Brands, Medical Use, Clinical Data
- Radiation-Sensitizing Agents
- Immunosuppressive Agents
- Antineoplastic Agents
- Lyophilized powder for injection
Brands / Synonyms
DDFC; DFDC; Gemcin; Gemcitabina [Inn-Spanish]; Gemcitabine HCl; Gemcitabine hydrochloride; Gemcitabinum [Inn-Latin]; Gemtro; Gemzar; Gemzar
For the first-line treatment of patients with metastatic breast cancer, locally advanced (Stage IIIA or IIIB), or metastatic (Stage IV) non-small cell lung cancer and as first-line treatment for patients with adenocarcinoma of the pancreas.
Gemcitabine is an antineoplastic anti-metabolite. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (or DNA synthesis phase of the cell cycle), stopping normal development and division. Gemcitabine blocks an enzyme which converts the cytosine nucleotide into the deoxy derivative. In addition, DNA synthesis is further inhibited because Gemcitabine blocks the incorporation of the thymidine nucleotide into the DNA strand.
Mechanism of Action
Gemcitabine inhibits thymidylate synthetase, leading to inhibition of DNA synthesis and cell death. Gemcitabine is a prodrug so activity occurs as a result of intracellular conversion to two active metabolites, gemcitabine diphosphate and gemcitabine triphosphate by deoxycitidine kinase. Gemcitabine diphosphate inhibits ribonucleotide reductase, the enzyme responsible for catalyzing synthesis of deoxynucleoside triphosphates required for DNA synthesis. Gemcitabine triphosphate (diflurorodeoxycytidine triphosphate) competes with endogenous deoxynucleoside triphosphates for incorporation into DNA.
Myelosuppression, paresthesias, and severe rash were the principal toxicities, LD50=500 mg/kg (orally in mice and rats)
Biotrnasformation / Drug Metabolism
Transformed via nucleoside kinases to two active metabolites, gemcitabine diphosphate and gemcitabine triphosphate. Can also undergo deamination via cytidine deaminase to an inactive uracil metabolite (dFdU).
Gemzar is contraindicated in those patients with a known hypersensitivity to the drug (see
Allergic under ADVERSE REACTIONS).
No specific drug interaction studies have been conducted. For information on the pharmacokinetics of
Gemzar and cisplatin in combination, see Drug Interactions under CLINICAL