Epirubicin

Structural formula
General
Non-proprietary name	Epirubicin
other names	(8 R , 10 S ) -10 - [(2 S , 4 S , 5 R , 6 S ) -4-amino-5-hydroxy-6-methyl-oxan-2-yl] oxy-6,11-dihydroxy -8- (2-hydroxyacetyl) -1-methoxy-8-methyl-9,10-dihydro-7 H -tetracene-5,12-dione ( IUPAC ) ; Epirubicini hydrochloridum;
Molecular formula	C 27 H 29 NO 11 (epirubicin) ; C 27 H 29 NO 11 HCl (epirubicin hydrochloride ) ;
Brief description	orange-red crystals (epirubicin hydrochloride)
External identifiers / databases
PubChem	41867
ChemSpider	38201
DrugBank	DB00445
Wikidata	Q425122
Drug information
ATC code	L01 DB03
Drug class	Anthracyclines
Mechanism of action	DNA intercalation, topoisomerase II inhibition
properties
Molar mass	543.52 g mol −1 (epirubicin) ; 579.98 g mol −1 (epirubicin) ;
Physical state	firmly
Melting point	185 ° C (decomposition) (epirubicin hydrochloride)
solubility	very bad in water (93 mg l −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: 302-340-350-360
	P: 201-280-301 + 312 + 330-308 + 313
Toxicological data	16.07 mg kg −1 ( LD 50 , mouse , iv ) ; 14.27 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 .

Epirubicin is an organic chemical compound that is one of the derivatives of anthraquinone and glycosides . The compound is a stereoisomer of doxorubicin (also adriamycin ) and belongs to the group of anthracyclines . The red-orange, crystalline powder decomposes in sunlight and is hydrolyzed in the presence of water .

Epirubicin is a cytotoxic antibiotic which has been used for many years as a basic drug in the drug therapy of cancer diseases and is now an important component in combination chemotherapy for various malignant tumors. Epirubicin is used as a hydrochloride (trade name: Farmorubicin ( Pfizer ) and others) as a cytostatic . Epirubicin hydrochloride has been in clinical use since the 1980s and is used intravenously in the chemotherapy of breast cancer (breast cancer), non-Hodgkin lymphoma , sarcoma , gastric cancer, ovarian cancer, and other solid cancers. It is also used to prevent recurrence after bladder cancer.

Epirubicin and Adriamycin have a cytotoxic and mutagenic effect through direct damage to the DNA and inhibition of DNA polymerase and RNA polymerase . The cardiotoxicity of epirubicin is lower than that of daunorubicin.

The spectrum of side effects is similar to that of the other anthracyclines. The following can occur: allergies, cardiomyopathy (dose-dependent), bone marrow depression (worsening blood count), nausea, vomiting, hair loss and others.

Trade names

Monopreparations

Axirubicin-e (D), Bendaepi (D), Ellence (USA), Epi-cell (D, A), Farmorubicin (D, A, CH), Riboepi (D), various generics (D, A, CH)

Delivery bottlenecks

In January 2020, Der Spiegel reported that there were delivery bottlenecks for epirubicin in Germany. One reason is that a factory in Ukraine could not deliver as a result of the war. Other providers pointed out that production was not economically viable. In a joint statement by the German Society for Urology , the German Society for Hematology and Medical Oncology and the German Society for Senology , it was recommended that doxorubicin be used in the event of delivery problems with epirubicin . The data situation is assessed as follows:

Replacement of epirubicin
tumor	Replacement drug	evidence
Bladder cancer	Docorubicin, mitomycin C	indirect comparison
Hepatocellular carcinoma	Docorubicin	indirect comparison
small cell lung cancer	Docorubicin	indirect comparison
Stomach cancer	Docorubicin	indirect comparison
Breast cancer	Docorubicin	randomized trials
Adenocarcinoma of the esophagus	Docorubicin	indirect comparison
Soft tissue sarcomas	Docorubicin	randomized trials

Web links

FDA: Epirubicin (engl.)

