Ziv-Aflibercept - Uses, Dosage, Side Effects, Drug Warnings, and Precautions

Overview:

Ziv-aflibercept is administered with other medicines like Fluorouracil, Irinotecan, and Leucovorin for treating advanced cancer of the colon or rectum that is resistant to or has progressed after an Oxaliplatin therapy. It is usually administered in patients who have already been treated with other cancer medications that were not effective enough. Ziv-aflibercept acts by changing the amount of blood that reaches the tumor. This medicine must be administered by or under the direct supervision of the doctor.

Warnings and Precautions:

• The patient must visit the doctor regularly to check the progress to see if the medicine is working properly and to decide if they should continue it further.

• The doctor will check the blood, urine, and blood pressure regularly while the medicine is administered. The patient should monitor the blood pressure at home. If any changes to normal blood pressure are noticed, the doctor must be informed immediately.

• Using this medicine in pregnant women can harm their unborn babies. An effective form of birth control should be used to avoid pregnancy during treatment for at least one month after the last dose. If the patient becomes pregnant, the doctor must be informed right away.

• This medicine can increase the incidence of bleeding problems. The doctor must be informed if any signs of bleeding, blood in the urine, lightheadedness, shortness of breath, or vomiting of blood are noticed.

• Inform the doctor in case of severe diarrhea, vomiting, nausea, or stomach pain as they might indicate serious stomach problems.

• Inform the doctor right away in case of headache, confusion, seizures, blurred vision, or other visual problems. These might indicate symptoms of a rare and serious brain condition called reversible posterior leukoencephalopathy syndrome (RPLS).

• Ziv-aflibercept can temporarily lower the white blood cell count in the blood, with increased chances of getting an infection. It can also decrease the number of platelets that are necessary for proper blood clotting. Certain precautions must be taken, especially when the blood count is low, to decrease the risk of infection or bleeding:

1. People with infections must be avoided. Check with the doctor immediately if there is an infection leading to fever, cough, chills, hoarseness, painful or difficult urination, lower back or side pain,

2. Check with the doctor immediately if there is blood in the cough or if any unusual bleeding or bruising, tarry, black, stools, blood in the urine, or stools are noticed.

3. The patient must be careful while using a regular toothbrush, dental floss, or toothpick. The dentist might recommend other ways to clean the teeth and gums to avoid any bleeding and infection.

4. To avoid bleeding and infection the patient must not touch their eyes or the inside of their nose without washing their hands.

5. The patient should use sharp objects such as a safety razor or nail cutters carefully.

6. Avoid sports or other situations where bruising or injury can take place.

For Patients:

Why Is Ziv-Aflibercept Prescribed?

Ziv-aflibercept is used in combination with other medications for treating cancer of the colon or rectum that has metastasized or spread to other parts of the body. Ziv-aflibercept belongs to the class of antiangiogenic agents. It acts by stopping the formation of blood vessels that bring oxygen and nutrients to tumors. Thereby, retarding the growth and spread of tumors.

What Is the Dosage of Ziv-Aflibercept?

The Ziv-aflibercept injection is available in the form of a solution to be injected intravenously (into a vein) over at least one hour by a doctor or nurse. Ziv-aflibercept is usually given once every 14 days. The doctor might delay the treatment or adjust the dose if certain side effects are experienced by the patients. It is important to inform the doctor if any unusual signs are noticed during the treatment with Ziv-aflibercept.

What Special Dietary Instructions Should be Followed?

Unless the doctor recommends any alteration, a normal diet should be continued.

What Side Effects Can This Medication Cause?

Ziv-aflibercept may cause the following side effects:

• Loss of appetite.

• Weight loss.

• Sores in the mouth or throat.

• Tiredness.

• Voice changes.

• Hemorrhoids.

• Diarrhea.

• Dry mouth.

• Darkening of the skin.

• Dryness, thickness, cracking, or blistering of skin on the palms of the hands and the soles of the feet.

Some side effects can be serious leakage of fluids through an opening in the skin:

• Slow or difficult speech.

• Headache.

• Dizziness or faintness.

• Weakness or numbness of an arm or leg.

• Chest pain.

• Shortness of breath.

• Seizures.

• Extreme tiredness.

• Confusion.

• Change in vision or loss of vision.

• Sore throat, fever, chills, ongoing cough, congestion, or other signs of infection.

• Swelling of the face, eyes, stomach, hands, feet, ankles, or lower legs.

• Unexplained weight gain.

• Foamy urine.

• Pain, tenderness, warmth, redness, or swelling in one leg only.

Ziv-aflibercept may cause other side effects. One must call the doctor if they have any unusual problems while receiving this medication.

Precautions:

Before starting the medication, the risks and benefits must be calculated carefully The following should be considered before administering this drug:

• Allergies: The doctor must be informed about any unusual or allergic reaction to this medicine or any other medicines. The patient should also inform the healthcare professional about other types of allergies, like allergies to foods, preservatives, dyes, or animals.

