Ziv-aflibercept

Ziv-aflibercept is a prescription medication used in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) for metastatic colorectal cancer that is resistant to or has progressed after an oxaliplatin regimen.

• Ziv-aflibercept is available under the following different brand names: Zaltrap

Common side effects of Ziv-aflibercept include:

• diarrhea
• sores on the mouth and lips
• fatigue
• high blood pressure (hypertension)
• weight loss
• loss of appetite
• stomach or abdominal pain
• headache
• weakness
• nosebleeds
• hoarse voice
• low white blood cell count (neutropenia)
• high levels of protein in the urine
• increased liver enzymes
• low blood platelet count
• changes in kidney function

Serious side effects of Ziv-aflibercept include:

• hemorrhage
• impaired wound healing
• fistula formation
• hypertension
• proteinuria
• diarrhea and dehydration
• gastrointestinal perforation

Rare side effects of Ziv-aflibercept include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, light-headedness, or passing out

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Injectable solution

• 25 mg/mL (4-mL, 8-mL single-dose vials)

Colorectal Cancer

Adult dosage

• 4 mg/kg IV every 2 weeks; administer before any component of the FOLFIRI regimen on the day of treatment

Dosage Considerations – Should be Given as Follows:

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Ziv-aflibercept has no noted severe interactions with any other drugs
• Ziv-aflibercept has no noted serious interactions with any other drugs
• Ziv-aflibercept has no noted moderate interactions with any other drugs
• Ziv-aflibercept has no noted minor interactions with any other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Ziv-aflibercept?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Ziv-aflibercept?”

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 and more before elective surgery; resume therapy for 4 weeks and more 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 the 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 every 2 weeks 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 hypertensive encephalopathy or a hypertensive crisis
• Increased risk of arterial thromboembolic events (eg, TIA, CVA, and angina pectoris); discontinue if a thromboembolic event occurs
• Increased risk of higher incidence of neutropenic complications (febrile neutropenia and neutropenic infection); monitor CBC with the differential count at baseline and before initiation of each cycle; delay if the neutrophil count exceeds 1.5 x 109/L and more
• Increased risk of severe diarrhea, especially in patients aged 65 years and more; 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 of 1 and more; suspend if proteinuria is 2 g/24hr and more, and resume when it is 2 g/24hr and less; if reoccurs, suspend until it is 2 g/24hr and less and permanently reduce dose to 2 mg/kg for subsequent cycles; discontinue in patients who develop TMA or nephrotic syndrome

Pregnancy and Lactation

• 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
• 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 the presence of the drug in human milk or its effects on breastfed infants or 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 the last dose