Zaltrap

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Aflibercept

Method of action: Antitumour, Inhibiting Neoangiogenesis, Ophthalmologicals

Treatment option: Colorectal Cancer, Cancer

Medically reviewed

Marina Burgos

Last updated on 22/12/2025

This page provides general, reference-level information compiled from official medical sources. It is not a substitute for professional medical advice, diagnosis, or treatment. For decisions about your health, please consult a qualified healthcare professional.

Overview of Zaltrap

Quick Facts

Property	Description
Active ingredient	Aflibercept (Ziv-aflibercept)
Form	Solution for Intravenous Infusion (Systemic)
Pharmacological Class	Vascular Endothelial Growth Factor (VEGF) Inhibitor
Common Use	Targeted therapy for metastatic cancer
Origin	Biologic (Recombinant fusion protein)

What Type of Medicine is Aflibercept (Zaltrap)?

Zaltrap is an antineoplastic agent classified as a Vascular Endothelial Growth Factor (VEGF) Inhibitor, intended for use in advanced cancer management. The active ingredient, Aflibercept (or Ziv-aflibercept), is a biologic medicine, meaning it is a large, engineered protein—not a traditional small-molecule chemical drug. This medicine is supported by pharmacological studies demonstrating its high-affinity binding properties to multiple growth factors, a distinctive feature in its class.

Composition, Origin, and Form

The core component of Zaltrap is the Aflibercept molecule, which is structurally created as a recombinant fusion protein by fusing portions of the human VEGF receptors 1 and 2 to a part of a human antibody protein. This complex structure makes it a potent "VEGF Trap." Zaltrap is prepared as a sterile, aqueous solution for intravenous infusion. This formulation is strictly intended for systemic administration into a vein, which is critical for distributing the therapeutic protein throughout the body for targeted cancer therapy.

How Does Zaltrap Generally Benefit the Body?

The primary function of Aflibercept is to slow the growth and progression of disease by intervening in the process of angiogenesis, the formation of new blood vessels. The drug works by acting as a decoy receptor that binds to and neutralizes key growth factors—specifically VEGF-A, VEGF-B, and Placenta Growth Factor (PlGF)—that signal the creation of new blood vessels. By locking onto these factors, Zaltrap effectively inhibits angiogenesis, limiting the supply of oxygen and nutrients tumors need to survive and spread. This comprehensive blockade of signaling pathways is the cornerstone of its benefit in managing metastatic disease.

What side effects are possible with Zaltrap?

Possible Side Effects and Safety Information

The official safety documents for Aflibercept (Zaltrap) detail the adverse reactions observed in clinical use, which are often classified according to the organ system affected and the frequency of occurrence.

Adverse Reaction Scope

Classification Area	Documented Characteristics
Key Adverse Reaction Categories	The safety profile is heavily characterized by Vascular disorders (e.g., hemorrhage, hypertension), Gastrointestinal disorders (e.g., diarrhea, perforation, fistula), and Blood and lymphatic system disorders (e.g., neutropenia, leukopenia).
Frequency Classification	Adverse reactions classified as Very Common (ge 1/10) include Leukopenia, Diarrhea, Neutropenia, Proteinuria (protein in the urine), Stomatitis (mouth sores), Fatigue, and Hypertension (high blood pressure). Arterial Thromboembolic Events (ATEs) are classified as Uncommon.
System-Organ Classes Involved	Primary affected systems, as categorized in official documents, are Vascular disorders, Gastrointestinal disorders, Renal and urinary disorders, and Blood and lymphatic system disorders.
Serious Adverse Reactions	Officially documented serious risks include severe and sometimes fatal Hemorrhage, Gastrointestinal Perforation, Compromised Wound Healing, Fistula Formation, and Arterial Thromboembolic Events (such as stroke or myocardial infarction).
Population-Specific Safety	Older patients (ge 65 years) may experience an increased incidence of severe diarrhea and dehydration compared to younger patients. No dose adjustment is specified for mild-to-moderate renal or hepatic impairment.
Exposure-Related Patterns	The development of Hypertension requiring management was frequently reported to occur within the first two cycles of treatment in over half of affected patients.
Safety-Related Restrictions	Administration must be withheld for at least four weeks prior to elective surgery and should not be resumed until at least four weeks after major surgery and the wound is fully healed, due to the documented risk of compromised wound healing. The medicine is not to be initiated in patients with severe hemorrhage.

