Gemcitabine Hydrochloride (5 brand names, 3 dosage forms, 3 routes)
Available dosage forms: SOLUTION, INJECTABLE, SYSTEM.
Routes of administration: INTRAVENOUS, INJECTION, INTRAVESICAL.
Brand Names
- AVGEMSI
- GEMCITABINE HYDROCHLORIDE
- GEMZAR
- INFUGEM
- INLEXZO
Contraindications
Gemcitabine Injection is contraindicated in patients with a known hypersensitivity to gemcitabine. Reactions include anaphylaxis [see Adverse Reactions (6.1)].
Adverse Reactions
The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity [see Contraindications (4)] Schedule-Dependent Toxicity [see Warnings and Precautions (5.1)] Myelosuppression [see Warnings and Precautions (5.2)] Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.3)] Pulmonary Toxicity and Respiratory Failure [see Warnings and Precautions (5.4)] Hemolytic Uremic Syndrome [see Warnings and Precautions (5.5)] Hepatic Toxicity [see Warnings and Precautions (5.6)] Exacerbation of Radiation Therapy Toxicity [see Warnings and Precautions (5.8)] Capillary Leak Syndrome [see Warnings and Precautions (5.9)] Posterior Reversible Encephalopathy Syndrome [see Warnings and Precautions (5.10)]
Mechanism of Action
Gemcitabine kills cells undergoing DNA synthesis and blocks the progression of cells through the G1/S-phase boundary. Gemcitabine is metabolized by nucleoside kinases to diphosphate (dFdCDP) and triphosphate (dFdCTP) nucleosides. Gemcitabine diphosphate inhibits ribonucleotide reductase, an enzyme responsible for catalyzing the reactions that generate deoxynucleoside triphosphates for DNA synthesis, resulting in reductions in deoxynucleotide concentrations, including dCTP. Gemcitabine triphosphate competes with dCTP for incorporation into DNA. The reduction in the intracellular concentration of dCTP by the action of the diphosphate enhances the incorporation of gemcitabine triphosphate into DNA (self-potentiation). After the gemcitabine nucleotide is incorporated into DNA, only one additional nucleotide is added to the growing DNA strands which eventually results in the initiation of apoptotic cell death.
Overdosage
There is no known antidote for overdoses of gemcitabine. Myelosuppression, paresthesias, and severe rash were the principal toxicities seen when a single dose as high as 5,700 mg/m2 was administered by intravenous infusion over 30 minutes every 2 weeks to several patients in a dose-escalation study. In the event of suspected overdose, monitor with appropriate blood counts and provide supportive therapy, as necessary.