Recommended Dose and Schedule

The recommended dosage of ZALTRAP is 4 mg per kg of actual body weight as an intravenous infusion over 1 hour every two weeks in combination with FOLFIRI until disease progression or unacceptable toxicity. Administer ZALTRAP prior to any component of the FOLFIRI regimen on the day of treatment.

Refer to prescribing information for irinotecan, fluorouracil, and leucovorin for the recommended dosage and dosage modifications for these drugs.

Dosage Modifications for Adverse Reactions

Discontinue ZALTRAP for:

• Severe hemorrhage [see Warnings and Precautions (5.1)]
• Gastrointestinal perforation [see Warnings and Precautions (5.2)]
• Impaired wound healing [see Warnings and Precautions (5.3)]
• Fistula formation [see Warnings and Precautions (5.4)]
• Hypertensive crisis or hypertensive encephalopathy [see Warnings and Precautions (5.5)]
• Arterial thromboembolic events (ATE) [see Warnings and Precautions (5.6)]
• Nephrotic syndrome or thrombotic microangiopathy (TMA) [see Warnings and Precautions (5.7)]
• Reversible posterior leukoencephalopathy syndrome (RPLS) [see Warnings and Precautions (5.10)]

Temporarily suspend ZALTRAP:

• At least 4 weeks prior to elective surgery [see Warnings and Precautions (5.3)].
• For uncontrolled hypertension until controlled. Upon resumption, permanently reduce the ZALTRAP dose to 2 mg per kg [see Warnings and Precautions (5.5)].
• For proteinuria of 2 grams per 24 hours or more. Resume when proteinuria is less than 2 grams per 24 hours. For recurrent proteinuria, suspend ZALTRAP until proteinuria is less than 2 grams per 24 hours and then permanently reduce the ZALTRAP dose to 2 mg per kg [see Warnings and Precautions (5.7)].

Preparation and Administration