Ziv-aflibercept

Dosage Forms & Strengths

injection, IV

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

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

Ziv-aflibercept is a prescription medication used to treat cancer of the colon (large intestine) or rectum that has spread to other parts of the body. Ziv-aflibercept belongs to a group of drugs called antiangiogenic agents. These work by stopping the formation of blood vessels that bring oxygen and nutrients to tumors. This may slow the growth and spread of tumors.

Ziv-aflibercept injection come as a solution to be injected intravenously (into a vein) over at least 1 hour by a healthcare professional. Ziv-aflibercept is usually given once every 14 days.

Common side effects include loss of appetite, weight loss, and sores in the mouth or throat.

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if ziv-aflibercept crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using this medication.

Since this medication is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.
 

WARNING: HEMORRHAGE, GASTROINTESTINAL PERFORATION, COMPROMISED WOUND HEALING

See full prescribing information for complete boxed warning.

• Hemorrhage: Severe and sometimes fatal hemorrhage, including gastrointestinal (GI) hemorrhage, has been reported in patients who have received ziv-aflibercept. Do not administer ziv-aflibercept to patients with severe hemorrhage.
• Gastrointestinal Perforation: Discontinue ziv-aflibercept therapy in patients who experience GI perforation.
• Compromised Wound Healing: Discontinue ziv-aflibercept in patients with compromised wound healing. Suspend ziv-aflibercept for at least 4 weeks prior to elective surgery, and do not resume for at least 4 weeks following major surgery and until the surgical wound is fully healed.

You should not use this medicine if you have severe bleeding or uncontrolled hypertension (high blood pressure).

If you need surgery, tell the surgeon ahead of time that you are using ziv-aflibercept.

Ziv-aflibercept may cause serious and sometimes fatal bleeding. Call your doctor at once if you have any signs of unusual bleeding, including easy bruising, bloody stools, coughing up blood, or feeling light-headed or short of breath.

• Your pharmacist can provide more information about ziv-aflibercept.

• Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.
• Disclaimer: Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 1.03.

Date modified: October 13, 2017
Last reviewed: January 04, 2016

Antineoplastic agent; a recombinant humanized fusion protein and vascular endothelial growth factor A (VEGF-A), VEGF-B, and placental growth factor (PlGF) antagonist.1

Contraindications

• Manufacturer states none known.1

Warnings/Precautions

Warnings

Increased risk of bleeding or hemorrhage, including severe and sometimes fatal hemorrhage.1 Grade 3 or 4 hemorrhagic events (e.g., GI hemorrhage, hematuria, postprocedural hemorrhage) reported.1 Severe intracranial hemorrhage and pulmonary hemorrhage/hemoptysis, including fatal cases, also reported.1

Monitor for signs and symptoms of bleeding.1 Do not initiate ziv-aflibercept in patients with severe hemorrhage.1 Discontinue therapy if severe hemorrhage occurs.1 (See Boxed Warning.)

GI perforation, sometimes fatal, reported.1

Monitor for signs and symptoms of GI perforation.1 Discontinue ziv-aflibercept if GI perforation occurs.1 (See Boxed Warning.)

Grade 3 compromised wound healing reported.1

Temporarily suspend ziv-aflibercept therapy ≥4 weeks prior to elective surgery.1 Do not resume therapy until ≥4 weeks following major surgery and after surgical incision has fully healed.1 Do not initiate or resume therapy in patients undergoing minor surgery (e.g., central venous access port placement, biopsy, tooth extraction) until after surgical incision has fully healed.1

Discontinue ziv-aflibercept in patients with compromised wound healing.1 (See Boxed Warning.)

