Ovarian Cancer: Gemcitabine in combination with carboplatin is indicated for the treatment of patients with advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based therapy. Breast Cancer: Gemcitabine in combination with paclitaxel is indicated for the first-line treatment of patients with metastatic breast cancer after failure of prior anthracycline-containing adjuvant chemotherapy, unless anthracyclines were clinically contraindicated. Non-Small Cell Lung Cancer: Gemcitabine is indicated in combination with cisplatin for the first-line treatment of patients with inoperable, locally advanced (Stage IIIA or IIIB), or metastatic (Stage IV) non-small cell lung cancer. Pancreatic Cancer: Gemcitabine is indicated as first-line treatment for patients with locally advanced (nonresectable Stage II or Stage III) or metastatic (Stage IV) adenocarcinoma of the pancreas. Gemcitabine is indicated for patients previously treated with 5-FU.
Gemcitabine (dFdC) is metabolised intracellularly by nucleoside kinases to the active diphosphate (dFdCDP) and triphosphate (dFdCTP) nucleosides. The cytotoxic action of Gemcitabine appears to be due to inhibition of DNA synthesis by two actions of dFdCDP and dFdCTP. First, dFdCDP inhibits ribonucleotide reductase which is uniquely responsible for catalysing the reactions that generate the deoxynucleoside triphosphates for DNA synthesis. Inhibition of this enzyme by dFdCDP causes a reduction in the concentrations of deoxynucleosides in general, and especially in that of dCTP. Secondly, dFdCTP competes with dCTP for incorporation into DNA. Likewise, a small amount of Gemcitabine may also be incorporated into RNA. Thus, the reduction in the intracellular concentration of dCTP potentiates the incorporation of dFdCTP into DNA (self-potentiation). DNA polymerase epsilon is essentially unable to remove Gemcitabine and repair the growing DNA strands. After Gemcitabine is incorporated into DNA, one additional nucleotide is added to the growing DNA strands. After this addition, there is essentially a complete inhibition in further DNA synthesis (masked chain termination). After incorporation into DNA, Gemcitabine then appears to induce the programmed cellular death process known as apoptosis.
Intravenous (Adult)- Advanced non-small cell lung cancer: 1000 mg/m2 on days 1, 8 and 15 of each 28-day cycle; or 1250 mg/m2 on days 1 and 8 of each 21-day cycle. Pancreatic carcinoma: 1000 mg/m2 once wkly for up to 7 wk followed by 1 wk of rest. Continue thereafter with once wkly infusions for 3 consecutive wk out of 4. Ovarian carcinoma: To be given before carboplatin: 1000 mg/m2 on days 1 and 8 of each 21-day cycle. Breast cancer: Usually in combination with a taxane such as paclitaxel: 1250 mg/m2 on days 1 and 8 of each 21-day cycle. Bladder cancer: To be given before cisplatin. 1000 mg/m2 on days 1, 8 and 15 of each 28-day cycle.
No confirmed interactions have been reported with the use of Gemcitabine. No specific drug interaction studies have been conducted.
Concurrent radical radiotherapy; pregnancy, lactation; hypersensitivity. Children, hepatic and renal impairment. May impair ability to drive or operate machinery. Discontinue on 1st sign of microangiopathic haemolytic anaemia. Prolonged infusion time (>60 minutes) and more frequent than wkly dosing may increase toxicity. Monitor CBC before every dose. Increased risk of haemolytic uraemic syndrome and/or thrombocytcpenic purpura which may lead to irreversible renal failure.
Bone marrow suppression as manifested by leukopenia, thrombocytopenia, anaemia and myelosuppression. Mild GI effects; rashes; renal impairment, pulmonary toxicity, influenza-like symptoms; interstitial pneumonia, pulmonary oedema. Proteinuria, haematuria and haemolytic uraemic syndrome. Elevation of serum transaminase.
Category D: There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
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 5700 mg/m2 was administered by IV infusion over 30 minutes every 2 weeks to several patients in a Phase 1 study. In the event of suspected overdose, the patient should be monitored with appropriate blood counts and should receive supportive therapy, as necessary.
Store the vial in original carton at 20° to 25°C, away from light. Do not refrigerate as crystallisation may occur. Keep out of the reach of children.
.png&w=384&q=75)