1.1 Ovarian Cancer

Gemzar in combination with carboplatin is indicated for the treatment of patients with advanced ovarian cancer that has relapsed at least 6months after completion of platinum-based therapy.

1.2 Breast Cancer

Gemzar 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.

1.3 Non-Small Cell Lung Cancer

Gemzar is indicated in combination with cisplatin for the first-line treatment of patients with inoperable, locally advanced (StageIIIA orIIIB), or metastatic (StageIV) non-small cell lung cancer.

1.4 Pancreatic Cancer

Gemzar is indicated as first-line treatment for patients with locally advanced (nonresectable StageII or StageIII) or metastatic (StageIV) adenocarcinoma of the pancreas. Gemzar is indicated for patients previously treated with 5-FU.

2.1 Ovarian Cancer

Gemzar should be administered intravenously at a dose of 1000mg/m2 over 30minutes on Days1 and 8 of each 21-day cycle. Carboplatin AUC4 should be administered intravenously on Day1 after Gemzar administration. Patients should be monitored prior to each dose with a complete blood count, including differential counts. Patients should have an absolute granulocyte count ≥1500x106/L and a platelet count ≥100,000x106/L prior to each cycle.

2.2 Breast Cancer

Gemzar should be administered intravenously at a dose of 1250mg/m2 over 30minutes on Days1 and8 of each 21-day cycle. Paclitaxel should be administered at 175mg/m2 on Day1 as a 3-hour intravenous infusion before Gemzar administration. Patients should be monitored prior to each dose with a complete blood count, including differential counts. Patients should have an absolute granulocyte count ≥1500x106/L and a platelet count ≥100,000x106/L prior to each cycle.

2.3 Non-Small Cell Lung Cancer

Twoschedules have been investigated and the optimum schedule has not been determined [see Clinical Studies (14.3)]. With the 4-week schedule, Gemzar should be administered intravenously at 1000mg/m2 over 30minutes on Days1, 8, and 15 of each 28-day cycle. Cisplatin should be administered intravenously at 100mg/m2 on Day1 after the infusion of Gemzar. With the 3-week schedule, Gemzar should be administered intravenously at 1250mg/m2 over 30minutes on Days 1 and 8 of each 21-day cycle. Cisplatin at a dose of 100mg/m2 should be administered intravenously after the infusion of Gemzar on Day1. See prescribing information for cisplatin administration and hydration guidelines.

2.4 Pancreatic Cancer

Gemzar should be administered by intravenous infusion at a dose of 1000mg/m2 over 30minutes onceweekly for up to 7weeks (or until toxicity necessitates reducing or holding a dose), followed by a week of rest from treatment. Subsequent cycles should consist of infusions once weekly for 3consecutive weeks out of every 4weeks.

2.5 Preparation and Administration Precautions

Caution should be exercised in handling and preparing Gemzar solutions. The use of gloves is recommended. If Gemzar solution contacts the skin or mucosa, immediately wash the skin thoroughly with soap and water or rinse the mucosa with copious amounts of water. Although acute dermal irritation has not been observed in animal studies, 2of 3rabbits exhibited drug-related systemic toxicities (death, hypoactivity, nasal discharge, shallow breathing) due to dermal absorption.

Procedures for proper handling and disposal of anti-cancer drugs should be considered. Several guidelines on this subject have been published [see References (15)].

2.6 Preparation for Intravenous Infusion Administration

The recommended diluent for reconstitution of Gemzar is 0.9%Sodium Chloride Injection without preservatives. Due to solubility considerations, the maximum concentration for Gemzar upon reconstitution is 40mg/mL. Reconstitution at concentrations greater than 40mg/mL may result in incomplete dissolution, and should be avoided.

To reconstitute, add 5 mL of 0.9% Sodium Chloride Injection to the 200-mg vial or 25 mL of 0.9% Sodium Chloride Injection to the 1-g vial. Shake to dissolve. These dilutions each yield a gemcitabine concentration of 38 mg/mL which includes accounting for the displacement volume of the lyophilized powder (0.26 mL for the 200-mg vial or 1.3 mL for the 1-g vial). The total volume upon reconstitution will be 5.26 mL or 26.3 mL, respectively. Complete withdrawal of the vial contents will provide 200 mg or 1 g of gemcitabine, respectively. Prior to administration the appropriate amount of drug must be diluted with 0.9% Sodium Chloride Injection. Final concentrations may be as low as 0.1 mg/mL.

Reconstituted Gemzar is a clear, colorless to light straw-colored solution. After reconstitution with 0.9%Sodium Chloride Injection, the pH of the resulting solution lies in the range of2.7 to3.3. The solution should be inspected visually for particulate matter and discoloration prior to administration, whenever solution or container permit. If particulate matter or discoloration is found, do not administer.

When prepared as directed, Gemzar solutions are stable for 24hours at controlled room temperature 20°to25°C(68°to77°F) [see USP Controlled Room Temperature]. Discard unused portion. Solutions of reconstituted Gemzar should not be refrigerated, as crystallization may occur.

