Dosing & Uses
Dosage Forms & Strengths
injectable solution
- 25mg/mL (4-mL, 8-mL single-dose vials)
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 q2weeks; administer before any component of the FOLFIRI regimen on the day of treatment
Continue until disease progression or unacceptable toxicity occurs
Dosage Modifications
Discontinue
- Severe hemorrhage
- Gastrointestinal perforation
- Impaired 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
- 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 impairment
- No dosage adjustment necessary
Hepatic impairment
- Mild-to-moderate (total bilirubin >1 to ≤3x ULN and any AST): No dosage adjustment necessary
- Severe (total bilirubin >3x ULN): Not studied
Safety and efficacy not established
Adverse Effects
>10%
All grades
- Leukopenia (78%)
- Diarrhea (69%)
- Neutropenia (67%)
- Proteinuria (62%)
- AST increased (62%)
- ALT increased (50%)
- Stomatitis (50%)
- Thrombocytopenia (48%)
- Fatigue (48%)
- Hypertension (41%)
- Decreased weight (32%)
- Decreased appetite (32%)
- Epistaxis (28%)
- Abdominal pain (27%)
- Dysphonia (25%)
- Increased serum creatinine (23%)
- Asthenia (18%)
- Dyspnea (12%)
- Upper abdominal pain (11%)
Grade 3-4
- Neutropenia (37%)
- Diarrhea (19%)
- Hypertension (19%)
- Leukopenia (16%)
- Stomatitis (13%)
- Fatigue (13%)
- Palmar-plantar erythrodysesthesia syndrome (11%)
1-10%
All grades
- Urinary tract infection (9%)
- Oropharyngeal pain (8%)
- Skin hyperpigmentation (8%)
- Venous thromboembolic events (9%)
- Hemorrhoids (6%)
- Rectal hemorrhage (5%)
- Proctalgia (5%)
- Pulmonary embolism (5%)
Grade 3-4
- Proteinuria (8%)
- Asthenia (5%)
- Abdominal pain (4%)
- Palmar-plantar erythrodysesthesia syndrome (3%)
- Thrombocytopenia (3%)
- AST increased (3%)
- ALT increased (3%)
- Decreased weight (3%)
- Decreased appetite (3%)
- Upper abdominal pain (1%)
<1%
Grade 3-4
- Dyspnea (0.8%)
- Rectal hemorrhage (0.7%)
- Dysphonia (0.5%)
- Proctalgia (0.3%)
- Epistaxis (0.2%)
- Oropharyngeal pain (0.2%)
Posmarketing Reports
Arterial (including aortic), aneurysms, dissections, and rupture
Warnings
Contraindications
None
Cautions
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
Gastrointestinal (GI) perforation including fatal GI perforation can occur; monitor for signs and symptoms of bleeding, and discontinue if needed
Grade 3 impaired wound healing was reported; 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
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 109/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
May cause fetal harm based on findings from animal studies and its mechanism of action
Proteinuria
- Severe proteinuria, nephrotic syndrome, and thrombotic microangiopathy (TMA) occurred more frequently
- 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
Pregnancy & Lactation
Pregnancy
Based on findings from animal reproduction studies and its mechanism of action, fetal harm may cause when administered to pregnant women
Insufficient data available in pregnant women exposed to ziv-aflibercept to assess the risk
Advise pregnant women of the potential risk to a fetus
Animal data
- Administration of ziv-aflibercept during organogenesis was embryotoxic and teratogenic in rabbits at exposure levels ~0.3 times the human exposure at the 4 mg/kg/dose
Pregnancy testing
- Verify pregnancy status in females of reproductive potential before initiating ziv-aflibercept
Contraception
- Females or reproductive potential: Use effective contraception during treatment and for 1 month following the last dose
Infertility
- Advise female and male patients of reproductive potential that treatment may impair reproductive function and fertility
Lactation
There are no data on presence of drug in human milk, or effects on breastfed infant or on milk production
Owing to the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment and for 1 month following last dose
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.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
Absorption
Steady state concentrations reached by second dose
Patients weighing ≥100 kg had a 29% increase in systemic exposure compared to patients weighing 50-100 kg
Distribution
Accumulation ratio: 1.2 (4mg/kg q2Week)
Elimination
Half-life: 6 days (4mg/kg q2Week)
Administration
IV Compatibilities
0.9% NaCl
Dextrose 5% (D5W)
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
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Zaltrap intravenous - | 200 mg/8 mL (25 mg/mL) vial |  | |
| Zaltrap intravenous - | 100 mg/4 mL (25 mg/mL) vial |  |
Copyright © 2010 First DataBank, Inc.
