Leaflet: information for the user

Naveruclif 5 mg/ml powder for solution for infusion

paclitaxel

Read this leaflet carefully before you start 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 questions, consult your doctor or nurse.
• This medicine has been prescribed for you only, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the leaflet

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

Naveruclif contains, as its active ingredient, paclitaxel bound to human albumin protein, in the form of tiny particles called nanoparticles. Paclitaxel belongs to a group of medications called "taxanes" that are used in cancer treatment.

• Paclitaxel is the part of the medication that affects cancer; it acts by preventing cancer cells from dividing, which means they die.
• Albumin is the part of the medication that helps paclitaxel dissolve in the blood and cross blood vessel walls to reach the tumor. This means that other chemical agents that can cause life-threatening side effects are not needed. These 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

• Metastatic breast cancer (cancer that has spread to other parts of the body).
• Naveruclif is used in metastatic breast cancer when at least one other therapy has been tried but was not effective and the case is not suitable for treatment with a group of medications called "anthracyclines".
• People with metastatic breast cancer who received Naveruclif when another treatment had failed had a greater chance of experiencing a reduction in tumor size, and lived longer than people who received an alternative treatment.

Pancreatic cancer

• Naveruclif is used in combination with a medication called gemcitabine if you have metastatic pancreatic cancer (cancer that has spread to other parts of the body). People with metastatic pancreatic cancer (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 in combination with a medication 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 radiation therapy is not suitable for treating the disease.

• If you are allergic to paclitaxel or any of the other components of this medication (listed in section 6);
• If you are breastfeeding;
• If you have a low white blood cell count (neutrophil count <1500) 3 before starting treatment. Your doctor will advise you accordingly).

Warnings and Precautions

Consult your doctor or nurse before starting to use Naveruclif

• If you have reduced renal function;
• If you have severe liver disease;
• If you have heart disease.

If you experience any of these conditions while receiving treatment with Naveruclif, inform your doctor or nurse. Your doctor may decide to interrupt treatment or reduce the dose:

• If you experience any abnormal 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 respiratory problems, such as difficulty breathing or dry cough.

Children and Adolescents

Naveruclif is only indicated for adults and should not be administered to children or adolescents under 18 years of age.

Other Medications and Naveruclif

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

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

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

Pregnancy, Breastfeeding, and Fertility

Paclitaxel may cause severe congenital defects, so it should not be used if you are pregnant. Your doctor will request a pregnancy test before starting treatment with Naveruclif.

Women of childbearing age should use effective contraceptive methods during and for one month after completing treatment with Naveruclif.

Naveruclif should not be used during breastfeeding as it is unknown whether the active ingredient paclitaxel passes into breast milk.

Men treated with Naveruclif are advised to use effective contraceptive methods and avoid fathering children during treatment and for six months after completing it, as well as to inform themselves about the possibility of preserving sperm before starting treatment, given the possibility of irreversible infertility.

Consult your doctor before using this medication.

Driving and Operating 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 medications as part of your treatment, consult your doctor about your ability to drive and use machines.

Naveruclif contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per 100 mg; it is essentially "sodium-free".

A doctor or nurse will administer Naveruclif into a vein through an intravenous infusion system. The dose you receive will be calculated based on your body surface area and blood test results. The usual dose for breast cancer is 260 mg/m2of body surface area, administered over 30 minutes. The usual dose for advanced pancreatic cancer is 125 mg/m2of body surface area, administered over 30 minutes. The usual dose for non-small cell lung cancer is 100 mg/m2of body surface area, administered over

30 minutes.

How often will Naveruclif be administered?

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 administering the Naveruclif dose.

If you have any other questions about the use of this medication, ask your doctor or nurse.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Side effectsvery commoncan affect more than 1 in 10 people:

• Loss of hair (most cases of hair loss occurred within less than a month after starting treatment with Naveruclif. When it occurs, hair loss is pronounced (more than 50%) in most patients)
• Skin rash
• Abnormal decrease in the number of some types of white blood cells (neutrophils, lymphocytes, or leukocytes) 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 sensation)
• Pain in one or more joints
• Muscle pain
• Nausea, diarrhea, constipation, mouth pain, loss of appetite
• Vomiting
• Weakness and fatigue, fever
• Dehydration, altered taste, weight loss
• Low potassium levels in the blood
• Depression, sleep problems
• Headache
• Chills
• Difficulty breathing
• Dizziness
• Swelling of the mucous membranes and soft tissues
• Increased liver values in liver function tests
• Pain in the limbs
• Cough
• Abdominal pain
• Nasal bleeding

Side effectscommoncan affect up to 1 in 10 people:

• Itching, dry skin, nail problems
• Infection, fever with a decrease in the number of a type of white blood cell (neutrophils) in the blood, redness, ulcers, severe blood infection that may be due to a decrease in white blood cells
• Decrease in all blood cell values
• Pain in the chest or throat
• Indigestion, abdominal discomfort
• Stuffy nose
• Pain in the back, bone pain
• Decrease in muscle coordination or difficulty reading, increased or decreased tearing, eyelash loss
• Changes in heart rate or rhythm, heart failure
• Low or high blood pressure
• Redness or swelling at the injection site
• Anxiety
• Pulmonary infection
• Urinary tract infection
• Intestinal obstruction, inflammation of the large intestine, inflammation of the bile duct
• Acute renal insufficiency
• Increased bilirubin in the blood
• Coughing up blood
• Dry mouth, difficulty swallowing
• Muscle weakness
• Blurry vision

