Generic Name: ziv-aflibercept
Dosage Form: injection solution, concentrate
WARNING: HEMORRHAGE, GASTROINTESTINAL PERFORATION, COMPROMISED WOUND HEALING
Hemorrhage: Severe and sometimes fatal hemorrhage, including gastrointestinal (GI) hemorrhage, has been reported in the patients who have received Zaltrap in combination with FOLFIRI. Monitor patients for signs and symptoms of GI bleeding and other severe bleeding. Do not administer Zaltrap to patients with severe hemorrhage [see Dosage and Administration (2.2), Warnings and Precautions (5.1)].

Gastrointestinal Perforation: Gastrointestinal (GI) perforation including fatal GI perforation can occur in patients receiving Zaltrap. Discontinue Zaltrap therapy in patients who experience GI perforation [see Dosage and Administration (2.2), Warnings and Precautions (5.2)].

Compromised Wound Healing: Severe compromised wound healing can occur in patients receiving Zaltrap/FOLFIRI. Discontinue Zaltrap in patients with compromised wound healing. Suspend Zaltrap for at least 4 weeks prior to elective surgery, and do not resume Zaltrap for at least 4 weeks following major surgery and until the surgical wound is fully healed [see Dosage and Administration (2.2), Warnings and Precautions (5.3)].

Indications and Usage for Zaltrap
Zaltrap Dosage and Administration
Recommended Dose and Schedule
Administer Zaltrap 4 mg per kg as an intravenous (IV) infusion over 1 hour every two weeks. Administer Zaltrap prior to any component of the FOLFIRI regimen on the day of treatment [see Clinical Studies (14)].

Continue Zaltrap until disease progression or unacceptable toxicity.

Dose Modification / Treatment Delay Recommendations
Discontinue Zaltrap for:

•Severe hemorrhage [see Boxed Warning, Warnings and Precautions (5.1)]
•Gastrointestinal perforation [see Boxed Warning, Warnings and Precautions (5.2)]
•Compromised wound healing [see Boxed Warning, 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 [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:

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•At least 4 weeks prior to elective surgery [see Warnings and Precautions (5.3)]
•For recurrent or severe 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. 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)].
For toxicities related to irinotecan, 5-fluorouracil (5-FU), or leucovorin, refer to the current respective prescribing information.

Preparation for Administration
Inspect vials visually prior to use. Zaltrap is a clear, colorless to pale yellow solution. Do not use vial if the solution is discolored or cloudy or