Fluconazole

Structural formula
General
Non-proprietary name	Fluconazole
other names	2- (2,4-difluorophenyl) -1,3-bis (1 H -1,2,4-triazol-1-yl) -2-propanol; Fluconazolum ( Latin );
Molecular formula	C 13 H 12 F 2 N 6 O
External identifiers / databases
EC number	627-806-0
ECHA InfoCard	100.156.133
PubChem	3365
DrugBank	DB00196
Wikidata	Q411478
Drug information
ATC code	D01 AC15 ; J02 AC01 ;
Drug class	Antifungal agent
Mechanism of action	Inhibition of the biosynthesis of ergosterol in mushrooms
properties
Molar mass	306.27 g · mol -1
Physical state	firmly
Melting point	138-140 ° C
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Caution
H and P phrases	H: 302-315-319-335
	P: 261-305 + 351 + 338
Toxicological data	1273 mg kg −1 ( LD 50 , mouse , ip )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Fluconazole is a drug from the group of antimycotics , which is one of the triazole derivatives .

Mechanism of action

Fluconazole usually has a fungistatic effect in therapeutic doses , but - depending on the dose - it can also show a fungicidal effect in some organisms . Like other imidazole and triazole derivatives , fluconazole inhibits the 14-alpha-demethylase of the cytochrome P450 system of the fungal cell. This interrupts the conversion of lanosterol to ergosterol , which leads to membrane defects in the fungal cell. Fluconazole inhibits human demethylase significantly less.

Spectrum of activity

Fluconazole is effective against a wide range of pathogenic fungi, including a. against Candida spp. (except Candida krusei , Candida glabrata , Candida norvegensis and Candida inconspicua ), Cryptococcus neoformans , Epidermophyton spp., Microsporum spp. and Histoplasma capsulatum . There is also a therapeutic gap for molds and dimorphic fungi.

unwanted effects

The most common side effects of fluconazole are nausea, vomiting and diarrhea, as well as an increase in certain enzymes such as aminotransferases and alkaline phosphatase ; severe liver damage is rare. Fluconazole is a strong inhibitor of CYP2C9 and a weak inhibitor of CYP3A4 . There is a risk of interactions with numerous active substances, which are also often metabolized by means of these enzymes.

Reproductive toxicity was found in animal experiments ; in humans there have been reports of the occurrence of congenital malformations in children whose mothers have been treated with high doses of fluconazole (400 to 800 mg / day) over a long period of time. A study to check the teratogenicity of fluconazole showed no increased rate of malformations apart from the rare Fallot tetralogy.

Indications

Fluconazole is used for the topical and systemic treatment of fungal infections , including:

Mucous membrane candidoses
severe fungal infections of the skin and mucous membranes
systemic fungal infections

Trade names

Monopreparations

Canifug-Fluco (D), Diflucan (D, A, CH), Difluzol (A), Flucazol (CH), Fluconax (CH), Flucosept (A), Flucozal (A), Flunazul (D), Fungata (D, A), various generics (D, A, CH)

Web links

Entry on Fluconazole at Vetpharm, accessed August 4, 2012.
University of Würzburg: The Candida albicans fungus becomes even more resistant to fluconazole - Doi

Individual evidence

↑ Entry on fluconazole. In: Römpp Online . Georg Thieme Verlag, accessed on November 11, 2014.
↑ ^a ^b Fluconazole data sheet from Sigma-Aldrich , accessed on April 1, 2011 ( PDF ).

↑ Entry on fluconazole in the ChemIDplus database of the United States National Library of Medicine (NLM) .

^ Marianne Abele-Horn: Antimicrobial Therapy. Decision support for the treatment and prophylaxis of infectious diseases. With the collaboration of Werner Heinz, Hartwig Klinker, Johann Schurz and August Stich, 2nd, revised and expanded edition. Peter Wiehl, Marburg 2009, ISBN 978-3-927219-14-4 , p. 271.

↑ ^a ^b Technical information Diflucan iv, as of June 2009.

↑ Use of long-term, high-dose Diflucan (fluconazole) during pregnancy may be associated with birth defects in infants , FDA Drug Safety Communication of August 3, 2011.

↑ Ditte M lgaard-Nielsen, Bj rn Pasternak, Anders Hviid: Use of Oral Fluconazole during Pregnancy and the Risk of Birth Defects. In: New England Journal of Medicine. 369, 2013, pp. 830-839, doi : 10.1056 / NEJMoa1301066 .

This text is based in whole or in part on the entry Fluconazole in Flexikon , a wiki of the DocCheck company . The takeover took place on October 31, 2007 under the then valid GNU license for free documentation .

[1] Entry on fluconazole. In: Römpp Online . Georg Thieme Verlag, accessed on November 11, 2014.

[sigma-2] Fluconazole data sheet from Sigma-Aldrich , accessed on April 1, 2011 ( PDF ).

[ChemIDplus-3] Entry on fluconazole in the ChemIDplus database of the United States National Library of Medicine (NLM) .

[4] Marianne Abele-Horn: Antimicrobial Therapy. Decision support for the treatment and prophylaxis of infectious diseases. With the collaboration of Werner Heinz, Hartwig Klinker, Johann Schurz and August Stich, 2nd, revised and expanded edition. Peter Wiehl, Marburg 2009, ISBN 978-3-927219-14-4 , p. 271.

[FI-5] Technical information Diflucan iv, as of June 2009.

[6] Use of long-term, high-dose Diflucan (fluconazole) during pregnancy may be associated with birth defects in infants , FDA Drug Safety Communication of August 3, 2011.

[DOI10.1056/NEJMoa1301066-7] Ditte M lgaard-Nielsen, Bj rn Pasternak, Anders Hviid: Use of Oral Fluconazole during Pregnancy and the Risk of Birth Defects. In: New England Journal of Medicine. 369, 2013, pp. 830-839, doi : 10.1056 / NEJMoa1301066 .