NAVIREL 10 mg /Ml Concentrate

Contents of the leaflet

1. Package Leaflet: Information for the User
2. Navirel, 10 mg/ml, Concentrate for Solution for Infusion
   1. Read all of this leaflet carefully before using this medicine because it contains important information for you.
   2. Contents of the pack
3. What Navirel is and what it is used for
4. Before you are given Navirel
   1. When Navirel must not be given:
   2. Warnings and precautions
   3. Children and adolescents
   4. Navirel and other medicines
   5. Pregnancy, breast-feeding and fertility
   6. Driving and using machines
5. How Navirel is given
   1. Navirel should only be prepared and given by a healthcare professional who has experience in the use of anticancer medicines.
   2. Navirel should always be given by injection into a vein.
   3. Overdose of Navirel
6. Possible side effects
   1. Uncommon side effects (may affect up to 1 in 100 people)
   2. Rare side effects (may affect up to 1 in 1,000 people)
   3. Frequency not known (cannot be estimated from the available data)
   4. Very common side effects (may affect more than 1 in 10 people)
   5. Common side effects (may affect up to 1 in 10 people)
   6. Uncommon side effects (may affect up to 1 in 100 people)
   7. Rare side effects (may affect up to 1 in 1,000 people)
   8. Very rare side effects (may affect up to 1 in 10,000 people)
   9. Frequency not known (cannot be estimated from the available data)
   10. Reporting of side effects
7. How to store Navirel
8. Contents of the pack and other information
   1. What Navirel contains
   2. What Navirel looks like and contents of the pack
   3. Marketing Authorisation Holder and Manufacturer
   4. This medicinal product is authorised in the Member States of the European Economic Area under the following names:
   5. Date of last revision of the package leaflet: 10/2024.
   6. How to use Navirel
   7. How to store Navirel

Package Leaflet: Information for the User

Navirel, 10 mg/ml, Concentrate for Solution for Infusion

Winorelbine

Read all of this leaflet carefully before using this medicine because it contains important information for you.

• You should keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

• 1. What Navirel is and what it is used for
• 2. Before you are given Navirel
• 3. How Navirel is given
• 4. Possible side effects
• 5. How to store Navirel
• 6. Contents of the pack and other information

1. What Navirel is and what it is used for

Navirel is a concentrate for solution for infusion. The active substance in Navirel, winorelbine, belongs to a group of medicines used to treat cancer. These medicines are called cytostatics, as they slow down or stop the growth of cancer cells. Navirel is used to treat certain types of lung cancer (non-small cell lung cancer) and breast cancer.

2. Before you are given Navirel

When Navirel must not be given:

• You are allergic to winorelbine or any other similar medicines used to treat cancer (alkaloids) or any of the other ingredients of this medicine (listed in section 6);
• You have a low white blood cell count or have had a severe infection in the last 2 weeks;
• You have a low platelet count;
• You have severe liver disease not caused by cancer;
• You have recently received or are going to receive a live vaccine (e.g. yellow fever vaccine);
• You are pregnant;
• You are breast-feeding.

Warnings and precautions

Before you are given Navirel, tell your doctor, pharmacist or nurse if:

• You have had radiotherapy which included the liver in the radiation field;
• You have liver problems;
• You have recently received or are going to receive a live vaccine (e.g. oral polio vaccine);
• You are taking certain medicines, such as phenytoin (for epilepsy) or itraconazole (for fungal infections);
• You have had a heart attack or have angina;
• You have symptoms of infection (e.g. fever, chills); you should contact your doctor immediately so that they can perform any necessary tests;
• You are Japanese, as you may be at increased risk of developing lung disease.

You must avoid contact of the medicine with your eyes. There is a risk of severe irritation, even corneal ulceration. If the medicine comes into contact with your eyes, they should be flushed immediately with plenty of sodium chloride solution. You should tell your doctor immediately if you experience pain at the injection site during or after the infusion. This may be a sign of an injection error and the infusion should be stopped immediately.

Children and adolescents

Navirel should not be given to children, as there is not enough information on its use in children.

