25 mg/ml concentrate for infusion solution
aflibercept
What ZALTRAP is and what it is used for
What Z ALTRAP is and how it works
Z ALTRAP contains the active substance aflibercept, which is a protein that blocks the growth of new blood vessels within a tumor. A tumor needs nutrients and oxygen from the blood to grow. By blocking the growth of blood vessels, Z ALTRAP can cause the growth of a tumor to stop or slow down.
What Z ALTRAP is used for
Z ALTRAP is a medicine used to treat advanced colon or rectal cancer (parts of the colon) in adults. It will be given with other medicines, called ‘chemotherapy’, such as 5-fluorouracil, folinic acid, and irinotecan.
What you need to know before you use ZALTRAP
Do not use ZALTRAP
- if you are allergic to aflibercept or any of the other ingredients of this medicine (listed in section 6).
- in your eyes as it can seriously damage them.
Also, read the package leaflet for the other medicines (“chemotherapy”) that are part of your treatment to see if they are right for you. If you are not sure, talk to your doctor, pharmacist, or nurse if there is any reason why you cannot use these medicines.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before you receive Z ALTRAP and during your treatment if:
- you have problems with bleeding or notice any bleeding after treatment (see section 4) or if you feel extremely tired, weak, dizzy, or have a change in the color of your stools. If the bleeding is severe, your doctor will stop treatment with Z ALTRAP. This is because Z ALTRAP can increase the risk of bleeding.
- you have any problem in your mouth or with your teeth such as poor dental status, gum disease, or planned tooth extraction, especially if you have previously been treated with bisphosphonates (used to treat or prevent bone diseases). A side effect called osteonecrosis (bone damage in the jaw) has been reported in cancer patients treated with ZALTRAP. You may be advised to have a dental examination before starting ZALTRAP treatment. While being treated with ZALTRAP, you should maintain good oral hygiene (including regular tooth brushing) and have routine dental check-ups. If you wear dentures/dentures, make sure they fit properly. If you have previously received or if you receive intravenous bisphosphonate treatment, dental treatment or dental surgery (e.g. tooth extraction) should be avoided. Inform your doctor about your dental treatment and tell your dentist that you are being treated with ZALTRAP. Contact your doctor or dentist immediately if during and after treatment with ZALTRAP you develop any problems in your mouth or with your teeth such as loose teeth, pain or swelling, or non-healing or oozing sores as these may be signs of osteonecrosis of the jaw.
- you have diseases where your bowel is inflamed, such as an infected part of the bowel wall (also called diverticulitis ), peptic ulcer, or colitis. This is because Z ALTRAP can increase the risk of developing holes in the intestinal wall. If this should happen to you, your doctor will stop treatment with Z ALTRAP.
- you have had an abnormal tube-like connection or passage inside your body between internal organs and skin or other tissue (also called a fistula ). If such a connection or passage develops during your treatment, your doctor will stop treatment with Z ALTRAP.
- you have high blood pressure. Z ALTRAP may increase your blood pressure (see section 4) and your doctor will need to monitor your blood pressure and may change your blood pressure medicines or your Z ALTRAP dose. It is therefore also important to tell your doctor, pharmacist, or nurse if you have any other heart problems as high blood pressure can make them worse.
- if you or have had an aneurysm (enlargement and weakening of a vessel wall) or a rupture in a vessel wall.
- if you experience shortness of breath ( dyspnoea ) when you exert yourself or when you lie down, feel very tired, or have swollen legs, these symptoms may be signs of heart failure.
- you have seen signs of a blood clot (see section 4). Signs of a blood clot can vary depending on where it is located (e.g. lungs, bones, heart, or brain) but can cause symptoms such as chest pain, cough, shortness of breath, or difficulty breathing. Other signs may include swelling in one or both legs, pain or tenderness in one or both legs, discoloration, and warmth in the skin of the affected leg, or visible veins. It can also appear as a sudden feeling of numbness or weakness in the face, arms, or legs. Other signs may include feeling confused, having problems with vision, walking, coordination, or balance, problems pronouncing words, or slurred speech. If you experience any of these symptoms, contact your doctor immediately as your doctor may want to treat your symptoms and stop treatment with Z ALTRAP.