Resulting Safety Structure

The most frequent adverse reactions are related to the gastrointestinal and blood/lymphatic systems, as well as vascular effects, including high blood pressure.
The key regulatory concerns are defined by the risk of rare but high-consequence events, specifically Gastrointestinal Perforation, severe Hemorrhage, and the risk of Arterial Thromboembolic Events.
Safety constraints are tied to the peri-operative period and pregnancy, reflecting the drug’s potential for Compromised Wound Healing and Embryo-Fetal Toxicity.

Connection to the overall safety profile:

The official safety information confirms that the medicine's risk profile is structured by effects related to its vascular-targeting mechanism, leading to a documented set of frequent systemic adverse events and specific, serious complications. The safety profile requires awareness of risks involving the vascular system and gastrointestinal integrity, as stated in regulatory documents.

Overdose and Emergency Response

The official regulatory information for Zaltrap defines the emergency context not by a unique overdose dose, but by the occurrence of severe, life-threatening toxicities that require immediate medical intervention.

Documented Overdose Presentations

The following clinical manifestations are officially linked to severe toxicity and require urgent action:

System	Severe Manifestation/Symptom Cluster
Hemorrhage	Signs of internal bleeding (e.g., vomiting blood, bloody or black stools, severe headache, coughing up blood)
Gastrointestinal	Symptoms of Gastrointestinal Perforation (e.g., severe abdominal pain, fever, vomiting)
Vascular/CNS	Signs of Hypertensive Crisis (e.g., sudden severe headache, confusion, seizures) or Arterial Thromboembolic Events (ATE) (e.g., chest pain, sudden weakness)
Neurological	Symptoms of Reversible Posterior Leukoencephalopathy Syndrome (RPLS) (e.g., visual changes, severe headache, confusion)

When Immediate Medical Help is Required

Regulators mandate that patients seek immediate medical attention or go to the nearest emergency facility for any signs of these severe events, including severe hemorrhage, GI perforation, or an ATE. The medicine must be Discontinued immediately upon the confirmation of these life-threatening events, which may include fatal hemorrhage or fatal GI perforation. Management involves providing symptomatic and supportive treatment; no specific antidote is documented. Patients 65 years of age and older may have an increased incidence of severe diarrhea and dehydration, requiring close monitoring.

Therapeutic Uses of Zaltrap

What Zaltrap Treats: Main Uses and Benefits

Zaltrap is an antineoplastic agent used in situations involving the malignant condition known as metastatic colorectal cancer (mCRC), where the cancer has spread from its original site. The agent is applied when patients experience conditions characterized by periods of heightened symptoms following certain prior therapy, and its use is considered relevant in the management of advanced disease. The medication is specifically applied in addressing mCRC that has worsened or progressed following an oxaliplatin-containing regimen.

This clinical scenario typically involves second-line treatment, and the agent is considered relevant when supportive symptom management is appropriate alongside standard chemotherapy (FOLFIRI). The therapeutic approach is used in contexts involving heightened systemic burden to address symptoms related to systemic imbalance. The support Zaltrap offers contributes to easing the overall symptomatic burden by assisting with the management of the malignant condition.

“This intervention is commonly used when advanced disease requires systemic management to assist with managing the symptoms related to malignant conditions that interfere with daily functioning.”

Quick Fact

Property	Description
Indication Focus	Metastatic colorectal cancer (mCRC)
Context of Use	Second-line therapy, used after progression on an oxaliplatin-containing regimen
Therapeutic Benefit	Supports management of symptoms related to malignant conditions and easing the overall symptomatic burden

Eligibility and Restrictions for Use

Who Can and Cannot Use Zaltrap?

Eligibility for Zaltrap (aflibercept) is strictly defined by regulatory authorities based on patient population and pre-existing conditions.

Eligibility Status Summary

Status	Population/Condition
Approved Use	Adults with metastatic colorectal cancer that has progressed following an oxaliplatin-containing regimen.
Contraindicated	Patients with severe hemorrhage or known severe hypersensitivity to the drug. Also, patients with NYHA class III or IV congestive heart failure (per EU labeling).
Not Established	Pediatric patients (under 18 years) and patients with severe hepatic impairment.
Conditional Use	Patients with pre-existing hypertension must have the condition adequately controlled before starting.

