NAVERUCLIF 5 mg/ml POWDER FOR DISPERSION FOR INFUSION

Introduction

Package Leaflet: Information for the User

Naveruclif 5 mg/ml powder for dispersion for infusion

paclitaxel

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

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information

1. What is Naveruclif and what is it used for
2. What you need to know before you use Naveruclif
3. How to use Naveruclif
4. Possible side effects
5. Storage of Naveruclif
6. Contents of the pack and further information

1. What is Naveruclif and what is it used for

Naveruclif contains the active substance paclitaxel bound to human albumin, in the form of tiny particles called nanoparticles. Paclitaxel belongs to a group of medicines called “taxanes” which are used in cancer.

• Paclitaxel is the part of the medicine that affects cancer; it works by preventing cancer cells from dividing, which means they die.
• Albumin is the part of the medicine that helps paclitaxel to dissolve in the blood and pass through the walls of blood vessels to reach the tumour. This means that other chemical agents that can cause life-threatening side effects are not needed. Such side effects occur much less frequently with Naveruclif.

What is Naveruclif used for

Naveruclif is used to treat the following types of cancer:

Breast cancer

• Breast cancer that has spread to other parts of the body (this is called “metastatic” breast cancer).
• Naveruclif is used in metastatic breast cancer when at least one other therapy has been tried but has not worked and your case is not suitable for treatment with a group of medicines called “anthracyclines”.
• People with metastatic breast cancer who received Naveruclif when another treatment had failed, were more likely to experience a reduction in tumour size, and lived longer than people who received an alternative treatment.

Pancreatic cancer

• Naveruclif is used together with a medicine called gemcitabine if you have metastatic pancreatic cancer. People with metastatic pancreatic cancer (pancreatic cancer that has spread to other parts of the body) who received Naveruclif with gemcitabine in a clinical trial lived longer than people who only received gemcitabine.

Lung cancer

• Naveruclif is also used together with a medicine called carboplatin if you have the most common type of lung cancer, called “non-small cell lung cancer”.

Naveruclif is used in non-small cell lung cancer when surgery or radiotherapy are not suitable to treat the disease.

2. What you need to know before you use Naveruclif

• if you are allergic to paclitaxel or any of the other ingredients of this medicine (listed in section 6);
• if you are breast-feeding;
• if you have a low white blood cell count (neutrophil count <1500 cells mm3 before starting treatment. your doctor will advise you about this).< li>

Warnings and precautions

Talk to your doctor or nurse before you start using Naveruclif

• if you have reduced kidney function;
• if you have severe liver disorders;
• if you have heart disorders.

If you experience any of these disorders while being treated with Naveruclif, tell your doctor or nurse. Your doctor may decide to stop treatment or reduce the dose:

• if you experience any unusual bruising, bleeding or signs of infection such as sore throat or fever;
• if you experience numbness, tingling, pins and needles, sensitivity to touch or muscle weakness;
• if you experience breathing problems, such as difficulty breathing or dry cough.

Children and adolescents

Naveruclif is only intended for adults and must not be given to children or adolescents under 18 years of age.

Other medicines and Naveruclif

Tell your doctor if you are using or have recently used any other medicines, including those obtained without a prescription, including herbal medicines. This is because Naveruclif may affect the way some medicines work. Similarly, some medicines may affect the way Naveruclif works.

Be careful and talk to your doctor when using Naveruclif at the same time as any of the following:

• medicines for treating infections (i.e. antibiotics such as erythromycin, rifampicin, etc.; if in doubt about whether the medicine you are taking is an antibiotic, ask your doctor, nurse or pharmacist), and medicines for treating fungal infections (e.g. ketoconazole)
• medicines used to help stabilize mood, also called antidepressants (e.g. fluoxetine)
• medicines used to treat seizure disorders (epilepsy) (e.g. carbamazepine, phenytoin)
• medicines used to help reduce blood lipid levels (e.g. gemfibrozil)
• medicines used for stomach acid or stomach ulcers (e.g. cimetidine)
• medicines used to treat HIV and AIDS (e.g. ritonavir, saquinavir, indinavir, nelfinavir, efavirenz, nevirapine)
• the medicine called clopidogrel, which is used to prevent blood clots.

Pregnancy, breast-feeding and fertility

Paclitaxel may cause serious birth defects, so it must not be used if you are pregnant. Your doctor will ask for a pregnancy test before starting treatment with Naveruclif.

