Do not re-enter the vial after the initial puncture. Discard any unused portion left in the vial.

Withdraw the prescribed dose of Zaltrap and dilute in 0.9% sodium chloride solution, USP or 5% dextrose solution for injection, USP to achieve a final concentration of 0.6–8 mg/mL.

Use polyvinyl chloride (PVC) infusion bags containing bis (2-ethylhexyl) phthalate (DEHP) or polyolefin infusion bags.

Store diluted Zaltrap at 2–8°C (36–46°F) for up to 4 hours. Discard any unused portion left in the infusion bag.

Administration
Administer the diluted Zaltrap solution as an intravenous infusion over 1 hour through a 0.2 micron polyethersulfone filter. Do not use filters made of polyvinylidene fluoride (PVDF) or nylon.

Do not administer as an intravenous (IV) push or bolus.

Do not combine Zaltrap with other drugs in the same infusion bag or intravenous line.

Administer Zaltrap using an infusion set made of one of the following materials:

•PVC containing DEHP
•DEHP free PVC containing trioctyl-trimellitate (TOTM)
•polypropylene
•polyethylene lined PVC
•polyurethane
Dosage Forms and Strengths
Zaltrap is available as:

•100 mg per 4 mL (25 mg per mL) solution, single-use vial
•200 mg per 8 mL (25 mg per mL) solution, single-use vial
Warnings and Precautions
Hemorrhage
Patients treated with Zaltrap have an increased risk of hemorrhage, including severe and sometimes fatal hemorrhagic events. In patients with mCRC, bleeding/hemorrhage (all grades) were reported in 38% of patients treated with Zaltrap/FOLFIRI compared to 19% of patients treated with placebo/FOLFIRI. Grade 3–4 hemorrhagic events, including gastrointestinal hemorrhage, hematuria, and post-procedural hemorrhage, were reported in 3% of patients receiving Zaltrap/FOLFIRI compared with 1% of patients receiving placebo/FOLFIRI. Severe intracranial hemorrhage and pulmonary hemorrhage/hemoptysis including fatal events have also occurred in patients receiving Zaltrap.

Monitor patients for signs and symptoms of bleeding. Do not initiate Zaltrap in patients with severe hemorrhage. Discontinue Zaltrap in patients who develop severe hemorrhage [see Dosage and Administration (2.2)].

Gastrointestinal Perforation
Gastrointestinal (GI) perforation including fatal GI perforation can occur in patients receiving Zaltrap. Across three Phase 3 placebo-controlled clinical studies (colorectal, pancreatic, and lung cancer populations), the incidence of GI perforation (all grades) was 0.8% for patients treated with Zaltrap and 0.3% for patients treated with placebo. Grade 3–4 GI perforation events occurred in 0.8% of patients treated with Zaltrap and 0.2% of patients treated with placebo.

Monitor patients for signs and symptoms of GI perforation. Discontinue Zaltrap therapy in patients who experience GI perforation [see Dosage and Administration (2.2)].

Compromised Wound Healing
Zaltrap impairs wound healing in animal models [see Nonclinical Toxicology (13.2)].

Grade 3 compromised wound healing was reported in 2 patients (0.3%) treated with Zaltrap/FOLFIRI regimen and in none of the patients treated with placebo/FOLFIRI regimen.

Suspend Zaltrap for at least 4 weeks prior to elective surgery. Do not resume Zaltrap for at least 4 weeks following major surgery and