High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

ziv a-flib-er-sept

Trade Name(s)

  • Zaltrap

Ther. Class.


Pharm. Class.

fusion proteins


Used in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) for metastatic colorectal cancer that is resistant to/progressed after an oxaliplatin-containing regimen.


Binds to human vascular endothelial growth factor (VEGF-A), resulting in decreased neovascularization and decreased vascular permeability. Also inhibits proliferation of endothelial cells, decreasing growth of new blood vessels.

Therapeutic Effect(s):

Decreased spread of colorectal cancer.


Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism and Excretion: Unknown.

Half-life: 6 days (range 4–7 days).

TIME/ACTION PROFILE (plasma concentrations)

IVrapid end of infusionunknown


Contraindicated in:

  • OB:  Pregnancy;
  • Lactation:  Lactation.

Use Cautiously in:

  • Elective surgery;
  •  Rep:  Women of reproductive potential;
  • Pedi:  Safety and effectiveness not established in children;
  • Geri:  ↑ risk of adverse effects in older adults, especially diarrhea/dehydration.

Adverse Reactions/Side Effects


Derm: impaired wound healing, palmar-plantar erythrodysesthesia syndrome, skin hyperpigmentation

EENT: dysphonia

F and E: dehydration

GI: abdominal pain, anorexia, diarrhea, ↑ liver enzymes, fistula formation, GI PERFORATION, stomatitis

GU: ↑serum creatinine, ↓ fertility, NEPHROTIC SYNDROME, proteinuria


Metabolic: weight loss


* CAPITALS indicate life-threatening.
Underline indicate most frequent.



↑ risk of bone marrow depression with other  antineoplastics  or  radiation therapy.


IV (Adults): 4 mg/kg every 2 wk until disease progression or unacceptable toxicity.


Solution for injection: 25 mg/mL


  • Monitor for signs and symptoms of bleeding. Do not initiate ziv-aflibercept in patients with severe hemorrhage. Discontinue in patients who develop severe hemorrhage.
  • Monitor for signs and symptoms of GI perforation. Discontinue therapy in patients with GI perforation or who develop a fistula.
  • Monitor BP every 2 wk or more frequently as needed during therapy. Treat with antihypertensive agents. Temporarily suspend ziv-aflibercept in patients with uncontrolled hypertension until controlled, and permanently reduce dose to 2 mg/kg for subsequent cycles. Discontinue in hypertensive crisis or with hypertensive encephalopathy.
  • Monitor for arterial thrombotic events (TIA, CVA, angina). Discontinue therapy in patients with an arterial thrombotic event.
  • Assess for diarrhea during therapy. Geri:  Incidence is greater with elderly patients.

Lab Test Considerations:

Monitor proteinuria by urine dipstick and urinary protein creatinine ratio (UPCR) for development or worsening proteinuria. Obtain 24-hr urine collection in patients with ≥2+ for protein or UPCR >1. Suspend therapy for proteinuria ≥2 g/24 hr and resume when proteinuria is <2 g/24 hr. If recurrent, suspend until proteinuria <2 g/24 hr and then permanently reduce ziv-aflibercept dose to 2 mg/kg. Discontinue therapy in patients who develop nephrotic syndrome.

  • Monitor CBC with differential at baseline and before each cycle. Delay therapy until neutrophil count is ≥1.5 × 109 /L.
  • May cause ↑ serum AST and ALT.


  • High Alert: Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double-check single, daily, and course-of-therapy dose limits; have second practitioner independently double-check original order, dose calculations, and infusion pump settings.
  • Hold therapy for at least 28 days before elective surgery and at least 28 days following major surgery; surgical incision should be fully healed before resuming therapy due to potential for impaired wound healing.
  • Administer ziv-aflibercept prior to other components of the FOLFIRI regimen on the day of treatment.

IV Administration

  • Intermittent Infusion:  Solution should be clear and colorless to pale yellow; do not administer solutions that are discolored or contain particulate matter. Do not re-enter vial after initial puncture; discard unused portion. Dilution:  Withdraw prescribed dose and dilute with 0.9% NaCl or D5W. Concentration: 0.6–8 mg/mL. Use polyvinyl chloride (PVC) infusion bags containing bis (2-ethylhexyl) phthalate (DEHP) or polyolefin infusion bags. Store infusion bags for up to 4 hr; discard unused portion.
  • Rate: Infuse over 1 hr through a 0.2-micron polyethersulfone filter. Do not use filters made of polyvinylidene fluoride or nylon every 2 wk. Do not administer as IV push or bolus. Use infusion set made of PVC containing DEHP, DEHP free PVC containing trioctyl-trimellitate, polypropylene, polypropylene lined PVC, or polyurethane.
  • Y-Site Incompatibility: Do not combine with other drugs in same infusion bag or IV line.

Patient/Family Teaching

  • Explain purpose of therapy and potential adverse effects to patient.
  • Advise patient to notify health care professional immediately if signs of bleeding (light-headedness), hypertension (severe headache, light-headedness, neurologic symptoms), severe diarrhea, vomiting, severe abdominal pain, fever or other signs of infection, or symptoms of arterial thromboembolic events occur.
  • Advise patient to maintain adequate hydration to minimize risk and to notify health care professional promptly if signs and symptoms of RPLS (headache, seizures, weakness, confusion, high BP, blindness or change in vision, problems thinking) occur. Symptoms usually resolve within days.
  • Advise patient to notify health care provider of therapy prior to surgery or if had recent surgery.
  • Rep:  May cause fetal harm. Advise women of reproductive potential of the need for effective contraception during and for at least 3 mo after completion of therapy. Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding.
  • Emphasize importance of monitoring lab values to monitor for adverse reactions.

Evaluation/Desired Outcomes

Decrease in spread of metastatic colorectal cancer.