Key Restrictions

Females of reproductive potential must verify non-pregnant status and, along with males, use effective contraception during and for a period after the last dose, due to the risk of fetal harm. The medicine must be withheld for at least 4 weeks prior to elective surgery and following major surgery until the surgical wound is fully healed. While no dose change is required for mild-to-moderate renal or hepatic impairment, patients with severe impairment should be treated with caution due to very limited data.

What should I know about interactions with other medicines?

Interactions with other medicines and products

The official interaction profile for Zaltrap (Aflibercept/Ziv-aflibercept) is defined by mandated administration constraints and documented outcomes with co-administered chemotherapy agents.

Administration and Timing Constraints

A primary regulatory requirement is the physical separation of Zaltrap from all other medicinal products. Regulatory labeling strictly prohibits co-administration with any other drug or substance in the same infusion bag or intravenous line due to physical compatibility considerations. Additionally, a specific administration sequence is mandatory: Zaltrap must be administered prior to any component of the FOLFIRI regimen on the day of treatment. This constraint is required to ensure the correct systemic distribution order.

Pharmacokinetic and Pharmacodynamic Outcomes

Formal studies confirm Zaltrap has no clinically important pharmacokinetic interactions with the core components of its combination therapy. Specifically, no significant PK interaction was found with irinotecan (including its active metabolite SN-38) or fluorouracil. This indicates that Zaltrap does not substantially alter the therapeutic exposure of these chemotherapy agents. However, official data reports a pharmacodynamic risk reinforcement: use of Zaltrap in combination with the FOLFIRI regimen is associated with an increased incidence of hemorrhage (including severe Grade ge 3) compared to FOLFIRI alone. There are no known restrictions documented regarding food, alcohol, or herbal supplements that necessitate specific interaction-related timing or avoidance rules.

Mechanism of Action

Zaltrap's mechanism centers on molecular intervention in the process of angiogenesis, the formation of new blood vessels. The drug, Aflibercept, is a recombinant fusion protein that functions as a ligand trap to suppress this process. Aflibercept binds and neutralizes circulating growth factor ligands: Vascular Endothelial Growth Factor A (VEGF-A) and Placenta Growth Factor (PlGF). By trapping these signaling molecules, the drug competitively inhibits their ability to activate their natural cell-surface receptors, VEGFR-1 and VEGFR-2, on endothelial cells. The sustained signal blockade interrupts the VEGF/PlGF pathway, which directly suppresses the signals required for endothelial cell proliferation and migration involved in new vessel formation. The overall physiological consequence is the disruption of pathological neovascularization, which leads to a constraint on the nutrient and oxygen supply routes necessary for proliferation. This constraint on vascular support influences system-level dynamics by modulating the capacity for proliferation.

Dosage and Administration Information

The administration of Zaltrap (aflibercept) is based on a precise, standardized protocol established in combination with the FOLFIRI chemotherapy regimen. The medicine is prepared and administered exclusively as an intravenous (IV) infusion and must not be given as an IV push or bolus.

Administration Scope

Entity	Instruction
Route of administration	Exclusively Intravenous (IV) Infusion over 1 hour.
Dosing schedule	Standard dose is 4 mg per kg of actual body weight, administered in combination with FOLFIRI.
Dose Reduction	A permanent reduction to 2 mg per kg is specified for subsequent cycles following the resolution of certain dose-limiting toxicities, such as recurrent severe proteinuria.
Age-group rules	No dose adjustment is required for older adults or in cases of mild to moderate hepatic impairment.

Frequency and Timing Protocol

Treatment is administered every two weeks (bi-weekly), defining the duration of one cycle, and is continued until disease progression or unacceptable toxicity is observed. The IV infusion must be administered over 1 hour and must be given prior to any component of the FOLFIRI regimen on the treatment day. Prior to infusion, the concentrated solution must be diluted using appropriate diluents, such as 0.9% Sodium Chloride or 5% Dextrose Injection, and must be administered through a 0.2-micron polyethersulfone filter.

Furthermore, a critical procedural rule requires that Zaltrap must be suspended for at least four weeks before any elective surgical procedure. The medicine must not be resumed for a minimum of four weeks after major surgery, ensuring the surgical wound is fully healed.