Women of childbearing age must use effective contraceptive methods during and up to one month after finishing treatment with Naveruclif.

Naveruclif must not be used during breast-feeding as it is not known whether the active substance paclitaxel passes into breast milk.

Men treated with Naveruclif are advised to use effective contraceptive methods and avoid fathering a child during treatment and for six months after finishing it, as well as to seek advice on the possibility of preserving their sperm before starting treatment, given the possibility that treatment with Naveruclif may cause irreversible infertility.

Talk to your doctor before using this medicine.

Driving and using machines

Some people may feel tired or dizzy after receiving Naveruclif. If this happens to you, do not drive or use any tools or machines.

If you are taking other medicines as part of your treatment, talk to your doctor about your ability to drive and use machines.

Naveruclif contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per 100 mg; this is essentially “sodium-free”.

3. How to use Naveruclif

Naveruclif will be administered to you by a doctor or nurse into a vein through an intravenous infusion system. The dose you receive will be calculated based on your body surface area and the results of your blood tests. The usual dose for breast cancer is 260 mg/m2 of body surface area, administered over 30 minutes. The usual dose for advanced pancreatic cancer is 125 mg/m2 of body surface area, administered over 30 minutes. The usual dose for non-small cell lung cancer is 100 mg/m2 of body surface area, administered over 30 minutes.

How often will you be given Naveruclif?

For the treatment of metastatic breast cancer, Naveruclif is usually administered once every three weeks (on day 1 of a 21-day cycle).

For the treatment of metastatic pancreatic cancer, Naveruclif is administered on days 1, 8 and 15 of each 28-day cycle, with gemcitabine administered immediately after Naveruclif.

For the treatment of non-small cell lung cancer, Naveruclif is administered once a week (i.e. on days 1, 8 and 15 of a 21-day cycle), with carboplatin administered once every three weeks (i.e. only on day 1 of each 21-day cycle), immediately after the Naveruclif dose.

If you have any further questions on the use of this medicine, ask your doctor or nurse.

4. Possible side effects

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

The very commonside effects may affect more than 1 in 10 people:

• Hair loss (most cases of hair loss occurred within a month after starting treatment with Naveruclif. When it occurs, hair loss is usually severe (more than 50%) in most patients)
• Rash
• Abnormal decrease in the number of some types of white blood cells (neutrophils, lymphocytes or leucocytes) in the blood
• Decrease in red blood cells
• Decrease in the number of platelets in the blood
• Effect on peripheral nerves (pain, numbness, tingling or loss of sensitivity)
• Pain in one or more joints
• Muscle pain
• Nausea, diarrhoea, constipation, mouth pain, loss of appetite
• Vomiting
• Weakness and fatigue, fever
• Dehydration, altered taste, weight loss
• Low potassium levels in the blood
• Depression, sleep disorders
• Headache
• Chills
• Breathing difficulties
• Dizziness
• Swelling of the mucous membranes and soft tissues
• Increased liver values in liver function tests
• Pain in the limbs
• Cough
• Abdominal pain
• Nosebleeds

The commonside effects may affect up to 1 in 10 people:

• Itching, dry skin, nail disorders
• Infection, fever with a decrease in the number of a type of white blood cell (neutrophils) in the blood, flushing, mouth ulcers, severe blood infection that may be due to a reduction in white blood cells
• Decrease in all blood cell values
• Chest pain or throat pain
• Indigestion, abdominal discomfort
• Nasal congestion
• Back pain, bone pain
• Decrease in muscle coordination or difficulty reading, increased or decreased tears, eyelash loss
• Changes in heart rate or rhythm, heart failure
• Low or high blood pressure
• Redness or swelling at the injection site
• Anxiety
• Lung infection
• Urinary tract infection
• Intestinal obstruction, inflammation of the large intestine, inflammation of the bile duct
• Acute kidney failure
• Increased bilirubin in the blood
• Coughing up blood
• Dry mouth, difficulty swallowing
• Muscle weakness
• Blurred vision

The uncommonside effects may affect up to 1 in 100 people:

