Included as part of the PRECAUTIONS section.

Patients receiving therapy with Gemzar (gemcitabine hcl) should be monitored closely by a physician experienced in the use of cancer chemotherapeutic agents.

Infusion Time

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 (gemcitabine hcl) 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].

Pulmonary

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

Renal

Hemolytic Uretnic Syndrome (HUS) and/or renal failure have been reported following one or more doses of Gemzar (gemcitabine hcl) . 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].

Gemzar (gemcitabine hcl) 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].

Hepatic

Serious hepatotoxicity, including liver failure and death, has been reported in patients receiving Gemzar (gemcitabine hcl) alone or in combination with other potentially hepatotoxic drugs [see ADVERSE REACTIONS].

Gemzar (gemcitabine hcl) 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 (gemcitabine hcl) 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].

Pregnancy

Gemzar (gemcitabine hcl) 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 (gemcitabine hcl) 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].

Laboratory Tests

Patients receiving Gemzar (gemcitabine hcl) 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 DOSAGE AND ADMINISTRATION].

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 (gemcitabine hcl) .

Non-concurrent (given > 7 days apart) — Analysis of the data does not indicate enhanced toxicity when Gemzar (gemcitabine hcl) is administered more than 7 days before or after radiation, other than radiation recall. Data suggest that Gemzar (gemcitabine hcl) can be started after the acute effects of radiation have resolved or at least one week after radiation.

Concurrent (given together or ≤ 7 days apart) — Preclinical and clinical studies have shown that Gemzar (gemcitabine hcl) has radiosensitizing activity. Toxicity associated with this multimodality therapy is dependent on many different factors, including dose of Gemzar (gemcitabine hcl) , frequency of Gemzar (gemcitabine hcl) administration, dose of radiation, radiotherapy planning technique, the target tissue, and target volume. In a single trial, where Gemzar (gemcitabine hcl) at a dose of 1000 mg/m² was administered concurrently for up to 6 consecutive weeks with therapeutic thoracic radiation to patients with non-small cell lung cancer, significant toxicity in the form of severe, and potentially life-threatening mucositis, especially esophagitis and pneumonitis was observed, particularly in patients receiving large volumes of radiotherapy [median treatment volumes 4795 cm³]. Subsequent studies have been reported and suggest that Gemzar (gemcitabine hcl) administered at lower doses with concurrent radiotherapy has predictable and less severe toxicity. However, the optimum regimen for safe administration of Gemzar (gemcitabine hcl) with therapeutic doses of radiation has not yet been determined in all tumor types.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal studies to evaluate the carcinogenic potential of Gemzar (gemcitabine hcl) 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 IP 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 administered intravenously (about 1/200 the human dose on a mg/m² basis) and fetotoxicity or embryolethality was observed at 0.25 mg/kg/day administered intravenously (about 1/1300 the human dose on a mg/m² basis).

Use In Specific Populations

Pregnancy

Pregnancy Category D. See 'WARNINGS and PRECAUTIONS' section.

Gemzar (gemcitabine hcl) can cause fetal harm when administered to a pregnant woman. Based on its mechanism of action, Gemzar (gemcitabine hcl) is expected to result in adverse reproductive effects. There are no adequate and well-controlled studies of Gemzar (gemcitabine hcl) in pregnant women. - 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. If this 1 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 WARNINGS AND PRECAUTIONS].

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Gemzar (gemcitabine hcl) , 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.

Pediatric Use

The safety and effectiveness of Gemzar (gemcitabine hcl) in pediatric patients has not been established. Gemzar (gemcitabine hcl) was evaluated in a Phase 1 trial in pediatric patients with refractory leukemia and determined that the maximum tolerated dose was 10 mg/m²/min for 360 minutes three times weekly followed by a one-week rest period. Gemzar (gemcitabine hcl) was also evaluated in a Phase 2 trial in patients with relapsed acute lymphoblastic leukemia (22 patients) and acute myelogenous leukemia (10 patients) using 10 mg/m²/min for 360 minutes three times weekly followed by a one-week rest period. Toxicities observed included bone marrow suppression, febrile neutropenia, elevation of serum transaminases, nausea, and rash/desquamation, which were similar to those reported in adults. No meaningful clinical activity was observed in this Phase 2 trial.

Geriatric Use

Gemzar clearance is affected by age [see CLINICAL PHARMACOLOGY]. There is no evidence, however, that unusual dose adjustments [see DOSAGE AND ADMINISTRATION] 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. In the randomized clinical trial of Gemzar (gemcitabine hcl) in combination with carboplatin for recurrent ovarian cancer [see Clinical Studies], 125 women treated with Gemzar (gemcitabine hcl) plus carboplatin were < 65 years and 50 were ≥ 65 years. Similar effectiveness was observed between older and younger women. There was significantly higher Grade 3/4 neutropenia in women 65 years of age or older. Overall, there were no other substantial differences in toxicity profile of Gemzar (gemcitabine hcl) plus carboplatin based on age.

Renal

Hemolytic Uremic Syndrome (HUS) and/or renal failure have been reported following one or more doses of Gemzar (gemcitabine hcl) . 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].

Gemzar (gemcitabine hcl) 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 WARNINGS AND PRECAUTIONS].

Hepatic

Serious hepatotoxicity, including liver failure and death, has been reported in patients receiving Gemzar (gemcitabine hcl) alone or in combination with other potentially hepatotoxic drugs [see ADVERSE REACTIONS].

Gemzar (gemcitabine hcl) 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 (gemcitabine hcl) 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 WARNINGS AND PRECAUTIONS].

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 [see DOSAGE AND ADMINISTRATION] are necessary in women. In general, in single-agent studies of Gemzar (gemcitabine hcl) , 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. There was a greater tendency in women, especially older women, not to proceed to the next cycle.

Last reviewed on RxList: 4/4/2011
This monograph has been modified to include the generic and brand name in many instances.