The compatibility of Gemzar with other drugs has not been studied. No incompatibilities have been observed with infusion bottles or polyvinyl chloride bags and administration sets.

5.1 Infusion Time

Caution — Prolongation of the infusion time beyond 60minutes and more frequent than weeklydosing have been shown to increase toxicity [see Clinical Studies (14.5)].

5.2 Hematology

Gemzar can suppress bone marrow function as manifested by leukopenia, thrombocytopenia, and anemia [see Adverse Reactions (6.1)], and myelosuppression is usually the dose-limiting toxicity. Patients should be monitored for myelosuppression during therapy [see Dosage and Administration (2.1, 2.2, 2.3, and 2.4)].

5.3 Pulmonary

Pulmonary toxicity has been reported with the use of Gemzar. In cases of severe lung toxicity, Gemzar therapy should be discontinued immediately and appropriate supportive care measures instituted [see Adverse Reactions (6.1 and 6.2)].

5.4 Renal

Hemolytic Uremic Syndrome(HUS) and/or renal failure have been reported following one or more doses of Gemzar. Renal failure leading to death or requiring dialysis, despite discontinuation of therapy, has been reported. The majority of the cases of renal failure leading to death were due to HUS [see Adverse Reactions (6.1 and 6.2)].

Gemzar should be used with caution in patients with preexisting renal impairment as there is insufficient information from clinical studies to allow clear dose recommendation for these patient populations [see Use in Specific Populations (8.6)].

5.5 Hepatic

Serious hepatotoxicity, including liver failure and death, has been reported in patients receiving Gemzar alone or in combination with other potentially hepatotoxic drugs [see Adverse Reactions (6.1 and 6.2)].

Gemzar should be used with caution in patients with preexisting hepatic insufficiency as there is insufficient information from clinical studies to allow clear dose recommendation for these patient populations. Administration of Gemzar in patients with concurrent liver metastases or a preexisting medical history of hepatitis, alcoholism, or liver cirrhosis may lead to exacerbation of the underlying hepatic insufficiency [see Use in Specific Populations (8.7)].

5.6 Pregnancy

Gemzar can cause fetal harm when administered to a pregnant woman. In pre-clinical studies in mice and rabbits, gemcitabine was teratogenic, embryotoxic, and fetotoxic. There are no adequate and well-controlled studies of Gemzar in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus [see Use in Specific Populations (8.1)].

5.7 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 [see Dosage and Administration (2.1, 2.2, 2.3, and 2.4)].

Laboratory eva luation of renal and hepatic function should be performed prior to initiation of therapy and periodically thereafter [see Dosage and Administration (2.4)].

5.8 Radiation Therapy

A pattern of tissue injury typically associated with radiation toxicity has been reported in association with concurrent and non-concurrent use of Gemzar.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Most adverse reactions are reversible and do not need to result in discontinuation, although doses may need to be withheld or reduced.

Gemzar has been used in a wide variety of malignancies, both as a single-agent and in combination with other cytotoxic drugs.

Single-Agent Use:

Myelosuppression is the principal dose-limiting toxicity with Gemzar therapy. Dosage adjustments for hematologic toxicity are frequently needed [see Dosage and Administration (2.1, 2.2, 2.3, and 2.4)].

The data in Table4 are based on 979patients receiving Gemzar as a single-agent administered weekly as a 30-minute infusion for treatment of a wide variety of malignancies. The Gemzar starting doses ranged from 800to 1250mg/m2. Data are also shown for the subset of patients with pancreatic cancer treated in 5clinical studies. The frequency of all grades and severe (WHO Grade3 or4) adverse reactions were generally similar in the single-agent safety database of 979patients and the subset of patients with pancreatic cancer. Adverse reactions reported in the single-agent safety database resulted in discontinuation of Gemzar therapy in about10% of patients. In the comparative trial in pancreatic cancer, the discontinuation rate for adverse reactions was 14.3% for the Gemzar arm and 4.8% for the 5-FU arm. All WHO-graded laboratory adverse reactions are listed in Table4, regardless of causality. Non-laboratory adverse reactions listed in Table4 or discussed below were those reported, regardless of causality, for at least10% of all patients, except the categories of Extravasation, Allergic, and Cardiovascular and certain specific adverse reactions under the Renal, Pulmonary, and Infection categories.

Table 4: Selected WHO-Graded Adverse Reactions in Patients Receiving Single-Agent Gemzar WHO Grades (% incidence)a

a Grade based on criteria from the World Health Organization (WHO).
b N=699-974; all patients with laboratory or non-laboratory data.
c N=161-241; all pancreatic cancer patients with laboratory or non-laboratory data.
d N=979.
e Regardless of causality.
f Table includes non-laboratory data with incidence for all patients≥10%. For approximately60% of the patients, non-laboratory adverse reactions were graded only if assessed to be possibly drug-related.
	All Patientsb			Pancreatic Cancer Patientsc			Discontinuations (%)d
	All Grades	Grade 3	Grade 4	All Grades	Grade 3	Grade 4	All Patients
Laboratorye
Hematologic
Anemia	68	7	1	73	8	2	<1
Leukopenia	62	以下是“全球医药”详细资料

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