Fidaxomicin

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Structural formula
Structural formula of fidaxomicin
General
Non-proprietary name Fidaxomicin
other names
  • Lipiarmycin
  • Dificid
  • Clostomycin B1
  • Tiacumicin B
  • Difimicin
Molecular formula C 52 H 74 Cl 2 O 18
Brief description

white solid

External identifiers / databases
CAS number 873857-62-6
EC number 692-555-6
ECHA InfoCard 100.220.590
PubChem 10034073
ChemSpider 8209640
DrugBank DB08874
Wikidata Q5446672
Drug information
ATC code

A07 AA12

Drug class

Macrocycline antibiotics

Mechanism of action

Inhibition of bacterial RNA polymerase

properties
Molar mass 1058.04 g · mol -1
solubility

soluble in ethanol, methanol, DMF or DMSO, limited solubility in water

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS hazard labeling
no classification available
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Fidaxomicin (trade name Dificlir ; manufacturer Astellas Pharma ) is a drug from the relatively new group of macrocyclines that is used in the treatment of intestinal infections with Clostridioides difficile .

Clinical information

application areas

Fidaxomicin is indicated in adults for the treatment of intestinal infections with the pathogenic (toxin-forming) Clostridioides difficile . The recommended daily dose is 200 mg twice a day, regardless of meals.

Adverse effects and restrictions on use

In the patient groups observed, the following side effects were found with the following average frequency: vomiting (12 out of 1,000 people), nausea (27 out of 1,000 people) and constipation (12 out of 1,000 people).

It is believed that fidaxomicin can inhibit the P-glycoprotein of the intestine. As a result, the parallel intake of known strong P-glycoprotein inhibitors such as ciclosporin , clarithromycin , verapamil , dronedarone , amiodarone or ketoconazole should be avoided.

Use in special patient groups

Although there is currently no evidence of harm to the fetus or the breast-fed newborn , the use of fidaxomicin is not recommended during pregnancy and breastfeeding for safety reasons. Animal studies have shown that fidaxomicin is not teratogenic .

For patients with severe kidney or liver disease, the use of fidaxomicin should be carried out under close observation and caution.

Pharmacological properties

Fidaxomicin is a bactericidal macrocycline antibiotic that is biotechnologically produced by the actinomycete Dactylosporangium aurantiacum spp. hamdenesis is produced. The macrocycline antibiotic inhibits protein synthesis in the bacterium by binding to the DNA-dependent RNA polymerase - this also happens with rifamycins .

The almost water-insoluble antibiotic is hardly absorbed through the intestine and therefore only has a local effect. Therefore, most of it is excreted in the stool . The half-life in the intestine is 8 to 10 hours.

Benefit assessment of the Federal Joint Committee

After an assessment by the Institute for Quality and Efficiency in Health Care (IQWiG), the Federal Joint Committee (G-BA) passed a resolution on July 4, 2013 on the additional benefit compared to the comparator therapy vancomycin . This establishes proof of an additional benefit in seriously ill patients. However, there is no suitable preparation of the side effects. Studies on use in the mildly ill were not presented.

literature

  • Fidaxomicin . In: New Medicines . Volume 60, May 2013, No. 5.
  • Johannes Hausmann, Stefan Zeuzem, Oliver Schröder: Fidaxomicin — The Next Step? A New Narrow-Spectrum Macrocyclic Antibiotic for the Management of Clostridium Difficile Infection . In: Gastroenterology . tape 141 , no. 3 , September 2011, p. 1116–1118 , doi : 10.1053 / j.gastro.2011.07.014 , PMID 21801724 .
  • Derrick W. Crook et al: Fidaxomicin Versus Vancomycin for Clostridium difficile Infection: Meta-analysis of Pivotal Randomized Controlled Trials . In: Clinical Infectious Diseases . 55, Suppl. 2, January 8, 2012, p. 93-103 , doi : 10.1093 / cid / cis499 , PMID 22752871 .
  • Jennifer S. Hardesty, Paul Juang: Fidaxomicin: A Macrocyclic Antibiotic for the Treatment of Clostridium difficile Infection . In: Pharmacotherapy . tape 31 , no. 9 , 2011, p. 877-886 , doi : 10.1592 / phco.31.9.877 , PMID 21923589 .
  • Federal Joint Committee: Resolution of the Federal Joint Committee on an amendment to the Drugs Directive (AM-RL): Annex XII - Resolutions on the benefit assessment of drugs with new active ingredients according to § 35a SGB V - Fidaxomicin . In: Medicines Directive (AM-RL): Annex XII . July 4, 2013 ( PDF ).

Individual evidence

  1. ↑ a b uniscience: fidaxomicin (PDF; 138 kB).
  2. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
  3. ↑ Decision on additional benefit
  4. ↑ Institute for Quality and Efficiency in Health Care: Fidaxomicin in Clostridium difficile infection: additional benefit not proven . April 15, 2013 ( [1] ).