10 mg / mL concentrate for infusion solution 
ramucirumab

Read all of this leaflet carefully before you start using this medicine. It contains information that is important to you.

– Save this information, you may need to read it again.

– If you have any further questions, ask your doctor.

– If you get any side effects, talk to your doctor. This also applies to any side effects not mentioned in this information.

In this leaflet: 
1. What Cyramza is and what it is used for 
2. What you need to know before you use Cyramza 
3. How to use Cyramza 
4. Possible side effects 
5. How to store Cyramza 
6. Contents of the packaging and other information 

1. What Cyramza is and what it is used for

Cyramza is a cancer drug that contains the active substance ramucirumab which is a monoclonal antibody. It is a specialized protein that can recognize and attach to another protein in the blood vessels called “VEGF receptor 2”. This receptor is needed for the development of new blood vessels. For cancer to grow, new blood vessels must be developed. By attaching to and blocking “VEGF receptor 2”, this drug cuts off the blood supply to the cancer cells.

Cyramza is given in combination with paclitaxel, another anti-cancer medicine, to treat advanced cancer of the stomach (or cancer of the transition between the esophagus and stomach) in adults whose disease has worsened after treatment with cancer drugs.

Cyramza is used to treat advanced cancer of the stomach (or cancer of the transition between the esophagus and stomach) in adults whose disease has worsened after treatment with cancer drugs and for whom treatment with Cyramza in combination with paclitaxel is not appropriate.

Cyramza is used to treat advanced cancer of the colon or rectum (parts of the colon) in adults. It is given together with other medicines called “FOLFIRI chemotherapy” which include “5-fluorouracil”, “folic acid” and “irinotecan”.

Cyramza is given in combination with erlotinib, another cancer drug as the first treatment for advanced non-small-cell lung cancer where the cancer cells have a specific change ( mutation ) in the epidermal growth factor receptor gene in adults.

Cyramza is given in combination with docetaxel, another anti-cancer drug, to treat advanced lung cancer in adults whose disease has worsened after treatment with anti-cancer drugs.

Cyramza is used to treat advanced liver cancer or non-surgical liver cancer in adults who have previously been treated with another cancer drug (sorafenib) and who have an elevated level of a certain protein, alpha-feta protein, in their blood.

2. What you need to know before using Cyramza

Do not use Cyramza

You should not get Cyramza

– if you are allergic to ramucirumab or any of the other ingredients of this medicine (listed in section 6).

– if X-rays show that there is a cavity in the lung cancer or if the lung cancer is close to large blood vessels.

Warnings and cautions

Tell your doctor or nurse before receiving Cyramza if you:

– has any disease that increases the risk of bleeding. Also, tell your doctor if you are taking any medicines that may increase the risk of bleeding or affect the blood’s ability to coagulate. In these cases, the doctor should take regular blood tests to check the risk of bleeding.

– has liver cancer and has previously had bleeding from enlarged blood vessels in the esophagus (esophagus) or has high blood pressure in the portal vein which carries blood from the intestines and spleen to the liver.

– have lung cancer and have recently had to bleed from the lung (coughed up bright red blood) or if you regularly take non-steroidal anti-inflammatory drugs ( NSAIDs ) or drugs that affect the blood’s ability to clot.

– has high blood pressure. Cyramza may increase the incidence of high blood pressure. If you already have high blood pressure, your doctor will make sure it is under control before you receive Cyramza. Your doctor will check your blood pressure and, if necessary, adjust your blood pressure medication during the time you are being treated with Cyramza. Treatment with Cyramza may need to be stopped temporarily until the high blood pressure is under control with medication, or should be stopped permanently if the blood pressure cannot be controlled properly.

– if you have or have had an aneurysm (enlargement and weakening of a vessel wall) or a rupture in a vessel wall.

– should undergo a planned operation, if you have recently undergone an operation or if you have poor wound healing after an operation. Cyramza may increase the risk of wound healing problems. You should not receive Cyramza for at least 4 weeks before undergoing a planned operation, and your doctor will decide when you can start treatment again. If you have a wound that heals poorly during treatment, treatment with Cyramza may be stopped until the wound has completely healed.

– has a serious liver disease (“cirrhosis”) and diseases associated with it, e.g. large fluid accumulation in the abdomen (“ascites”). Your doctor will discuss whether the possible benefits of the treatment outweigh the possible risks for you. If you have liver cancer, your doctor will check you for signs and symptoms of confusion and/or disorientation associated with chronic liver problems and will stop treatment with Cyramza if you develop any of these signs and symptoms.

