Gemita Special Precautions

General: A physician experienced in the use of cancer chemotherapeutic agents should do close monitoring of patients receiving therapy with gemcitabine. There is no need for discontinuation of gemcitabine therapy as most adverse events are reversible, although doses may need to be withheld or reduced. Women, especially older women had a tendency, not to proceed to the next cycle.
Caution: If the infusion time is prolonged beyond 60 minutes and frequency is more than weekly dosing then there is an increase in toxicity.
Laboratory Test: Complete blood count (CBC), including differential and platelet count should be monitored prior to each dose for patients receiving gemcitabine. When marrow suppression is detected therapy should be suspended or modified. Prior to initiation of therapy and periodically thereafter the Laboratory evaluation of renal and hepatic function should be performed.
Hematology: Gemcitabine suppresses bone marrow function. Manifestations of bone marrow suppression are leucopenia, thrombocytopenia and anemia Myelosuppression is usually the dose-limiting toxicity. Patients should be monitored for myelosuppression during therapy.
Renal: With the use of gemcitabine (HUS) Hemolytic-Uremic Syndrome and/or renal failure have been reported rarely.
Pulmonary: Pulmonary toxicity has been reported with the use of gemcitabine. In cases of severe lung toxicity, gemcitabine therapy should be discontinued immediately and appropriate supportive measures instituted.
Hepatic: Serious hepatotoxicity, including liver failure and death, has been reported very rarely in patients receiving gemcitabine alone or in combination with other potentially hepatotoxic drugs.
Gender: Gemcitabine clearance is affected by gender. Older women were more likely not to proceed to a subsequent cycle and to experience grade 3/4 neutropenia and thrombocytopenia. In single agent studies of gemcitabine adverse reaction rates were similar in men and women.
Radiation Therapy: A pattern of tissue injury typically associated with radiation toxicity has been reported in association with concurrent and non-concurrent use of gemcitabine.
Patients with Renal or Hepatic Impairment: Caution should be exercised for use of gemcitabine in patients with preexisting renal impairment or hepatic insufficiency. Gemcitabine has not been studied in patients with significant renal or hepatic impairment. Administration of gemcitabine 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.
Carcinogenesis, Mutagenesis, Impairment of Fertility: To evaluate the carcinogenic potential of gemcitabine, long-term animal studies have not been conducted. In a mouse lymphoma (L5178Y) assay, gemcitabine induced forward mutations in vitro 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 assay, and did not cause unscheduled DNA synthesis in vitro. In male mice fertility was affected at gemcitabine doses of 0.5 mg/kg/day (about 1/700 the human dose on a mg/m² basis) 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 I.V. (about 1/200 the human dose on a mg/m² basis) and fetotoxicity or embryolethality was observed at 0.25 mg/kg/day I.V. (about 1/1300 the human dose on a mg/m² basis).
Use in Children: Gemcitabine has not been studied in pediatric patients. Safety and effectiveness in pediatric patients have not been established.
Use in the Elderly: Age affects the clearance of gemcitabine. There is no evidence, that unusual dose adjustments are necessary in patients over 65. In the elderly, Grade 3/4 thrombocytopenia is more common.