• Weight gain, increased lactate dehydrogenase in the blood, altered kidney function, increased glucose in the blood, increased phosphorus in the blood
• Decreased or absent reflexes, involuntary movements, nerve pain, fainting, dizziness when standing, tremors, facial nerve paralysis
• Irritated eyes, eye pain, red eyes, itching eyes, double vision, reduced vision, or flashing lights, blurred vision due to inflammation of the retina (cystoid macular edema)
• Ear pain, ringing in the ears
• Coughing up mucus, shortness of breath when walking or climbing stairs, runny nose or dry nose, decreased breath sounds, fluid in the lungs, hoarseness, blood clots in the lungs
• Gas, stomach cramps, gum pain, rectal bleeding
• Painful urination (dysuria), need to urinate more often than usual (urinary frequency), blood in the urine, involuntary loss of urine (urinary incontinence)
• Nail pain, nail disorders, nail loss, hives, skin pain, photosensitivity reaction, skin pigmentation disorders, increased sweating, night sweats, white patches on the skin, sores, facial swelling
• Low phosphorus levels in the blood, fluid retention, low albumin levels in the blood, increased thirst, low calcium levels in the blood, low blood sugar levels, low sodium levels in the blood
• Pain and swelling in the nose, skin infections, catheter-related infections
• Bruising
• Pain and swelling at the tumour site, tumour necrosis
• Low blood pressure when standing, cold extremities
• Difficulty walking, swelling
• Allergic reaction
• Decreased liver function, increased liver size
• Chest pain
• Nervousness
• Small bleeding spots on the skin due to blood clots
• A condition that involves the destruction of red blood cells and acute kidney failure

The rareside effects may affect up to 1 in 1,000 people:

• Skin reaction to another agent or lung inflammation after radiation
• Blood clots
• Very slow heart rate, heart attack
• Medicine leakage outside the vein
• Disorder of the heart's electrical conduction system (atrioventricular block)

The very rareside effects may affect up to 1 in 10,000 people:

• Severe skin and mucous membrane inflammation (Stevens-Johnson syndrome, toxic epidermal necrolysis)

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

• Hardening/thickening of the skin (scleroderma).

Reporting of side effects

If you experience any side effects, talk to your doctor 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 Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Naveruclif

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 vial after EXP. The expiry date is the last day of the month shown.

Unopened vial: Store the vial in the outer packaging to protect it from light.

After the first reconstitution, the dispersion should be used immediately. If not used immediately, the vial with the dispersion should be placed in its outer packaging to protect it from light and should be stored in the refrigerator (2°C-8°C) for a maximum of 24 hours.

The reconstituted dispersion in the infusion bag can be stored in the refrigerator (2°C-8°C) for a maximum of 24 hours, protected from light.

The physical and chemical stability during use has been demonstrated for 24 hours at 2°C-8°C when protected from light, followed by 4 hours at 25°C when not protected from light.

Your doctor or pharmacist is responsible for disposing of any unused Naveruclif correctly.

6. Contents of the pack and further information

The active substance is paclitaxel.

• Each vial contains 100 mg of paclitaxel bound to albumin in a nanoparticle formulation. After reconstitution, each ml of dispersion contains 5 mg of paclitaxel bound to albumin in a nanoparticle formulation.
• The other ingredient is albumin (human) (contains sodium caprylate and N-acetyl-L-tryptophan), see section 2 “Naveruclif contains sodium”.

Appearance and pack size

Naveruclif is a white to yellow powder or lyophilized cake for dispersion for infusion. Naveruclif is available in glass vials containing 100 mg of paclitaxel bound to albumin in a nanoparticle formulation.

Each pack contains 1 vial.

Marketing authorisation holder and manufacturer

Marketing authorisation holder

Accord Healthcare S.L.U.

World Trade Center

Moll de Barcelona, s/n

Edifici Est 6ª planta

08039 Barcelona

Spain

Manufacturer

Accord Healthcare Polska Sp.z.o.o.

Ul. Lutomierska 50,

95-200, Pabianice, Poland

or

Laboratori Fundació Dau

C / C, 12-14 Pol. Ind.

Zona Franca, Barcelona, 08040, Spain

You can obtain further information on this medicine from the representative of the marketing authorisation holder:

AT / BE / BG / CY / CZ / DE / DK / EE / ES / FI / FR / HR / HU / IE / IS / IT / LT / LV / LX / MT / NL / NO / PL / PT / RO / SE / SI / SK / UK (NI)

Accord Healthcare S.L.U.

Tel: +34 93 301 00 64

EL

Win Medica Α.Ε.

