Ziv-aflibercept

(ziv uh-flib-ur-sept)

Trade/other name(s): Zaltrap, aflibercept

Why would this drug be used?

This drug is used to treat colorectal cancer and is being studied for use against other cancers. It may also be used to treat other conditions.

How does this drug work?

Ziv-aflibercept attaches to proteins in the body such as VEGF-A and VEGF-B, which are required to grow blood vessels. It is thought that by doing this, the drug stops tumors from being able to create new blood vessels. This limits the tumors’ supply of nutrients, which in turn may slow or stop their growth. New blood vessel growth is called angiogenesis, so ziv-aflibercept is sometimes referred to as an anti-angiogenic drug.

This drug may also work by making tumor blood vessels (which are usually leaky) more stable, allowing chemotherapy to get into cancer cells more effectively.

Before taking this medicine

Tell your doctor…

• If you are allergic to anything, including medicines, dyes, additives, or foods.
• If you have ever had heart disease, stroke, transient ischemic attack, or blood clots in the legs or lungs. This drug may raise your risk of heart or blood vessel problems (see “Precautions” below).
• If you have ever coughed up blood or had serious bleeding. This drug may raise your risk of bleeding in the lungs, brain, intestines, or other sites (see “Precautions” below).
• If you ever had high blood pressure. This drug may raise your risk of developing uncontrolled high blood pressure (see “Precautions” below).
• If you have ever had any other medical conditions such as kidney disease, liver disease (including hepatitis), congestive heart failure, diabetes, gout, or infections. These conditions may require that your medicine dose, regimen, or timing be changed.
• If you have had any type of surgery in the past month, or if you are planning to have surgery. This drug might interfere with wound healing (see “Precautions” below).
• If you are pregnant, trying to get pregnant, or if there is any chance of pregnancy. This drug may affect the fetus if taken during pregnancy (see “Precautions” below).
• If you are breastfeeding. It is not known whether this drug passes into breast milk. If it does, it may affect the baby. Women should not breast-feed during treatment with this drug.
• If you think you might want to have children in the future. This drug might affect fertility. Talk with your doctor about the possible risk with this drug and the options that may preserve your ability to have children.
• About any other prescription or over-the-counter medicines you are taking, including vitamins and herbs. In fact, keeping a written list of each of these medicines (including the doses of each and when you take them) with you in case of emergency may help prevent complications if you get sick.

Interactions with other drugs

Ziv-aflibercept is not known to interact directly with other drugs, although this does not necessarily mean that no drug interactions exist.

Any drugs or supplements that interfere with blood clotting can raise the risk of bleeding during treatment with this drug. These include:

• Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn) and many others
• Warfarin (Coumadin), dabigatran (Pradaxa), or other blood thinners, including any type of heparin injections
• Clopidogrel (Plavix)
• Vitamin E

Note that many cold, flu, fever, and headache remedies contain aspirin or ibuprofen. Ask your pharmacist if you aren’t sure what is in the medicines you take.

Check with your doctor, nurse, or pharmacist about your other medicines, herbs, and supplements, and whether alcohol can cause problems with this medicine.

Interactions with foods

No serious interactions with food are known at this time. Check with your doctor, nurse, or pharmacist about whether some foods may be a problem.

Tell all the doctors, dentists, nurses, and pharmacists you visit that you are taking this drug.

How is this drug taken or given?

When used for colorectal cancer, ziv-aflibercept is given as an infusion into a vein (intravenous, or IV) over about an hour. It is usually given once every 2 weeks. The dose depends on your weight.

Precautions

This drug can cause bleeding, which in some cases can be serious or even life-threatening. Be sure your doctor knows if you take any medicines that may affect your body’s ability to stop bleeding (see “Interactions with other drugs”). Tell your doctor right away if you cough up blood or have unusual bruising, nosebleeds, unexpected or severe vaginal bleeding, bleeding gums when you brush your teeth, vomit that is bloody or looks like coffee grounds, or black, tarry stools. This drug can also cause bleeding into the brain, which is a type of stroke. Tell your doctor right away if you have sudden loss of coordination, vision changes, severe headache, numbness, or trouble speaking or moving.

In rare cases, this drug can cause a hole (perforation) in the intestines. It is important to tell your doctor or nurse right away if you develop stomach (abdominal) pain, and have nausea, vomiting, constipation, fever, or any other symptom with it.

This drug can affect your body’s ability to heal wounds. It should not be used within 4 weeks before elective surgery or within 4 weeks after major surgery (although it may be started sooner after minor surgery if the surgical wound is fully healed).

Rarely, this drug may cause an abnormal opening, known as a fistula, to form between parts of the body that are not normally connected, such as the intestines and the bladder, or the intestines and the skin. Tell your doctor if you have any changes in urination (including passing air when urinating) or bowel movements.

