Neurotoxicity; Hemoliytic Anemic Risk
- Fludarabine injection should be administered under the supervision of a qualified physician experienced in the use of antineoplastic therapy.
Bone Marrow Suprression
- Fludarabine for Injection can severely suppress bone marrow function.
Central Nervous System Effects
- When used at high doses in dose ranging studies in patients with acute leukemia, fludarabine for injection was associated with severe neurologic effects, including blindness, coma, and death.
- This severe central nervous system toxicity occurred in 36% of patients treated with doses approximately four times greater (96 mg/m2/day for 5 to 7 days) than the recommended dose.
- Similar nervous system toxicity, including comas, seizures, agitation and confusion, has been reported in patients treated at doses in the range of the dose recommended for chronic lymphocytic leukemia.
- 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 fludarabine for injection.
- Patients undergoing treatment with fludarabine for injection should be evaluated and closely monitored for hemolysis.
- In a clinical investigation useing fludarabine for injection in combination with pentostatin (deoxycoformycin) for the treatment of refractory chronic lymphocytic leukemia (CLL), there was an unacceptably high incidence of fatal pulmonary toxicity. Therefore, the use of fludarabine for injection in combination with pentostatin is not recommended.
MONITORING RECOMMENDATIONS RELATED TO BLACK BOX DATA
- Closely monitor for hemolysis. Perform periodic peripheral blood counts.
- Severe CNS toxicity occurred in 36% patients receiving doses approximately 4 times greater than the recommended dose.(96 mg/m2/day for 5 to 7 days). At recommended doses, severe CNS toxicity is rare.
Updated January 2018