Action and Spectrum

Actions and Spectrum: 

• ziv-aflibercept is a medication used to treat certain types of cancer, specifically metastatic colorectal cancer and advanced-stage ovarian cancer. It works by inhibiting the growth and spread of cancer cells by preventing the formation of new blood vessels that tumors need to grow and survive. 
• ziv-aflibercept is a recombinant fusion protein that binds to and neutralizes vascular endothelial growth factor (VEGF), a protein that promotes the growth of new blood vessels. By neutralizing VEGF, ziv-aflibercept prevents the formation of new blood vessels, limiting the supply of nutrients and oxygen to cancer cells and preventing them from growing and spreading. 
• In addition to its use in cancer treatment, ziv-aflibercept has been approved to treat certain eye diseases, such as neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME). In these conditions, ziv-aflibercept works by blocking VEGF and preventing the growth of abnormal blood vessels in the eye, which can cause vision loss. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

All grades 

Diarrhea (69%) 

Proteinuria (62%) 

ALT increased (50%) 

Thrombocytopenia (48%) 

Hypertension (41%) 

Decreased appetite (32%) 

Epistaxis (28%) 

Dysphonia (25%) 

Asthenia (18%) 

Dyspnea (12%) 

Upper abdominal pain (11%) 

Leukopenia (78%) 

Neutropenia (67%) 

AST increased (62%) 

Stomatitis (50%) 

Fatigue (48%) 

Decreased weight (32%) 

Abdominal pain (27%) 

Increased serum creatinine (23%)  

Grades 3 to 4 

Diarrhea (19%) 

Leukopenia (16%) 

Fatigue (13%) 

Neutropenia (37%) 

Hypertension (19%) 

Stomatitis (13%) 

Palmar-plantar erythrodysesthesia syndrome (11%) 

1-10% 

All grades 

Oropharyngeal pain (8%) 

Venous thromboembolic events (9%) 

Rectal bleeding (5%) 

Pulmonary embolism (5%) 

Urinary tract infection (9%) 

Skin hyperpigmentation (8%) 

Hemorrhoids (6%) 

Proctalgia (5%)  

Grades 3-4 

Asthenia (5%) 

Palmar-plantar erythrodysesthesia syndrome (3%) 

AST increased (3%) 

Decreased weight (3%) 

Upper abdominal pain (1%) 

Proteinuria (8%) 

Abdominal pain (4%) 

Thrombocytopenia (3%) 

ALT increased (3%) 

Decreased appetite (3%) 

<1% 

Grades 3-4 

Rectal bleeding (0.7%) 

Proctalgia (0.3%) 

Oropharyngeal pain (0.2%) 

Dyspnea (0.8%) 

Dysphonia (0.5%) 

Epistaxis (0.2%) 

Post-marketing Reports 

Aneurysms 

Arterial (including aortic) 

Dissections and rupture 

Black Box Warning

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

ziv-aflibercept is contraindicated in patients with a previous severe allergic reaction to ziv-aflibercept or any of its components 

Caution: 

• Bleeding: ziv-aflibercept can increase the risk of bleeding, especially in patients taking blood-thinning medications. Patients should be closely monitored for signs of bleeding, such as easy bruising or bleeding gums. 

• Hypertension: ziv-aflibercept can cause an increase in blood pressure, which can lead to complications such as heart attack or stroke. Patients should have their blood pressure regularly monitored during treatment. 

• Gastrointestinal perforation: ziv-aflibercept can increase the risk of gastrointestinal perforation, a hole in the wall of the stomach or intestines. Patients should be monitored for symptoms such as severe abdominal pain, nausea, and vomiting. 

• Impaired wound healing: ziv-aflibercept can impair the healing of wounds, including surgical incisions. Patients should inform their doctor if they have any upcoming surgeries. 

• Pregnancy and breast-feeding: ziv-aflibercept may harm an unborn baby and is not recommended for use during pregnancy. It is also unknown if it passes into breast milk and could harm a nursing baby. Patients should discuss the risks and benefits of using ziv-aflibercept during pregnancy and breastfeeding with their doctor. 

