Itraconazole

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Structural formula
Structure of itraconazole
Mixture of diastereomers, both diastereomers are racemates . The figure shows only one enantiomer of each of the two diastereomers.
General
Non-proprietary name Itraconazole
other names

(2 R * , 4 S * ) -1- sec -Butyl-4- {4- [4- (4 - {[ cis -2- (2,4-dichlorophenyl) -2- (1,2,4- triazol-1-ylmethyl) -1,3-dioxolan-4-yl] methoxy} phenyl) piperazin-1-yl] phenyl} -4,5-dihydro-1,2,4-triazol-5-one

Molecular formula C 35 H 38 Cl 2 N 8 O 4
External identifiers / databases
CAS number 84625-61-6
EC number 617-596-9
ECHA InfoCard 100.123.596
PubChem 55283
DrugBank DB01167
Wikidata Q411229
Drug information
ATC code

J02 AC02

Drug class

Antifungal agent

properties
Molar mass 705.64 g · mol -1
Physical state

firmly

Melting point

166.2 ° C

pK s value

3.7

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
07 - Warning

Caution

H and P phrases H: 302-315-319-335
P: 261-305 + 351 + 338
Toxicological data

320 mg kg −1 ( LD 50 ,  rat ,  oral )

As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Itraconazole is a systemic antimycotic from the group of triazoles which, when administered orally, is largely absorbed in the intestine and enters the bloodstream . The rate of absorption is influenced by the acidic environment of the stomach. The drug is also available for intravenous therapy.

Like all other antifungal drugs, itraconazole is only effective against certain types of fungus. The metabolism takes place via the cytochrome CYP3A4.

The half-life depends on the dosage and the duration of ingestion and is 15 hours for a single dose of 100 mg, 25 hours for a single dose of 400 mg and 42 hours for a single dose of 400 mg per day for 2 weeks.

Itraconazole requires a prescription in Germany and may contain a. the risk of heart failure and liver damage.

Because of the variable bioavailability, serum levels must be determined when itraconazole is taken as capsules or juice.

Stereoisomerism

Itraconazole is a mixture of two diastereomers , each of which is racemic . Thus the drug is a mixture of four stereoisomers.

Area of ​​application / effectiveness

The antifungal effect of itraconazole is based on the reduction of the ergosterol synthesis in the fungal cells, which is an essential part of the cell membrane there.

Itraconazole is used for the therapy and prophylaxis of systemic mycoses, especially in oral and esophageal candidiasis.

The effectiveness has been proven by in-vitro studies for infections caused by:

as well as various other mushrooms and yeasts.

Infections with often decreased sensitivity (increased MIC ) to itraconazole are:

Itraconazole is ineffective against:

The number of detected strains with resistance to itraconazole has increased significantly in Aspergillus fumigatus since the 2000s. The increasing use of azoles in agriculture is blamed for this.

Interactions

Itraconazole needs an acidic environment to be absorbed from the digestive tract. The use of stomach acid blockers or basic medication can hinder the absorption of the substance.

Side effects

Common side effects that have occurred in clinical studies include: headache, nausea, diarrhea, abdominal pain, indigestion, flatulence, liver dysfunction, runny nose and sinusitis, upper respiratory tract infection, rash.

Trade names

Monopreparations
Sempera (D), Siros (D), Sporanox (A, CH), numerous generics (D, A, CH) Veterinary medicine
Fungitraxx, Itrafungol

literature

  • 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. 272.

Web links

Individual evidence

  1. ↑ a b entry on itraconazole. In: Römpp Online . Georg Thieme Verlag, accessed on September 30, 2014.
  2. ↑ a b c Itraconazole data sheet from Sigma-Aldrich , accessed on April 6, 2011 ( PDF ).
  3. ↑ a b Information Itraconazole STADA 100 mg capsules (PDF; 79 kB).
  4. ↑ ZCT: New introduction of itraconazole iv , 1/2005.
  5. ↑ ZCT: launch itraconazole , 4/1991.
  6. ↑ Risks of nail fungus treatment ... Itraconazole (SEMPERA and others): Heart failure . In: Arznei-Telegram 2001; Vol. 32, No. 6, p. 63.
  7. ↑ Axapharm - patient information  ( page no longer available , search in web archives )  Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice. (PDF; 82 kB).@1@ 2Template: Dead Link / www.axapharm.ch  
  8. ↑ European Pharmacopoeia . Deutscher Apotheker Verlag Stuttgart, 6th edition, 2008, pp. 2927-2929, ISBN 978-3-7692-3962-1 .
  9. ^ 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. 272.
  10. ↑ Matt Richtel, Andrew Jacobs: A Mysterious Infection, Spanning the Globe in a Climate of Secrecy . In: New York Times , April 6, 2018
  11. ^ Joseph Heitman: Emergence of Azole-Resistant Aspergillus fumigatus Strains due to Agricultural Azole Use Creates an Increasing Threat to Human Health . October 2013, PMID 3812019
  12. ^ Matthew J. Cervelli, Graeme R Russ: Principles of Drug Therapy in Chronic Kidney Disease and Renal Replacement Therapy . In: Jürgen Floege, Richard J Johnson, John Feehally: Comprehensive Clinical Nephrology . 4th edition. St. Louis 2010, p. 883.
  13. ↑ Itraconazole: Side Effects . Entry in Onmeda .