Individual evidence

↑ ^a ^b ^c ^d F. von Bruchhausen, S. Ebel, AW Frahm, E. Hackenthal: Hagers Handbook of Pharmaceutical Practice. Vol. 8 Substances E – O. 5th edition, pp. 49-51, Birkhäuser, 1991, ISBN 978-3-540-52688-9 .
↑ ^a ^b ^c Entry on epirubicin in the ChemIDplus database of the United States National Library of Medicine (NLM) .
↑ ^a ^b Datasheet Epirubicin hydrochloride from Sigma-Aldrich , accessed on February 18, 2018 ( PDF ).
↑ ^a ^b C. Bertazzoli, C. Rovero a. a .: Experimental systemic toxicology of 4′-epidoxorubicin, a new, less cardiotoxic anthracycline antitumor agent. In: Toxicology and Applied Pharmacology. 79, 1985, p. 412, doi : 10.1016 / 0041-008X (85) 90139-5 .
↑ A. Paul Launchbury, Nassir Habboubi: epirubicin and doxorubicin: a comparison of Their characteristics, therapeutic activity and toxicity . In: Cancer Treatment Reviews . tape 19 , no. 3 , July 1993, p. 197-228 , doi : 10.1016 / 0305-7372 (93) 90036-Q ( elsevier.com [accessed July 4, 2020]).
↑ Martin U. Müller , Der Spiegel : Delivery problems with drugs: Now a cancer drug is also affected - DER SPIEGEL - Wissenschaft. Retrieved January 26, 2020 .
↑ Epirubicin - supply bottleneck. Retrieved January 26, 2020 .
^ Statement by the German Society for Urology e. V., the German Society for Hematology and Medical Oncology e. V. (DGHO) and the German Society for Senology e. V. (DGS) on epirubicin in the therapy of solid tumors . In: Senologie - Journal for Mammadiagnostik und -therapie . tape 17 , no. June 02 , 2020, ISSN 1611-6453 , p. 78–80 , doi : 10.1055 / a-1159-5257 ( thieme-connect.de [accessed on July 4, 2020]).

[hager-1] F. von Bruchhausen, S. Ebel, AW Frahm, E. Hackenthal: Hagers Handbook of Pharmaceutical Practice. Vol. 8 Substances E – O. 5th edition, pp. 49-51, Birkhäuser, 1991, ISBN 978-3-540-52688-9 .

[chemid-2] Entry on epirubicin in the ChemIDplus database of the United States National Library of Medicine (NLM) .

[Sigma-3] Datasheet Epirubicin hydrochloride from Sigma-Aldrich , accessed on February 18, 2018 ( PDF ).

[toxapph-4] C. Bertazzoli, C. Rovero a. a .: Experimental systemic toxicology of 4′-epidoxorubicin, a new, less cardiotoxic anthracycline antitumor agent. In: Toxicology and Applied Pharmacology. 79, 1985, p. 412, doi : 10.1016 / 0041-008X (85) 90139-5 .

[5] A. Paul Launchbury, Nassir Habboubi: epirubicin and doxorubicin: a comparison of Their characteristics, therapeutic activity and toxicity . In: Cancer Treatment Reviews . tape 19 , no. 3 , July 1993, p. 197-228 , doi : 10.1016 / 0305-7372 (93) 90036-Q ( elsevier.com [accessed July 4, 2020]).

[6] Martin U. Müller , Der Spiegel : Delivery problems with drugs: Now a cancer drug is also affected - DER SPIEGEL - Wissenschaft. Retrieved January 26, 2020 .

[7] Epirubicin - supply bottleneck. Retrieved January 26, 2020 .

[8] Statement by the German Society for Urology e. V., the German Society for Hematology and Medical Oncology e. V. (DGHO) and the German Society for Senology e. V. (DGS) on epirubicin in the therapy of solid tumors . In: Senologie - Journal for Mammadiagnostik und -therapie . tape 17 , no. June 02 , 2020, ISSN 1611-6453 , p. 78–80 , doi : 10.1055 / a-1159-5257 ( thieme-connect.de [accessed on July 4, 2020]).