Miconazole

Miconazole

Drug Nomenclature

Date of monograph revision: 30-Oct-1997; 10-Aug-2001; 08-Aug-2002; 06-Sep-2005; 14-Jul-2006
Synonyms: Miconazol; Miconazolum; Mikonatsoli; Mikonazol; Mikonazolas; R-18134
BAN: Miconazole
INN: Miconazole [rINN (en)]
INN: Miconazol [rINN (es)]
INN: Miconazole [rINN (fr)]
INN: Miconazolum [rINN (la)]
INN: Миконазол [rINN (ru)]
Chemical name: 1-[2,4-Dichloro-β-(2,4-dichlorobenzyloxy)phenethyl]imidazole
Molecular formula: C18H14Cl4N2O =416.1
CAS: 22916-47-8
ATC code: A01AB09; A07AC01; D01AC02; G01AF04; J02AB01; S02AA13
Read code: y00UW [Genital]; y00q1 [Oropharyngeal]; y08DO [Systemic]; y02UR
Chemical Structure of Miconazole

Chemical Structure of Miconazole

Pharmacopoeias:

In Eur. (see Go to European Pharmacopoeia Convention Signatories), Jpn, and US.

Ph. Eur. 5.5 (Miconazole). A white or almost white powder. It exhibits polymorphism. M.p. 83 degrees to 87 degrees. Very slightly soluble in water; soluble in alcohol; freely soluble in methyl alcohol. Protect from light.

USP 29 (Miconazole). A white to pale cream powder. It may exhibit polymorphism. M.p. 78 degrees to 88 degrees. Insoluble in water; soluble 1 in 9.5 of alcohol, 1 in 2 of chloroform, 1 in 15 of ether, 1 in 4 of isopropyl alcohol, 1 in 5.3 of methyl alcohol, and 1 in 9 of propylene glycol; freely soluble in acetone and in dimethylformamide. Store at a temperature of 25 degrees, excursions permitted between 15 degrees and 30 degrees. Protect from light.

Miconazole Nitrate

Drug Nomenclature

Date of monograph revision: 30-Oct-1997; 10-Aug-2001; 08-Aug-2002; 06-Sep-2005; 14-Jul-2006
Synonyms: Miconazol, nitrato de; Miconazoli Nitras; Mikonatsolinitraatti; Mikonazol-nitrát; Mikonazolnitrat; Mikonazolo nitratas; Nitrato de miconazol [erINNM]; R-14889
BAN: Miconazole Nitrate [BANM]
USAN: Miconazole Nitrate
INN: Miconazole Nitrate [rINNM (en)]
INN: Nitrato de miconazol [rINNM (es)]
INN: Miconazole, Nitrate de [rINNM (fr)]
INN: Miconazoli Nitras [rINNM (la)]
INN: Миконазола Нитрат [rINNM (ru)]
Molecular formula: C18H14Cl4N2O,HNO3 =479.1
CAS: 22832-87-7
ATC code: A01AB09; A07AC01; D01AC02; G01AF04; J02AB01; S02AA13
Read code: y0133 [Skin]
Pharmacopoeias:

In Chin., Eur. (see Go to European Pharmacopoeia Convention Signatories), Int., Jpn, Pol., and US.

Ph. Eur. 5.5 (Miconazole Nitrate). A white or almost white powder. Very slightly soluble in water; slightly soluble in alcohol; sparingly soluble in methyl alcohol. Protect from light.

USP 29 (Miconazole Nitrate). A white or practically white, crystalline powder, with not more than a slight odour. Soluble 1 in 6250 of water, 1 in 312 of alcohol, 1 in 75 of methyl alcohol, 1 in 525 of chloroform, 1 in 1408 of isopropyl alcohol, 1 in 119 of propylene glycol; freely soluble in dimethyl sulfoxide; soluble in dimethylformamide; insoluble in ether. Protect from light.

Adverse Effects

After oral use of miconazole, nausea and vomiting have been reported, and also diarrhoea (usually on long-term treatment). There have been allergic reactions, rarely, and isolated reports of hepatitis.