Navirel and other medicines

Tell your doctor, pharmacist or nurse about all the medicines you are taking, or have recently taken, and those you plan to take. Your doctor should be particularly careful if you are taking:

• Medicines that prevent blood clotting (anticoagulants);
• Medicines for epilepsy, such as phenytoin, phenobarbital and carbamazepine;
• Antibiotics, such as rifampicin, clarithromycin and erythromycin;
• Antiviral medicines, such as ritonavir;
• Antifungal medicines, such as itraconazole and ketoconazole;
• A cancer medicine called mitomycin C;
• Medicines that weaken the immune system, such as cyclosporin and tacrolimus;
• Medicines for heart problems, such as verapamil and quinidine;
• A herbal medicine containing St. John's Wort (Hypericum perforatum).

While you are being treated with Navirel, you should not have live vaccines (e.g. oral polio vaccine, measles vaccine), as they may cause a severe reaction. You should not have yellow fever vaccine while you are being treated with Navirel, as it contains live viruses.

Pregnancy, breast-feeding and fertility

Navirel must not be given to pregnant women unless clearly necessary. If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. Navirel must not be given to women who are breast-feeding. If treatment with Navirel is necessary, you must stop breast-feeding. During treatment with Navirel and for at least 7 months after the end of treatment, women must use effective contraception to prevent pregnancy, as Navirel may harm the baby. Men treated with Navirel are advised to use effective contraception during and for up to 4 months after treatment in order to prevent their partner from becoming pregnant. Before treatment, you should ask your doctor about the possibility of storing sperm because Navirel may cause irreversible infertility.

Driving and using machines

After receiving winorelbine, you may experience side effects that affect your ability to drive or use machines. If you feel unwell, do not perform tasks that require attention, such as driving or using machines.

3. How Navirel is given

Navirel should only be prepared and given by a healthcare professional who has experience in the use of anticancer medicines.

Before each dose of Navirel, a blood sample will be taken to check that you have a sufficient number of blood cells to receive Navirel. If the results are not satisfactory, the dose may be delayed and you may need to have further tests until the results return to normal. Navirel is usually given once a week. The usual dose for adults is 25-30 mg/m². You should always follow the instructions of your doctor. Adjusting the dose

• If you have severe liver problems, your doctor may change the dose of Navirel. You should follow the instructions of your doctor.
• If you have kidney problems, the dose does not need to be changed. You should follow the instructions of your doctor.

Navirel should always be given by injection into a vein.

Navirel will be given as an injection into a peripheral vein over 6 to 10 minutes. After the injection, a sodium chloride solution will be given into the same vein to ensure that the medicine is spread evenly throughout your body.

Overdose of Navirel

Your doctor will make sure that you receive the correct dose of Navirel for your condition. However, if you have any doubts or experience any symptoms of overdose, such as fever, signs of infection or constipation, you should contact your doctor, hospital or pharmacist. If you have any further questions about the use of this medicine, ask your doctor, pharmacist or nurse.

4. Possible side effects

Like all medicines, Navirel can cause side effects, although not everybody gets them. You should tell your doctor immediatelyif you experience any of the following symptoms, as they may be signs of a serious side effect:

Uncommon side effects (may affect up to 1 in 100 people)

• Cough, fever and chills, which may be signs of a severe infection that can lead to organ failure and blood infection.
• Difficulty breathing (dyspnoea) or difficulty breathing due to narrowing of the airways (bronchospasm).

Rare side effects (may affect up to 1 in 1,000 people)

• Severe chest pain that may spread to the neck and arms, which may be caused by a lack of blood flow to the heart (angina or heart attack).
• Signs of very low blood pressure, such as severe dizziness and fainting when standing up.
• Severe constipation with abdominal pain in case of inability to empty the bowels for several days (paralytic ileus).