• Allergic reactions: Some patients may experience an allergic reaction to ziv-aflibercept. Signs of an allergic reaction include difficulty breathing, swelling of the face, lips, tongue, or throat, and hives or rash. Patients should seek immediate medical attention if they experience any of these symptoms. 

Pregnancy / Lactation

Pregnancy consideration: ziv-aflibercept may harm an unborn baby and is not recommended during pregnancy. 

Lactation:  

• Excretion of the drug in human breast milk is unknown 
• It is recommended that women who are breastfeeding not receive ziv-aflibercept unless the potential benefit justifies the potential risk to the infant. 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.   

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

ziv-aflibercept is a medication used to treat certain types of cancer, including colorectal, lung, and ovarian cancer. It works by blocking the growth of blood vessels that supply tumors with nutrients and oxygen, slowing down or stopping the growth of cancer cells.  

The pharmacology of ziv-aflibercept involves several vital mechanisms: 

• Vascular endothelial growth factor (VEGF) blockade: ziv-aflibercept is a fusion protein comprising the extracellular domain of the VEGF receptor 1 and 2 and the Fc region of human IgG1. By binding to VEGF-A, VEGF-B, and placental growth factor (PlGF), ziv-aflibercept blocks their interaction with their receptors, thereby inhibiting the formation of new blood vessels. 
• Reduced angiogenesis: By blocking the formation of new blood vessels, ziv-aflibercept reduces the supply of oxygen and nutrients to the tumor, which can slow down or stop the growth of cancer cells. 
• Improved chemotherapy efficacy: ziv-aflibercept can also enhance the efficacy of chemotherapy by reducing the formation of new blood vessels and improving drug delivery to the tumor. 

Pharmacodynamics: 

The pharmacodynamics of ziv-aflibercept are complex and involve multiple mechanisms of action that work together to inhibit angiogenesis and improve the efficacy of chemotherapy. By blocking the formation of new blood vessels, ziv-aflibercept can help to slow down or stop the growth of tumors, and may be effective in treating various types of cancers, including colorectal, lung, and ovarian cancer. 

Pharmacokinetics: 

Absorption 

ziv-aflibercept is administered as an intravenous infusion, and its absorption is irrelevant. 

Distribution 

ziv-aflibercept has a large volume of distribution, indicating that it distributes widely throughout the body. The protein binds to plasma proteins to a moderate extent. 

Metabolism 

ziv-aflibercept is not metabolized by the liver. It is broken down into smaller peptides and amino acids by proteolytic enzymes in the reticuloendothelial system. 

Elimination and Excretion 

The half-life of ziv-aflibercept is approximately 11 days, and it is eliminated from the body through the reticuloendothelial system. The drug is not excreted through the kidneys. 

Adminstartion

Administration: 

• ziv-aflibercept is administered as an intravenous infusion (IV) in a medical facility such as a hospital or clinic. The dosage and frequency of administration depend on the type of cancer being treated, the patient’s medical history, and other factors that the healthcare provider will consider. 
• The recommended dose for ziv-aflibercept is usually based on the patient’s weight, with a standard dose of 4 mg/kg administered every two weeks. The infusion is typically given over about one hour. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: ziv-afilbercept 

Why do we use ziv-afilbercept? 

ziv-aflibercept is a medication used to treat certain types of cancer, including: 

• Metastatic colorectal cancer: ziv-aflibercept, combined with chemotherapy, is indicated for treating patients with metastatic colorectal cancer that has progressed after previous treatment with an oxaliplatin-containing regimen. 
• Non-small cell lung cancer: ziv-aflibercept, in combination with chemotherapy, is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer. 
• Metastatic prostate cancer: ziv-aflibercept, combined with chemotherapy, is indicated for treating metastatic castration-resistant prostate cancer patients who have previously received docetaxel chemotherapy. 
• Ovarian cancer: ziv-aflibercept, in combination with chemotherapy, is indicated for the treatment of patients with platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.