Zaltrap

• Sanofi-Aventis U.S. LLC

Zaltrap is part of the drug class:

• OTHER ANTINEOPLASTIC AGENTS

No drug interactions have been studied by the manufacturer. However, you should tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Not all drug interactions are known or reported and new drug interactions are continually being reported.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

This medication falls into category C. You or your partner should use birth control to prevent pregnancy during your treatment with Zaltrap and for at least 3 months after you stop using the medication. If you or your partner become pregnant while using Zaltrap, call your doctor. Zaltrap may harm the fetus (unborn baby).

Zaltrap injection come as a solution to be injected intravenously (into a vein) over at least 1 hour by a healthcare professional. Zaltrap is usually given once every 14 days.

• Your pharmacist can provide more information about ziv-aflibercept.

• Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.
• Disclaimer: Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 1.03.

Date modified: October 13, 2017
Last reviewed: January 04, 2016

Absorption

Bioavailability

Free ziv-aflibercept: Exhibits linear pharmacokinetics over dosage range of 2–9 mg/kg.1 Steady-state concentrations reached by the second dose; accumulation ratio is approximately 1.2.1

VEGF-bound ziv-aflibercept: Time to steady-state concentrations estimated to be 70 days (corresponding to sixth dose).8

Special Populations

Age, race, and gender have no clinically important effects on exposure to free ziv-aflibercept.1

Systemic exposure increased by 29% in patients weighing ≥100 kg.1

Mild (total bilirubin concentration >1–1.5 times the ULN and any AST concentration) or moderate (total bilirubin concentration >1.5–3 times the ULN and any AST concentration) hepatic impairment does not substantially affect systemic exposure.1 Data not available for patients with severe hepatic impairment (total bilirubin concentration >3 times the ULN and any AST concentration).1

Mild (Clcr of 50–80 mL/minute), moderate (Clcr of 30–50 mL/minute), or severe (Clcr <30 mL/minute) renal impairment does not substantially affect systemic exposure.1

Distribution

Extent

Not known whether ziv-aflibercept is distributed into human milk.1

Elimination

Half-life

Free ziv-aflibercept: Approximately 6 days (range: 4–7 days).1

VEGF-bound ziv-aflibercept: Estimated to be approximately 15 days.8

Special Populations

Mild (total bilirubin concentration >1–1.5 times the ULN and any AST concentration) or moderate (total bilirubin concentration >1.5–3 times the ULN and any AST concentration) hepatic impairment does not substantially alter clearance of ziv-aflibercept.1 Data not available for patients with severe hepatic impairment (total bilirubin concentration >3 times the ULN and any AST concentration).1

Mild (Clcr of 50–80 mL/minute), moderate (Clcr of 30–50 mL/minute), or severe (Clcr <30 mL/minute) renal impairment does not substantially affect systemic exposure.1

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

• 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, ulcers, or white spots 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

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Abdominal or stomach pain
• decreased appetite
• diarrhea
• lack or loss of strength
• redness, swelling, or pain of the skin
• runny nose
• scaling of the skin on the hands and feet
• swelling or inflammation of the mouth
• tingling of the hands and feet
• ulceration of the skin

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as an infusion into a vein over a period of time.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache.
• Belly pain.
• Weight loss.
• Loose stools (diarrhea).
• Feeling tired or weak.
• Not hungry.
• Mouth irritation or mouth sores.
• Runny nose.
• Change in voice.
• Change in color of skin.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Zaltrap, in combination with 5-fluorouracil, leucovorin, irinotecan-(FOLFIRI), is indicated for patients with metastatic colorectal cancer (mCRC) that is resistant to or has progressed following an oxaliplatin-containing regimen [see Clinical Studies (14)].

Recommended Dose and Schedule

Administer Zaltrap 4 mg per kg as an intravenous (IV) infusion over 1 hour every two weeks. Administer Zaltrap prior to any component of the FOLFIRI regimen on the day of treatment [see Clinical Studies (14)].

Continue Zaltrap until disease progression or unacceptable toxicity.

