Usual Adult Dose for Chronic Lymphocytic Leukemia

25 mg/m2 IV over 30 minutes for 5 days every 28 days; following a maximal tumor response, 3 additional cycles are recommended

Comments:

• The optimal duration of treatment has not been clearly established.
• The dose may be decreased or delayed for hematologic or nonhematologic toxicity.
• Physicians should consider delaying or discontinuing the drug if neurotoxicity occurs.

Use: 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 this drug in previously untreated or nonrefractory patients with CLL have not been established

Renal Dose Adjustments

CrCl 30 to 70 mL/min: Reduce dose by 20%.
CrCl less than 30 mL/min: Not recommended.

Liver Dose Adjustments

Data not available

Dose Adjustments

This drug may cause/enhance toxicity in advanced age, renal insufficiency, and bone marrow impairment. These patients should be monitored for excessive toxicity and the dose modified accordingly.

Precautions

US BOXED WARNINGS:

• This drug should be administered under the supervision of a physician experienced in the use of antineoplastic therapy.
• This drug can severely suppress bone marrow function.
• When used at high doses in dose-ranging studies in patients with acute leukemia it 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 4 times greater (96 mg/m2/day for 5 to 7 days) than the recommended dose. Similar severe central nervous system toxicity, including coma, 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 (e.g., hemolytic anemia, autoimmune thrombocytopenia/thrombocytopenic purpura (ITP), Evan's syndrome, acquired hemophilia) have been reported after one or more cycles of therapy. Patients should be monitored for hemolysis.

CONTRAINDICATIONS:

• Hypersensitivity to the active component or any of the ingredients

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Caution should be exercised in the handling and preparation of this drug.
• 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.

Storage requirements:

• Store at 20C to 25C (68F to 77F).

Reconstitution/preparation techniques:

• This drug should be prepared by aseptically adding sterile water for injection.
• When reconstituted with 2 mL of sterile water for injection, the solid cake should fully dissolve in 15 seconds or less; each mL of the resulting solution will contain 25 mg of fludarabine phosphate, 25 mg of mannitol, and sodium hydroxide to adjust the pH to 7.7. The pH range for the final product is 7.2 to 8.2.
• The reconstituted product contains no antimicrobial preservative and should be used within 8 hours of reconstitution.

IV compatibility:
Sterile water for injection

General:

• This drug is cytotoxic. Procedures for proper handling and disposal should be considered.

Monitoring:

• It is recommended to monitor the CBC with differential, platelet count, AST, ALT, creatinine, serum albumin, and uric acid during therapy.