Navelbine

Patient Information Leaflet

NAVELBINE, 10 mg/ml, concentrate for solution for infusion
Vinorelbinum
Please read all of this leaflet carefully before using this medicine because it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm them even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

1. What Navelbine is and what it is used for
2. Important information before using Navelbine
3. How to use Navelbine
4. Possible side effects
5. How to store Navelbine
6. Contents of the pack and other information

1. What Navelbine is and what it is used for

Navelbine contains the active substance vinorelbine (as tartrate) and belongs to a group of medicines called Vinca alkaloids, which are used in cancer treatment.
Navelbine is used in the treatment of certain types of lung cancer and certain types of breast cancer in patients over 18 years of age.

2. Important information before using Navelbine

When not to use Navelbine

• if the patient is allergic to the active substance (vinorelbine) or to other drugs containing Vinca alkaloids used in cancer treatment, or to any of the other ingredients of this medicine (listed in section 6);
• during breastfeeding;
• if the patient has low neutrophil granulocytes and/or low platelet count, or if they are currently suffering from or have recently had (within the last two weeks) an acute infection;
• if the patient has recently been vaccinated against yellow fever or plans to receive such vaccination.

Warnings and precautions
Before starting treatment with Navelbine, talk to your doctor or pharmacist if:

• the patient has previously experienced a heart attack or severe chest pain;
• the patient has undergone radiotherapy, particularly if the liver was within the irradiated field;
• the patient is experiencing signs of infection such as fever, chills, or cough;
• vaccination is planned. Administration of live, attenuated vaccines (e.g. measles, mumps, rubella vaccine) together with Navelbine is not recommended, as it may increase the risk of life-threatening vaccine-induced disease;
• liver function is impaired;
• the patient is pregnant.

Before and during treatment with Navelbine, blood cell counts must be monitored to ensure the treatment is safe for the patient. If blood test results are unsatisfactory, the doctor may recommend repeating the test or may delay treatment until blood parameters return to normal.

Children and adolescents
Navelbine is not recommended for use in children under 18 years of age.

Navelbine and other medicines
Inform your doctor about all medicines the patient is currently taking or has recently taken, as well as any medicines they plan to take.
The doctor should pay particular attention if the patient is taking the following medicines:

• anticoagulant drugs (blood thinners);
• anticonvulsants (e.g. phenytoin);
• antifungal drugs (e.g. itraconazole);
• anticancer drugs such as mitomycin C or lapatinib;
• immunosuppressive drugs such as cyclosporine and tacrolimus.

Concomitant use of Navelbine with other myelosuppressive drugs (causing changes in blood cell counts) may increase the severity of certain adverse effects.

Pregnancy, breastfeeding and effects on fertility
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor before using this medicine and seek genetic counseling, as vinorelbine may damage genetic material in cells, posing a potential risk to the unborn child. Navelbine should not be used during pregnancy unless the expected benefits clearly outweigh the potential risks.
Breastfeeding must be discontinued during treatment with Navelbine.
Women of childbearing potential must use effective contraception during treatment and for 7 months after treatment ends.
Men receiving Navelbine should not plan to father a child during treatment and for 4 months after its completion. Before starting treatment, men should seek advice regarding sperm preservation due to the possibility of irreversible infertility caused by Navelbine therapy. Effective contraception must be used by both men and women during treatment and for 4 months after treatment ends.

Driving and operating machinery
No studies have been conducted on the effects of Navelbine on the ability to drive or operate machinery. Under no circumstances should patients drive or operate machinery if they feel unwell or if the doctor determines that such activities should be avoided.

3. How to use Navelbine

This medicine should always be used exactly as recommended by the doctor. If in doubt, consult
your doctor or pharmacist.
During and before starting treatment with Navelbine, your doctor will recommend a blood test (blood morphology).
The dose will be determined based on the test results, the patient's body surface area, and the patient's overall
condition. The doctor will recommend a dose appropriate for the patient and will determine the duration of treatment.
Method and route of administration
Navelbine must be diluted before administration. Navelbine may only be administered intravenously as an infusion lasting between 6 and 10 minutes. After completion of the infusion, the vein should be thoroughly flushed with sterile physiological saline solution.
Use of a higher than recommended dose of Navelbine
Administration of Navelbine should be carried out under strict medical supervision. If a higher than recommended dose of Navelbine is administered, severe adverse reactions related to changes in blood morphology may occur, which may lead to symptoms of infection (such as fever, chills, cough) and severe constipation. Medical advice should be sought immediately if any of the above symptoms occur in the patient.
Discontinuation of Navelbine treatment
The decision to discontinue treatment will be made by the doctor. If the patient wishes to discontinue treatment independently, they should speak with their doctor.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
You should contact your doctor immediately if the following adverse reactions occur during treatment with Navelbine:

