Miconazole

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. Miconazole is also known to bind to tubulin and inhibit its polymerization.

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; Kalpanax in Indonesia; 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

References

1. (1 January 2022). "Oravig- miconazole tablet".
2. "Miconazole Nitrate". The American Society of Health-System Pharmacists.
3. (22 July 2022). "Miconazole Monograph for Professionals".
4. (2006). "Analogue-based Drug Discovery". John Wiley & Sons.
5. (2023). "The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023)". World Health Organization.
6. [[British National Formulary]] '45' March 2003
7. (August 2012). "Fungal cytochrome P450 sterol 14α-demethylase (CYP51) and azole resistance in plant and human pathogens". Applied Microbiology and Biotechnology.
8. (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.
9. (2025). "NanoDSF Screening for Anti-tubulin Agents Uncovers New Structure–Activity Insights". Journal of Medicinal Chemistry.
10. (2019). "Austria-Codex". Österreichischer Apothekerverlag.
11. (2020). "Austria-Codex". Österreichischer Apothekerverlag.
12. "Imidazole derivative tincture and method of manufacture".
13. (June 2022). "A comparison of three crystalline forms of miconazole: solvent-free, ethanol monosolvate and hemihydrate". Acta Crystallographica Section C.
14. (8 October 1999). "Kodak Chemicals: Process E-6 Publication: Z-119".
15. (1 November 2004). "Kodak Chemicals: Q-LAB Process Control Handbook: Publication Z-6".
16. "History".
17. "Mochida Pharmaceutical Co., list of product ingredients".