Miconazole

Miconazole
Clinical data
Trade names	Desenex, Monistat, Oravig, others
AHFS/Drugs.com	Monograph
MedlinePlus	a601203
Routes of; administration	Topical, vaginal, sublabial
ATC code	A01AB09 (WHO) A07AC01 (WHO) D01AC02 (WHO) G01AF04 (WHO) J02AB01 (WHO) S02AA13 (WHO);
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;
Pharmacokinetic data
Bioavailability	<1% after application to the skin
Protein binding	88.2%
Metabolism	CYP3A4
Elimination half-life	20–25 hrs
Excretion	Mainly feces
Identifiers
	IUPAC name (RS)-1-(2-(2,4-Dichlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl)-1H-imidazole;
CAS Number	22916-47-8 ;
PubChem CID	4189;
IUPHAR/BPS	2449;
DrugBank	DB01110 ;
ChemSpider	4044 ;
UNII	7NNO0D7S5M;
KEGG	D00416 ;
ChEBI	CHEBI:6923 ;
ChEMBL	ChEMBL91 ;
CompTox Dashboard (EPA)	DTXSID6023319 ;
ECHA InfoCard	100.041.188
Chemical and physical data
Formula	C18H14Cl4N2O
Molar mass	416.12 g·mol−1
3D model (JSmol)	Interactive image;
Chirality	Racemic mixture
	SMILES Clc1cc(Cl)ccc1C(Cn2ccnc2)OCc3ccc(Cl)cc3Cl;
	InChI 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 ; Key:BYBLEWFAAKGYCD-UHFFFAOYSA-N ;
	(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]

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]

drugs that also prolong the QT interval because of potential problems with the heart rhythm
ergot alkaloids
statins
triazolam and oral midazolam
sulfonamides with a potential to cause hypoglycaemia (low blood sugar)

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

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]}

References

^ ^a ^b "Oravig- miconazole tablet". DailyMed. 1 January 2022. Archived from the original on 14 August 2022. Retrieved 20 June 2023.
^ ^a ^b ^c ^d ^e ^f ^g ^h "Miconazole Nitrate". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016.
^ "Miconazole Monograph for Professionals". Drugs.com. 22 July 2022. Archived from the original on 21 September 2022. Retrieved 20 June 2023.
^ Hamilton R (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 180. ISBN 9781284057560.
^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 502. ISBN 9783527607495. Archived from the original on 2016-12-20.
^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
^ ^a ^b Haberfeld H, ed. (2019). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Daktarin 2%-Creme.
^ ^a ^b ^c ^d ^e Haberfeld H, ed. (2020). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Daktarin 2%-orales Gel.
^ ^a ^b British National Formulary '45' March 2003
^ 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.
^ 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.
^ 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.
^ 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.
^ "Kodak Chemicals: Process E-6 Publication: Z-119". Kodak. 8 October 1999. Archived from the original on 15 July 2007. Retrieved 20 June 2023.
^ "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.
^ "History". achh.army.mil. Archived from the original on 2024-03-03. Retrieved 2024-03-03.

[Oravig_FDA_label-1] "Oravig- miconazole tablet". DailyMed. 1 January 2022. Archived from the original on 14 August 2022. Retrieved 20 June 2023.

[AHFS2016-2] ^ ^a ^b ^c ^d ^e ^f ^g ^h "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.

[Ric2015-4] Hamilton R (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 180. ISBN 9781284057560.

[Fis2006-5] Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 502. ISBN 9783527607495. Archived from the original on 2016-12-20.

[WHO21st-6] World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.

[AC-7] Haberfeld H, ed. (2019). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Daktarin 2%-Creme.

[AC-gel-8] Haberfeld H, ed. (2020). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Daktarin 2%-orales Gel.

[BNF-9] 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.

[pmid16608920-11] 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.

[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 2024-03-03. Retrieved 2024-03-03.

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Miconazole

Medical uses

Side effects

Interactions

Contraindications

Pharmacology

Mechanism of action

Pharmacokinetics

Chemistry

Other uses

Brands and formulations

References

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