Gemcitabine

Structural formula
General
Non-proprietary name	Gemcitabine
other names	2 ', 2'-difluorodeoxycytidine; 4-Amino-1- [3,3-difluoro-4-hydroxy-5- (hydroxymethyl) tetrahydrofuran-2-yl] -1 H -pyrimidin-2-one ( IUPAC );
Molecular formula	C 9 H 11 F 2 N 3 O 4
External identifiers / databases
EC number	619-100-6
ECHA InfoCard	100.124.343
PubChem	60750
ChemSpider	54753
DrugBank	DB00441
Wikidata	Q414143
Drug information
ATC code	L01 BC05
Drug class	Antimetabolite , cytostatic agent
properties
Molar mass	263,20 g · mol -1
Physical state	firmly
Melting point	287–292 ° C (gemcitabine hydrochloride )
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances danger
H and P phrases	H: 360
	P: 201-308 + 313
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Gemcitabine (2 ′, 2′-difluorodeoxycytidine) is a nucleoside composed of cytosine and a difluorinated deoxyribose . It is a chemical analog of the nucleoside cytidine . It is used as a cytostatic in chemotherapy .

pharmacology

Mechanism of action

Gemcitabine is a cytostatic and is classified in the group of antimetabolites and belongs to the group of pyrimidine analogues. It is a prodrug that is only converted into its actual active form in the human cell.

The cytostatic effect of gemcitabine is based on the fact that instead of the human nucleoside cytidine, the active form of gemcitabine, gemcitabine diphosphate, is built into the DNA . This interrupts DNA synthesis and leads to cell death .

Absorption and distribution in the body

Since gemcitabine is only converted into the active form in the cell by an enzyme, this enzyme is of particular importance. The effectiveness of gemcitabine depends on the dose, but also on the duration of the infusion . Gemcitabine diphosphate is broken down into a cytostatically inactive substance
in the liver , blood and kidneys . It is excreted via the kidneys.
The biological half-life depends on the sex and age of the patient. It takes about 40 to 90 minutes.

Therapeutic use

application areas

Therapy for adenocarcinoma of the pancreas (most common form of pancreatic cancer)

Monotherapy or in combination with paclitaxel or with erlotinib

Non-small cell lung cancer

Combination with cisplatin

Breast cancer (breast cancer)

Combination with paclitaxel

Bladder cancer

Combination with cisplatin

Ovarian cancer (ovarian cancer)

Combination with carboplatin

Relapse therapy for lymphomas (non-Hodgkin and Hodgkin lymphomas)

Combination with dexamethasone

Biliary tract cancer

Monotherapy or in combination with cisplatin

unwanted effects

The most common side effects, which were observed in over 10 percent of those treated, are bone marrow damage , which manifests itself in a reduced number of granulocytes , platelets and leukocytes and anemia , shortness of breath , nausea and vomiting , increase in liver enzymes, allergic rashes and hair loss . Hematuria and proteinuria , as well as flu-like symptoms and edema .

The toxic side effects on the kidneys, liver and blood require careful monitoring of the patient in order to be able to make dose adjustments if necessary.

Side effects that are serious or can become severe, such as Stevens-Johnson syndrome , toxic epidermal necrolysis , posterior reversible encephalopathy syndrome (PRES), capillary leak syndrome , interstitial pneumonia , pulmonary edema , adult acute respiratory distress syndrome (ARDS), and anaphylactic reactions occur rarely (0.01-0.1 percent) to very rarely (less than 0.01 percent of those treated).

Interactions

Radiation therapy for certain clinical pictures

Contraindications

Gemcitabine must not be used in the following cases:

If you are hypersensitive to gemcitabine,
Gemcitabine should not be given in the case of moderately to severely impaired liver function or severely impaired kidney function, as no relevant studies have been carried out.

dosage

Depending on the clinical picture, 1,000–2,000 mg / m ² body surface area .

literature

Pharmaceutical Therapy Criticism, Munich, 2005 Volume 37, pp. 121–128.
Technical information: Gemzar.
Textbook of Primary Care Medicine, 3rd ed, Mosby 2001.

Trade names

Monopreparations

Cytogembin (A), Ebegemcit (A), Gemcapyr (A), Gemcitara (A), Gemzar (D, A, CH, EU), Tabinell (A), various generics (D, A, CH)

Web links

Commons : Gemcitabine - collection of pictures, videos and audio files

Ricarda Wessinghage: Malignant liver diseases: prospect of a new therapy option with gemcitabine. Clinic of the Johann Wolfgang Goethe University, Frankfurt a. M., press release from September 15, 2006 at Informationsdienst Wissenschaft (idw-online.de), accessed on August 24, 2015.

Individual evidence

^ The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals . 14th edition, 2006, ISBN 978-0-911910-00-1 , p. 755.
↑ ^a ^b Data sheet Gemcitabine hydrochloride from Sigma-Aldrich , accessed on April 3, 2011 ( PDF ).
↑ David Goldstein, Robert Hassan El-Maraghi, Pascal Hammel, Volker Heinemann, Volker Kunzmann: nab-Paclitaxel Plus Gemcitabine for Metastatic Pancreatic Cancer: Long-Term Survival From a Phase III Trial . In: Journal of the National Cancer Institute . tape 107 , no. 2 , February 1, 2015, p. dju413 , doi : 10.1093 / jnci / dju413 , PMID 25638248 .

[MerckIndex-1] The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals . 14th edition, 2006, ISBN 978-0-911910-00-1 , p. 755.

[Sigma-2] Data sheet Gemcitabine hydrochloride from Sigma-Aldrich , accessed on April 3, 2011 ( PDF ).

[3] David Goldstein, Robert Hassan El-Maraghi, Pascal Hammel, Volker Heinemann, Volker Kunzmann: nab-Paclitaxel Plus Gemcitabine for Metastatic Pancreatic Cancer: Long-Term Survival From a Phase III Trial . In: Journal of the National Cancer Institute . tape 107 , no. 2 , February 1, 2015, p. dju413 , doi : 10.1093 / jnci / dju413 , PMID 25638248 .