Gemzar Warnings, Precautions, Pregnancy, Nursing, Abuse - Gemcitabine Hcl

Gemzar Warnings, Precautions, Pregnancy, Nursing, Abuse - Gemcitabine Hcl

WARNINGS

Caution : Prolongation of the infusion time beyond 60 minutes and more frequent than weekly dosing have been shown to increase toxicity (see CLINICAL STUDIES).

Hematology : Gemzar can suppress bone marrow function as manifested by leukopenia, thrombocytopenia, and anemia (see ADVERSE REACTIONS), and myelosuppression is usually the dose-limiting toxicity. Patients should be monitored for myelosuppression during therapy. See DOSAGE AND ADMINISTRATION for recommended dose adjustments.

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 Pulmonary under Single-Agent Use and under Post-marketing experience in ADVERSE REACTIONS section).

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 rarely reported. The majority of the cases of renal failure leading to death were due to HUS (see Renal under Single-Agent Use and under Post-marketing experience in ADVERSE REACTIONS section).

Hepatic : Serious hepatotoxicity, including liver failure and death, has been reported very rarely in patients receiving Gemzar alone or in combination with other potentially hepatotoxic drugs (see Hepatic under Single-Agent Use and under Post-marketing experience in ADVERSE REACTIONS section).

Pregnancy : Pregnancy Category D. Gemzar can cause fetal harm when administered to a pregnant woman. Gemcitabine is embryotoxic causing fetal malformations (cleft palate, incomplete ossification) at doses of 1.5 mg/kg/day in mice (about 1/200 the recommended human dose on a mg/m² basis). Gemcitabine is fetotoxic causing fetal malformations (fused pulmonary artery, absence of gall bladder) at doses of 0.1 mg/kg/day in rabbits (about 1/600 the recommended human dose on a mg/m² basis). Embryotoxicity was characterized by decreased fetal viability, reduced live litter sizes, and developmental delays. There are no studies of Gemzar in pregnant women. If Gemzar is used during pregnancy, or if the patient becomes pregnant while taking Gemzar, the patient should be apprised of the potential hazard to the fetus.

General : Patients receiving therapy with Gemzar should be monitored closely by a physician experienced in the use of cancer chemotherapeutic agents. Most adverse events are reversible and do not need to result in discontinuation, although doses may need to be withheld or reduced.

There was a greater tendency in women, especially older women, not to proceed to the next cycle.

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).

Laboratory evaluation of renal and hepatic function should be performed prior to initiation of therapy and periodically thereafter (see WARNINGS).

Carcinogenesis, Mutagenesis, Impairment of Fertility : Long-term animal studies to evaluate the carcinogenic potential of Gemzar have not been conducted. Gemcitabine induced forward mutations in vitro in a mouse lymphoma (L5178Y) 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. Gemcitabine I.P. 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 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).

Pregnancy

Category D. See WARNINGS.

Nursing Mothers

It is not known whether Gemzar or its metabolites are excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions from Gemzar in nursing infants, the mother should be warned and a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother and the potential risk to the infant.

Elderly Patients

Gemzar clearance is affected by age (see CLINICAL PHARMACOLOGY). There is no evidence, however, that unusual dose adjustments, (i.e., other than those already recommended in the DOSAGE AND ADMINISTRATION section) are necessary in patients over 65, and in general, adverse reaction rates in the single-agent safety database of 979 patients were similar in patients above and below 65. Grade 3/4 thrombocytopenia was more common in the elderly.

Gender

Gemzar clearance is affected by gender (see CLINICAL PHARMACOLOGY). In the single-agent safety database (N=979 patients), however, there is no evidence that unusual dose adjustments (i.e., other than those already recommended in the DOSAGE AND ADMINISTRATION section) are necessary in women. In general, in single-agent studies of Gemzar, adverse reaction rates were similar in men and women, but women, especially older women, were more likely not to proceed to a subsequent cycle and to experience Grade 3/4 neutropenia and thrombocytopenia.

Pediatric Patients

Gemzar has not been studied in pediatric patients. Safety and effectiveness in pediatric patients have not been established.

Patients with Renal or Hepatic Impairment

Gemzar should be used with caution in patients with preexisting renal impairment or hepatic insufficiency. Gemzar has not been studied in patients with significant renal or hepatic impairment.