Local irritation and sensitivity reactions may occur when miconazole nitrate is used topically; contact dermatitis has been reported.

After the intravenous infusion of miconazole, phlebitis, nausea, vomiting, diarrhoea, anorexia, pruritus, rash, febrile reactions, flushes, drowsiness, and hyponatraemia have been reported. Other effects include hyperlipidaemia, aggregation of erythrocytes, anaemia, and thrombocytosis. Transient tachycardia and other cardiac arrhythmias have followed the rapid intravenous injection of miconazole (but see also Effects on the Heart, Go to Effects on the heart.). Rare adverse effects include acute psychosis, arthralgia, and anaphylaxis. Many of these adverse effects have been associated with the injection vehicle, which contains polyethoxylated castor oil (Go to Polyoxyl Castor Oils).

Effects on the heart.

Bradycardia, progressing to fatal ventricular fibrillation and cardiac arrest, occurred in a heart transplant patient during intravenous infusion of miconazole for an invasive fungal infection.1

  1. 1. Coley KC, Crain JL. Miconazole-induced fatal dysrhythmia. Pharmacotherapy 1997; 17: 379–82. PubMed

Overdosage.

A report1 of a generalised tonic-clonic convulsion that occurred in an infant 10 to 15 minutes after the inadvertent infusion of miconazole 500 mg instead of 50 mg.

  1. 1. Coulthard K, et al Convulsions after miconazole overdose. Med J Aust 1987; 146: 57–8. PubMed

Precautions

Miconazole oral gel should be avoided in patients with hepatic impairment.

Intravaginal preparations of miconazole may damage latex contraceptives and additional contraceptive measures are therefore necessary during local administration.

Miconazole has been fetotoxic at high doses in animals and its use is generally not recommended during pregnancy. For a discussion of the caution needed when using azole antifungals during pregnancy, see under Pregnancy in Precautions of Fluconazole, Go to Pregnancy..

Porphyria.

Miconazole is considered to be unsafe in patients with porphyria because it has been shown to be porphyrinogenic in in-vitro systems.

Interactions

Miconazole can inhibit the metabolism of drugs metabolised by the cytochrome P450 isoenzymes CYP3A4 and CYP2C9, and may thus have effects similar to those of fluconazole (Go to Interactions). Miconazole may enhance the activity of oral anticoagulants, sulfonylurea hypoglycaemics, or phenytoin. Adverse effects have been reported when miconazole was given with carbamazepine.

There is a risk of cardiac arrhythmias if miconazole is used with astemizole, cisapride, or terfenadine and such combinations should be avoided.

Anticoagulants.

The anticoagulant activity of coumarin anticoagulants can be potentiated by miconazole given orally,1 intravaginally,2 or topically.3 As of December 2002 the Australian Adverse Drug Reactions Advisory Committee had received 18 reports of significant increases in the INR of patients previously stabilised on warfarin within 1 to 2 weeks of starting treatment with miconazole oral gel.4

  1. 1. Ortín M, et al. Miconazole oral gel enhances acenocoumarol anticoagulant activity: a report of three cases. Ann Pharmacother 1999; 33: 175–7. PubMed
  2. 2. Lansdorp D, et al. Potentiation of acenocoumarol during vaginal administration of miconazole. Br J Clin Pharmacol 1999; 47: 225–26. PubMed
  3. 3. Devaraj A, et al. Interaction between warfarin and topical miconazole cream. BMJ 2002; 325: 77. PubMed
  4. 4. Australian Adverse Drug Reactions Advisory Committee (ADRAC). Miconazole oral gel elevates INR—a reminder. Aust Adverse Drug React Bull 2002; 21: 14. Available at: online (accessed 28/06/05)

Antimicrobial Action

Miconazole is an imidazole antifungal with similar antimicrobial activity to that of ketoconazole (Go to Antimicrobial Action). It also has some activity against Aspergillus spp., Cryptococcus neoformans, Pseudallescheria boydii, and some Gram-positive bacteria including staphylococci and streptococci.