• Chest pain, shortness of breath, and fainting, which may be symptoms of a blood clot in the lung vessels (pulmonary embolism);
• Headaches, altered mental status, 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;
• Signs of severe infection, such as cough, fever, and chills;
• Severe constipation associated with abdominal pain due to lack of bowel movements for several days;
• Severe dizziness, feeling of emptiness in the head when standing up, which may indicate a significant drop in blood pressure;
• Severe chest pain not previously experienced, which may be a sign of heart dysfunction due to insufficient blood flow; this is known as ischemic heart disease, such as angina pectoris or myocardial infarction (in some cases leading to death);
• Difficulty breathing, which may be a symptom of a condition called acute respiratory distress syndrome and may be severe and life-threatening;
• Dizziness, low blood pressure, rash affecting the entire body, or swelling of the eyelids, lips, and throat, which may be signs of an allergic reaction.

Very common adverse reactions (may occur in more than 1 in 10 patients):

• Nausea; vomiting, constipation;
• Decreased number of red blood cells (anemia), which may lead to paleness and cause weakness and shortness of breath;
• Decreased number of white blood cells, which may increase susceptibility to infections;
• Weakness of the lower limbs;
• Reduced reaction speed; occasionally sensory disturbances;
• Hair loss, usually not severe, during prolonged treatment;
• Inflammation or pain in the mouth and throat;
• Reactions at the site of Navelbine administration, such as redness, burning sensation, discoloration of veins;
• Liver function abnormalities (abnormal liver function test results).

Common adverse reactions (may occur in fewer than 1 in 10 patients):

• Decreased number of platelets, which increases the risk of bleeding and hemorrhagic spots (bruising);
• Joint pain;
• Jaw pain;
• Muscle pain;
• Fatigue (weakness, asthenia);
• Fever;
• Pain in various parts of the body, such as chest pain, pain at the site of the tumor;
• Diarrhea;
• Infections at various sites.

Uncommon adverse reactions (may occur in fewer than 1 in 100 patients):

• Significant difficulty in movement and sensory disturbances related to touch;
• Dizziness;
• Sudden hot flushes and redness of the face and neck;
• Cold hands and feet;
• Difficulty breathing or wheezing (shortness of breath, bronchospasm);
• Blood infection (sepsis) with symptoms such as fever and worsening general health;
• High blood pressure.

Rare adverse reactions (may occur in fewer than 1 in 1000 patients):

• Heart attack (ischemic heart disease, angina pectoris, myocardial infarction, in some cases leading to death);
• Lung disease (inflammatory condition and fibrosis), in some cases leading to death;
• Severe abdominal and back pain (pancreatitis);
• Low sodium levels in the blood (which may lead to symptoms such as fatigue, disorientation, muscle twitching, loss of consciousness);
• Ulceration at the site of Navelbine administration (local necrosis);
• Skin rashes such as hives and skin eruptions (generalized skin reactions).

Very rare adverse reactions (may occur in fewer than 1 in 10,000 patients):

• Irregular heartbeat (tachycardia); palpitations; cardiac rhythm disturbances.

Adverse reactions with unknown frequency (frequency cannot be determined from available data):

• Abdominal pain, gastrointestinal bleeding;
• Heart failure, which may cause shortness of breath and ankle swelling;
• Redness of the palms and soles;
• Low sodium levels in the blood leading to weakness, muscle tremors, fatigue, confusion, loss of consciousness, associated with overproduction of a hormone causing fluid retention (Syndrome of Inappropriate Antidiuretic Hormone Secretion - SIADH);
• Loss of muscle control, possibly accompanied by gait disturbances, speech problems, changes and disturbances in eye movement (ataxia);
• Headache;
• Chills with fever;
• Cough;
• Loss of appetite;
• Weight loss;
• Darker skin coloration along the veins.

