= Additional active ingredients
PRESENTATION AND DOSSAGE
VIAL: 1 x 1000 mg
VIAL: 1 x 200 mg
Treatment of patients with bladder cancer at the invasive stage. In combination with paclitaxel, for the treatment of patients with unresectable, locally recurrent or metastatic breast cancer who have relapsed following adjuvant/neoadjuvant chemotherapy. Prior chemotherapy should have included an anthracycline unless clinically contraindicated. In combination with carboplatin, for the treatment of patients with recurrent epithelial ovarian carcinoma who have relapsed at least six months after platinum-based therapy. Alone or in combination with other chemotherapeutic agents, for the therapeutic activity of advanced or relapsed epithelial ovarian carcinoma. Locally advanced or metastatic adenocarcinoma of the pancreas and 5-FU refractory pancreatic cancer in adult patients. Non-small cell lung cancer, ovarian cancer (used in experimental trials).
Hypersensitivity to the active substance or to any of the excipients. Breast-feeding.
Patients should have an absolute granulocyte count of at least 1,500 (x106/L) prior to initiation of gemcitabine + paclitaxel combination. Patients should be monitored prior to each dose for platelet, leucocyte and granulocyte counts and, if necessary, the dose of gemcitabine may be either reduced or withheld in the presence of hematological toxicity. Periodic checks of liver and kidney functions should be performed. Should be discontinued at the first signs of any evidence of microangiopathic hemolytic anemia. Should not be given with concurrent radical, as opposed to palliative, radiotherapy. Patients with compromised bone marrow function should be monitored prior to each dose for platelet, leucocyte and granulocyte counts.
Pregnancy and lactation: Should be avoided. Patients should be cautioned against driving or operating machinery until it is established that they do not become somnolent. See prescribing information for full details.
Anemia, leucopenia and thrombocytopenia can occur. Thrombocythemia, nausea, vomiting, rash, edema/peripheral edema, alopecia, somnolence, diarrhea.
No specific interaction studies have been performed .
Radiotherapy: Concurrent (given together or ≤ 7 days apart) – Toxicity associated with this multimodality therapy is dependent on many different factors, including dose of gemcitabine, frequency of gemcitabine administration, dose of radiation, radiotherapy planning technique, the target tissue, and target volume. Pre-clinical and clinical studies have shown that gemcitabine has radiosensitising activity. In a single trial, where gemcitabine at a dose of 1,000 mg/m2 was administered concurrently for up to 6 consecutive weeks with therapeutic thoracic radiation to patients with non-small cell lung cancer, significant toxicity in the form of severe, and potentially life-threatening mucositis, especially oesophagitis, and pneumonitis was observed, particularly in patients receiving large volumes of radiotherapy [median treatment volumes 4,795 cm3]. Studies done subsequently have suggested that it is feasible to administer gemcitabine at lower doses with concurrent radiotherapy with predictable toxicity, such as a phase II study in non-small cell lung cancer, where thoracic radiation doses of 66 Gy were applied concomitantly with an administration with gemcitabine (600 mg/m2, four times) and cisplatin (80 mg/m2, twice) during 6 weeks. The optimum regimen for safe administration of gemcitabine with therapeutic doses of radiation has not yet been determined in all tumour types. Non-concurrent (given >7 days apart) – Analysis of the data does not indicate any enhanced toxicity when gemcitabine is administered more than 7 days before or after radiation, other than radiation recall. Data suggest that gemcitabine can be started after the acute effects of radiation have resolved or at least one week after radiation. Radiation injury has been reported on targeted tissues (e.g., oesophagitis, colitis, and pneumonitis) in association with both concurrent and non-concurrent use of gemcitabine.
Others: Yellow fever and other live attenuated vaccines are not recommended due to the risk of systemic, possibly fatal, disease, particularly in immunosuppressed patients.
