InfoCons Consumer Protection informs you – Naveruclif – Package Leaflet

Before anything else

Read all of this leaflet carefu lly 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.

ℹ️ 1. What Naveruclif is and what it is used for

Naveruclif contains, as its activ e substance, paclitaxel attach ed to the human protein albumin, in the form of tiny particles known as nanoparticles. Paclitaxel belon gs to a group of medicines called “taxanes” used in cancer.  Paclitaxel is the part of the m edicine that affects the cancer, it works by stopping cancer cells from dividing – this means that they die.  Albumin is the part of the medicine that helps paclitaxel disso lve in the blood and get across the walls of the blood vessels into the tumour. This means that other chemicals that can cause side effects that can be life threatening are not needed. Such side effects occur far less with Naveruclif.

What Naveruclif is used for

Naveruclif is used to treat the following types of cancer:

Breast Cancer  Breast cancer which has spread to other parts of the body (this is called “metastatic” breast cancer).  Naveruclif is used in metastatic breast cancer when at least on e other therapy has been tried but has not worked and you are unsuitable for treatments contai ning a group of medicines called “anthracyclines”.  People with metastatic breast canc er who received Naveruclif where another therapy had failed, were more likely to experience a reduction in tumour si ze, and lived longer than people who took an altern ative therapy.

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

39 Lung Cancer  Naveruclif is also used together with a medicine called carbopl atin if you have the most common type of lung cancer, ca lled “non-small cell lung cancer” .  Naveruclif is used in non-small cell lung cancer where surgery or radiotherapy would not be suitable to treat the disease.

⚠️ 2. What you need to know before you are given Naveruclif

Do not use Naveruclif

 if you are allergic to Paclitaxel or any of the other ingredien ts of this medicine (listed in section 6).  if you are breast-feeding  if you have a low white blood cell count (baseline neutrophil counts <1500 cells/mm3 – your doctor will advise you on this).

Warnings and precautions

Talk to your doctor or nurse before using Naveruclif  if you have poor kidney function;  if you have severe liver problems;  if you have heart problems.

Talk to your doctor or nurse if you experience any of these con ditions whilst being treated with Naveruclif, your doctor may wish to stop treatment or reduce th e dose:  if you experience any abnormal bruising, bleeding, or signs of infections such as a sore throat or a fever;  if you experience numbness, tingling, pricking sensations, sensitivity to touch, or muscle weakness;  if you experience breathing probl ems, like shortness of breath or dry cough.

Children and adolescents

Naveruclif is only for adults an d should not be taken by childr en and adolescents aged below 18 years.

Other medicines and Naveruclif

Tell your doctor if you are taking or have recently taken any o ther medicines. This includes medicines obtained without a prescription , including herbal medicines. Th is is because Naveruclif can affect the way some other medicines work. Also, some other medicines can a ffect the way Na veruclif works.

Take care and speak to your doctor when taking Naveruclif at th e same time as any of the following:  medicines for treating infections (i.e. antibiotics such erythromycin, rifampicin, etc.; ask your doctor, nurse or pharmacist if you are unsure whether the medic ine you are taking is an antibiotic), and including medi cines for treatin g fungal infect ions (e.g. ketoconazole)  medicines used to help you stabilize your mood also sometimes r eferred to as anti-depressants (e.g. fluoxetine)  medicines used to treat seizures (epilepsy) (e.g. carbamazepine , phenytoin)  medicines used to help you lower blood lipid levels (e.g. gemfibrozil)  medicine used for heartburn or s tomach ulcers (e.g. cimetidine)  medicines used to treat HIV and AIDS (e.g. ritonavir, saquinavi r, indinavir, nelfinavir, efavirenz, nevirapine)  a medicine called clopidogrel used to prevent blood clots.

40 Pregnancy, breast-feeding and fertility Paclitaxel may cause serious bir th defects and sh ould therefore not be used if you are pregnant. Your doctor will arrange a pregnancy test before starting treatment with Naveruclif.

Women of childbearing age should use effective contraception during and for at least 6 months after receiving treatment with Naveruclif.

Do not breast feed when taking N averuclif as it is not known if the active ingredie nt paclitaxel passes into the mother’s milk.

Male patients are advised to use effective contraception and to avoid fathering a child during and for at least 3 months after treatment and should seek advice on conser vation of sperm prior to treatment because of the possibility of i rreversible infertility due to t herapy with Naveruclif.

Ask your doctor for advice b efore taking this medicine.

Driving and using machines

Some people may feel tired or dizzy after being given Naverucli f. If this happens to you, do not drive or use any tools or machines.

If you are given other medicines as part of your treatment, you should ask your doctor for advice on

driving and using machines. Naveruclif contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per 100 mg, that is to say essentially ‘sodium free’.