Side effectsuncommoncan affect up to 1 in 100 people:

• Weight gain, increased lactate dehydrogenase in the blood, renal function alteration, increased blood glucose, increased blood phosphorus
• Decreased or absent reflexes, involuntary movements, nerve pain, fainting, dizziness when standing, tremors, facial nerve paralysis
• Irritated eyes, eye pain, red eyes, itchy eyes, double vision, reduced vision, flashing lights, blurry vision due to retinal inflammation (cystoid macular edema)
• Ear pain, ringing in the ears
• Coughing up mucus, shortness of breath when walking or climbing stairs, runny nose, decreased respiratory sounds, fluid in the lung, loss of voice, blood clot in the lungs, dry throat
• Gas, stomach cramps, toothache, rectal bleeding
• Painful urination (dysuria), frequent urination, blood in the urine, involuntary loss of urine (urinary incontinence)
• Nail pain, nail problems, nail loss, hives, skin pain, photosensitivity reaction, skin pigmentation disorders, increased sweating, night sweats, white skin patches, sores, facial swelling
• Decreased phosphorus in the blood, fluid retention, low albumin in the blood, increased thirst, decreased calcium in the blood, decreased blood sugar, decreased sodium in the blood
• Pain and swelling in the nose, skin infections, catheter-related infection
• Bruising
• Pain at the tumor site, tumor necrosis
• Decreased blood pressure when standing, cold extremities
• Difficulty walking, swelling
• Allergic reaction
• Decreased liver function, enlarged liver
• Pain in the chest
• Nervousness
• Small skin bleeding due to blood clots
• A condition that involves the destruction of red blood cells and acute renal insufficiency

Side effectsrarecan affect up to 1 in 1,000 people:

• Reaction to another agent or pulmonary inflammation after radiation
• Blood clots
• Slow pulse, heart attack
• Medication leakage outside the vein
• Conduction system disorder of the heart (atrioventricular block)

Side effectsvery rarecan affect up to 1 in 10,000 people:

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

Frequencyunknown(cannot be estimated from available data)

• Hardening/thickening of the skin (scleroderma).

Reporting of side effects

If you experience any type of side effect, consult your doctor or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them

directly through thesnational notification system included in theApéndice V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the box and vial after CAD/EXP. The expiration date is the last day of the month indicated.

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

After the first reconstitution, the dispersion must be used immediately. If not used immediately, the vial with the dispersion must be placed inside its outer packaging to protect it from light and must 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.

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 properly disposing of any unused Naveruclif residue.

The active principle is paclitaxel.

Appearance of the product and contents of the package

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

Each package contains 1 vial.

Holder of the marketing authorization and responsible for manufacturing

Tholder of the marketing authorization

Accord Healthcare S.L.U.

World Trade Center

Moll de Barcelona, s/n

Edifici Est 6ª planta

08039 Barcelona

Spain

Responsible for manufacturing

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 request more information about this medication by contacting the local representative of the marketing authorization 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.

Tel: +30 210 74 88 821

Date of the last review of this leaflet:

The detailed information about this medication is available on the website of the European Medicines Agency:http://www.ema.europa.eu/.

Doctors or healthcare professionals

This information is intended solely for doctors or healthcare professionals:

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

Paclitaxel is a cytotoxic anticancer drug, so Naveruclif must be handled with caution, just like 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 washed 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 recommended to closely monitor the infusion site for any signs of extravasation during administration of the medication. Limiting the infusion time of Naveruclif to 30 minutes, as instructed, reduces the likelihood of reactions associated with infusion.

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 device that incorporates a 15 µm filter.

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

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

After adding the solution, leave the vial to stand for a minimum of 5 minutes to ensure proper humidification of the solute. Then, gently and carefully agitate the vial or invert it slowly for at least 2 minutes until the powder is completely redispersed. Avoid forming foam. If foam or lumps form, leave the dispersion 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 precipitation or sedimentation, gently invert the vial again to achieve complete redispersion before use.

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

The exact total volume of the 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, PVC or non-PVC intravenous infusion bag.

The use of medical devices containing silicone oil as a lubricant (i.e., IV administration sets and bags) for reconstituting and administering Naveruclif may lead to the formation of protein filaments. Naveruclif should be administered using an infusion device that incorporates a 15 µm filter to prevent the administration of these filaments. The use of a 15 µm filter eliminates the filaments without altering the physical or chemical properties of the reconstituted medication.

The use of filters with a pore size less than 15 µm may lead to filter blockage.

No special containers or equipment for administration without di(2-ethylhexyl)phthalate (DEHP) are required to prepare or administer Naveruclif infusions.

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

The disposal of unused medication and all materials that have come into contact with it should 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 do 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 reconstitution and filling method of the infusion bags eliminates 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. It can then be stored in the infusion bag for 4 hours at a temperature below 25°C.