– have severe kidney problems. There are limited data on the use of Cyramza in patients with severe renal impairment.

Talk to your doctor or nurse immediately if any of the following apply to you (or you are not sure ) during treatment with Cyramza or at any time thereafter:

– The blocking in the artery is of a thrombus ( “arterial thromboembolic events”): Cyramza can lead to blood clots in the artery engines. Arterial blood clots can lead to serious diseases, e.g. heart attack or stroke. Symptoms of a heart attack may include chest pain or heaviness in the chest. Symptoms of a stroke may include sudden numbness or weakness in the arm, leg, and face, feeling confused, difficulty speaking or difficulty understanding others, sudden difficulty walking or balance and coordination problems, or sudden dizziness. Treatment with Cyramza will close permanently if you get a blood clot in the artery engines.

– A hole in the intestinal wall (“gastrointestinal perforation”): Cyramza may increase the risk of developing a hole in the intestinal wall. Symptoms include severe abdominal pain, vomiting, fever, or chills. Treatment with Cyramza will be stopped permanently if you get a hole in the intestinal wall.

– Severe bleeding: Cyramza may increase the risk of severe bleeding. Symptoms may include extreme tiredness, weakness, dizziness, or discoloration of the stool. Cyramza treatment will be stopped permanently if you experience severe bleeding.

– Infusion-related reaction: Infusion-related reactions may occur during treatment as Cyramza is given as an intravenous infusion via a drip (see section 3). Your doctor or nurse will check if you get any side effects during the infusion. Symptoms may include; increased muscle tension, back pain, chest pain and/or tightness in the chest, chills, hemorrhage, breathing problems, wheezing and tingling, or numbness in the hands or feet. In severe cases, symptoms may include shortness of breath caused by narrowed airways, faster heartbeat, and fainting. Cyramza treatment will be permanently discontinued if you experience a severe infusion-related reaction.

– A rare but serious condition in the brain called “posterior reversible encephalopathy syndrome” or “PRES”: Cyramza may increase the risk of developing this condition. The symptoms are characterized by seizures, headaches, nausea, vomiting, blindness, or decreased consciousness, with or without high blood pressure. Your treatment with Cyramza will be stopped if you experience this brain condition.

– Abnormal tubular connections or passages in the body (“fistula”): Cyramza may increase the risk of abnormal tubular connections or passages in the body between internal organs and skin or other tissues. Treatment with Cyramza will end permanently if you get a fistula.

– Abnormal urine tests (“proteinuria”): Cyramza may increase the risk of developing or worsening abnormal levels of protein in the urine. Treatment with Cyramza may need to be temporarily stopped until the protein level in the urine has decreased and thereafter treatment may be resumed at a lower dose. If the protein level in the urine does not decrease sufficiently, the treatment can be stopped permanently.

– Inflammation of the mouth (“stomatitis”): Cyramza, when given in combination with chemotherapy, may increase the risk of developing inflammation of the mouth. Symptoms may include a burning sensation in the mouth, ulceration, blisters, or swelling. Your doctor may prescribe treatment to help with the symptoms.

Fever or infection: You may have a body temperature of 38ºC or more during treatment (because you may have fewer white blood cells than normal, which is very common). Symptoms may include sweating or other signs of infection, such as headache, pain in the arms and legs, or decreased appetite. Infection one (blood poisoning) can become serious and cause death.

– Elderly people with lung cancer: Your doctor will carefully evaluate the most appropriate treatment for you.

Children and young people

Cyramza should not be given to patients under 18 years of age as there is no information on how it works in this age group.

Other medicines and Cyramza

Tell your doctor if you are taking, have recently taken, or might take any other medicines. This also applies to over-the-counter medicines and herbal medicines.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, tell your doctor before using this medicine. You should avoid getting pregnant when you receive this medicine and for at least 3 months after the last dose of Cyramza. Talk to your doctor about which contraceptive is best for you.

Because Cyramza inhibits the development of new blood vessels, it can reduce the likelihood of you getting pregnant or keeping your fetus. It can also harm the unborn baby. You should not use this medicine if you are pregnant. If you become pregnant while receiving treatment with Cyramza, your doctor will discuss whether the benefits of the treatment outweigh the possible risk to you and the unborn baby.

