Usual Adult Dose for Myelodysplastic Syndrome

FIRST TREATMENT CYCLE: 75 mg/m2 IV or subcutaneously daily for 7 days; repeat cycles every 4 weeks
SUBSEQUENT CYCLES: After 2 cycles, may increase dose to 100 mg/m2 if no beneficial effect is seen and if no toxicity other than nausea and vomiting has occurred
DURATION OF THERAPY: Minimum of 4 to 6 cycles; may continue treatment if the patient continues to benefit

Comments:

• Premedicate patients for nausea and vomiting.

Use: Treatment of patients with the following French-American-British (FAB) myelodysplastic syndrome (MDS) subtypes: refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS) if accompanied by neutropenia or thrombocytopenia or requiring transfusions; refractory anemia with excess blasts (RAEB); refractory anemia with excess blasts in transformation (RAEB-T); and chronic myelomonocytic leukemia (CMMoL)

Usual Adult Dose for Acute Myeloid Leukemia

FIRST TREATMENT CYCLE: 75 mg/m2 IV or subcutaneously daily for 7 days; repeat cycles every 4 weeks
SUBSEQUENT CYCLES: After 2 cycles, may increase dose to 100 mg/m2 if no beneficial effect is seen and if no toxicity other than nausea and vomiting has occurred
DURATION OF THERAPY: Minimum of 4 to 6 cycles; may continue treatment if the patient continues to benefit

Comments:

• Premedicate patients for nausea and vomiting.

Use: Treatment of patients with the following French-American-British (FAB) myelodysplastic syndrome (MDS) subtypes: refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS) if accompanied by neutropenia or thrombocytopenia or requiring transfusions; refractory anemia with excess blasts (RAEB); refractory anemia with excess blasts in transformation (RAEB-T); and chronic myelomonocytic leukemia (CMMoL)

Renal Dose Adjustments

Unexplained reductions in serum bicarbonate levels to less than 20 mEq/L: Reduce dose by 50% for the next course.
Unexplained elevations of BUN or serum creatinine: Delay the next cycle until values return to normal or baseline and reduce dose by 50% for the next course.

Liver Dose Adjustments

Patients with severe preexisting hepatic impairment are at higher risk for toxicity.
Advanced malignant hepatic tumors: Use is contraindicated.

Dose Adjustments

Baseline WBC 3 x 10(9)/L or greater, absolute neutrophil count (ANC) 1.5 x 10(9)/L or greater, AND platelets 75 x 10(9)/L or greater:

• ANC less than 0.5 x 10(9)/L and platelets less than 25 x 10(9)/L: Administer 50% of the dose in the next course.
• ANC 0.5 to 1.5 x 10(9)/L and platelets 25 to 50 x 10(9)/L: Administer 67% of the dose in the next course.
• ANC greater than 1.5 x 10(9)/l and platelets greater than 50 x 10(9)/L: Administer 100% of the dose in the next course.

Baseline WBC less than 3 x 10(9)/L, ANC less than 1.5 x 10(9)/L, OR platelets less than 75 x 10(9)/L, base dose adjustments on nadir counts and bone marrow biopsy cellularity at the time of the nadir unless there is clear improvement in differentiation (percentage of mature granulocytes is higher and ANC is higher than at onset of that course) at the time of the next cycle, in which case continue the current dose:

• Bone marrow biopsy cellularity (BMBC) of 30% to 60% at time of nadir: Administer 100% of the dose in the next course.
• BMBC of 15% to 30% at time of nadir: Administer 50% of the dose in the next course.
• BMBC Less Than 15% at time of nadir: Administer 33% of the dose in the next course.

BASELINE WBC less than 3 x 10(9)/L, ANC less than 1.5 x 10(9)/L, OR platelets less than 75 x 10(9)/L AND WBC or platelet nadir 50% to 75% decrease in counts from baseline:

• BMBC of 30% to 60% at nadir time: Administer 100% of the dose in the next course.
• BMBC of 15% to 30% at nadir time: Administer 50% of the dose in the next course.
• BMBC Less Than 15% at nadir time: Administer 33% of the dose in the next course.

BASELINE WBC less than 3 x 10(9)/L, ANC less than 1.5 x 10(9)/L, OR platelets less than 75 x 10(9)/L AND WBC or platelet nadir greater than 75% decrease in counts from baseline:

• BMBC of 30% to 60% at nadir time: Administer 75% of the dose in the next course.
• BMBC of 15% to 30% at nadir time: Administer 50% of the dose in the next course.
• BMBC Less Than 15% at nadir time: Administer 33% of the dose in the next course.
• Give the next course 28 days after the start of the preceding course provided that both the WBC and platelet counts are greater than 25% above the nadir and rising.
• At the time of the next cycle, continue the current dose if there is clear improvement in differentiation (i.e., percentage of mature granulocytes and ANC is higher than at onset of that course).
• If greater than 25% increase above the nadir is not seen by Day 28: Reassess counts every 7 days.
• If 25% increase is not seen by Day 42: Reduce the scheduled dose by 50%.

Precautions

CONTRAINDICATIONS:

• Hypersensitivity to the active component or any of the ingredients
• Hypersensitivity to mannitol
• Advanced malignant hepatic tumors

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:

• Obtain complete blood counts, liver chemistries and serum creatinine prior to the first dose.
• Subcutaneous administration: Divide doses greater than 4 mL equally into 2 syringes and inject into 2 separate sites. Rotate sites (thigh, abdomen, upper arm) for each injection; give new injections at least 1 inch/2.5 cm from the previous site and avoid areas that are tender, bruised, red, or hardened.
• IV administration: Administer the total dose over a period of 10 to 40 minutes; complete the administration within 45 to 60 minutes of reconstitution.

Storage requirements:

• Store unreconstituted vials at 25C (77F); excursions permitted to 15C to 30C (59F to 86F).

Monitoring:

• Hematologic: Complete blood counts (prior to therapy initiation and with each cycle); signs and symptoms of bleeding (during therapy)
• Hepatic: Liver chemistries (prior to therapy initiation and with each cycle)
• Metabolic: Signs and symptoms of tumor lysis syndrome (during therapy)
• Renal: Serum creatinine, serum bicarbonate, and electrolytes (prior to therapy initiation and with each cycle)