Citagem Special Precautions

General: Gemcitabine should only be administered under the supervision of a qualified physician experienced in cancer chemotherapeutic drugs. Most adverse effects are reversible and do not need discontinuation, although doses may need to be withheld or reduced.
IV infusion of gemcitabine over periods exceeding 60 minutes and administration more frequent than once a week may be associated with increased toxicity (e.g., myelosuppression).
Gemcitabine should be used with extreme caution in patients whose bone marrow reserve may have been compromised by prior irradiation or chemotherapy, or whose bone marrow function is recovering from previous chemotherapy.
Hematologic Effects: Myelosuppression is the dose-limiting toxicity of gemcitabine, including leukopenia, thrombocytopenia and anemia. Patients receiving the drug may require red blood cell transfusions or, less frequently, platelet transfusions. Patients should be monitored for myelosuppression during therapy and doses should be modified accordingly (see Laboratory Tests as follows and Dosage & Administration).
Respiratory Effects: Acute shortness of breath with a temporal relationship to gemcitabine administration may occur. Pulmonary toxicity has also been reported with the use of gemcitabine. In cases of severe lung toxicity, gemcitabine therapy should be discontinued immediately and appropriate supportive care measures instituted (see Adverse Reactions).
Renal Effects: Hemolytic-uremic syndrome (HUS) and/or renal failure have been reported in patients receiving one or more doses of gemcitabine. In rare cases, renal failure leading to death or requiring dialysis have occurred despite discontinuance of gemcitabine therapy. Cases of renal failure leading to death were typically caused by HUS (see Laboratory Tests as follows).
Hepatic Effects: Serious hepatotoxicity, including hepatic failure and death, has been reported in patients receiving gemcitabine alone or in combination with other potentially hepatotoxic agents.
Laboratory Tests: Patients receiving gemcitabine 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 myelosuppression is detected (see Dosage & Administration).
Laboratory evaluation of renal and hepatic function should be performed prior to initiation of therapy and periodically thereafter. The diagnosis of HUS should be considered and gemcitabine should be discontinued immediately in patients who develop anemia with evidence of microangiopathic hemolysis, elevation of serum bilirubin or LDH, reticulocytosis, and/or severe thrombocytopenia with or without evidence of renal failure [e.g., elevation of serum creatinine or blood urea nitrogen (BUN)].
Effects on the Ability to Drive and Use Machines: No studies on the effects on the ability to drive and use machines have been performed. However, gemcitabine has been reported to cause mild to moderate somnolence, especially in combination with alcohol consumption. Patients should be cautioned against driving or operating machinery until it is established that they do not become somnolent.
Patients with Renal or Hepatic Impairment: Gemcitabine should be used with caution in patients with pre-existing renal impairment or hepatic insufficiency as there is insufficient information from clinical studies to allow clear dose recommendations for these populations. Gemcitabine has not been studied in patients with significant renal or hepatic impairment. Use of gemcitabine in patients with current liver metastases or a history of hepatitis, alcoholism or cirrhosis may lead to exacerbation of the underlying hepatic insufficiency.
Women: Gemcitabine clearance is reduced and half-life is increased in women. Dose reductions, including withholding of doses in some cases, may be more likely in this population. However, there are currently no recommended dose adjustments specifically for women.
There was a greater tendency in women, especially older women, not to proceed to the next cycle.
Carcinogenicity, Mutagenicity and Impairment of Fertility: Long-term animal studies to evaluate carcinogenic potential of gemcitabine have not been conducted. Gemcitabine induced forward mutations in vitro in a mouse lymphoma assay and was clastogenic in an in vivo mouse micronucleus assay. Gemcitabine was negative when tested using the Ames, in vivo sister chromatid exchange, and in vitro chromosomal aberration assays, and did not cause unscheduled DNA synthesis in vitro. Intraperitoneal gemcitabine doses of 0.5 mg/kg/day (about 1/700 the human dose on a mg/m² basis) in male mice had an effect on fertility with moderate to severe hypospermatogenesis, decreased fertility, and decreased implantations. In female mice, fertility was not affected but maternal toxicities were observed at 1.5 mg/kg/day IV (about 1/200 the human dose on a mg/m² basis) and fetotoxicity or embryolethality was observed at 0.025 mg/kg/day (about 1/300 the human dose on a mg/m² basis).
Use in Children (<17 years old): The safety and efficacy of gemcitabine have not been established in pediatric patients <17 years old.
Use in Elderly (>65 years old): Since gemcitabine clearance is reduced and half-life is increased in geriatric patients, dose reductions, including withholding of doses in some cases, may be more likely. However, there is no evidence that dose adjustments based on age are necessary in patients over 65 years old. In general, adverse reaction rates in the single-agent safety database of 979 patients were similar in patients above and below 65 years old. Grade 3/4 thrombocytopenia was more common in the elderly.