Usual Adult Dose for Pancreatic Cancer

70 mg/m2 IV over 90 minutes every 2 weeks

Comments:

• This drug should be administered prior to leucovorin and fluorouracil.
• A corticosteroid and an antiemetic should be given 30 minutes prior to administration of this drug.

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Serum bilirubin above upper limit of normal: Data not available; the manufacturer product information indicates that there is no recommended dose for this patient population.

Dose Adjustments

HOMOZYGOUS UGT1A1*28 ALLELE:

• Initial Dose: 50 mg/m2 IV over 90 minutes
• Maintenance Dose: Increase dose to 70 mg/m2 IV over 90 minutes as tolerated in subsequent cycles

• Occurrence: Withhold therapy; initiate loperamide for late onset diarrhea of any severity; administer IV or subcutaneous atropine 0.25 to 1 mg (unless contraindicated) for early onset diarrhea of any severity.
• For patients receiving 70 mg/m2: Therapy can be resumed upon recovery to Grade 1 or less at 50 mg/m2 (first occurrence) or 43 mg/m2 (second occurrence).
• For patients homozygous for UGT1A1*28 allele: Therapy can be resumed upon recovery to Grade 1 or less at 43 mg/m2 (first occurrence) or 35 mg/m2 (second occurrence).
• This drug should be discontinued in all patients who experience a third occurrence.

• Discontinue therapy.

• Avoid concomitant use if possible.
• Substitute non-enzyme inducing therapies at least 2 weeks prior and discontinue strong CYP450 3A4 inhibitors at least 1 week prior to initiation of this drug.

Precautions

US BOXED WARNINGS:
SEVERE NEUTROPENIA:

• Fatal neutropenic sepsis occurred in 0.8% of patients receiving this drug.
• Severe or life-threatening neutropenic fever or sepsis occurred in 3% and severe or life-threatening neutropenia occurred in 20% of patients receiving this drug in combination with fluorouracil and leucovorin.
• Withhold this drug for absolute neutrophil count below 1500/mm3 or neutropenic fever.
• Monitor blood cell counts periodically during therapy.

• Severe diarrhea occurred in 13% of patients receiving this drug in combination with fluorouracil and leucovorin.
• Do not administer this drug to patients with bowel obstruction.
• Withhold this drug for diarrhea of Grade 2 to 4 severity.
• Administer loperamide for late diarrhea of any severity.
• Administer atropine (if not contraindicated) for early diarrhea of any severity.

• Hypersensitivity to the active component or any of the ingredients

Dialysis

Data not available

Other Comments

Administration advice:

• The manufacturer product information should be consulted for any recommended dosing adjustments to fluorouracil or leucovorin.
• The diluted solution of this drug should be administered within 4 hours of preparation when stored at room temperature or within 24 hours when stored under refrigerated conditions (2C to 8 C; 36F to 46 F).
• The diluted solution should be allowed to come to room temperature prior to administration.
• In-line filters should not be used.

• The diluted solution should be protected from light and not frozen.
• Any unused portion should be discarded.

• Preparation, handling, and disposal of this drug should be performed in a manner consistent with safe procedures for cytotoxic agents.
• The manufacturer product information should be consulted.

• This drug is not indicated as a single agent for the treatment of patients with metastatic adenocarcinoma of the pancreas.
• Do not substitute the liposomal formulation of this drug for the non-liposomal formulation because they are not equivalent.

• This drug is not indicated as a single agent for metastatic adenocarcinoma of the pancreas.
• There are no known effective treatment interventions for overdosage.

• Hematologic: CBC (Days 1 and 8 of every cycle and more frequently if clinically indicated)