Zaltrap

Medical Editor: John P. Cunha, DO, FACOEP Last updated on RxList: 11/18/2021
Zaltrap Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Zaltrap?

Zaltrap (ziv-aflibercept) injection for intravenous infusion is a recombinant fusion protein consisting of Vascular Endothelial Growth Factor (VEGF) fused to the Fc portion of human IgG indicated for patients with metastatic colorectal cancer (mCRC).

What Are Side Effects of Zaltrap?

Common side effects of Zaltrap include:

Dosage for Zaltrap

Zaltrap is available in single-use vials in two strengths: 100 mg/4 mL (25 mg/mL) and 200 mg/8 mL (25 mg/mL). Zaltrap is dosed as 4 mg/kg as an intravenous infusion over 1 hour, every 2 weeks.

What Drugs, Substances, or Supplements Interact with Zaltrap?

Zaltrap may interact with other drugs. Tell your doctor all medications and supplements you use.

Zaltrap During Pregnancy and Breastfeeding

Zaltrap should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether Zaltrap is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious side effects in nursing infants, a decision should be made as to whether to discontinue nursing or to discontinue the drugs, taking into account the important of the drug to the mother. The safety and effectiveness of Zaltrap has not been examined in the pediatric population.

Additional Information

Our Zaltrap Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

QUESTION

What are risk factors for developing colon cancer? See Answer
Zaltrap Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Ziv-aflibercept can make it easier for you to bleed. Call your doctor or seek emergency medical attention if you have:

  • easy bruising, unusual bleeding (nose, mouth, vagina, rectum), or any bleeding that will not stop;
  • signs of bleeding inside your body--feeling light-headed; pink or brown urine; bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds; or
  • signs of bleeding in the brain--sudden weakness (especially on one side of the body), severe headache, problems with speech or vision.

Call your doctor at once if you have:

  • severe or ongoing vomiting or diarrhea;
  • blisters or ulcers in your mouth, red or swollen gums, trouble swallowing;
  • any wound that will not heal;
  • headache, confusion, thinking problems, vision loss, seizure;
  • signs of a blood clot--chest pain, sudden numbness or weakness;
  • signs of perforation (a hole or tear) in your stomach or intestines--fever, ongoing stomach pain, change in bowel habits;
  • signs of a fistula (abnormal passageway) in your lower body--rectal pain, foul-smelling vaginal discharge, pain or swelling in your lower stomach, problems with urination or bowel movements.
  • dehydration symptoms--feeling very thirsty or hot, being unable to urinate, heavy sweating, or hot and dry skin;
  • signs of a kidney disorder--puffy eyes, swelling in your ankles or feet, weight gain, urine that looks foamy; or
  • low white blood cell counts--fever, mouth sores, skin sores, sore throat, cough, trouble breathing.

Older adults may be more likely to have severe diarrhea or get dehydrated.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

Common side effects may include:

  • increased blood pressure;
  • low white blood cells;
  • bruising or bleeding, nosebleeds;
  • stomach pain, diarrhea;
  • mouth sores, loss of appetite, weight loss;
  • headache, feeling tired;
  • hoarse voice; or
  • abnormal kidney or liver function tests.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Zaltrap (Ziv-Aflibercept Injection for Intravenous Infusion)

SLIDESHOW

Digestive Disorders: Common Misconceptions See Slideshow
Zaltrap Professional Information

SIDE EFFECTS

The following clinically significant adverse reactions are described elsewhere in the labeling:

  • Hemorrhage [see WARNINGS AND PRECAUTIONS]
  • Gastrointestinal Perforation [see WARNINGS AND PRECAUTIONS]
  • Impaired Wound Healing [see WARNINGS AND PRECAUTIONS]
  • Fistula Formation [see WARNINGS AND PRECAUTIONS]
  • Hypertension [see WARNINGS AND PRECAUTIONS]
  • Arterial Thromboembolic Events [see WARNINGS AND PRECAUTIONS]
  • Proteinuria [see WARNINGS AND PRECAUTIONS]
  • Neutropenia and Neutropenic Complications [see WARNINGS AND PRECAUTIONS]
  • Diarrhea and Dehydration [see WARNINGS AND PRECAUTIONS]
  • Reversible Posterior Leukoencephalopathy Syndrome [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of ZALTRAP in combination with FOLFIRI was evaluated in VELOUR (EFC102621) [see Clinical Studies]. Patients received ZALTRAP 4 mg per kg (N=611) or placebo (N=605) intravenously every two weeks (one cycle) in combination with FOLFIRI. Patients received a median of 9 cycles of ZALTRAP/FOLFIRI.

The most common Grade 3-4 adverse reactions (≥5%) in the ZALTRAP/FOLFIRI arm were neutropenia, diarrhea, hypertension, leukopenia, stomatitis, fatigue, proteinuria, and asthenia.