Microbiological interactions.

A study in vitro indicating antimicrobial synergism of miconazole and benzoyl peroxide against Staphylococcus spp. and Propionibacterium acnes.1

For the effect on antifungal activity of giving azoles and amphotericin B together, see Go to Microbiological interactions..

  1. 1. Vanden Bossche H, et al Synergism of the antimicrobial agents miconazole and benzoyl peroxide. Br J Dermatol 1982; 107: 343–8. PubMed

Pharmacokinetics

Miconazole is incompletely absorbed from the gastrointestinal tract. Peak plasma concentrations of 1 microgram/mL are achieved about 4 hours after a dose of 1 g daily. Over 90% is reported to be bound to plasma proteins.

Miconazole is metabolised in the liver to inactive metabolites. From 10 to 20% of an oral dose is excreted in the urine, mainly as metabolites, within 6 days. About 50% of an oral dose may be excreted unchanged in the faeces. The elimination pharmacokinetics of miconazole have been described as triphasic, with a biological half-life of about 24 hours.

Very little miconazole is removed by haemodialysis.

There is little absorption through skin or mucous membranes when miconazole nitrate is applied topically.

Reviews.

  1. 1. Daneshmend TK, Warnock DW. Clinical pharmacokinetics of systemic antifungal drugs. Clin Pharmacokinet 1983; 8: 17–42. PubMed

Uses and Administration

Miconazole is an imidazole antifungal used as miconazole base or nitrate in the treatment of superficial candidiasis (Go to Candidiasis), and of the skin infections dermatophytosis and pityriasis versicolor (Go to Skin infections). It has also been given intravenously by infusion in the treatment of disseminated fungal infections, but other azoles are now more commonly used.

Miconazole may be given by mouth as an oral gel containing 20 mg/g (24 mg/mL) for the treatment of oropharyngeal and intestinal candidiasis. The usual adult dose is 5 to 10 mL four times daily (equivalent to a total of about 15 mg/kg daily). Children under the age of 2 years may be given the oral gel in a dose of 2.5 mL twice daily; those aged between 2 and 6 years, 5 mL twice daily; and those aged over 6 years, 5 mL four times daily. For the treatment of oral lesions the oral gel is applied directly.

Miconazole nitrate is usually applied twice daily as a 2%  cream, lotion, or powder in the treatment of fungal infections of the skin including candidiasis, dermatophytosis, and pityriasis versicolor. In the treatment of vaginal candidiasis, 5 g of a 2%  intravaginal cream is inserted into the vagina once daily for 10 to 14 days or twice daily for 7 days. Miconazole nitrate pessaries may be inserted in dosage regimens of 100 mg once daily for 7 or 14 days, 100 mg twice daily for 7 days, 200 or 400 mg daily for 3 days, or in a single dose of 1200 mg.

Acanthamoeba keratitis.

Miconazole has been applied topically in Acanthamoeba keratitis (Go to Acanthamoeba infections.) in combination with systemic treatment with either ketoconazole or itraconazole.

Skin disorders.

Topical preparations containing an imidazole such as ketoconazole or miconazole, usually with hydrocortisone, are used in the management of seborrhoeic dermatitis (Go to Seborrhoeic dermatitis). A cream containing miconazole nitrate 2% and benzoyl peroxide 5% has been used topically in the treatment of acne (Go to Acne).

Preparations

Single-ingredient Preparations

The symbol ¤ denotes a preparation which is discontinued or no longer actively marketed.