Recent Clinical Evidence

Research evidence / Overview of studies for Zaltrap

Evidence for Use in Metastatic Colorectal Cancer (mCRC)

This section summarizes the core clinical evidence that informed the regulatory approval of Zaltrap, detailing the large, randomized controlled trials (RCTs) that evaluated outcomes in patients whose cancer had progressed after prior treatment. The primary research for Zaltrap is available in the context of advanced metastatic colorectal cancer (mCRC). Specifically, studies were applied in research contexts involving fluctuating or unstable symptoms in patients whose disease had progressed after being treated with a chemotherapy regimen containing oxaliplatin. Zaltrap was studied for use when combined with the FOLFIRI chemotherapy regimen (irinotecan, 5-fluorouracil, and folinic acid).

The main evidence was observed in a single large, international Phase III clinical trial where adult patients were randomly assigned into two groups: one receiving Zaltrap combined with FOLFIRI, and the other receiving a placebo (an inactive substance) plus FOLFIRI. This type of study is designed to evaluate measured outcomes between the study groups.

Study Design and Measured Outcomes

Researchers designed the key trial to monitor outcomes related to how the disease progressed in the observed populations. Primary research examined Overall Survival (OS), which measures the average length of time patients lived following their enrollment in the study. Secondary measurements used in research exploring how symptoms change over time included Progression-Free Survival (PFS), which is the amount of time that passed before the cancer worsened or death occurred. Additionally, the studies monitored the Overall Response Rate (ORR), reporting on the percentage of patients who experienced a pre-defined reduction in tumor size.

Long-Term Studies and Follow-up

This part provides an overview of the duration of the key clinical trials, summarizing the length of time patients were monitored for outcomes and addressing the extent of available data on long-term outcomes and consistency of the measured changes.

The primary study was observed in patients over a period considered intermediate to long-term for this type of advanced cancer research, with a median follow-up period of approximately 22 months. However, long-term outcome data are not fully established, and there is limited data for long-term outcomes beyond the final analysis date of the core study. The consistency of these measured outcomes following treatment discontinuation is not fully characterized by the original data.

Key Limitations and Areas of Ongoing Research

The regulatory review of the primary data indicates that the magnitude of the measured difference in overall survival was noted by some assessors. Furthermore, the evidence quality varies across studies when moving beyond the pivotal Phase III trial, and comparative evidence is lacking for direct head-to-head assessments against other active, non-chemotherapy treatments used in this setting. The research also describes that the Zaltrap combination was associated with a higher rate of patient discontinuation compared to the other group.

Key Studies & References

Frequently Asked Questions (FAQ)

Common questions about Zaltrap (FAQ)

Q: Is Zaltrap used as a first-line treatment for metastatic colorectal cancer?

According to official product information, Zaltrap is indicated for use in metastatic colorectal cancer after the disease has worsened following initial treatment that included an oxaliplatin-containing regimen. This describes use after a patient’s cancer has progressed on a prior line of therapy.

Q: Can Zaltrap affect how wounds heal after surgery? (Focus on the duration of the restriction)

Yes, official safety documents address the risk of compromised wound healing. Regulatory documents describe that the medicine should be withheld for a period of at least four weeks before any elective surgical procedure. Treatment should not be started again until at least four weeks after major surgery, and only if the surgical wound is fully and properly healed.

Q: Can Zaltrap treatment be stopped abruptly?

Official information states that Zaltrap treatment is typically continued until the cancer worsens or the patient experiences unacceptable side effects. The official label describes specific serious toxicities (such as severe bleeding or gastrointestinal perforation) that are conditions for permanent discontinuation of the medicine.

Q: What are the most commonly reported side effects of Zaltrap?

The most common adverse reactions reported (meaning they occurred in 20% or more of patients in studies) include conditions such as low white blood cell counts (leukopenia and neutropenia), high blood pressure, diarrhea, painful mouth sores, protein in the urine (proteinuria), and fatigue. These findings are detailed in the official prescribing information.

Q: Are there long-term side effects associated with Zaltrap treatment?

Regulatory documents list serious adverse reactions such as impaired wound healing, the formation of abnormal connections between organs (fistula formation), and dangerous blood clots in the arteries (arterial thromboembolic events). The safety of restarting the medicine after certain complications related to wound healing has not been established in official documents.