- you have kidney problems ( protein in the urine) because your doctor will monitor your kidney function and may need to adjust Z ALTRAP – dose one.
- your white blood cell count is too low. Z ALTRAP can reduce the number of white blood cells in your blood and your doctor will monitor the levels of your white blood cells and may give you additional medicines to increase the levels. If your white blood cell count is low, your doctor may need to delay your treatment.
- you have severe or persistent diarrhea, feel sick (nausea), or have vomiting, this can cause a large loss of body fluids ( dehydration ). Your doctor may need to treat you with other medicines and/or fluids intravenously.
- you have or have ever had an allergy – serious allergic reactions may occur during treatment with Z ALTRAP (see section 4). Your doctor may need to treat the allergic reaction or stop treatment with Z ALTRAP.
- you have had a tooth extracted or other surgery in the last 4 weeks, or if you are going to have surgery or dental or medical treatment, or if you have a surgical wound that has not healed. Your doctor may temporarily pause your treatment before and after surgery.
- you have seizures (convulsions). If you experience vision changes or become confused, your doctor may stop your treatment with Z ALTRAP.
- you are 65 years of age or older and develop diarrhea, dizziness, weakness, weight loss, or severe loss of body fluids (so-called ‘dehydration’). Your doctor will monitor you closely.
- your daily activities are limited or worsened during treatment. Your doctor will monitor you closely.
If any of the above apply to you (or if you are not sure), talk to your doctor, pharmacist, or nurse before you receive Z ALTRAP and during your treatment.
During your treatment, your doctor will carry out several tests to monitor your body function and see how the medicine is working. The tests may include blood and urine samples, X-rays, or other scanning techniques, and/or other tests.
Z ALTRAP is given by drip ( infusion ) into one of your veins ( intravenously ) to treat advanced cancer of the colon or rectum. Z ALTRAP must not be injected into the eyes as it can seriously damage them.
Children and young people
This medicine is not for children and adolescents under 18 years of age. Safety and benefit have not been demonstrated when using Z ALTRAP in children and adolescents.
Other medicines and ZALTRAP
Tell your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines. This also includes over-the-counter medicines and herbal remedies.
Pregnancy, breastfeeding, and fertility
You should not use Z ALTRAP during pregnancy unless you and your doctor decide that the benefit to you is greater than the possible risk to you and your unborn baby.
If you are a woman of childbearing potential, you should use an effective method of contraception (see the section on “Contraceptive methods” below for further details on male and female methods of contraception). This medicine can harm the unborn baby because it can stop the development of new blood vessels.
Talk to your doctor before receiving this medicine if you are breastfeeding. It is not known whether this drug is excreted in breast milk.
Z ALTRAP can affect male and female fertility. Talk to your doctor for advice before you plan to become a parent of a child.
Contraceptive
methods Men and women of childbearing age must use effective contraception:
- during treatment with Z ALTRAP and
- until at least 6 months after the last treatment.
Driving ability and use of machinery
You may have side effects that affect your vision, concentration, or ability to react. If this happens, do not drive or use tools or machines.
ZALTRAP contains sodium
This medicine contains up to 22 mg of sodium (the main component of cooking/table salt) in each vial. This corresponds to 1.1% of the recommended maximum daily intake of sodium for an adult.
How ZALTRAP is given
Z ALTRAP will be given to you by a doctor or nurse experienced in the use of ‘chemotherapy’. It is given as a drip ( infusion ) into one of your veins ( intravenously ). Z ALTRAP should not be injected into the eyes as it can seriously damage them.
This medicine must be diluted before it is given. Practical information regarding the handling and administration of Z ALTRAP for doctors, nurses, and pharmacists is provided in this leaflet.
How much and how often you will receive treatment
- The drip ( infusion one) lasts for about 1 hour.
- You will usually receive an infusion every two weeks.
- The recommended dose is 4 mg per kilogram of your body weight. Your doctor will determine the right dose for you.
- Your doctor will decide how often you should receive the medicine and if the dose needs to be changed.
Z ALTRAP will be given with other chemotherapy drugs such as 5-fluorouracil, folinic acid, and irinotecan. Your doctor will determine the appropriate dose of these other chemotherapy drugs.
The treatment will continue as long as your doctor thinks the treatment is beneficial for you and the side effects are acceptable.
If you have any further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.
Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them. The side effects listed below have been seen when Z ALTRAP was given together with chemotherapy.
Serious side effects are
Talk to your doctor immediately if you notice any of the following serious side effects ar- you may need urgent medical treatment:
- Bleeding: Very common (may affect more than 1 in 10 people) – this includes bleeding from the nose but also serious bleeding in the gut and other parts of the body, which can lead to death. Symptoms may include feeling very tired, weak, and/or dizzy, or your stool changing color.
- Pain in the mouth, teeth, and/or jaw, swelling or non-healing sores in the mouth or jaw, oozing sores, numbness or a feeling of heaviness in the jaw or tooth loss: Uncommon (may affect up to 1 in 100 people) – These symptoms may be signs of bone damage in the jaw ( osteonecrosis ). Tell your doctor and dentist immediately if you experience such symptoms during treatment with ZALTRAP or after stopping treatment.
- Hole in the gut (also called gastrointestinal perforation ): Uncommon (may affect up to 1 in 100 people) – this is a hole in the stomach, esophagus, or intestine. This can lead to death. Symptoms of it can be stomach pain, nausea (vomiting), fever, or chills.
- Connections or passages inside the body between internal organs and the skin or other tissues (also called fistulas ). Common (may affect up to 1 in 10 people) – these abnormal tube-like connections or passages can form between your gut and your skin, for example. Depending on where it occurs, you may sometimes get an unusual discharge from this spot. If you are unsure, consult your doctor.
- High blood pressure (also called hypertension ): Very common (may affect more than 1 in 10 people) – this may develop or worsen. If blood pressure it is not under control, it can cause a stroke, and heart and kidney problems. Your doctor will monitor your blood pressure throughout your treatment.
- Heart failure; Uncommon ( may affect up to 1 in 100 people) – Symptoms may include shortness of breath when you lie down or exert yourself, extensive tiredness, or swollen legs.
- Blockage of an artery due to a blood clot (also called arterial thromboembolic events): Common (may affect up to 1 in 10 people) – this can lead to a stroke or heart attack. Symptoms can be chest pain or heaviness in the chest, sudden numbness or weakness in the face, arms, or legs. Other symptoms may include confusion, vision problems, problems with walking, coordination or balance, or problems with speaking or slurred speech.
- Blockage of veins due to a blood clot (also called venous thromboembolic events): Common (may affect up to 1 in 10 people) – this may include a blood clot in the lungs or legs. Symptoms may include chest pain, cough, weakness, difficulty breathing, or coughing up blood. Other symptoms may include swelling of one or both legs, pain or tenderness in one or both legs when standing or walking, warmth on the skin of the affected leg, red or discolored skin on the affected leg, or visible veins.
- Protein in the urine (also called proteinuria ). Very common (may affect more than 1 in 10 people) – this is often seen in tests. It may include swelling of the feet or the whole body and may be linked to kidney disease.
- Low white blood cell count (also called neutropenia ): Very common (may affect more than 1 in 10 people) – this can cause serious infection. Your doctor will test your blood regularly and check your white blood cell count throughout your treatment. They may also prescribe a medicine called “G-CSF” which helps prevent complications if the number of white blood cells is too low. Symptoms of the infection can be fever, chills, cough, burning when throwing up, or muscle aches. You should check your body temperature frequently during treatment with this medicine.
- Diarrhea and dehydration: Very common (may affect more than 1 in 10 people) diarrhea Common (may affect up to 1 in 10 people) dehydration – severe diarrhea and nausea (vomiting) can cause you to lose too much body fluid ( dehydration ) and body salts ( electrolyte er). Symptoms may include dizziness, especially when standing up from a sitting position. You may need to go to the hospital for treatment. Your doctor may give you medicine to stop or treat diarrhea and nausea (vomiting).
- Allergic reactions: Common (may affect up to 1 in 10 people) – this can happen within minutes of your infusion. Symptoms of an allergic reaction may include rash or itching, red skin, feeling dizzy or faint, shortness of breath, the feeling of tightness in the chest or throat, or facial swelling. Tell your doctor or nurse immediately if you experience any of these symptoms during or shortly after an infusion of Z ALTRAP.