Τηλ: +30 210 74 88 821

Date of last revision of this leaflet:

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu/.

Healthcare professionals

This information is intended only for healthcare professionals:

Instructions for use, preparation, and disposal Precautions for preparation and administration

Paclitaxel is a cytotoxic antineoplastic medication, so Naveruclif must be handled with caution, as with other potentially toxic drugs. Gloves, safety glasses, and protective clothing should be used. In case of skin contact, the affected area should be washed immediately and thoroughly with water and soap. In case of contact with mucous membranes, they should be rinsed thoroughly with plenty of water. Naveruclif should only be prepared and administered by experienced personnel in the handling of cytotoxic agents. Pregnant women should not handle Naveruclif.

Due to the possibility of extravasation, it is advisable to closely monitor the infusion site in case it occurs during medication administration. Limiting the infusion time of Naveruclif to 30 minutes, according to the instructions, reduces the likelihood of infusion-related reactions.

Reconstitution and administration of the medication

Naveruclif should be administered under the supervision of a qualified oncologist in specialized units for the administration of cytotoxic agents.

Naveruclif is supplied as a sterile lyophilized powder for reconstitution before use. After reconstitution, each ml of dispersion contains 5 mg of paclitaxel bound to albumin in a nanoparticle formulation. The reconstituted Naveruclif dispersion is administered intravenously using an infusion set that incorporates a 15 µm filter.

Using a sterile syringe, 20 ml of sodium chloride 9 mg/ml (0.9%) solution for infusion should be slowly injected into a vial of Naveruclif over a minimum of 1 minute.

The solution should be directed towards the inner wall of the vial. The solution should not be injected directly into the powder, as foam will be produced.

After adding the solution, the vial should be allowed to stand for a minimum of 5 minutes to ensure proper wetting of the solute. Then, it should be gently and carefully agitated and/or slowly inverted for at least 2 minutes until the powder is completely redispersed. Foam formation should be avoided. If foam or clumps form, the dispersion should be allowed to stand for at least 15 minutes until the foam disappears.

The reconstituted dispersion should have a milky and homogeneous appearance without visible precipitates. Some sedimentation of the reconstituted dispersion may occur. If there are signs of precipitate or sedimentation, the vial should be gently inverted again to achieve complete redispersion before use.

Inspect the dispersion in the vial for particles. Do not administer the reconstituted dispersion if particles are observed in the vial.

The exact total volume of 5 mg/ml dispersion needed for the patient should be calculated, and the appropriate amount of reconstituted Naveruclif should be injected into an empty, sterile intravenous infusion bag made of PVC or non-PVC material.

The use of medical products containing silicone oil as a lubricant (i.e., syringes and IV bags) to reconstitute and administer Naveruclif may result in the formation of protein filaments. Naveruclif should be administered using an infusion set that incorporates a 15 µm filter to prevent the administration of these filaments. The use of a 15 µm filter eliminates the filaments and does not alter the physical or chemical properties of the reconstituted medication.

The use of filters with a pore size smaller than 15 µm may result in filter blockage.

There is no need to use solution containers or DEHP-free administration equipment specifically for preparing or administering Naveruclif infusions.

After administration, it is recommended to thoroughly flush the intravenous line with sodium chloride 9 mg/ml (0.9%) injectable solution to ensure complete administration of the dose.

Disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.

Stability

Unopened vials of Naveruclif remain stable until the date indicated on the packaging, provided they are stored in the outer packaging to protect them from light. Freezing or refrigeration does not negatively affect the stability of the medication. This medication does not require any special storage temperature.

Stability of the reconstituted dispersion in the vial

Chemical and physical stability has been demonstrated for 24 hours at 2°C-8°C in the original packaging, protected from light.

Stability of the reconstituted dispersion in the infusion bag

Chemical and physical stability has been demonstrated for 24 hours at 2°C-8°C protected from light, followed by 4 hours at 25°C, not protected from light.

However, from a microbiological point of view, unless the method of reconstitution and filling of the infusion bags rules out the risk of microbial contamination, the product should be used immediately after reconstitution and filling of the infusion bags.

If not used immediately, the storage times and conditions of the product in use are the responsibility of the user.

The total storage time, combining the reconstituted medication in the vial and in the infusion bag when refrigerated and protected from light, is 24 hours. Subsequently, it can be stored in the infusion bag for 4 hours at a temperature below 25°C.