Frequency not known (cannot be estimated from the available data)

• Signs of a severe allergic reaction, including wheezing, swelling of the lips, tongue and throat or body, difficulty swallowing, rash, dizziness and fainting (anaphylactic reaction or anaphylactic shock, anaphylactoid reaction).
• Chest pain, difficulty breathing and fainting, which may be signs of a blood clot in the lungs (pulmonary embolism).
• Headache, altered mental state, which may lead to confusion and coma, seizures, blurred vision and high blood pressure, which may be signs of a neurological disorder, such as posterior reversible encephalopathy syndrome.
• Difficulty breathing, which may be a sign of a condition called acute respiratory distress syndrome and may be severe and life-threatening.

The following is a list of other side effects that may occur:

Very common side effects (may affect more than 1 in 10 people)

• Suppression of bone marrow function with a decrease in the number of red blood cells, which may cause pale skin and weakness or shortness of breath, and a decrease in the number of a certain type of white blood cell (neutrophils), which usually recovers within 5 to 7 days.
• Constipation, vomiting, inflammation of the mucous membranes of the mouth, inflammation of the oesophagus.
• After long-term chemotherapy, cases of loss of certain reflexes (deep tendon reflexes) and muscle weakness in the legs have been reported.
• Asymptomatic and transient increase in liver function test values.
• Hair loss, which is usually mild.
• Reactions at the injection site, such as redness, burning pain, changes in vein colour and local phlebitis.
• Weakness, fatigue, fever, pain in various locations, including chest pain and pain at the tumour site.

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

• Decrease in the number of platelets (cells that help stop bleeding); this is usually mild.
• Bacterial, viral or fungal infections in various parts of the body, such as the respiratory, urinary or gastrointestinal tract, with a severity ranging from mild to moderate, which usually resolve with appropriate treatment.
• Shortness of breath or skin reactions due to hypersensitivity to winorelbine.
• Diarrhoea, usually mild or moderate.
• Muscle pain, joint pain, jaw pain.
• Increased creatinine levels in the blood, a substance that reflects kidney function.

Uncommon side effects (may affect up to 1 in 100 people)

• Nerve damage (peripheral neuropathy) with symptoms such as tingling or numbness and increased or decreased muscle tension (paresthesia).
• Low blood pressure.
• High blood pressure.
• Flush with sudden reddening of the face and neck.
• Cold hands and feet.
• Difficulty breathing or wheezing (dyspnoea and bronchospasm).

Rare side effects (may affect up to 1 in 1,000 people)

• Severe decrease in sodium levels in the blood, which may cause fatigue and disorientation, slight muscle tremors, seizures or coma.
• Pancreatitis (inflammation of the pancreas, which regulates blood sugar levels) with symptoms such as severe abdominal pain radiating to the back.
• Transient changes in the ECG, including changes in heart rhythm.
• Difficulty breathing due to lung disease (interstitial lung disease).
• Fainting (syncope).
• Generalised skin reactions.
• Severe skin reactions at the injection site, such as tissue death (necrosis at the injection site).

Very rare side effects (may affect up to 1 in 10,000 people)

• Blood infection with complications and blood infection leading to death.
• Heart rhythm disorders, such as rapid heart rate (tachycardia), palpitations and irregular heartbeat (arrhythmias).
• Impaired respiratory function (respiratory failure).
• Guillain-Barré syndrome (symptoms include weakness or paralysis of the legs and arms, breathing problems and blood pressure problems).

Frequency not known (cannot be estimated from the available data)

• Generalised infection with fever and a significantly decreased number of a certain type of white blood cell, which may lead to death (septic neutropenia).
• Decrease in the number of a certain type of white blood cell with fever (febrile neutropenia).
• Severe decrease in the number of all blood cells, which may cause fatigue, increased bruising and increased risk of infection.
• Syndrome of inappropriate antidiuretic hormone secretion (SIADH), with symptoms such as weight gain, nausea, muscle cramps.
• Lack of appetite.
• Lack of muscle control [may be associated with abnormal gait, changes in speech and eye movement disorders (ataxia)].
• Headache.
• Dizziness.
• Heart failure, which may cause shortness of breath and swelling of the ankles.
• Cough.
• Abdominal pain.
• Bleeding from the digestive tract.
• Severe diarrhoea.
• Palmar-plantar erythrodysesthesia (symptoms include numbness, tingling, burning or itching, redness of the skin [like sunburn], swelling, discomfort, pain, rash).
• Chills with fever.
• Darker skin colour along the veins.
• Weight loss.