- Slow wound healing or wounds that do not heal: Uncommon (may affect up to 1 in 100 people) – this is when a scar has difficulty healing or staying together or when a healed wound comes back up. Your doctor will stop treatment with this medicine for at least 4 weeks before a planned operation and until the wounds are completely healed.
- A side effect affecting your nervous system (called posterior reversible encephalopathic syndrome or ‘PRES’): Uncommon (may affect up to 1 in 100 people) – symptoms may include headache, vision changes, feeling confused, or seizures involving consciousness with or without high blood pressure.
Talk to your doctor immediately if you notice any of the side effects above.
Other side effects include:
Very common (may affect more than 1 in 10 people)
- decreased number of white blood cells ( leukopenia )
- reduced number of cells in the blood that help it clot ( thrombocytopenia )
- decreased appetite
- headache
- nosebleed
- change in the voice, eg development of a hoarse voice
- breathing difficulties
- painful sores in the mouth
- stomach pain
- swelling and numbness in the hands and feet that may occur due to chemotherapy (called Hand-Foot Syndrome or “Palmar Plantar Erythrodyesthesia”)
- feeling tired or weak
- weight loss
- kidney problems with an increase in creatinine (a marker of kidney function)
- liver problems with an increase in liver enzymes.
Common (may affect up to 1 in 10 people)
- urinary tract infection
- inflammation of the nose and upper part of the throat
- pain in the mouth or throat
- Runny nose
- hemorrhoids, bleeding, or pain in the rectum
- inflammation inside the mouth
- toothache
- changes in the skin pigment
Uncommon (may affect up to 1 in 100 people)
- an increase in protein in the urine, an increase in cholesterol in the blood, and swelling due to excess fluid ( edema ) (also called “nephrotic syndrome”)
- blood clots in very small blood vessels (also called “thrombotic microangiopathy”).
Frequency not known (cannot be estimated from available data)
- an enlargement and weakening of a vessel wall or a rupture in a vessel wall ( aneurysms and arterial dissections).
How to store ZALTRAP
Keep this medicine out of the sight and reach of children.
Use before the expiry date which is stated on the outer carton and the vial label after EXP. The expiration date is the last day of the specified month.
Store in a refrigerator (2 °C – 8 °C).
Store in the original packaging. Light sensitive.
Information on the storage and shelf life of Z ALTRAP after dilution when it is ready for use is described in the section “Practical information for healthcare professionals regarding the preparation and handling of Z ALTRAP 25 mg/ml concentrate for solution for infusion ” at the end of this package insert.
Do not use Z ALTRAP if you notice particles or discoloration in the vial or infusion bag
Medicines must not be thrown into the drain or among the household waste. Ask the pharmacist how to dispose of medicines that are no longer used. These measures will help to protect the environment.
Contents of the packaging and other information
Contents of ZALTRAP
- The active substance is aflibercept. One ml of the concentrate contains 25 mg of aflibercept. A 4 ml vial of concentrate contains 100 mg of aflibercept. One 8 ml vial of concentrate contains 200 mg of aflibercept.
- Other ingredients are: sucrose, sodium chloride, sodium citrate dihydrate, citric acid monohydrate, polysorbate 20, sodium phosphate dibasic heptahydrate, sodium phosphate monobasic monohydrate, sodium hydroxide and/or hydrochloric acid and water for injections
Appearance and package sizes of the medicine
Z ALTRAP is a concentrate for infusion liquid, solution (sterile concentrate). The concentrate is a clear, colorless pale yellow solution.
- 4 ml concentrate in a 5 ml vial of clear borosilicate glass (type 1) sealed with a flanged stopper with a flip-off cap and an inset, coated sealing stopper. Pack size of 1 or 3 vials.
- 8 ml of concentrate in a 10 ml vial of clear borosilicate glass (type 1) sealed with a flanged cap with a flip-off cap and an inserted, coated sealing stopper.
Pack size of 1 vial.
Not all pack sizes may be marketed.
Marketing Authorisation Holder
sanofi-aventis groupe
54, rue La Boétie
75008 Paris
France
Manufacturer
Sanofi-Aventis Deutschland GmbH
Industriepark Hoechst
65926 Frankfurt am Main
Germany
Contact the representative of the Marketing Authorization Holder if you would like to know more about this medicine:
Sanofi AB
Phone: +46 (0)8 634 50 00