It is not known if the drug passes into breast milk and may affect a breast-fed baby. Therefore, you should not breast-feed when receiving Cyramza and for at least 3 months after receiving the last dose.

Driving and using machines

Cyramza has no or negligible effect on the ability to drive and use machines. If you get any symptoms that affect your ability to concentrate and react, do not drive or use machines until these effects subside.

Cyramza contains sodium

One 10 ml vial contains less than 1 mmol sodium (23 mg), ie essentially ‘ sodium-free’. is almost “sodium-free”.

One 50 ml vial contains approximately 85 mg of sodium (the main ingredient in table salt/table salt). This corresponds to approximately 4% of the highest recommended daily intake of sodium for adults.

3. How to use Cyramza

This cancer treatment is given by a doctor or a nurse.

Dosage and frequency of administration

The amount of Cyramza needed to treat your illness will be calculated by your doctor or pharmacist at the hospital and depends on how much you weigh.

The recommended dose of Cyramza for the treatment of gastric cancer, for the treatment of advanced cancer of the colon or rectum, and the treatment of liver cancer is 8 mg per kg body weight every two weeks.

The recommended dose of Cyramza for the treatment of lung cancer is 10 mg per kg body weight every two weeks when given in combination with erlotinib or once every three weeks when given in combination with docetaxel.

How many infusions you receive depends on how you respond to the treatment. Your doctor will discuss this with you.

Premedication

You may be given other medicines to reduce the risk of an infusion-related reaction before you receive Cyramza. If you get an infusion-related reaction during treatment with Cyramza, you will receive premedication with all subsequent infusions.

Dose adjustments

During each infusion, your doctor or nurse will check for side effects.

If you get an infusion-related reaction during treatment, you will receive the rest of the current infusion one and all subsequent infusions over a longer period of time.

The amount of protein in the urine will be checked regularly during treatment. Depending on the amount of protein, treatment with Cyramza may be interrupted temporarily. When the amount of protein has dropped to a certain level, treatment is started again with a lower dose.

Method of administration and method of administration

Cyramza is a concentrate for solution for infusion (also known as “sterile concentrate”). The hospital pharmacist, nurse, or doctor has diluted the concentrate in the vial with sodium chloride 9 mg/ml (0.9%) solution before use. This medicine is given as an infusion by drip over a period of about 60 minutes.

Cyramza treatment is temporarily stopped if you:

– gets high blood pressure, until it is under the control of blood pressure medication

– has wound healing problems, until the wound has healed

– will undergo a planned operation, four weeks before the operation.

Cyramza treatment is permanently discontinued if you:

– get a blood clot in the artery are

– gets a hole in the intestinal wall

– gets a severe bleeding

– has a severe infusion-related reaction

– gets high blood pressure which can not be controlled with blood pressure medication

– get more than a certain amount of protein in the urine or if you develop serious kidney disease ( nephrotic syndrome )

– get abnormal tubular connections or passages in the body between internal organs and skin or other tissues ( fistula )

– becomes confused and/or disoriented in connection with chronic liver problems

– renal impairment (associated with liver failure).

When you receive Cyramza in combination with paclitaxel or docetaxel

Paclitaxel and docetaxel are also given as a drip into a vein ( intravenous infusion ) over a period of about 60 minutes. If you are receiving Cyramza in combination with either paclitaxel or docetaxel, Cyramza will be given first.

The amount of paclitaxel and docetaxel, respectively, depends on the size of your body surface area. The doctor or hospital pharmacist calculates the body surface area by measuring height and weight and then calculating which dose is right for you.

The recommended dose of paclitaxel is 80 mg per square meter (m 2 ) of body surface area once a week for three weeks followed by one week without treatment.

The recommended dose of docetaxel is 75 mg per square meter (m 2 ) of body surface area once every three weeks.

If you are of East Asian descent, you can receive a reduced starting dose of docetaxel of 60 mg per square meter (m 2 ) of body surface area once every three weeks.

Before you receive an infusion of paclitaxel, you must have a blood test to check that you have enough blood cells and that your liver is working well.

Read the package leaflet for paclitaxel and docetaxel respectively for further information.

When you get Cyramza in combination with FOLFIRI

FOLFIRI chemotherapy is given as an intravenous infusion, after the end of infusion one of Cyramza. Read the package leaflet for the other medicines that are part of your treatment to see if they are suitable for you. If you are not sure, ask your doctor, pharmacist, or nurse if there is any reason why you can not take these medicines.