During or after the infusion, you may experience a burning sensation and redness at the injection site. This may be a sign of an injection error and you should tell your doctor or nurse immediately and the infusion should be stopped immediately.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in the "Further information" section. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Navirel

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 label after EXP. The expiry date refers to the last day of that month. Store in a refrigerator (2°C - 8°C). Do not freeze. Store in the original package to protect from light. 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 protect the environment.

6. Contents of the pack and other information

What Navirel contains

The active substance is winorelbine (as tartrate), at a concentration of 10 mg/ml. Each 1 ml vial contains 10 mg of winorelbine (as tartrate). Each 5 ml vial contains 50 mg of winorelbine (as tartrate). The other ingredient is water for injections.

What Navirel looks like and contents of the pack

Navirel is a clear, colourless to pale yellow concentrate for solution for infusion (sterile concentrate) in a glass vial. The pack sizes are 1 ml or 5 ml of concentrate in packs of 1 vial or 10 vials. Also available in multipacks containing 10 single packs, each containing 1 vial. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

medac Gesellschaft für klinische Spezialpräparate mbH Theaterstr. 6 22880 Wedel Germany Tel.: +48 22 43000-30 Fax: +48 22 43000-31 e-mail: [email protected]

This medicinal product is authorised in the Member States of the European Economic Area under the following names:

Cyprus Navirel 10 mg/ml πυκνό διάλυμα για παρασκευή διαλύματος προς έγχυση Czech Republic Navirel 10 mg/ml koncentrát pro infuzní roztok Denmark Navirel 10 mg/ml koncentrat til infusionsvæske, opløsning Netherlands Navirel 10 mg/ml concentraat voor oplossing voor infusie Iceland Navirel 10 mg/ml innrennslisþykkni, lausn Germany Navirel 10 mg/ml Konzentrat zur Herstellung einer Infusionslösung Norway Navirel 10 mg/ml konsentrat til infusjonsvæske Poland Navirel Portugal Vinorelbina Navirel 10 mg/ml concentrado para solução para perfusão Slovakia Navirel 10 mg/ml infúzny koncentrát Sweden Navirel 10 mg/ml koncentrat till infusionsvätska, lösning

Date of last revision of the package leaflet: 10/2024.

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Information intended for healthcare professionals only:

How to use Navirel

Winorelbine should only be prepared and administered by a healthcare professional. Protective equipment, including safety glasses, disposable gloves, a face mask and a disposable gown, should be worn. In case of spillage or leakage, the product should be wiped up. You must avoid contact of the product with your eyes. If the solution comes into contact with your eyes, they should be flushed immediately with plenty of sodium chloride solution (0.9%). After preparation, all surfaces that have come into contact with the product should be thoroughly cleaned and your hands and face should be washed. No incompatibilities have been observed between the content of the Navirel medicinal product, 10 mg/ml, concentrate for solution for infusion, and sodium chloride 9 mg/ml (0.9%) solution for injection or glucose 5% (w/v) solution for injection. Winorelbine should be administered in a slow bolus (over 6-10 minutes) after dilution in 20-50 ml of sodium chloride 9 mg/ml (0.9%) solution for injection or glucose 5% (w/v) solution for injection. After administration of winorelbine, at least 250 ml of sodium chloride 9 mg/ml (0.9%) solution for injection should always be administered as an infusion to flush the vein.

How to store Navirel

After opening and dilution: The product should be used immediately after opening and dilution. For single use only. Reconstituted solution: 24 hours if stored at 25°C or in a refrigerator (2°C - 8°C). From a microbiological point of view, the product should be used immediately. If not used immediately, the responsibility for the storage conditions and storage time before administration lies with the user, and the storage time should not exceed 24 hours at 2°C - 8°C, unless opening and dilution have been carried out under controlled and validated aseptic conditions. Do not use if the concentrate is not a clear, colourless to pale yellow solution without visible particles.