Gemzar - General Information
Gemzar is a nucleoside analog used as chemotherapy. It is marketed as Gemzar® by Eli Lilly and Company. As with fluorouracil and other analogues of pyrimidines, the drug replaces one of the building blocks of nucleic acids, in this case cytidine, during DNA replication. The process arrests tumor growth, as new nucleosides cannot be attached to the "faulty" nucleoside, resulting in apoptosis (cellular "suicide").
Gemzar is used in various carcinomas: non-small cell lung cancer, pancreatic cancer, bladder cancer and breast cancer. It is being investigated for use in oesophageal cancer, and is used experimentally in lymphomas and various other tumor types.
Pharmacology of Gemzar
Gemzar 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. Gemzar blocks an enzyme which converts the cytosine nucleotide into the deoxy derivative. In addition, DNA synthesis is further inhibited because Gemzar blocks the incorporation of the thymidine nucleotide into the DNA strand.
Gemzar for patients
General �� Patients receiving therapy with Gemzar should be monitored closely by a physician
experienced in the use of cancer chemotherapeutic agents. Most adverse events are reversible and
do not need to result in discontinuation, although doses may need to be withheld or reduced.
There was a greater tendency in women, especially older women, not to proceed to the next
Laboratory Tests �� Patients receiving Gemzar should be monitored prior to each dose with a
complete blood count (CBC), including differential and platelet count. Suspension or
modification of therapy should be considered when marrow suppression is detected.
No specific drug interaction studies have been conducted. For information on the pharmacokinetics of Gemzar and cisplatin in combination, see Drug Interactions under CLINICAL PHARMACOLOGY section.
Gemzar is contraindicated in those patients with a known hypersensitivity to the drug (see Allergic under ADVERSE REACTIONS).
Additional information about Gemzar
Gemzar Indication: 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.
Mechanism Of Action: Gemzar inhibits thymidylate synthetase, leading to inhibition of DNA synthesis and cell death. Gemzar is a prodrug so activity occurs as a result of intracellular conversion to two active metabolites, gemcitabine diphosphate and gemcitabine triphosphate by deoxycitidine kinase. Gemzar diphosphate inhibits ribonucleotide reductase, the enzyme responsible for catalyzing synthesis of deoxynucleoside triphosphates required for DNA synthesis. Gemzar triphosphate (diflurorodeoxycytidine triphosphate) competes with endogenous deoxynucleoside triphosphates for incorporation into DNA.
Drug Interactions: Anisindione The agent increases the effect of anticoagulant
Acenocoumarol The agent increases the effect of anticoagulant
Dicumarol The agent increases the effect of anticoagulant
Warfarin The agent increases the effect of anticoagulant
Paclitaxel Paclitaxel increases the effect/toxicity of gemcitabine
Food Interactions: Not Available
Generic Name: Gemcitabine
Synonyms: Not Available
Drug Category: Radiation-Sensitizing Agents; Immunosuppressive Agents; Antimetabolites; Antineoplastic Agents; Antiviral Agents
Drug Type: Small Molecule; Approved
Toxicity (Overdose): Myelosuppression, paresthesias, and severe rash were the principal toxicities, LD50=500 mg/kg (orally in mice and rats)
Protein Binding: Plasma protein binding is negligible (<10%)
Biotransformation: 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).
Half Life: Short infusions ranged from 32 to 94 minutes, and the value for long infusions vary from 245 to 638 minutes, depending on age and gender.
Dosage Forms of Gemzar: Powder, for solution Intravenous
Chemical IUPAC Name: 4-amino-1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one
Chemical Formula: C9H11F2N3O4
Gemcitabine on Wikipedia: https://en.wikipedia.org/wiki/Gemcitabine
Organisms Affected: Humans and other mammals