Reporting of adverse reactions
If any adverse symptoms occur, including any not listed in this leaflet, you should inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Navelbine

Keep this medicine out of the sight and reach of children.
Store Navelbine at a temperature between 2°C and 8°C (in the refrigerator). Protect from light.
Do not freeze.
Do not use Navelbine after the expiry date stated on the vial and carton following:
(EXP). The expiry date refers to the last day of the stated month.
Navelbine must be prepared for infusion and handled only by hospital personnel.
Medicines should not be disposed of via wastewater or household waste. Ask your
pharmacist how to dispose of medicines no longer required. Such measures will help protect
the environment.

6. Contents of the package and other information

What Navelbine contains

• The active substance is vinorelbine in the form of vinorelbine tartrate.
• 1 ml of concentrate for solution for infusion contains 10 mg of vinorelbine.
• Excipient: water for injections.

What Navelbine looks like and contents of the pack
Navelbine is available as a concentrate for solution for infusion and is packaged in vials (1 ml or 5 ml) made of colorless glass, with a stopper made of black chlorobutyl rubber or grey butyl rubber coated with fluorinated ethylene propylene resin D (ETFE), sealed with a grey aluminium cap and a blue polypropylene flip-off cap, placed in a polystyrene box (intermediate packaging), inside a cardboard box.
Navelbine is a colorless or pale yellow solution.
Navelbine is available in:

• packs containing 10 vials of 1 ml,
• packs containing 10 vials of 5 ml. Not all pack sizes may be marketed.

Marketing Authorization Holder
Pierre Fabre Medicament
Les Cauquillous
81500 Lavaur
France
Manufacturer
FAREVA PAU
Fareva Pau 1,
Avenue du Bearn
64320 IDRON
France
For further information, contact the Marketing Authorization Holder's representative:
Pierre Fabre Medicament Polska Sp. z o.o.
ul. Belwederska 20/22
00-762 Warsaw
Tel: 022 559 63 00

Information intended exclusively for medical professionals:

Only hospital staff experienced in handling cytostatic drugs should be responsible for the preparation and administration of Navelbine. To prevent contact of the drug or its solution with the skin and eyes, personnel must wear gowns, goggles, gloves, and face masks. In case of spillage, the solution should be wiped up immediately.
Contact of the drug with the eyes should be avoided. In the event of accidental exposure to the eye, it should be thoroughly irrigated with sodium chloride 9 mg/ml (0.9%) solution.
After completion of the drug administration procedure, personnel should thoroughly clean all surfaces used for drug preparation and wash their hands and face.

It has been demonstrated that after reconstitution of Navelbine in sodium chloride 9 mg/ml (0.9%) for injection or in 5% glucose solution for injection, Navelbine is physically and chemically stable for 1 day at 20 °C ± 5 °C when exposed to light, for 40 days at 20 °C ± 5 °C when protected from light, or for 40 days under refrigerated conditions (from 2 °C to 8 °C) protected from light, in containers made of neutral glass, polyvinyl chloride (PVC), polyethylene, or in bags made of vinyl acetate.

From a microbiological standpoint, the solution should be used immediately. If not used immediately, the user is responsible for the storage conditions and duration, which normally should not exceed 24 hours at a temperature of 2 °C to 8 °C, unless the product has been opened and diluted under controlled and validated aseptic conditions.

No incompatibility has been observed between Navelbine and containers made of neutral glass, or bags made of PVC (polyvinyl chloride), vinyl acetate, polyethylene, or infusion sets made of PVC.

It is recommended that Navelbine be administered as an intravenous infusion over 6 to 10 minutes after dilution in 20–50 ml of 9 mg/ml (0.9%) sodium chloride solution for injection or 5% glucose solution for injection.

After administration, the vein should be flushed thoroughly with 250 ml of physiological saline solution.

Navelbine must be administered exclusively by intravenous infusion. Prior to initiating the infusion, it must be confirmed that the needle is properly positioned within the vein. Extravasation of Navelbine into surrounding tissues may cause irritation.

In such a case, the infusion should be stopped immediately, the vein flushed with physiological saline solution, and the remaining dose administered into another vein.

In the event of extravasation of Navelbine from the vein into surrounding tissues, to prevent phlebitis, intravenous glucocorticosteroids should be administered immediately.

Navelbine should be stored at a temperature of 2°C to 8°C (in a refrigerator). Protect from light. Do not freeze.

Any unused portions of the medicinal product or waste materials should be disposed of in accordance with local regulations.