Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

ziv-aflibercept (Rx)Brand and Other Names:Zaltrap

 
 
 

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injection, IV

  • 100mg/4mL vial (25mg/mL)
  • 200mg/8mL vial (25mg/mL)
more...

Colorectal Cancer

Indicated in combination with 5-fluorouracil, leucovorin, irinotecan (FOLFIRI) for metastatic colorectal cancer that is resistant to or has progressed after an oxaliplatin regimen

4 mg/kg IV infused over 1 hr q2weeks; administer before any component of the FOLFIRI regimen on the day of treatment 

Continue until disease progression or unacceptable toxicity occurs

Dosage Modification/Treatment Delay

Discontinue

  • Severe hemorrhage
  • Gastrointestinal perforation
  • Compromised wound healing
  • Fistula formation
  • Hypertensive crisis or hypertensive encephalopathy
  • Arterial thromboembolic events
  • Nephrotic syndrome or thrombotic microangiopathy (TMA)
  • Reversible posterior leukoencephalopathy syndrome (RPLS)

Temporarily suspend dosing

  • At least 4 weeks prior to elective surgery
  • For recurrent or severe hypertension, until controlled; once resumed, permanently reduce dose to 2 mg/kg
  • Proteinuria >2 g/24 hr; resume when proteinuria <2 g/24 hr
  • For recurrent proteinuria, suspend therapy until proteinuria <2 g/24 hr and then permanently reduce dose to 2 mg/kg

Renal & Hepatic Impairment

Renal impairment: No dose adjustment required

Hepatic impairment: No dose adjustment required

Safety and efficacy not established

Next

Adverse Effects

>10%

Leukopenia (78%)

Diarrhea (69%)

Neutropenia (67%)

Proteinuria (62%)

Increased AST (62%)

Stomatitis (50%)

Increased ALT (50%)

Thrombocytopenia (48%)

Fatigue (48%)

Hypertension (41%)

Hemorrhage (38%)

Decreased appetite (32%)

Decreased weight (32%)

Epistaxis (28%)

Abdominal pain (27%)

Dysphonia (25%)

Increased serum creatinine (23%)

Headache (22%)

Asthenia (18%)

Dyspnea (12%)

Palmar-Plantar Erythrodysesthesia Syndrome (11%)

1-10%

UTI (9%)

Dehydration (9%)

Oropharyngeal pain (8%)

Rhinorrhea (6%)

Hemorrhoids (6%)

Rectal hemorrhage (5%)

Proctalgia (5%)

Skin hyperpigmentation (8%)

Arterial thromboembolic events (2.6%)

Fistulas (1.5%)

<1%

GI perforation (0.8%)

RPLS (0.5%)

Postmarketing Reports

Osteonecrosis of the jaw

Cardiac failure, ejection fraction decreased

Previous
Next

Warnings

Black Box Warnings

Increased risk of hemorrhage, including severe and sometimes fatal hemorrhagic events (eg, severe intracranial hemorrhage, pulmonary hemorrhage/hemoptysis); monitor for signs and symptoms of bleeding, and discontinue if needed; do not administer with severe hemorrhage

Increased risk of GI perforation including fatalities; monitor for signs and symptoms of bleeding, and discontinue if needed

Shown to impair wound healing; suspend therapy for ≥4 weeks prior to elective surgery; resume therapy ≥4 weeks following major surgery or until surgical wound has healed; for minor surgical procedures (eg, tooth extraction, biopsy, central venous access port placement), resume therapy once surgical wound has healed completely; discontinue in patients with compromised wound healing

Contraindications

None

Cautions

May increase hemorrhage risk (see Black Box Warnings)

May cause GI perforation (see Black Box Warnings)

May impair wound healing (see Black Box Warnings)

Increased risk of fistula formation involving GI and non-GI sites; discontinue if fistula develops

Increased risk of Grade 3-4 hypertension; monitor BP q2weeks or more frequently if indicated; treat with appropriate antihypertensive therapy; temporarily suspend if hypertension uncontrolled, and permanently reduce dose to 2 mg/kg for subsequent cycles once blood pressure normalizes; discontinue with hypertensive encephalopathy or hypertensive crisis