Other Warnings and Precautions

Increased incidence of fistula formation involving GI and non-GI sites (i.e., anal, enterovesical, enterocutaneous, colovaginal, intestinal) reported.1 2

Discontinue ziv-aflibercept if fistula formation occurs.1

Increased risk of grade 3 or 4 hypertension, including hypertensive crisis.1 Hypertension usually develops during the first 2 cycles of therapy;1 limited data indicate a median time to onset of 3.5 days.7 Hypertension reportedly reversible or manageable following discontinuance of ziv-aflibercept or initiation of appropriate supportive measures.7

Monitor BP every 2 weeks or more frequently as clinically indicated during therapy.1 If hypertension occurs, treat with appropriate antihypertensive therapy, and monitor BP regularly.1 If hypertension recurs or becomes severe, temporarily interrupt therapy until controlled, then resume therapy at a permanently reduced dosage.1 (See Hypertension under Dosage and Administration.) Discontinue ziv-aflibercept if hypertensive crisis or hypertensive encephalopathy occurs.1

Ziv-aflibercept has not been evaluated in patients with NYHA class III or IV heart failure.1

Increased incidence of arterial thromboembolic events (e.g., TIA, cerebrovascular accident, angina pectoris), including grade 3 or 4 events, reported.1

Discontinue ziv-aflibercept if an arterial thromboembolic event occurs.1

Increased incidence of severe proteinuria (including grade 3 or 4 proteinuria), nephrotic syndrome, and thrombotic microangiopathy reported.1 Limited data indicate a median time to onset of 15 days for proteinuria; proteinuria reportedly reversible or manageable following discontinuance of ziv-aflibercept or initiation of appropriate supportive measures.7

Monitor urine dipstick and urinary protein creatinine ratio for development or worsening of proteinuria.1 Further assessment (e.g., 24-hour urine collection) recommended if >1+ urine dipstick reading occurs.1 Interrupt ziv-aflibercept therapy for proteinuria ≥2 g per 24 hours; resume therapy when proteinuria declines to <2 g per 24 hours.1 If proteinuria recurs, interrupt therapy until proteinuria declines to <2 g per 24 hours, then resume therapy at a permanently reduced dosage.1 (See Proteinuria under Dosage and Administration.)

Discontinue ziv-aflibercept if nephrotic syndrome or thrombotic microangiopathy occurs.1

Increased incidence of neutropenic complications (e.g., febrile neutropenia, neutropenic infection), including grade 3 or 4 events, reported.1

Monitor CBC counts, including differential, at baseline and prior to initiation of each cycle.1 Delay ziv-aflibercept therapy until neutrophil count is ≥1500/mm3.1

Increased incidence of grade 3 or 4 diarrhea or dehydration reported.1 Diarrhea more likely to occur in patients ≥65 years of age; monitor such patients closely for diarrhea and dehydration.1

Reversible posterior leukoencephalopathy syndrome (RPLS) reported.1

If manifestations of RPLS occur, confirm diagnosis by magnetic resonance imaging (MRI) and discontinue ziv-aflibercept therapy.1 Symptoms of RPLS usually resolve or improve within days, but ongoing neurologic sequelae or death have occurred in some patients.1

Potential for immunogenicity.1 3 Development of anti-product antibodies and neutralizing antibodies reported.1 Mean free ziv-aflibercept trough concentrations reportedly lower in patients with positive neutralizing antibodies than in overall population; clinical relevance of neutralizing antibodies not established.1

Specific Populations

Category C.1 (See Advice to Patients.)

Not known whether distributed into milk.1 Discontinue nursing or the drug.1

Safety and efficacy not established in pediatric patients <18 years of age.1 2 8

No overall differences in efficacy (i.e., overall survival) in geriatric patients (≥65 years of age) compared with younger adults.1 Increased incidence of diarrhea, dizziness, asthenia, weight loss, and dehydration compared with younger adults.1

Closely monitor for diarrhea and dehydration.1 (See Diarrhea and Dehydration under Cautions.)

Systemic exposure and clearance not affected by mild or moderate hepatic impairment.1 (See Absorption: Special Populations and also Elimination: Special Populations, under Pharmacokinetics.)

Systemic exposure and clearance not affected by mild, moderate, or severe renal impairment.1 (See Absorption: Special Populations and also Elimination: Special Populations, under Pharmacokinetics.)

Common Adverse Effects

Leukopenia,1 diarrhea,1 2 neutropenia,1 proteinuria,1 elevated aminotransferase (i.e., AST, ALT) concentrations,1 stomatitis,1 2 fatigue,1 thrombocytopenia,1 hypertension,1 2 weight loss,1 decreased appetite,1 2 epistaxis,1 2 abdominal pain,1 2 dysphonia,1 2 elevated Scr,1 headache.1