Q: Are there dietary restrictions or specific foods to avoid while on Zaltrap?

Based on official drug interaction studies, there are no known specific restrictions documented regarding food, alcohol, or herbal supplements that require special timing or avoidance rules directly related to Zaltrap itself.

Q: Does Zaltrap interact with common pain relievers or supplements?

Official documents confirm that Zaltrap has no clinically important pharmacokinetic interactions with the chemotherapy drugs it is given with. Specific mention of common pain relievers or supplements is not present in the official pharmacokinetic interaction data.

Q: How often are the serious side effects of Zaltrap reported?

Official documents specify the frequency of certain serious risks based on clinical trials. For example, severe internal or external bleeding (Grade 3-4 hemorrhage) was reported in 3% of patients, and serious blood clots in the arteries (arterial thromboembolic events or ATEs) were reported in 2.6% of patients.

Q: Does Zaltrap cause hair loss like traditional chemotherapy?

Hair loss, medically known as alopecia, is not listed as one of the very common or common adverse reactions in the official prescribing information for Zaltrap.

Q: How quickly should a patient expect to see research-related changes from Zaltrap?

In clinical studies, researchers monitor tumor response and disease control over time. Measurements like the Overall Response Rate were first assessed at the first planned tumor scan, which was typically around eight weeks into the treatment protocol.

Q: Does Zaltrap make the immune system weaker?

Official product information lists a reduction in certain white blood cells (leukopenia and neutropenia) as very common side effects. Additionally, infections are also classified as a very common adverse reaction in patients receiving the medicine.

Q: Does Zaltrap cause changes in the voice?

Yes, an alteration in the voice, such as hoarseness (dysphonia), is an adverse reaction that is reported in the official prescribing information.

Q: Is Zaltrap a cure for metastatic colorectal cancer?

Zaltrap is an antineoplastic agent (a type of cancer treatment) indicated to treat metastatic colorectal cancer that has progressed. The official label describes the medicine's role in managing the disease and slowing its progression, but does not describe the medicine as providing a cure for this advanced stage of cancer.

Q: Is it normal to have protein in the urine while taking Zaltrap?

Official safety data indicates that having protein in the urine (proteinuria) is a Very Common adverse reaction associated with Zaltrap. This means it was observed in at least 1 out of every 10 patients in clinical studies.

Q: What are the results of the key clinical trials for Zaltrap?

The key regulatory trials demonstrated that combining Zaltrap with the FOLFIRI regimen led to statistically significant improvements in Overall Survival (the average length of time patients lived) and Progression-Free Survival (the time until the cancer worsened) compared to receiving FOLFIRI alone.

Q: What kind of specialized doctor usually prescribes Zaltrap?

Official documentation specifies that Zaltrap should be given under the supervision of a physician who is experienced in the use of antineoplastic medicinal products, which typically refers to an oncologist (a cancer specialist).

Q: Can elderly patients use Zaltrap?

Official product information states that no dose adjustment is required for patients aged 65 and over. However, official safety data indicates that patients in this age group may experience an increased incidence of severe diarrhea and dehydration compared to younger patients.

Q: Are there other uses for Zaltrap besides colorectal cancer?

The medicine is approved solely for the treatment of metastatic colorectal cancer that has progressed after an oxaliplatin-containing regimen. There are no other approved uses listed in the current official prescribing information.

How should Zaltrap be stored and disposed of?

How to Store and Dispose of Zaltrap

The unopened Zaltrap vials must be stored under refrigerated conditions at 2 C to 8 C (36 F to 46 F) and kept in the original outer carton to protect from light [Source 2.1]. The medicine must not be frozen [Source 1.2].

Stability and Disposal Requirements

Zaltrap is provided as a single-dose vial; any unused product remaining in the vial or the prepared infusion solution must be discarded [Source 1.2]. Once diluted, the solution has specific stability limits: up to 24 hours if refrigerated or up to 8 hours at controlled room temperature (20 C to 25 C) [Source 1.2]. Disposal of all unused medicine and related materials must follow local regulations for handling cytotoxic medicinal products and hazardous waste [Source 2.3].

Attention! Always consult to a doctor or pharmacist before using pills or medicines.