Aflibercept

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.

Ablibercept is a recombinant fusion protein that acts as a decoy receptor for the ligands, vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF). It prevents these ligands to binding to endothelial receptors, VEGFR-1 and VEGFR-2, to suppress neovascularization and decrease vascular permeability. This ultimately will slow vision loss or the progression of metastatic colorectal cancer.

4 mg/kg as an intravenous infusion over 1 hour every 2 weeks. Do not administer as an intravenous (IV) push or bolus.

No dedicated drug-drug interaction studies have been conducted for Zaltrap. No clinically important pharmacokinetic drug-drug interactions were found between ziv-Zaltrap and irinotecan/SN-38 or 5-FU, based on cross-study comparisons and population pharmacokinetic analyses.

Most common adverse reactions (all grades, ≥20% incidence and at least 2% greater incidence for the Zaltrap/FOLFIRI regimen) were leukopenia, diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache

Pregnancy category C. There are no adequate and well-controlled studies with Aflibercept in pregnant women. Aflibercept was embryotoxic and teratogenic in rabbits at exposure levels lower than human exposures at the recommended dose, with increased incidences of external, visceral, and skeletal fetal malformations. Aflibercept should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether Aflibercept is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Aflibercept, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Adverse reactions, sometimes severe and life-threatening or fatal, have been seen in clinical trials with Zaltrap, including:

Fistula Formation: Discontinue Zaltrap if fistula occurs.

Hypertension: Monitor blood pressure and treat hypertension. Temporarily suspend Zaltrap if hypertension is not controlled. Discontinue Zaltrap if hypertensive crisis develops.

Arterial Thromboembolic Events (ATE) (e.g., transient ischemic attacks, cerebrovascular accident, angina pectoris): Discontinue Zaltrap if ATE develops.

Proteinuria: Monitor urine protein. Suspend Zaltrap when proteinuria ≥ 2 grams per 24 hours. Discontinue Zaltrap if nephrotic syndrome or thrombotic microangiopathy (TMA) develops.

Neutropenia and Neutropenic Complications: Delay administration of Zaltrap/FOLFIRI until neutrophil count is ≥ 1.5 × 109/L.

Diarrhea and Dehydration: Incidence of severe diarrhea and dehydration is increased. Monitor elderly patients more closely.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Discontinue Zaltrap.

There have been no cases of overdose reported with Zaltrap. There is no information on the safety of Zaltrap given at doses exceeding 7 mg per kg every 2 weeks or 9 mg per kg every 3 weeks.

Store Zaltrap vials in a refrigerator at 2 to 8° C . Keep the vials in the original outer carton to protect from light.