This drug may cause high blood pressure or make it worse. If you are taking a drug for high blood pressure, talk to your doctor about this. Your blood pressure will be checked before treatment starts and while you are on this drug. If your blood pressure goes up, you may need to take medicine to help control it. Treatment with ziv-aflibercept may need to be delayed or stopped if you develop severe high blood pressure. Tell your doctor right away if you notice any possible symptoms of high blood pressure, including a severe headache, chest pain, or feeling dizzy or light-headed.

This drug may raise your risk of problems due to blood clots, including chest pain, strokes, transient ischemic attacks (“mini-strokes”), blood clots in leg veins (deep venous thrombosis), and blood clots in the lung (pulmonary embolism), even if you are taking medicine to thin the blood (anti-coagulation). Tell your doctor right away if you have chest pain, shortness of breath, sudden sweating, lightheadedness, vision changes, numbness, trouble speaking or moving, or swelling, pain, redness, or warmth in an arm or leg.

Ziv-aflibercept may damage your kidneys, which can cause protein in the urine (proteinuria). Your urine will be checked for this before and during treatment. If the amount of protein is high, your doctor may delay your treatment until your kidneys are working better and less protein is found in your urine. Treatment may need to be stopped altogether if there are signs of serious kidney damage.

Your doctor will test your blood throughout your treatment, looking for possible effects of the drug on blood counts or on organs such as the liver and kidneys. Based on the test results, you may be given medicines to help treat any effects. Your doctor may also need to reduce or delay your next dose of this drug, or even stop it altogether. Be sure to keep all of your appointments for lab tests and doctor visits.

This drug may lower your white blood cell count. This can increase your chance of getting an infection. Your doctor may need to delay your treatment if your white blood cell count is low. Be sure to let your doctor or nurse know right away if you have any signs of possible infection, such as fever (100.5° or higher), chills, pain when passing urine, new cough, or bringing up sputum.

This drug can raise your risk of serious diarrhea, especially if you are 65 or older. If left unchecked, it could lead to dehydration and serious chemical imbalances. If you are also getting the chemotherapy drug irinotecan, which can also cause diarrhea, your doctor will prescribe medicine to help prevent or control it. Make sure to take it as prescribed. Be sure to let your doctor or nurse know if you are having diarrhea, especially if it lasts more than 24 hours, or if you get lightheaded, dizzy, or faint.

In rare cases, this drug may cause a serious brain condition known as reversible posterior leukoencephalopathy syndrome (RPLS). Symptoms may include feeling sleepy or confused, headaches, vision problems (including blindness), or seizures. Call your doctor right away if you have any of these symptoms.

This drug can cause problems if taken during pregnancy. Both men and women who could have children should use effective birth control for at least 3 months after the last dose of this drug. Check with your doctor about what kinds of birth control can be used with this medicine.

Possible side effects

You will probably not have most of the following side effects, but if you have any talk to your doctor or nurse. They can help you understand the side effects and cope with them.

Common

• Low white blood cell count with increased risk of infection*
• Diarrhea*
• Protein in the urine*
• Mouth sores
• Low blood platelet count, which can increase the risk of bleeding
• High blood pressure*
• Weight loss
• Loss of appetite
• Feeling tired
• Nosebleeds*
• Abdominal (belly) pain
• Voice changes
• Headache
• Abnormal lab test results showing treatment may be affecting your liver or kidneys (your doctor will discuss what these results mean)

Less common

• Dehydration*
• Blood clots in a leg or lung*
• Urinary tract infection
• Mouth or throat pain
• Shortness of breath
• Runny nose
• Hemorrhoids
• Rectal pain or bleeding
• Darkening of skin
• Redness, swelling, pain, or blisters on the hands and feet (hand-foot syndrome)
• Feeling weak

Rare

• Stroke, transient ischemic attack (mini-stroke), or chest pain*
• Hole in the intestines (bowel perforation)*
• Formation of a fistula (abnormal connection), most often between the intestines and another organ or the skin*
• Slow healing of a wound or surgical incision (or re-opening of one that is healing)*
• Bleeding in the lungs, brain, intestines, or in other parts of the body*
• Kidney damage*
• Nervous system problems, with sleepiness, confusion, trouble with vision, or seizures*
• Reaction during drug infusion, with headache, chest pain, wheezing, sweating, or chills
• Death due to holes or bleeding in the intestine, bleeding in the lung or brain, stroke, infection, or other causes*

*See the “Precautions” section for more detailed information.

There are other side effects not listed above that can also occur in some patients. Tell your doctor or nurse if you develop these or any other problems.

FDA approval

Yes – first approved in 2012

Disclaimer: This information does not cover all possible uses, actions, precautions, side effects, or interactions. It is not intended as medical advice, and should not be relied upon as a substitute for talking with your doctor, who is familiar with your medical needs.