Dose Modification/Treatment Delay Recommendations

Discontinue Zaltrap for:

• Severe hemorrhage [see Boxed Warning, Warnings and Precautions (5.1)]
• Gastrointestinal perforation [see Boxed Warning, Warnings and Precautions (5.2)]
• Compromised wound healing [see Boxed Warning, Warnings and Precautions (5.3)]
• Fistula formation [see Warnings and Precautions (5.4)]
• Hypertensive crisis or hypertensive encephalopathy [see Warnings and Precautions (5.5)]
• Arterial thromboembolic events [see Warnings and Precautions (5.6)]
• Nephrotic syndrome or thrombotic microangiopathy (TMA) [see Warnings and Precautions (5.7)]
• Reversible posterior leukoencephalopathy syndrome (RPLS) [see Warnings and Precautions (5.10)]

Temporarily suspend Zaltrap:

• At least 4 weeks prior to elective surgery [see Warnings and Precautions (5.3)]
• For recurrent or severe hypertension, until controlled. Upon resumption, permanently reduce the Zaltrap dose to 2 mg per kg [see Warnings and Precautions (5.5)].
• For proteinuria of 2 grams per 24 hours. Resume when proteinuria is less than 2 grams per 24 hours. For recurrent proteinuria, suspend Zaltrap until proteinuria is less than 2 grams per 24 hours and then permanently reduce the Zaltrap dose to 2 mg per kg [see Warnings and Precautions (5.7)].

For toxicities related to irinotecan, 5-fluorouracil (5-FU), or leucovorin, refer to the current respective prescribing information.

Preparation for Administration

Inspect vials visually prior to use. Zaltrap is a clear, colorless to pale yellow solution. Do not use vial if the solution is discolored or cloudy or if the solution contains particles.

Do not re-enter the vial after the initial puncture. Discard any unused portion left in the vial.

Withdraw the prescribed dose of Zaltrap and dilute in 0.9% sodium chloride solution, USP or 5% dextrose solution for injection, USP to achieve a final concentration of 0.6–8 mg/mL.

Use polyvinyl chloride (PVC) infusion bags containing bis (2-ethylhexyl) phthalate (DEHP) or polyolefin infusion bags.

Store diluted Zaltrap at 2°–8°C (36°–46°F) for up to 24 hours, or at controlled room temperature 20°–25°C (68°–77°F) for up to 8 hours. Discard any unused portion left in the infusion bag.

Administration

Administer the diluted Zaltrap solution as an intravenous infusion over 1 hour through a 0.2 micron polyethersulfone filter. Do not use filters made of polyvinylidene fluoride (PVDF) or nylon.

Do not administer as an intravenous (IV) push or bolus.

Do not combine Zaltrap with other drugs in the same infusion bag or intravenous line.

Administer Zaltrap using an infusion set made of one of the following materials:

• PVC containing DEHP
• DEHP free PVC containing trioctyl-trimellitate (TOTM)
• polypropylene
• polyethylene lined PVC
• polyurethane

You should not be treated with Zaltrap if you are allergic to ziv-aflibercept, or if you have:

• severe bleeding; or

• severe or uncontrolled high blood pressure.

To make sure Zaltrap is safe for you, tell your doctor if you have:

• high blood pressure;

• open sores or skin wounds; or

• if you have had surgery or dental work within the past 4 weeks.

It is not known whether Zaltrap will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

Use birth control to prevent pregnancy while you are receiving Zaltrap, and for at least 3 months after your treatment ends, whether you are a man or a woman.

This medication may affect fertility (your ability to have children), whether you are a man or a woman.

It is not known whether ziv-aflibercept passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are using Zaltrap.

Since this medication is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

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

Zaltrap 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 in your digestive tract - severe stomach pain, bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds; or

• signs of bleeding in the brain - sudden numbness or weakness (especially on one side of the body), sudden severe headache, problems with speech or balance.

Call your doctor at once if you have:

• any wound that will not heal;

• severe or ongoing vomiting or diarrhea;

• chest pain;

• confusion, change in mental status, vision loss, seizure (convulsions);

• signs of infection - fever, chills, flu-like symptoms, swollen gums, mouth sores, skin sores, rapid heart rate, pale skin, feeling light-headed, pain or burning when you urinate;

• dangerously high blood pressure - severe headache, blurred vision, pounding in your neck or ears, nosebleed, anxiety;

• 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

• 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.

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

Common Zaltrap side effects may include:

• increased blood pressure;

• nosebleed;

• loss of appetite, stomach pain, diarrhea;

• headache, feeling tired;

• weight loss; 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.