Gemzar 1g Information
Gemzar 1g (Gmcitabine) Dosage And Administration
Gemzar is for intravenous use only. Gemzar may be administered on an outpatient basis.
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, 2 of 3 rabbits 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 .
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 40 mg/mL. Reconstitution at concentrations greater than 40 mg/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 of 2.7 to 3.3. 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 24 hours at controlled room temperature 20° to 25°C (68° to 77°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.
Gemzar 1g (Gmcitabine) Dosage Forms And Strengths
Gemzar (gemcitabine for injection, USP) is a white to off-white lyophilized powder available in sterile single-use vials containing 200 mg or 1 g gemcitabine.
Gemzar 1g (Gmcitabine) Contraindications
Gemzar is contraindicated in those patients with a known hypersensitivity to the drug.
Gemzar 1g (Gmcitabine) Warnings And Precautions
Patients receiving therapy with Gemzar should be monitored closely by a physician experienced in the use of cancer chemotherapeutic agents.
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 .
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 .
Serious hepatotoxicity, including liver failure and death, has been reported in patients receiving Gemzar alone or in combination with other potentially hepatotoxic drugs .
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 .
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 .
Laboratory evaluation of renal and hepatic function should be performed prior to initiation of therapy and periodically thereafter .
Gemzar 1g (Gmcitabine) Adverse Reactions
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.
The following adverse reactions have been identified during post-approval use of Gemzar. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
These adverse reactions have occurred after Gemzar single-agent use and Gemzar in combination with other cytotoxic agents. Decisions to include these events are based on the seriousness of the event, frequency of reporting, or potential causal connection to Gemzar.
Gemzar 1g (Gmcitabine) Drug Interactions
No specific drug interaction studies have been conducted. Information is available on the pharmacodynamics and pharmacokinetics of Gemzar in combination with cisplatin, paclitaxel, or carboplatin .
Gemzar 1g (Gmcitabine) Use In Specific Populations
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 .
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 .
Serious hepatotoxicity, including liver failure and death, has been reported in patients receiving Gemzar alone or in combination with other potentially hepatotoxic drugs .
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 .
Gemzar 1g (Gmcitabine) Overdosage
There is no known antidote for overdoses of Gemzar. Myelosuppression, paresthesias, and severe rash were the principal toxicities seen when a single dose as high as 5700 mg/m was administered by intravenous 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.
Gemzar 1g (Gmcitabine) Description
Gemzar (gemcitabine for injection, USP) is a nucleoside metabolic inhibitor that exhibits antitumor activity. Gemcitabine HCl is 2′-deoxy-2′,2′-difluorocytidine monohydrochloride (β-isomer).
The structural formula is as follows:
The empirical formula for gemcitabine HCl is CHFNO • HCl. It has a molecular weight of 299.66.
Gemcitabine HCl is a white to off-white solid. It is soluble in water, slightly soluble in methanol, and practically insoluble in ethanol and polar organic solvents.
The clinical formulation is supplied in a sterile form for intravenous use only. Vials of Gemzar contain either 200 mg or 1 g of gemcitabine HCl (expressed as free base) formulated with mannitol (200 mg or 1 g, respectively) and sodium acetate (12.5 mg or 62.5 mg, respectively) as a sterile lyophilized powder. Hydrochloric acid and/or sodium hydroxide may have been added for pH adjustment.
Gemzar 1g (Gmcitabine) Clinical Studies
Gemzar was studied in a randomized Phase 3 study of 356 patients with advanced ovarian cancer that had relapsed at least 6 months after first-line platinum-based therapy. Patients were randomized to receive either Gemzar 1000 mg/m on Days 1 and 8 of a 21-day cycle and carboplatin AUC 4 administered after Gemzar on Day 1 of each cycle or single-agent carboplatin AUC 5 administered on Day 1 of each 21-day cycle as the control arm. The primary endpoint of this study was progression free survival (PFS).