Argentina: Daktarin; Deralbine; Miconol; Micotgez; Micotral; Micotrim P; Micotrim S¤; Monizol; Nedis; Salicrem Miconazol¤; Australia: Chemists Own Zapazole¤; Daktarin; Eulactol Antifungal¤; Gyno-Daktarin¤; Hairscience Anti-Dandruff; Monistat¤; Resolve Thrush; Resolve; Austria: Daktarin; Gyno-Daktarin; Mycoderm¤; Belgium: Albistat¤; Daktar Duo¤; Daktar¤; Daktarin; Gyno-Daktarin; Brazil: Amicose¤; Anfugitarin; Biodol; Ciconazol; Daknax; Daktarin; Daktazol; Ginedak; Gino-Daczol; Ginotarin; Gyno-Daktarin; Micofim; Micogyn; Micoless¤; Miconax¤; Micotarin; Micozen; Mycosin; Vodol; Canada: Micatin; Micozole; Monazole¤; Monistat; Chile: Daktarin; Fungos¤; ZeaSorb AF; Czech Republic: Daktarin; Denmark: Brenazol; Brentan; Dumicoat¤; Finland: Daktarin; Dumicoat¤; Gyno-Daktarin; Medizol; France: Britane¤; Daktarin; Gyno-Daktarin; Germany: Amykon¤; Castellani mit Miconazol; Daktar; Decomyk; Derma-Mykotral; Dumicoat¤; Epi-Monistat¤; Fungur M; Gyno-Daktar; Gyno-Monistat¤; Gyno-Mykotral; InfectoSoor; Micobeta; Micotar ZP; Micotar; Mykoderm Mund-Gel; Mykoderm; Mykotin; Vobamyk; Greece: Daktarin; Fantersol; Medacter; Mezolitan; Untano; Hong Kong: Daktarin; Dermon; Funga; Fungo¤; Gyno-Daktarin¤; India: Daktarin; Gyno-Daktarin; Micogel; Zole; Ireland: Daktarin; Gyno-Daktarin; Israel: Daktarin; Gyno-Daktarin; Pitrion; Italy: Andergin¤; Daktarin; Fungiderm¤; Lampomicol¤; Micoderm¤; Micomax¤; Miconal; Micotef; Miderm; Nizacol; Pivanozolo; Prilagin¤; Japan: Florid-F; Malaysia: Antifungal; Becarin; Daktarin; Decozol; Fungo¤; Resolve; Setarin¤; Uniderm¤; Zarin; Mexico: Aloid; Daktarin; Dermifun; Falernol; Fucoderm; Fungicrem¤; Fungiquim; Ginazol; Gyno-Daktarin; K-Mizol; Lotrimin AF¤; Micoffen; Micosid¤; Mindosan V¤; Nacomic; Neomicol; Nimicon; Niscamil; Oz Crema; Piat¤; Netherlands: Albistat¤; Daktarin; Dermacure; Gyno-Daktarin; Norway: Daktar; Dumicoat¤; New Zealand: Daktarin; Fungo; Gyno-Daktarin¤; Hairscience Antidandruff; Micozole; Micreme; Portugal: Daktarin; Gyno-Daktarin; Micane; Russia: Daktarin (Дактарин); Gynezol (Гинезол); South Africa: Covarex; Daktarin; Dermazole; Gyno-Daktarin; Gynospor; Singapore: Antifungal¤; Candiplas¤; Daktarin; Decozol; Fungo¤; Hairscience; Liconar; Mycoban; Resolve; Zarin; Spain: Daktarin; Funginazol¤; Fungisdin; Medefungin¤; Pasedon; Tremix; Sweden: Daktar; Dumicoat¤; Switzerland: Daktar¤; Daktarin; Dumicoat¤; Monistat; Thailand: Candiplas¤; Daktarin; Funcort; Fungi-M; Fungisil; Liconar; Micazin; Minaza¤; Misone¤; Mysocort; Neomite¤; Nikarin; Noxraxin; Podakrin; Ranozol; Skindure; Tara; United Arab Emirates: Gyno-Mikozal; Mikozal; United Kingdom: Daktarin; Dermonistat¤; Dumicoat¤; Femeron¤; Gyno-Daktarin; Monistat¤; United States: Absorbine Antifungal Foot Powder; Anusol Antifungal Foot Powder¤; Breezee Mist Antifungal; Femizol-M; Fungoid; Lotrimin AF; M-Zole; Maximum Strength Desenex Antifungal; Micatin; Monistat; Neosporin AF; Ony-Clear¤; Podactin; Prescription Strength Desenex¤; Ting; Vagistat-3; ZeaSorb AF; Venezuela: Canidazol; Daktarin; Drinax; Gyno-Daktarin;

Multi-ingredient Preparations

The symbol ¤ denotes a preparation which is discontinued or no longer actively marketed.

