Gemcitabine
Indications
Gemcitabine is used for:
Lung cancer, pancreatic cancer, bladder cancer, breast cancer, ovarian carcinoma
Adult Dose
Pancreatic Cancer
Indicated as first-line treatment for locally advanced (nonresectable Stage II or Stage III) or metastatic (Stage IV) adenocarcinoma of the pancreas
1000 mg/m² IV infusion over 30 minutes once/week x7 weeks; rest 1 week, THEN
1000 mg/m² IV on Days 1, 8, and 15 of each 28-day cycle
Various regimens exist including monotherapy and in combination with other chemotherapy agents (eg, erlotinib, paclitaxel protein bound, capecitabine)
Non-small Cell Lung Cancer
1000 mg/m² IV infusion over 30 minutes on days 1, 8, and 15 of each 28-day cycle, OR
1250 mg/m² IV infusion over 30 minutes on days 1 and 8 of each 21-day cycle
Administer cisplatin 100 mg/m² IV after gemcitabine on day 1
Breast Cancer
1250 mg/m² IV infusion over 30 minutes on Days 1 and 8 of each 21-day cycle
With paclitaxel 175 mg/m² on Day 1 as a 3 hr infusion before gemcitabine
Ovarian Cancer
1000 mg/m² IV infusion over 30 minutes on Days 1 and 8 of each 21-day cycle
With carboplatin AUC 4 on Day 1 after gemcitabine
Child Dose
Renal Dose
Administration
IV Preparation
Reconstitute 200 mg vial with 5 mL 0.9% NaCl OR 1000 mg vial with 25 mL 0.9% NaCl
IV Administration
For IV infusion only
Concentrated injection (10 mg/mL) must be diluted to 2 mg/mL prior to administration
Infuse over 30 min
Avoid rapid infusions
Contra Indications
Concurrent radical radiotherapy; pregnancy, lactation; hypersensitivity.
Precautions
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.
Lactation: not known if excreted in breast milk; do not nurse
Pregnancy-Lactation
Interactions
May increase the anticoagulant effect of warfarin when used together.
Adverse Effects
Side effects of Gemcitabine :
>10%
N/V (69%),Anemia (65%),Elev LFTs (68%),Neutropenia (63%),Leukopenia (62%),Pain (48%),Proteinuria (45%),Fever (41%),Hematuria (35%),Rash (30%),Thrombocytopenia (24%),Dyspnea (23%),Constipation (23%),Diarrhea (19%),Flu-like syndrome (19%),Hemorrhage (17%),BUN increased (16%),Infection (16%),Alopecia (15%),Edema (13%),Elev bilirubin (13%)
1-10%
Paresthesia (2-10%),Creatinine increased (2-8%),Inj site reactions (4%),Bronchospasm (2%)
Potentially Fatal: Oesophagitis and pneumonitis when given with radical radiotherapy to the thorax.
Mechanism of Action
Gemcitabine is a synthetic pyrimidine nucleoside and cytarabine analogue which is metabolised intracellularly to active diphosphate and triphosphate nucleosides. It inhibits DNA synthesis by inhibiting DNA polymerase and ribonucleotide reductase. It also induces apoptosis and is primarily active against cells in the S-phase, but may also arrest cells at the G1-S border.