Patient characteristics are shown in . The addition of Gemzar to carboplatin resulted in statistically significant improvement in PFS and overall response rate as shown in and . Approximately 75% of patients in each arm received poststudy chemotherapy. Only 13 of 120 patients with documented poststudy chemotherapy regimen in the carboplatin arm received Gemzar after progression. There was not a significant difference in overall survival between arms.
Data from a multi-national, randomized Phase 3 study (529 patients) support the use of Gemzar in combination with paclitaxel for treatment of breast cancer patients who have received prior adjuvant/neoadjuvant anthracycline chemotherapy unless clinically contraindicated. Gemzar 1250 mg/m was administered on Days 1 and 8 of a 21-day cycle with paclitaxel 175 mg/m administered prior to Gemzar on Day 1 of each cycle. Single-agent paclitaxel 175 mg/m was administered on Day 1 of each 21-day cycle as the control arm.
The addition of Gemzar to paclitaxel resulted in statistically significant improvement in time to documented disease progression and overall response rate compared to monotherapy with paclitaxel as shown in and . Final survival analysis results at 440 events were Hazard Ratio of 0.86 (95%, CI: 0.71 – 1.04) for the ITT population, as shown in .
Data from 2 clinical trials evaluated the use of Gemzar in patients with locally advanced or metastatic pancreatic cancer. The first trial compared Gemzar to 5-Fluorouracil (5-FU) in patients who had received no prior chemotherapy. A second trial studied the use of Gemzar in pancreatic cancer patients previously treated with 5-FU or a 5-FU-containing regimen. In both studies, the first cycle of Gemzar was administered intravenously at a dose of 1000 mg/m over 30 minutes once weekly for up to 7 weeks (or until toxicity necessitated holding a dose) followed by a week of rest from treatment with Gemzar. Subsequent cycles consisted of injections once weekly for 3 consecutive weeks out of every 4 weeks.
The primary efficacy parameter in these studies was “clinical benefit response,” which is a measure of clinical improvement based on analgesic consumption, pain intensity, performance status, and weight change. Definitions for improvement in these variables were formulated prospectively during the design of the 2 trials. A patient was considered a clinical benefit responder if either:
The first study was a multicenter (17 sites in US and Canada), prospective, single-blinded, two-arm, randomized, comparison of Gemzar and 5-FU in patients with locally advanced or metastatic pancreatic cancer who had received no prior treatment with chemotherapy. 5-FU was administered intravenously at a weekly dose of 600 mg/m for 30 minutes. The results from this randomized trial are shown in . Patients treated with Gemzar had statistically significant increases in clinical benefit response, survival, and time to disease progression compared to 5-FU. The Kaplan-Meier curve for survival is shown in . No confirmed objective tumor responses were observed with either treatment.
Clinical benefit response was achieved by 14 patients treated with Gemzar and 3 patients treated with 5-FU. One patient on the Gemzar arm showed improvement in all 3 primary parameters (pain intensity, analgesic consumption, and performance status). Eleven patients on the Gemzar arm and 2 patients on the 5-FU arm showed improvement in analgesic consumption and/or pain intensity with stable performance status. Two patients on the Gemzar arm showed improvement in analgesic consumption or pain intensity with improvement in performance status. One patient on the 5-FU arm was stable with regard to pain intensity and analgesic consumption with improvement in performance status. No patient on either arm achieved a clinical benefit response based on weight gain.
The second trial was a multicenter (17 US and Canadian centers), open-label study of Gemzar in 63 patients with advanced pancreatic cancer previously treated with 5-FU or a 5-FU-containing regimen. The study showed a clinical benefit response rate of 27% and median survival of 3.9 months.
Gemzar 1g (Gmcitabine) How Supplied/storage And Handling
Gemzar (gemcitabine for injection, USP), is available in sterile single-use vials individually packaged in a carton containing:
200 mg white to off-white, lyophilized powder in a 10-mL size sterile single-use vial - NDC 0002-7501-01 (No. 7501)
1 g white to off-white, lyophilized powder in a 50-mL size sterile single-use vial - NDC 0002-7502-01 (No. 7502)
Gemzar 1g (Gmcitabine)
Gemzar 1g (Gmcitabine)
Gemzar 1g (Gmcitabine)