Patient Handout
ziv-aflibercept intravenous
ZIV-AFLIBERCEPT - INJECTION
(a-FLIB-er-sept)
COMMON BRAND NAME(S): Zaltrap
USES: Ziv-aflibercept is used to treat cancer of the colon and rectum.
HOW TO USE: This medication is given by injection into a vein by a health care professional. It is given as directed by your doctor, usually every 2 weeks. The medication is injected slowly into a vein over 1 hour.The dosage is based on your medical condition, weight, and response to treatment.You should receive this medication regularly to get the most benefit from it. To help you remember, mark your calendar to keep track of when to receive the next dose.
SIDE EFFECTS: Diarrhea, headache, mouth pain/sores, runny nose, voice changes, weight loss, weakness, tiredness, or darkening of the skin may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: diarrhea that is severe or doesn't stop, signs of kidney problems (such as change in the amount of urine), swelling hands/ankles/feet, signs of dehydration (such as muscle cramps, extreme thirst, dizziness), pain/redness/swelling/tingling/burning of the hands/feet, slow wound healing.Get medical help right away if you have any very serious side effects, including: chest/jaw/left arm pain, weakness on one side of the body, trouble speaking, confusion, sudden vision changes, seizure, sudden/severe back pain or headache.This medication may cause serious (possibly fatal) bleeding. It may also rarely cause a hole to open in the stomach or intestines (gastrointestinal perforation). Tell your doctor right away if you have symptoms such as stomach/abdominal pain that doesn't go away, easy or unusual bleeding/bruising (such as from cuts, gums, nosebleeds), pink/dark urine, bloody or black/tarry stools, vomit that looks like coffee grounds, coughing up blood, lightheadedness, unusual tiredness/weakness.This medication may lower your ability to fight infections. This may make you more likely to get a serious (rarely fatal) infection or make any infection you have worse. Tell your doctor right away if you have any signs of infection (such as sore throat that doesn't go away, fever, chills, cough).This medication may raise your blood pressure. Check your blood pressure regularly and tell your doctor if the results are high. Your doctor may control your blood pressure with medication.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
PRECAUTIONS: Before receiving ziv-aflibercept, tell your doctor or pharmacist if you are allergic to it; or to aflibercept; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: high blood pressure, kidney disease, recent surgery, recent injuries/wounds, recent/current infection, blood/bone marrow disorders (such as low platelet/neutrophil/red blood cell levels), bleeding problems (such as bleeding of the stomach/intestines), blood vessel problems (such as an aneurysm or a tear/break in the aorta or other blood vessels).Before having surgery or any medical procedure, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).This medication may cause wounds to heal slowly or poorly. You should not receive this medication for at least 4 weeks before and at least 4 weeks after major surgery, until wounds from the surgery are fully healed. Ask your doctor for specific instructions about when to stop and when to restart treatment with this medication.Ziv-aflibercept can make you more likely to get infections or may make current infections worse. Stay away from anyone who has an infection that may easily spread (such as chickenpox, COVID-19, measles, flu). Talk to your doctor if you have been exposed to an infection or for more details.Tell your health care professional that you are using ziv-aflibercept before having any immunizations/vaccinations. Avoid contact with people who have recently received live vaccines (such as flu vaccine inhaled through the nose).To lower the chance of getting cut, bruised, or injured, use caution with sharp objects like razors and nail cutters, and avoid activities such as contact sports.Older adults may be more sensitive to the side effects of this drug, especially diarrhea, dehydration, weight loss, and weakness.Tell your doctor if you are pregnant or plan to become pregnant. You should not become pregnant while using ziv-aflibercept. Ziv-aflibercept may harm an unborn baby. Your doctor should order a pregnancy test before you start this medication. Ask about reliable forms of birth control while using this medication and for 1 month after the last dose. If you become pregnant, talk to your doctor right away about the risks and benefits of this medication.It is unknown if this medication passes into breast milk. Because of the possible risk to the infant, breast-feeding is not recommended while using this drug and for 1 month after stopping treatment. Consult your doctor before breast-feeding.
DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Ziv-aflibercept is very similar to aflibercept. Do not use ziv-aflibercept while using the form of aflibercept that is also given by injection into a vein.
OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.
NOTES: Lab and/or medical tests (such as blood pressure, urine protein, complete blood count, liver function) should be done while you are using this medication. Keep all medical and lab appointments.
MISSED DOSE: It is important to get each dose of this medication as scheduled. If you miss a dose, ask your doctor or pharmacist right away for a new dosing schedule.
STORAGE: Not applicable. This medication is given in a hospital or clinic and will not be stored at home.
MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-888-633-4298 (US) or 1-800-668-1507 (Canada).
Information last revised March 2023. Copyright(c) 2023 First Databank, Inc.
IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.
Formulary
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- View the formulary and any restrictions for each plan.
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