Pharmaceutical compound
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| Clinical data | |
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| Trade names | Monistat, others |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a601203 |
| License data |
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| Routes of administration | Topical, vaginal, sublabial |
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| 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
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| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.041.188  |
| Chemical and physical data | |
| Formula | C18H14Cl4N2O |
| Molar mass | 416.12 g·mol |
| 3D model (JSmol) | |
| Chirality | Racemic mixture |
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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. It is used for ring worm of the body, groin (jock itch), and feet (athlete's foot). It is applied to the skin or vagina as a cream or ointment.
Common side effects include itchiness or irritation of the area in which it was applied. Use in pregnancy is believed to be safe for the baby. Miconazole is in the imidazole family of medications. It works by decreasing the ability of fungi to make ergosterol, an important part of their cell membrane.
Miconazole was patented in 1968 and approved for medical use in 1971. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication.
Medical uses
Miconazole is used externally for the treatment of ringworm, jock itch, and athlete's foot. Internal application is used for oral candidiasis or vaginal thrush (yeast infection).
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.
Interactions
Miconazole is partly absorbed in the intestinal tract when used orally, as with the oral gel, and possibly when used vaginally. 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. These interactions are not relevant for miconazole that is applied to the skin.
Contraindications
Miconazole is contraindicated for people who use certain drugs that are metabolized by CYP3A4, for the reasons mentioned above:
- 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. In addition to its antifungal actions, miconazole, similarly to ketoconazole, is known to act as an antagonist of the glucocorticoid receptor.
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), 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.
Chemistry
The solubilities of miconazole nitrate powder are 0.03% in water, 0.76% in ethanol and up to 4% in acetic acid. Miconazole crystallises as colourless prisms in the monoclinic space group P21/c.
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
Oral treatment: (brand names Daktarin in UK, Fungimin Oral Gel in Bangladesh):
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.
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) (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.)
Vaginal treatment (brand names Miconazex, Monistat, Femizol or Gyno-Daktarin in UK):
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.
References
- ^ "Oravig- miconazole tablet". DailyMed. 1 January 2022. Archived from the original on 14 August 2022. Retrieved 20 June 2023.
- ^ "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 20 December 2016.
- 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.
- ^ Haberfeld H, ed. (2019). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Daktarin 2%-Creme.
- ^ Haberfeld H, ed. (2020). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Daktarin 2%-orales Gel.
- ^ 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.
{{cite journal}}: CS1 maint: overridden setting (link) - 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 3 March 2024. Retrieved 3 March 2024.
- "Mochida Pharmaceutical Co., list of product ingredients". hc.mochida.co.jp (in Japanese). Retrieved 21 August 2024.
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- 21-Hydroxylase inhibitors
- Antiglucocorticoids
- Aromatase inhibitors
- Belgian inventions
- Chloroarenes
- CYP17A1 inhibitors
- CYP2C8 inhibitors
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- Phenylethanolamine ethers
- Imidazole antifungals
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- Otologicals
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