• Pediatric Population: Safety and efficacy have not been studied yet in the pediatric population. No appropriate studies have been performed to study the relationship between age and the effects of Ziv-aflibercept injection in the pediatric population.

• Geriatric Population: No proper studies performed to date have demonstrated any geriatric-specific problems that limit the usefulness of Ziv-aflibercept injection in the elderly. However, elderly patients are at a higher risk of adverse effects like diarrhea or dehydration. Therefore, it must be used cautiously in patients receiving Ziv-aflibercept injections.

• Breastfeeding: No adequate studies have been performed on women for determining infant risk when using this medication during breastfeeding. The potential benefits must be evaluated against the risks before taking this medication while breastfeeding.

How Is This Medicine Administered?

A health professional or nurse administers this medicine in a hospital or cancer treatment center. Ziv-aflibercept is administered through a needle placed for at least one hour intravenously and is given along with other cancer medications at an interval of two weeks.

Side Effects:

The doctor or nurse must be informed immediately if any of the following side effects occur:

More common:

• Anxiety

• Black, tarry stools.

• Bladder pain.

• Bleeding gums.

• Blood in the urine or stools.

• Bloody nose.

• Blurred vision.

• Chest pain.

• Confusion.

• Cough or hoarseness.

• Decreased urination.

• Difficult, burning, or painful urination.

• Dizziness or lightheadedness.

• Dry mouth.

• Excessive thirst.

• Fainting.

• Fever or chills.

• Frequent urge to urinate.

• Headache.

• Hoarseness.

• Lower back or side pain.

• Nervousness.

• Pain or swelling around the rectum.

• Pale skin.

• Pinpoint red spots on the skin.

• Pounding in the ears.

• Slow or fast heartbeat.

• Sore throat.

• Sores, or ulcers on the lips or in the mouth.

• Sudden shortness of breath or troubled breathing.

• Sunken eyes.

• Swollen glands.

• Unusual bleeding or bruising.

• Unusual tiredness or weakness.

• Voice changes.

• Wrinkled skin.

Less Common

• Pains in the chest, legs, or groin (especially calves of the legs).

• Severe headaches of sudden onset.

• Loss of coordination.

• Shortness of breath for no apparent reason.

• Slurred speech.

• Sudden vision changes.

• Troubled breathing.

• Rare Side Effects:

• Heartburn.

• Indigestion.

• Nausea.

• Severe abdominal or stomach pain, cramping, or burning.

• Vomiting resembling coffee grounds, severe and continuing.

Certain side effects might occur that usually do not require any medical attention. These side effects usually go away during treatment as the body adjusts to the medicine. Also, the healthcare professional can help to prevent, manage or reduce these side effects. The healthcare professional must be informed if the following side effects continue:

• Abdominal or stomach pain.

• Diarrhea.

• Decreased appetite.

• Redness, pain, or swelling of the skin.

• Lack or loss of strength.

• Scaling of the skin on the hands and feet.

• Runny nose.

• Swelling or inflammation of the mouth.

• Ulceration of the skin.

• Tingling of the hands and feet.

For Doctors:

Indications:

Ziv-aflibercept is used in combination with other medications for treating cancer of the colon or rectum that has metastasized or spread to other parts of the body. Ziv-aflibercept belongs to the class of antiangiogenic agents. It acts by stopping the formation of blood vessels that bring oxygen and nutrients to tumors. Thereby, retarding the growth and spread of tumors.

Mechanism of Action:

• Ziv-aflibercept is composed of a recombinant fusion protein made up of vascular endothelial growth factor (VEGF). Receptors one and two are fused to the Fc region of the human immunoglobulin G 1 (IgG1).

• Ziv-aflibercept inhibits the binding and activation of the cognate receptors by forming a bond with these endogenous ligands. This inhibition leads to reduced neovascularization and decreased vascular permeability.

• Ziv-aflibercept is manufactured by recombinant deoxyribonucleic acid (DNA) technology in a CHO (Chinese hamster ovary) K-1 mammalian expression system.

Drug Interactions:

Certain medicines must not be used together. However, in some cases, two different medications might be used together even if an interaction occurs. In such cases, the doctor might change the dose, or take necessary precautions. The healthcare professional must be informed if the patient is taking any prescribed or non prescribed medications.

Other Interactions:

Certain medicines must be avoided at or around the time of eating food or eating certain types of food as interactions might occur. The use of alcohol or tobacco with certain medicines might also lead to interactions. The patient should also discuss with the healthcare professional about the use of medicines with food, alcohol, or tobacco.

Other Medical Problems:

Other medical problems might also affect the use of this medicine. The patient must inform the doctor in the case of any other medical problems, especially:

• Angina or severe chest pain.

• Bleeding problems.

• Blood clotting problems.

