|Manufacturer:||Bayer HealthCare Pharmaceuticals Inc.|
Procedures for proper handling and disposal should be considered.
Consideration should be given to handling and disposal according to guidelines issued for cytotoxic drugs.
Several guidelines on this subject have been published.
1-4 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.Caution should be exercised in the handling and preparation of FLUDARA FOR INJECTION solution.
The use of latex gloves and safety glasses is recommended to avoid exposure in case of breakage of the vial or other accidental spillage.
If the solution contacts the skin or mucous membranes, wash thoroughly with soap and water; rinse eyes thoroughly with plain water.Avoid exposure by inhalation or by direct contact of the skin or mucous membranes.FLUDARA FOR INJECTION should not be handled by pregnant staff.
FLUDARA FOR INJECTION is indicated for the treatment of adult patients with B-cell chronic lymphocytic leukemia (CLL) who have not responded to or whose disease has progressed during treatment with at least one standard alkylating-agent containing regimen.The safety and effectiveness of FLUDARA FOR INJECTION in previously untreated or non-refractory patients with CLL have not been established.
(See BOXED WARNINGS)There are clear dose dependent toxic effects seen with FLUDARA FOR INJECTION.
Dose levels approximately 4 times greater (96 mg/m2/day for 5 to 7 days) than that recommended for CLL (25 mg/m2/day for 5 days) were associated with a syndrome characterized by delayed blindness, coma and death.
Symptoms appeared from 21 to 60 days following the last dose.
Thirteen of 36 patients (36%) who received FLUDARA FOR INJECTION at high doses (96 mg/m2/day for 5 to 7 days) developed this severe neurotoxicity.
This syndrome has been reported rarely (coma, seizures and agitation) or uncommonly (confusion) in patients treated with doses in the range of the recommended CLL dose of 25 mg/m2/day for 5 days every 28 days.
In postmarketing experience, neurotoxicity has been reported to occur either earlier or later than in clinical trials.
The effect of chronic administration of FLUDARA FOR INJECTION on the central nervous system is unknown; however, patients have received the recommended dose for up to 15 courses of therapy.
Patients should be observed for signs of neurologic effects.Severe bone marrow suppression, notably anemia, thrombocytopenia and neutropenia, has been reported in patients treated with FLUDARA FOR INJECTION.
In a Phase I study in adult solid tumor patients, the median time to nadir counts was 13 days (range, 3-25 days) for granulocytes and 16 days (range, 2-32) for platelets.
Most patients had hematologic impairment at baseline either as a result of disease or as a result of prior myelosuppressive therapy.
Cumulative myelosuppression may be seen.
While chemotherapy-induced myelosuppression is often reversible, administration of FLUDARA FOR INJECTION requires careful hematologic monitoring.Several instances of trilineage bone marrow hypoplasia or aplasia resulting in pancytopenia, sometimes resulting in death, have been reported in adult patients.
The duration of clinically significant cytopenia in the reported cases has ranged from approximately 2 months to approximately 1 year.
These episodes have occurred both in previously treated or untreated patients.Instances of life-threatening and sometimes fatal autoimmune phenomena such as hemolytic anemia, autoimmune thrombocytopenia/thrombocytopenic purpura (ITP), Evan's syndrome, and acquired hemophilia have been reported to occur after one or more cycles of treatment with FLUDARA FOR INJECTION in patients with or without a previous history of autoimmune hemolytic anemia or a positive Coombs' test and who may or may not be in remission from their disease.
Steroids may or may not be effective in controlling these hemolytic episodes.
The majority of patients rechallenged with FLUDARA FOR INJECTION developed a recurrence in the hemolytic process.
The mechanism(s) which predispose patients to the development of this complication has not been identified.
Patients undergoing treatment with FLUDARA FOR INJECTION should be evaluated and closely monitored for hemolysis.
Discontinuation of therapy with Fludara is recommended in case of hemolysis.
Transfusion-associated graft-versus-host disease has been observed after transfusion of non-irradiated blood in FLUDARA FOR INJECTION treated patients.
Fatal outcome as a consequence of this disease has been reported.
Therefore, to minimize the risk of transfusion-associated graft-versus-host disease, patients who require blood transfusion and who are undergoing, or who have received, treatment with FLUDARA FOR INJECTION should receive irradiated blood only.
In a clinical investigation using FLUDARA FOR INJECTION in combination with pentostatin (deoxycoformycin) for the treatment of refractory chronic lymphocytic leukemia (CLL) in adults, there was an unacceptably high incidence of fatal pulmonary toxicity.
Therefore, the use of FLUDARA FOR INJECTION in combination with pentostatin is not recommended.Of the 133 adult CLL patients in the two trials, there were 29 fatalities during study.Approximately 50% of the fatalities were due to infection and 25% due to progressive disease.