Increased risk of arterial thromboembolic events (eg, TIA, CVA, and angina pectoris); discontinue if thromboembolic event occurs

Increased risk of higher incidence of neutropenic complications (febrile neutropenia and neutropenic infection; monitor CBC with differential count at baseline and prior to initiation of each cycle; delay if neutrophil count ≥1.5 x 10^9/L

Increased risk of severe diarrhea, especially in patients aged ≥65 years; monitor closely

Increased risk of RPLS (also known as posterior reversible leukoencephalopathy syndrome); confirm RPLS diagnosis with MRI and discontinue if present; RPLS may resolve or improve within days, but some patients have experienced ongoing neurologic sequelae or death

Proteinuria

  • Increased risk of severe proteinuria, nephrotic syndrome and thrombotic microangiopathy (TMA)
  • Monitor by urine dipstick analysis and urinary protein creatinine ratio (UPCR)
  • Obtain 24-hour urine collection in patients with UPCR ≥1; suspend if proteinuria is ≥2 g/24hr, and resume when ≤2 g/24hr; if reoccurs, suspend until ≤2 g/24hr and permanently reduce dose to 2 mg/kg for subsequent cycles; discontinue in patients who develop TMA or nephrotic syndrome
Previous
Next

Pregnancy & Lactation

Pregnancy Category: C

Lactation: Unknown whether distributed in breast milk; because of potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue breast feeding or discontinue the drug, taking into account the importance of the drug to the mother

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

more...
Previous
Next

Pharmacology

Mechanism of Action

Recombinant fusion protein; soluble receptor that binds to human VEGF-A, VEGF-B and P1GF; binding to these endogenous ligands leads to inhibition of binding and activation of their cognate receptors, which can result in decreased neovascularization and decreased vascular permeability; in animals, shown to inhibit proliferation of endothelial cells, leading to inhibition of growth of new blood vessels

Distribution

Steady state concentrations reached by second dose

Accumulation ration: 1.2 after administration 4 mg/kg every two weeks

Elimination

Half-life: 6 days (range of 4-7 days)

Previous
Next

Administration

IV Preparation

Clear, colorless to pale yellow solution; do not use if solution if discolored or cloudy

Do not re-enter vial after initial puncture; discard unused portion

Withdraw prescribed dose and dilute in 0.9% NaCl or D5W to achieve final concentration of 0.6–8 mg/mL; use PVC infusion bags containing DEHP or polyolefin infusion bags

IV Administration

Administer diluted solution as IV infusion over 1 hr through a 0.2 micron polyethersulfone filter

Do not use filters made of polyvinylidene fluoride (PVDF) or nylon

Do not combine with other drugs in same infusion bag or IV line

Infusion set compatibility: Administer using infusion set of PVC containing DEHP, DEHP free PVC containing TOTM, polypropylene, polyethylene lined PVC, or polyurethane

Do not administer as an IV bolus

Storage

Unopened vials: Refrigerator at 2-8°C (36-46°F); keep in the original outer carton to protect from light

Diluted bags: May refrigerate at 2-8°C (36-46°F) for up to 4 hr; discard unused portion

Previous
Next

Images

Previous
Next

Formulary

FormularyPatient Discounts

To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

Adding plans allows you to:

  • View the formulary and any restrictions for each plan.
  • Manage and view all your plans together – even plans in different states.
  • Compare formulary status to other drugs in the same class.
  • Access your plan list on any device – mobile or desktop.

The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
Add or Remove Plans
Plans for
Select State:
Non-Medicare PlansMedicare Plans

Select a box to add or remove a plan.

Select a class to view formulary status for similar drugs

Additional Offers
Email to Patient

From:

To:

The recipient will receive more details and instructions to access this offer.

By clicking send, you acknowledge that you have permission to email the recipient with this information.

Email Forms to Patient

From:

To:

The recipient will receive more details and instructions to access this offer.

By clicking send, you acknowledge that you have permission to email the recipient with this information.

Previous
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.