Miconazole

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.[1] It is used for ring worm of the body, groin (jock itch), and feet (athlete's foot).[1] It is applied to the skin or vagina as a cream or ointment.[1]

Miconazole
Clinical data
Trade namesDesenex, Monistat, others
AHFS/Drugs.comMonograph
MedlinePlusa601203
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
  • UK: POM (Prescription only)
  • US: OTC / Rx-only
Pharmacokinetic data
Bioavailability<1% after application to the skin
Protein binding88.2%
MetabolismCYP3A4
Elimination half-life20–25 hrs
ExcretionMainly faeces
Identifiers
IUPAC name
  • (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
Chemical and physical data
FormulaC18H14Cl4N2O
Molar mass416.12 g·mol−1
3D model (JSmol)
ChiralityRacemic 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 Y
  • Key:BYBLEWFAAKGYCD-UHFFFAOYSA-N Y
  (verify)

Common side effects include itchiness or irritation of the area in which it was applied.[1] Use in pregnancy is believed to be safe for the baby.[2] Miconazole is in the imidazole family of medications.[1] It works by decreasing the ability of fungi to make ergosterol, an important part of their cell membrane.[1]

Miconazole was patented in 1968 and approved for medical use in 1971.[3] It is on the World Health Organization's List of Essential Medicines.[4]

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 or vaginal thrush (yeast infection). This oral gel may also be used for the lip disorder angular cheilitis and other associated systems.

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

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.[5][6]

Interactions

The substance is partly absorbed in the intestinal tract when used orally, as with the oral gel, and possibly when used vaginally.[7] 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.[6]

These interactions are not relevant for miconazole that is applied to the skin.[6]

Contraindications

Miconazole is contraindicated for people who use certain drugs that are metabolized by CYP3A4, for the reasons mentioned above:[6]

Pharmacology

Mechanism of action

Miconazole inhibits the fungal enzyme 14α-sterol demethylase, resulting in a reduced production of ergosterol.[8] In addition to its antifungal actions, miconazole, similarly to ketoconazole, is known to act as an antagonist of the glucocorticoid receptor.[9]

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[7]), 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.[5][6]

Chemistry

The solubilities of miconazole nitrate powder are 0.03% in water, 0.76% in ethanol and up to 4% in acetic acid.[10] Miconazole crystallises as colourless prisms in the monoclinic space group P21/c.[11]

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. Fuji Hunt also includes miconazole as a final rinse additive in their formulation of the C-41RA rapid access color negative developing process.

Brands and formulations
Vaginal miconazole 20 mg/g - Brazil

Oral treatment: (brand names Daktarin in UK, Fungimin Oral Gel in Bangladesh):

  • Oral gel 24 mg/ml (20 mg/g)
  • Oravig 50 mg once daily buccal tablet:

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.

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)

  • 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)

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

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

References
  1. "Miconazole Nitrate". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016.
  2. Hamilton R (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 180. ISBN 9781284057560.
  3. Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 502. ISBN 9783527607495. Archived from the original on 2016-12-20.
  4. 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.
  5. Haberfeld H, ed. (2019). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Daktarin 2%-Creme.
  6. Haberfeld H, ed. (2020). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Daktarin 2%-orales Gel.
  7. British National Formulary '45' March 2003
  8. 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): 825–40. doi:10.1007/s00253-012-4195-9. PMID 22684327. S2CID 17688962.
  9. 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): 329–39. doi:10.1124/mol.105.022046. PMID 16608920. S2CID 21455699.
  10. United States Patent 5461068 Archived 2014-09-10 at the Wayback Machine
  11. Kaspiaruk, H.; Chęcińska, L. (2022-06-01). "A comparison of three crystalline forms of miconazole: solvent-free, ethanol monosolvate and hemihydrate". Acta Crystallographica Section C: Structural Chemistry. 78 (6): 343–350. doi:10.1107/S2053229622004909. ISSN 2053-2296. PMID 35662134. S2CID 248839249.
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