Argentina: Adenil; Betacort Plus; Ciprocort; Cuta Crema; Daktozin; Delisan; Denvercrem; Dermizol Trio; Dermosona; Factor Dermico; Gentasol; Ginal Cent; Ginkan; Gynormal; Hifamonil Crema; Ladylen; Lazar-Cort Complex; Macril; Mailen; Miklogen; Monizol Cort Crema; Monizol Cort; Ovumix; Pentol; Protiderm; Tribiocort; Triliver; Triplex; Vagicural Plus; Australia: Daktozin; Resolve Plus; Resolve Tinea; Resolve Tinea; Resolve; Austria: Acne Plus; Acnidazil¤; Daktacort¤; Mycocort¤; Belgium: Acnidazil¤; Daktacort; Daktozin; Brazil: Amplium-G; Daktozin; Facyl M; Gino Pletil; Ginosutin M; Tizonil M; Trinizol M; Chile: Doxifen; Famidal Ad¤; Famidal; Ginecopast Dual; Ginecopast; Ginedazol Dual; Ginedazol; Medidos; Mizonase; Czech Republic: Daktozin; Klion-D; Mycosolon; Denmark: Acnidazil¤; Brentacort; Finland: Daktacort; France: Daktacort¤; Squaphane Masque-Creme; Squaphane P; Squaphane S; Squaphane; Germany: Acne Plus; Acnidazil¤; Daktar-Hydrocortison¤; Decoderm tri; InfectoSoor; Vobaderm; Greece: Antimycotic; Catrigel; Combi; Conazol; Daktodor; Expectein; Fumicon; Micoflup; Micogen; Oxigon; Panderm; Panmyk; Verdal; Hong Kong: Conazole; Daktacort; Fungo Soothing Balm; Hydro-Funga; Micosone; Hungary: Klion-D; Mycosolon; India: Betamil-M; Betnederm GM; Betnovate-GM; Betnovate-M; Candizole-T; Cloderm GM; Daktacort; Flucort-MZ; Flucreme NM; Lobate-GM; Lobate-M; Micogel F; Stecort-NM; Tenovate M; Valbet; Zole-F; Ireland: Daktacort; Israel: Daktacort; Italy: Acnidazil; Daktacort¤; Malaysia: Becacort¤; Daktacort; Decocort; Miconazole H; Neo-Penotran; Setarin H¤; Zaricort; Mexico: Bebektin; Daktacort; Netherlands: Acnecure¤; Acnidazil¤; Daktacort; Norway: Daktacort; New Zealand: Daktacort; Daktozin¤; Fungocort¤; Micreme H; Portugal: Daktacort; Russia: Klion-D (Клион-Д); Mycosolon (Микозолон); Neo-Penotran (Нео-Пенотран); South Africa: Acneclear; Acnidazil; Daktacort; Trialone; Singapore: Betnovate-GM¤; Betnovate-M¤; Conazole; Daktacort; Decocort; Neo-Penotran¤; Tri-Micon; Zaricort; Spain: Bexicortil; Blastoestimulina; Brentan; Dermisdin¤; Nutracel; Sweden: Cortimyk; Daktacort; Switzerland: Acne Creme Plus; Acnidazil¤; Daktacort; Decoderm bivalent; Thailand: Daktacort; Fungisil-T; Kelaplus; Ladocort; Tara-Plus; Timi; Trimicon; United Kingdom: Acnidazil¤; Acorvio Plus; Daktacort HC; Daktacort; United States: Fungoid HC; Venezuela: Daktozin;



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