The most frequent adverse reactions leading to permanent discontinuation in ≥1% of patients treated with ZALTRAP/FOLFIRI regimen were asthenia/fatigue, infections, diarrhea, dehydration, hypertension, stomatitis, venous thromboembolic events, neutropenia, and proteinuria.

The ZALTRAP dose was reduced and/or omitted in 17% of patients. Cycle delays >7 days occurred in 60% of patients treated with ZALTRAP/FOLFIRI.

The most common adverse reactions (≥20%) in the ZALTRAP/FOLFIRI arm were leukopenia, diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache.

Adverse reactions and laboratory abnormalities that occurred in ≥5% (all grades) of patients receiving ZALTRAP in combination with FOLFIRI and which occurred at ≥2% higher frequency in patients who received ZALTRAP/FOLFIRI compared to those who received placebo/FOLFIRI in VELOUR are shown in Table 1. VELOUR was not designed to demonstrate a statistically significant difference in adverse reaction rates for ZALTRAP/FOLFIRI as compared to placebo/FOLFIRI for any adverse reactions listed below.

Table 1: Selected Adverse Reactions and Laboratory Findings in VELOUR

Primary System Organ Class Preferred TermZALTRAP/ FOLFIRI
(N=611)
Placebo/ FOLFIRI
(N=605)
All grades
(%)
Grades 3-4
(%)
All grades
(%)
Grades 3-4
(%)
Blood and lymphatic system disorders
  Leukopenia78167212
  Neutropenia67375730
  Thrombocytopenia483352
Gastrointestinal disorders
  Diarrhea6919578
  Stomatitis5013335
  Abdominal Pain274242
  Abdominal Pain Upper11181
  Hemorrhoids6020
  Rectal Hemorrhage50.720.5
  Proctalgia50.320.3
Investigations
  AST increased623542
  ALT increased503392
  Weight decreased323140.8
Renal and urinary disorders
  Proteinuria*628411
  Serum creatinine increased230190.5
General disorders and administration site conditions
  Fatigue4813398
  Asthenia185133
Vascular disorders
  Hypertension4119111.5
Metabolism and nutrition disorders
  Decreased Appetite323242
  Dehydration9431
Respiratory, thoracic and mediastinal disorders
  Epistaxis280.270
  Dysphonia250.530
  Dyspnea120.890.8
  Oropharyngeal Pain80.230
  Rhinorrhea6020
Nervous system disorders
  Headache22290.3
Skin and subcutaneous tissue disorders
  Palmar-Plantar Erythrodysesthesia Syndrome11340.5
  Skin Hyperpigmentation8030
Infections
  Urinary Tract Infection90.860.8
Note: Adverse Reactions are reported using MedDRA version 13.1 and graded using NCI CTC version 3.0
* Compilation of clinical and laboratory data

Infections occurred at a higher frequency in patients receiving ZALTRAP/FOLFIRI (46%, all grades; 12%, Grade 3-4) than in patients receiving placebo/FOLFIRI (33%, all grades; 7%, Grade 3-4), including urinary tract infection, nasopharyngitis, upper respiratory tract infection, pneumonia, catheter site infection, and tooth infection.

In patients with mCRC, severe hypersensitivity reactions have been reported with ZALTRAP/FOLFIRI (0.3%) and placebo/FOLFIRI (0.5%).

In patients with mCRC, venous thromboembolic events (VTE), consisting primarily of deep venous thrombosis and pulmonary embolism, occurred in 9% of patients treated with ZALTRAP/FOLFIRI and 7% of patients treated with placebo/FOLFIRI. Grade 3-4 VTE occurred in 8% of patients treated with ZALTRAP/FOLFIRI and in 6% of patients treated with placebo/FOLFIRI. Pulmonary embolism occurred in 5% of patients treated with ZALTRAP/FOLFIRI and 3.4% of patients treated with placebo/FOLFIRI.

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.

In patients with various cancers across 15 studies, 1.4% (41/2862) of patients tested positive for antiproduct antibody (APA) at baseline. The incidence of APA development was 3.1% (53/1687) in patients receiving intravenous ziv-aflibercept and 1.7% (19/1134) in patients receiving placebo. Among patients who tested positive for APA and had sufficient samples for further testing, neutralizing antibodies were detected in 17 of 48 ziv-aflibercept-treated patients and in 2 of 40 patients receiving placebo.

The mean free ziv-aflibercept trough concentrations were lower in patients with positive neutralizing antibodies than in the overall population. The impact of neutralizing antibodies on efficacy and safety could not be assessed based on limited available data.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of ZALTRAP. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Musculoskeletal and connective tissue disorders: Osteonecrosis of the jaw

Cardiac disorders: Cardiac failure, ejection fraction decreased

Read the entire FDA prescribing information for Zaltrap (Ziv-Aflibercept Injection for Intravenous Infusion)

© Zaltrap Patient Information is supplied by Cerner Multum, Inc. and Zaltrap Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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