Non-Small Cell Lung Cancer: Combination use:
Adults: Gemcitabine in combination with cisplatin has been investigated using two dosing regimen. One regimen used a three week schedule and the other used a four week schedule. The three week schedule used gemcitabine 1250mg/mP2P, given by 30 minute intravenous infusion, on days 1 and 8 of each 21 day cycle. Dosage reduction with each cycle or within a cycle may be applied based upon the amount of toxicity experienced by the patient. The four week schedule used gemcitabine 1000mg/mP2P, given by 30 minute intravenous infusion, on days 1, 8, 15 of each 28 day cycle. Dosage reduction with each cycle or within a cycle may be applied based upon the amount of toxicity experienced by the patient. Cisplatin has been used at doses between 75-100mg/m2 once every 3 or 4 weeks.
Adults: The recommended dose of gemcitabine is 1,000mg/m2, given by 30 minute intravenous infusion. This should be repeated once weekly for three weeks, followed by a one week rest period. This four week cycle is then repeated. Dosage reduction is applied based upon the amount of toxicity experienced by the patient.
Combination use: Adults: Gemcitabine in combination with paclitaxel is recommended using paclitaxel (175mg/m2) administered on Day 1 over approximately 3 hours as an intravenous infusion, followed by gemcitabine (1250mg/m2) as a 30-minute intravenous infusion on Days 1 and 8 of each 21-day cycle. Dose reduction with each cycle or within a cycle may be applied based upon the amount of toxicity experienced by the patient. Patients should have an absolute granulocyte count of at least 1,500 (x106/L) prior to initiation of gemcitabine + paclitaxel combination.
Adults: The recommended dose of gemcitabine is 1,000mg/m2, given by 30-minute intravenous infusion. This should be repeated once weekly for up to 7 weeks, followed by a week of rest. Subsequent cycles should consist of injections once weekly for 3 consecutive weeks out of every 4 weeks. Dosage reduction is applied based upon the amount of toxicity experienced by the patient.
Combination use: Adults: The recommended dose for gemcitabine is 1000mg/ m2, given by 30 minute infusion. The dose should be given on days 1, 8, and 15 of each 28 day cycle in combination with cisplatin. Cisplatin is given at a recommended dose of 70mg/m2 on day 1 following gemcitabine or day 2 of each 28 day cycle. This four week cycle is then repeated. Dosage reduction with each cycle or within a cycle may be applied based upon the amount of toxicity experienced by the patient. A clinical trial showed more myelosuppression when cisplatin was used in doses of 100mg/m2.
Combination use: Adults: Gemcitabine in combination with carboplatin is recommended using gemcitabine 1000mg/m2 administered on Days 1 and 8 of each 21-day cycle as a 30-minute intravenous infusion. After gemcitabine, carboplatin will be given on Day 1 consistent with a target AUC of 4.0mg/ml•min. Dosage reduction with each cycle or within a cycle may be applied based upon the amount of toxicity experienced by the patient.
There is no known antidote for overdose of gemcitabine. Doses as high as 5,700mg/m2 have been administered by intravenous infusion over 30 minutes every 2 weeks with clinically acceptable toxicity. In the event of suspected overdose, the patient should be monitored with appropriate blood counts and receive supportive therapy, as necessary.
PREGNANCY & LACTATION
Pregnancy: There are no adequate data from the use of gemcitabine in pregnant women. Studies in animals have shown reproductive toxicity. Based on results from animal studies and the mechanism of action of gemcitabine, this substance should not be used during pregnancy unless clearly necessary. Women should be advised not to become pregnant during treatment with gemcitabine and to warn their attending physician immediately, should this occur after all.
Breast-feeding: It is not known whether gemcitabine is excreted in human milk and adverse effects on the suckling child cannot be excluded. Breast-feeding must be discontinued during gemcitabine therapy.
Fertility: In fertility studies gemcitabine caused hypospermatogenesis in male mice. Therefore, men being treated with gemcitabine are advised not to father a child during and up to 6 months after treatment and to seek further advice regarding cryoconservation of sperm prior to treatment because of the possibility of infertility due to therapy with gemcitabine.
MANUFACTURER & DISTRIBUTER:
Manufacturer: Eli Lilly Israel Ltd.