ZALTRAP, in combination with 5-fluorouracil, leucovorin, irinotecan-(FOLFIRI), is indicated for patients with metastatic colorectal cancer (mCRC) that is resistant to or has progressed following an oxaliplatin-containing regimen [see Clinical Studies].

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].

Continue ZALTRAP until disease progression or unacceptable toxicity.

Dose Modification / Treatment Delay Recommendations

Discontinue ZALTRAP for:

• Severe hemorrhage [see BOXED WARNING, WARNINGS AND PRECAUTIONS]
• Gastrointestinal perforation [see BOXED WARNING, WARNINGS AND PRECAUTIONS]
• Compromised wound healing [see BOXED WARNING, WARNINGS AND PRECAUTIONS]
• Fistula formation [see WARNINGS AND PRECAUTIONS]
• Hypertensive crisis or hypertensive encephalopathy [see WARNINGS AND PRECAUTIONS]
• Arterial thromboembolic events [see WARNINGS AND PRECAUTIONS]
• Nephrotic syndrome or thrombotic microangiopathy (TMA) [see WARNINGS AND PRECAUTIONS]
• Reversible posterior leukoencephalopathy syndrome (RPLS) [see WARNINGS AND PRECAUTIONS]

Temporarily suspend ZALTRAP:

• At least 4 weeks prior to elective surgery [see WARNINGS AND PRECAUTIONS]
• For recurrent or severe hypertension, until controlled. Upon resumption, permanently reduce the ZALTRAP dose to 2 mg per kg [see WARNINGS AND PRECAUTIONS].
• 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].

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 if the solution contains particles.

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

ZALTRAP is supplied in 5 mL and 10 mL vials containing ziv-aflibercept at a concentration of 25 mg/mL.

NDC 0024-5840-01: carton containing one (1) single-use vial of 100 mg per 4mL (25 mg/mL)

NDC 0024-5840-03: carton containing three (3) single-use vials of 100 mg per 4 mL (25 mg/mL)

NDC 0024-5841-01: carton containing one (1) single-use vial of 200 mg per 8 mL (25 mg/mL)

Storage and Handling

Store ZALTRAP vials in a refrigerator at 2 to 8°C (36 to 46°F). Keep the vials in the original outer carton to protect from light.

Manufactured by: sanofi-aventis U.S. LLC Bridgewater, NJ 08807. Revised: 08/2012

Last reviewed on RxList: 8/13/2012
This monograph has been modified to include the generic and brand name in many instances.