When you receive Cyramza in combination with erlotinib

Read the package leaflet for erlotinib for more information to see if they are right for you. If you are not sure, ask your doctor, pharmacist, or nurse if there is any reason why you can not get erlotinib.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Tell your doctor immediately if you experience any of the following serious side effects that have been observed with Cyramza (see also What you need to know before you use Cyramza ):

Common side effects are (may affect up to 1 in 10):

– holes in the gut wall: this is a hole that develops in the stomach or intestine. Symptoms include severe abdominal pain, vomiting, fever, or chills

– severe bleeding in the intestine: symptoms may include extreme fatigue, weakness, dizziness, or discoloration of the stool

– blood clots in the arteries: arterial blood clots can lead to a heart attack or a stroke. Symptoms of a heart attack may include chest pain or heaviness in the chest. Symptoms of a stroke may include sudden numbness or weakness in the arm, leg, and face, feeling confused, difficulty speaking or having difficulty understanding others, sudden difficulty walking or balance and coordination problems, or sudden dizziness.

Rare side effects are (may affect up to 1 in 1000):

– A state of the brain called the posterior reversible encephalopathy syndrome: Symptoms are characterized by seizures, headaches, nausea, vomiting, blindness, or impaired consciousness, with or without high blood pressure.

Tell your doctor if you experience any of the following side effects:

A very common side effect is (can occur in more than 1 in 10):

– feeling tired or weak

– low white blood cell count (may increase the risk of infection )

– infection s

– diarrhea

– hair loss

– nosebleeds

– inflammation of the lining of the mouth

– high blood pressure

lowering of red blood cells which can make the skin pale

– swelling of hands, feet, and legs due to fluid retention

– low platelet count ( blood cells that help the blood to coagulate)

– abdominal pain

– protein in the urine (abnormal urine sample)

– headache

– inflammation of the mucous membranes, such as the digestive organs or respiratory system

Common side effects are (may affect up to 1 in 10):

fever together with low white blood cell count

– low levels in the blood of a protein called albumin

infusion-related reactions

rash

– redness, swelling, numbness/tingling, or pain and/or peeling of the skin on the hands and/or feet (called hand-foot syndrome)

– hoarseness

– bleeding in the lungs

– low levels of sodium in the blood ( hyponatremia ) which can lead to fatigue and confusion or muscle twitching

– bleeding gums

confusion and/or disorientation in patients with chronic liver problems

– bowel obstruction, symptoms may include constipation and abdominal pain

– abnormal growth of blood vessels

– serious infection (blood poisoning)

– low levels of potassium in the blood ( hypokalaemia ) can lead to muscle weakness, twitching, or abnormal heart rhythm.

Rare side effects are (may affect up to 1 in 1000):

– abnormal blood clotting in small blood vessels.

Cyramza can cause changes in lab samples. From the side effect list above are these: low white blood cell count, low platelet count, low levels of albumin, sodium, and potassium, presence of protein in the urine.

Other side effects include the following:

No known frequency

An enlargement and weakening of a vessel wall or a rupture in a vessel wall ( aneurysms and arterial dissections).

5. How to store Cyramza

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and the vial label after “EXP”. The expiration date is the last day of the specified month.

Store in a refrigerator (2 ° C to 8 ° C).

Do not freeze.

Keep the vial in the outer carton. Sensitive to light.

The infusion solution must not be frozen or shaken. Do not administer the solution if you notice that it contains particles or is discolored.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6. Contents of the packaging and other information

Content declaration

– The active substance is ramucirumab. One ml of the sterile concentrate for solution for infusion contains 10 mg ramucirumab.

– a vial of 10 ml contains 100 mg ramucirumab.

– a vial of 50 ml contains 500 mg ramucirumab.

The other ingredients are histidine, histidine monohydrochloride, sodium chloride, glycine (E640), polysorbate 80 (E433), and water for injections (see section 2 “Cyramza contains sodium”).

What the medicine looks like and the contents of the pack

The concentrate for the infusion solution (or sterile concentrate) is a clear to slightly opalescent and colorless to slightly yellowish solution in a vial with a rubber stopper.

Cyramza is available in packs of:

– 1 vial of 10 ml

– 2 vials of 10 ml

– 1 vial of 50 ml

Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Eli Lilly Nederland BV, Papendorpseweg 83, 3528 BJ Utrecht, The Netherlands

Lilly France Fegersheim, 2 rue du Colonel Lilly, 67640 Fegersheim, France

Muhammad Nadeem

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