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(ziv a-flib-er-sept) ,


(trade name)


Therapeutic: antineoplastics
Pharmacologic: fusion proteins
Pregnancy Category: C


Used in combination with 5-fluorouracil, leucovorin and irinotecan-(FOLFIRI), for metastatic colorectal cancer (mCRC) 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 effects

Decreased spread of mCRC.


Absorption: IV administration results in complete bioavailability.
Distribution: Unknown.
Metabolism and Excretion: Unknown.
Half-life: 6 days (range 4–7 days).

Time/action profile (improved survival)

IV4–6 unknownunknown


Contraindicated in: Obstetric: Pregnancy (may cause fetal harm); Lactation: Should not be used in nursing mothers.
Use Cautiously in: Elective surgery; Geriatric: ↑ risk of adverse effects especially diarrhea/dehydration; Females/males with reproductive potential; Pediatric: Safety and effectivenessnot established.

Adverse Reactions/Side Effects

Central nervous system

  • reversible posterior leukoencephalopathy syndrome (life-threatening)
  • fatigue (most frequent)
  • headache (most frequent)

Ear, Eye, Nose, Throat

  • dysphonia


  • arterial thrombotic events (life-threatening)
  • hypertension (most frequent)


  • gi perforation (life-threatening)
  • abdominal pain (most frequent)
  • anorexia (most frequent)
  • diarrhea (most frequent)
  • fistula formation
  • ↑ liver enzymes (most frequent)
  • stomatitis


  • nephrotic syndrome (life-threatening)
  • ↑serum creatinine (most frequent)
  • proteinuria


  • impaired wound healing
  • Palmar-Plantar Erythrodysesthesia Syndrome
  • skin hyperpigmentation

Fluid and Electrolyte

  • dehydration (most frequent)


  • bleeding (life-threatening)
  • neutropenia (life-threatening)
  • thrombotic microangiopathy (life-threatening)
  • leukopenia (most frequent)
  • thrombocytopenia (most frequent)


  • weight loss (most frequent)


Drug-Drug interaction

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


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


Solution for intravenous administration (requires dilution): 25 mg/mL

Nursing implications

Nursing assessment

  • 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 hypertnesion 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. Geriatric: 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.

Potential Nursing Diagnoses

Diarrhea (Adverse Reactions)
Risk for impaired skin integrity (Adverse Reactions)


  • Administer ziv-aflibercept prior to other components of the FOLFIRI regimen on the day of treatment.
  • 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.
  • Intravenous 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. Diluent: 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 (PVDF) 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 (TOTM), 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 (lightheadedness), hypertension (severe headache, lightheadedness, 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 reversible posterior leukoencephalopathy syndrome (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. Ziv-aflibercept should be suspended for at least 4 wk prior to major surgery and until surgical wounds fully healed. For minor surgery, such as central venous access port placement, biopsy, and tooth extraction ziv-aflibercept may be initiated/resumed once wound is fully healed. Discontinuation is needed in patients with compromised wound healing.
  • Inform female patient that ziv-aflibercept can cause fetal harm. Advise women with reproductive potential and men of the need for effective contraception during and for at least 3 mo after completion of therapy. Notify health care provider immediately if pregnancy is planned or suspected or if breast feeding.
  • Emphasize importance of monitoring lab values to monitor for adverse reactions.

Evaluation/Desired Outcomes

  • Decrease in spread of metastatic colorectal cancer.
References in periodicals archive ?
In 2012, Memorial Sloan Kettering Cancer Center announced that it would not use the newly approved oncology drug Zaltrap because it proved to be no more effective than current treatment and carried a hefty price tag.
Blocking angiogenesis is a validated effective therapeutic approach against cancer, and several antiangiogenic agents (Avastin, Sutent, Nexavar, Votrient, Inlyta, Zaltrap, Stivarga, etc.
In 2012, Sanofi/Regeneron's Zaltrap (ziv-aflibercept) was approved by the FDA in combination with FOLFIRI for the treatment of metastatic CRC that has become resistant or progressed on prior oxaliplatin-containing combination therapy (FDA, press release, August 3, 2012).
Such figures roll together expenditures on items that have been overpriced (like the drug Zaltrap, which was initially priced twice as high as Avastin with little to no discernible advantage over the older drug) (18) with other interventions that are underfunded (like health information technology, personalized medicine, home health aides, care coordination, public health measures, and preventive care).
Several months later, Zaltrap was approved to treat colorectal cancer.
Last year, the poster child was Zaltrap, with an estimate of $75,000 to add 42 days of life to someone with metastatic colon cancer.
Another example is the recent decision by Memorial Sloan Kettering Cancer Center to eschew Zaltrap for colon-cancer (at $ 11,000 per month) in favor of Avastin, costing half the price, which captures the potential for real cost saving without sacrificing quality of care (Bach, Saltz, Wittes 2012).
Critics of Zaltrap say the drug provides the same survival benefit as Genentech's Avastin when either drug is added to standard chemo-therapy.
Sanofi (EURONEXT: SAN and NYSE: SNY), a diversified healthcare company, and Regeneron Pharmaceuticals Inc (NASDAQ: REGN), a fully integrated biopharmaceutical company, announced on Friday that the Committee for Medicinal Products for Human Use of the European Medicines Agency has adopted a positive opinion and recommended the granting of marketing authorisation for ZALTRAP injection for Intravenous Infusion, in combination with irinotecan/5-fluorouracil/folinic acid chemotherapy in adults.
Sanofi-Aventis and Regeneron Pharmaceuticals said that the Phase III VELOUR trial evaluating the investigational agent ZALTRAP or aflibercept, also known as VEGF Trap, in combination with the FOLFIRI chemotherapy regimen, 5-fluorouracil, and irinotecan] versus a regimen of FOLFIRI plus placebo met its primary endpoint of improving overall survival in the second-line treatment of metastatic colorectal cancer.
The subject of the public contract is the supply of drugs Avonex - L03AB07, Herceptin 150 mg - L01XC03, Rebif - L03AB07, Tarceva - L01XE03, Votrient - L01XE11, Zaltrap - L01XX44.