• A history of heart attacks.

• Hypertension or high blood pressure.

• Kidney disease.

• Neutropenia or low white blood cells.

• Proteinuria or protein in the urine.

• Stomach or intestinal problems like diarrhea, bleeding, fistula, and perforation.

• History of transient ischemic attacks (TIA or small strokes).

• Wound healing problems.

What Are the Drug Warnings and Precautions?

• Proteinuria: Severe proteinuria, thrombotic microangiopathy (TMA), and nephrotic syndrome is seen commonly in patients treated with Ziv-aflibercept. Proteinuria must be monitored by urine dipstick analysis and urinary protein creatinine ratio during Ziv-aflibercept therapy. Ziv-aflibercept should be suspended administration for proteinuria 2 grams per 24 hours or more. The medicine can be resumed when proteinuria is less than 2 grams per 24 hours. If it is recurrent, the medicine must be suspended until proteinuria is less than 2 grams per 24 hours, and then the dose can be reduced permanently to 2 mg per kg. Ziv-aflibercept should be discontinued in patients who develop nephrotic syndrome or TMA.

• Hemorrhage Patients: If hemorrhage patients are treated with Ziv-aflibercept they have a high risk of hemorrhage, leading to severe and sometimes even fatal hemorrhages. In patients with metastatic colorectal cancer, bleeding or hemorrhage was documented in 38 percent of patients treated with Ziv-aflibercept compared to 19 percent of patients that were given a placebo. Severe intracranial hemorrhage and pulmonary hemorrhage or hemoptysis fatal events have also occurred in patients receiving. Grade three and four hemorrhagic cases (for example, hematuria, gastrointestinal hemorrhage, and post-procedural hemorrhage) were observed in three percent of patients receiving Ziv-aflibercept compared with one percent of patients receiving a placebo. Patients must be monitored for signs and symptoms of bleeding.

• Gastrointestinal Perforation: Fatal gastrointestinal (GI) perforation can occur in patients receiving Ziv-aflibercept. Grade three and four GI perforation events occurred in 0.8 percent of patients treated with Ziv-aflibercept and 0.2 percent of patients treated with a placebo. Patients for signs and symptoms of GI perforation must be monitored and the medicine must be discontinued in patients who experience GI perforation.

• Compromised Wound Healing: Ziv-aflibercept has been documented to impair wound healing in animal models. The use of Ziv-aflibercept should be suspended for at least four weeks before elective surgery and should not be resumed at least four weeks after major surgery or until the surgical wound has healed completely. However, in the case of minor surgeries like a biopsy, and tooth extraction, Ziv-aflibercept can be resumed once the surgical wound is fully healed. Ziv-aflibercept must be discontinued in patients with compromised wound healing.

• Fistula Formation: Gastrointestinal and non-gastrointestinal sites are involved in fistula formation and a higher incidence is observed in patients treated with Ziv-aflibercept. In patients with metastatic colorectal cancer, fistulas at the enterovesical, anal, enterocutaneous, colo-vaginal, and intestinal sites have been reported in 1.5 percent of the patients treated with Ziv-aflibercept regimen, and 0.5 percent of patients treated with placebo regimen.

• Hypertension: The use of Ziv-aflibercept increases the risk of Grade 3 to 4 hypertension. In patients with Ziv-aflibercept developing Grade 3 to 4 hypertension, 54 percent had onset during the first two cycles of treatment. Blood pressure must be monitored every two weeks or more frequently as clinically indicated during treatment with Ziv-aflibercept. Appropriate anti-hypertensive therapy must be initiated and blood pressure must be monitored regularly. Ziv-aflibercept should be discontinued in patients with hypertensive crisis or hypertensive encephalopathy.

• Arterial Thromboembolic Events: Arterial thromboembolic events (ATE), like a cerebrovascular accident, transient ischemic attack, and angina pectoris, are observed more commonly in patients who received Ziv-aflibercept. Discontinue Ziv-aflibercept in patients who experience an ATE.

• Diarrhea and Dehydration: The incidence of severe diarrhea is high in patients treated with Ziv-aflibercept. The incidence of diarrhea is further increased in patients 65 years or older. These elderly patients must be monitored closely for diarrhea.

• Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS (also known as posterior reversible encephalopathy syndrome) has been documented in 0.5 percent of 3795 patients treated with Ziv-aflibercept monotherapy or in combination with chemotherapy. The diagnosis of this syndrome is confirmed with magnetic resonance imaging (MRI) and should be discontinued in patients who develop RPLS. Symptoms of this syndrome usually resolve or improve within days; however, some patients might experience neurologic sequelae or death eventually.

• Neutropenia and Neutropenic Complications: A greater incidence of neutropenic complications like febrile neutropenia and neutropenic infection have been observed in patients with Ziv-aflibercept. Complete blood count with differential count must be monitored before starting each cycle of Ziv-aflibercept.