Voriconazole

Structural formula
General
Non-proprietary name	Voriconazole
other names	(2 R , 3 S ) -2- (2,4-difluorophenyl) -3- (5-fluoro-4-pyrimidinyl) -1- (1 H -1,2,4-triazol-1-yl) -2 -butanol
Molecular formula	C 16 H 14 F 3 N 5 O
Brief description	white solid
External identifiers / databases
EC number	629-701-5
ECHA InfoCard	100.157.870
PubChem	71616
DrugBank	DB00582
Wikidata	Q412236
Drug information
ATC code	J02 AC03
Drug class	Antifungal agent
Mechanism of action	Ergosterol synthesis inhibitors
properties
Molar mass	349.3 g · mol -1
Physical state	firmly
Melting point	127 ° C
solubility	soluble in methanol
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
H and P phrases	H: 301-351-361-373-412
	P: 273-281-301 + 310
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Voriconazole (trade name VFend ; manufacturer: Pfizer ) is a drug used to treat patients with severe fungal infections ( mycoses ). Voriconazole is an inhibitor of ergosterol biosynthesis and belongs to the substance class of azole antimycotics.

Uptake and bioavailability

After oral administration, voriconazole has a bioavailability of approx. 96% of the applied dose. The maximum plasma concentration of voriconazole is reached 1 to 2 hours after administration.

The substance is offered as a powder for making a juice or a solution for infusion.

Metabolism (metabolism)

Voriconazole is metabolized in the liver by means of the cytochrome P450 enzymes CYP2C19, CYP2C9 and CYP3A4. The main metabolite of voriconazole is N -voriconazole oxide (72% of all voriconazole metabolites).

Interactions

Carbamazepine
Barbiturates such as phenobarbital , butalbital
Rifampicin
Sirolimus
Terfenadine
Astemizole
Cisapride
Ciclosporin
Tacrolimus
Anticoagulants such as phenprocoumon , warfarin, and coumarin
Benzodiazepines ' like midazolam , alprazolam
Calcium antagonists such as felodipine , nifedipine
Rifabutin
Phenytoin : Concomitant use of voriconazole and phenytoin lowers the C _max and AUC of voriconazole by 50–70%. Similarly, phenytoin reduces the effect of voriconazole. Since voriconazole significantly increases the C _max and AUC of phenytoin, regular phenytoin levels must be checked at shorter intervals than usual.
Omeprazole : Concomitant use of omeprazole and voriconazole increases the AUC and maximal concentration (C _max ) of voriconazole by approximately 15% and 40%, respectively. This leads to an increase in the effectiveness of voriconazole. However, dose adjustment (reduction) of voriconazole is not recommended. The C _max and AUC of omeprazole are increased two-fold by voriconazole. If voriconazole treatment is to be started in patients on omeprazole therapy, the omeprazole dose should be halved (if> 40 mg / day).

application areas

Voriconazole is a 2nd generation azole with good and broad in-vitro activity against molds. It is used for severe systemic fungal infections ( mycoses ), especially invasive aspergillosis . Even otherwise therapy-resistant infections with the infectious agents Scedosporium spp. (especially Scedosporium apiospermium and Scedosporium prolificans) and Fusarium spp. including Fusarium solani are treated with voriconazole. According to Abele-Horn, voriconazole is not effective against zygomycetes .

Web links

US package insert voriconazole ( Memento of July 5, 2010 in the Internet Archive ) (PDF; as of March 2008).
Aspergillosis Current state of knowledge on diagnosis, therapy, environmental conditions (PDF file; 658 kB) ITA article from Austria; 2001

Individual evidence

↑ ^a ^b ^c Datasheet Voriconazole, ≥98% (HPLC) from Sigma-Aldrich , accessed on November 5, 2019 ( PDF ).
↑ ^a ^b The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals. 14th edition, 2006, p. 1728, ISBN 978-0-911910-00-1 .
↑ Jörg Braun: Infectious Diseases. In: Jörg Braun, Roland Preuss (Ed.): Clinic Guide Intensive Care Medicine. 9th edition. Elsevier, Munich 2016, ISBN 978-3-437-23763-8 , pp. 437-519, here: p. 518 ( voriconazole ).
^ 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 , pp. 272 and 285 f.

[Sigma-1] Datasheet Voriconazole, ≥98% (HPLC) from Sigma-Aldrich , accessed on November 5, 2019 ( PDF ).

[MerckIndex-2] The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals. 14th edition, 2006, p. 1728, ISBN 978-0-911910-00-1 .

[3] Jörg Braun: Infectious Diseases. In: Jörg Braun, Roland Preuss (Ed.): Clinic Guide Intensive Care Medicine. 9th edition. Elsevier, Munich 2016, ISBN 978-3-437-23763-8 , pp. 437-519, here: p. 518 ( voriconazole ).

[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 , pp. 272 and 285 f.