ziv-aflibercept

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism/Excretion: Unknown.

Half-Life: 6 days (range 4–7 days).

Time/Action Profile ⬆ ⬇

(improved survival)

ROUTE	ONSET	PEAK	DURATION
IV	4–6	unknown	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

OB: Pregnancy (may cause fetal harm);
Lactation: Should not be used in nursing mothers.

Use Cautiously in:

Elective surgery;
Geri: ↑risk of adverse effects especially diarrhea/dehydration;
Females/males with reproductive potential;
Pedi: Safety and effectivenessnot established.

Adv. Reactions/Side Effects ⬆ ⬇

CNS: REVERSIBLE POSTERIOR LEUKOENCEPHALOPATHY SYNDROME, fatigue, headache

EENT: dysphonia

CV: ARTERIAL THROMBOTIC EVENTS, hypertension

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

GU: NEPHROTIC SYNDROME, ↑serum creatinine, proteinuria

Derm: impaired wound healing, Palmar-Plantar Erythrodysesthesia Syndrome, skin hyperpigmentation

F and E: dehydration

Hemat: BLEEDING, NEUTROPENIA, THROMBOTIC MICROANGIOPATHY, leukopenia, thrombocytopenia

Metab: weight loss

Interactions ⬆ ⬇

Drug-drug:

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

Route/Dosage ⬆ ⬇

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

Availability ⬆ ⬇

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

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. 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.

Implementation ⬆ ⬇

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.

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. 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.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