Tigecycline

Structural formula
General
Non-proprietary name	Tigecycline
other names	(4 S , 4a S , 5a R , 12a S ) -4,7-bis (dimethylamino) -9 - [( tert -butylamino) acetamido] -3,10,12,12a-tetrahydroxy-1,11-dioxo- 1,4,4a, 5,5a, 6,11,12a-octahydrotetracene-2-carbamide ( IUPAC ); Tigecyclinum ( Latin );
Molecular formula	C 29 H 39 N 5 O 8
External identifiers / databases
EC number	685-736-6
ECHA InfoCard	100.211.439
PubChem	5282044
DrugBank	DB00560
Wikidata	Q420595
Drug information
ATC code	J01 AA12
Drug class	Tetracycline antibiotic , glycylcycline
Mechanism of action	Inhibition of bacterial protein synthesis on their ribosomes
properties
Molar mass	585.65 g mol −1
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
H and P phrases	H: 319-360
	P: ?
Toxicological data	106 mg kg −1 ( LD 50 , rat , iv )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Tigecycline is a semi-synthetically produced antibiotic and the first member of the glycylcycline class . These are derivatives of the tetracyclines that have a glycylamido group in the 9-position on the D-ring. Tigecycline bypasses two important resistance mechanisms : the efflux pump and ribosomal protection mechanisms. The very broad spectrum of activity includes gram-positive , gram-negative , atypical and multi-resistant germs. Tigecycline was approved in November 2007 in Germany for the parenteral treatment of severe infections under the trade name Tygacil .

application areas

Tigecycline is indicated in adults and children aged 8 years and over to treat:

complicated skin and soft tissue infections (except for infections of the diabetic foot),
complicated intra-abdominal infections when other alternative antibiotics are not appropriate.

Tigecycline is not indicated for infections with Pseudomonas aeruginosa . Tigecycline is expressly only approved for the treatment of complicated skin and soft tissue infections and complicated intra-abdominal infections.

Tigecycline had shown increased mortality in clinical trials ; In particular, the course of the disease seems to be more unfavorable in patients who develop a superinfection during therapy with tigecycline - especially in the case of nosocomial pneumonia . Patients should be closely monitored for the development of superinfection.

If, after the start of therapy, it is determined that the focus of infection does not correspond to the approved indications, an alternative antibacterial therapy is recommended.

Mechanism of action

Tigecycline basically works like the classic tetracyclines , but binds to ribosomes with a five-fold higher affinity and thus makes protection proteins ineffective.

Tigecycline is not transported out of the target cell by the efflux pump and thus also acts against pathogens that are already resistant to other active ingredients.

metabolism

Less than 20% is metabolized, the half-life is 42 hours. 60% is excreted in the bile and faeces , 33% in the urine .

Side effects

There are no studies yet for children and adolescents under 18 years of age; initial evidence suggests delayed bone formation. Nausea and vomiting occur significantly more frequently than in comparison groups. The side effect is dose-dependent, therefore it is recommended to split the daily dose into two doses. There is an increased mortality rate with tigecycline. This is especially true for the treatment of pneumonia ; For example, 1.9% more deaths occurred with tigecycline in the treatment of hospital-acquired pneumonia than with comparison substances (14.1 vs. 12.2%), in the subgroup of ventilator-associated pneumonia there were even 6.8% more deaths ( 19.1 vs. 12.3%).

interaction

Tigecycline is not metabolized via the cytochrome P450 system , which has a positive effect on possible interactions. No antagonism to other antibiotic groups could be determined in vitro . If warfarin is administered at the same time , the blood coagulation parameters must be checked. The effectiveness of oral contraceptives may be impaired.

application

Tigecycline is given intravenously. You start with an initial dose of 100 mg, then 50 mg every 12 hours.

Individual evidence

↑ Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . A labeling of 4S, 4aS, 5aR, 12aS) -9- [2- (tert-butylamino) acetamido] -4,7-bis (dimethylamino) -1,4,4a, 5, Template: link text check / apostrophe is reproduced from a self-classification by the distributor 5a, 6,11, 12a-octahydro-3,10,12, 2a-tetrahydroxy-1, 11-dioxo-2-naphthacenecarboxamide (hydrochloride) in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on July 12, 2020 .

↑ Accessdata FDA: FDA Tygacil (tigecycline) iv injection label (PDF; 325 kB).

↑ fachinfo.de: Tygacil (PDF).

↑ ^a ^b Rote-Hand-Brief of the Drugs Commission of the German Medical Association (AkdÄ).

↑ FDA: FDA Drug Safety Communication: Increased risk of death with Tygacil (tigecycline) compared to other antibiotics used to treat similar infections .

[1] Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . A labeling of 4S, 4aS, 5aR, 12aS) -9- [2- (tert-butylamino) acetamido] -4,7-bis (dimethylamino) -1,4,4a, 5, Template: link text check / apostrophe is reproduced from a self-classification by the distributor 5a, 6,11, 12a-octahydro-3,10,12, 2a-tetrahydroxy-1, 11-dioxo-2-naphthacenecarboxamide (hydrochloride) in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on July 12, 2020 .

[2] Accessdata FDA: FDA Tygacil (tigecycline) iv injection label (PDF; 325 kB).

[3] .de: Tygacil (PDF).

[rhb2011148-4] Rote-Hand-Brief of the Drugs Commission of the German Medical Association (AkdÄ).

[5] FDA: FDA Drug Safety Communication: Increased risk of death with Tygacil (tigecycline) compared to other antibiotics used to treat similar infections .