Retrieved 20 June 2023.
  2. ^ a b c d e f g h i "Miconazole Nitrate". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016.
  3. ^ "Miconazole Monograph for Professionals". Drugs.com. 22 July 2022. Archived from the original on 21 September 2022. Retrieved 20 June 2023.
  4. ^ Hamilton R (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 180. ISBN 9781284057560.
  5. ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 502. ISBN 9783527607495. Archived from the original on 20 December 2016.
  6. ^ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
  7. ^ a b Haberfeld H, ed. (2019). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Daktarin 2%-Creme.
  8. ^ a b c d e Haberfeld H, ed. (2020). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Daktarin 2%-orales Gel.
  9. ^ a b British National Formulary '45' March 2003
  10. ^ Becher R, Wirsel SG (August 2012). "Fungal cytochrome P450 sterol 14α-demethylase (CYP51) and azole resistance in plant and human pathogens". Applied Microbiology and Biotechnology. 95 (4): 825–840. doi:10.1007/s00253-012-4195-9. PMID 22684327. S2CID 17688962.
  11. ^ Duret C, Daujat-Chavanieu M, Pascussi JM, Pichard-Garcia L, Balaguer P, Fabre JM, et al. (July 2006). "Ketoconazole and miconazole are antagonists of the human glucocorticoid receptor: consequences on the expression and function of the constitutive androstane receptor and the pregnane X receptor". Molecular Pharmacology. 70 (1): 329–339. doi:10.1124/mol.105.022046. PMID 16608920. S2CID 21455699.{{cite journal}}: CS1 maint: overridden setting (link)
  12. ^ US 5461068, Thaler I, Strauss R, "Imidazole derivative tincture and method of manufacture", issued 24 October 1995, assigned to Current Assignee Corwood Laboratories Inc and Bausch Health Companies Inc. 
  13. ^ Kaspiaruk H, Chęcińska L (June 2022). "A comparison of three crystalline forms of miconazole: solvent-free, ethanol monosolvate and hemihydrate". Acta Crystallographica Section C. 78 (Pt 6): 343–350. doi:10.1107/S2053229622004909. PMID 35662134. S2CID 248839249.
  14. ^ "Kodak Chemicals: Process E-6 Publication: Z-119". Kodak. 8 October 1999. Archived from the original on 15 July 2007. Retrieved 20 June 2023.
  15. ^ "Kodak Chemicals: Q-LAB Process Control Handbook: Publication Z-6". Kodak. 1 November 2004. Archived from the original on 7 February 2007. Retrieved 20 June 2023.
  16. ^ "History". achh.army.mil. Archived from the original on 3 March 2024. Retrieved 3 March 2024.
  17. ^ "Mochida Pharmaceutical Co., list of product ingredients". hc.mochida.co.jp (in jp). Retrieved 21 August 2024.{{cite web}}: CS1 maint: unrecognized language (link)
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