💊 3. How to use Naveruclif

Naveruclif will be given to you by a doctor or nurse into a vei n from an intravenous drip. The dose you receive is based on your body surface area and blood test resul ts. The usual dose is f or breast cancer is 260 mg/m 2 of body surface area given over a 30 minute period. The usual dose for advanced pancreatic cancer is 125 mg/m2 of body surface area given over a 30 minute period. The usual dose for non-small cell lung cancer is 100 mg/m2 of body surface area given over a 30 minute period.

How often will you receive Naveruclif?

For treatment of metastatic breast cancer, Naveruclif is usuall y given once every three weeks (on day 1 of a 21-day cycle).

For treatment of advanced pancreatic cancer, Naveruclif is give n on days 1, 8 and 15 of each 28-day treatment cycle with gemcitabine being given immediately after the Naveruclif.

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

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, altho ugh not everybody gets them.

The very common side effects may affect more than 1 in 10 people:  Loss of hair (the majority of ca ses of hair loss happened less than one month after starting Naveruclif. When it happens, hair loss is pronounced (over 50%) in the majority of patients) 41  Rash  Abnormal decrease in the number of types of white blood cells (neutrophils, lymphocytes or leukocytes) in the blood  Deficiency of red blood cells  Reduction in the number of platelets in the blood  Effect on peripheral nerves (pain, numbness, tingling or loss o f feeling)  Pain in a joint or joints  Pain in the muscles  Nausea, diarrhoea, constipation , sore mouth, loss of appetite  Vomiting  Weakness and tiredness, fever  Dehydration, taste disturbance, weight loss  Low levels of potassium in the blood  Depression, sleep problems  Headache  Chills  Difficulty in breathing  Dizziness  Swelling of mucosal and soft tissues  Increased liver function tests  Pain in extremities  Cough  Abdominal pain  Nose bleeds The common side effects may affect up to 1 in 10 people:  Itching, dry skin, nail disorder  Infection, fever with decrease in the number of a type of white blood cell (neutrophils) in the blood, flushing, thrush, severe infection in your blood which m ay be caused by reduced white blood cells  Reduction in all bl ood cell counts  Chest or throat pain  Indigestion, abdominal discomfort  Stuffy nose  Pain in back, bone pain  Diminished muscular coordination or difficulty in reading, incr eased or decreased tears, loss of eyelashes  Changes in heart rate or rhythm, heart failure  Decreased or increased blood pressure  Redness or swelling at the site whe re the needle entered the body  Anxiety  Infection in the lungs  Infection in the urinary tract  Obstruction in the gut, inflammation of the large bowel, inflammation of the bile duct  Acute kidney failure  Increased bilirubin in the blood  Coughing up blood  Dry mouth, difficulty in swallowing  Muscle weakness  Blurred vision 42 The uncommon side effects may affect up to 1 in 100 people:  Increased weight, increased lactat e dehydrogenase in the blood, decreased kidney function, increased blood sugar, increased phosphorus in the blood  Decreased or lack of reflexes, i nvoluntary movements, pain alon g a nerve, fainting, dizziness when standing up, shaking, facial nerve paralysis  Irritated eyes, painful eyes, red eyes, itchy eyes, double vision, reduced vision, or seeing flashing lights, blurred vision due to swelling of the retina ( cystoid macular oedema)  Ear pain, ringing in your ears  Coughing with phlegm, shortness of breath when walking or climb ing stairs, runny nose, or dry nose, decreased breath sounds, water on the lung, loss of v oice, blood clot in the lung, dry throat  Gas, stomach cramps, painful or sore gums, rectal bleeding  Painful urination, frequent urination, blood in the urine, inab ility to hold your urine  Fingernail pain, fingernail discomfort, loss of fingernails, hi ves, skin pain, red skin from sunlight, skin discolouration, increased sweating, night sweats , white areas on the skin, sores, swollen face  Decreased phosphorus in the blood, fluid retention, low albumin in the blood, increased thirst, decreased calcium in the blood , decreased sugar in the blood, d ecreased sodium in the blood  Pain and swelling in the nose, skin infections, infection due t o catheter line  Bruising  Pain at site of tumour , death of the tumour  Decreased blood pressure when standing up, coldness in your han ds and feet  Difficulty walking, swelling  Allergic reaction  Decreased liver function, increased size of liver  Pain in the breast  Restlessness  Small bleedings in your skin due to blood clots  A condition involving destruction of red blood cells and acute kidney failure The rare side effects may affect up to 1 in 1,000 people:  Skin reaction to another agent o r lung inflammation following r adiation  Blood clot  Very slow pulse, heart attack  Leaking of drug outside the vein  A disorder of the electrical conduction system of the heart (at rioventricular block) The very rare side effects may affect up to 1 in 10,000 people:  Severe inflammation/eruption of the skin and mucous membranes ( Stevens-Johnson syndrome, toxic epidermal necrolysis)

Not known side effects (frequency cannot be estimated from the available data)

 Hardening/thickening of the skin (scleroderma)

Reporting of side effects

If you get 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 repo rting system listed in Appendix V . By reporting side effects you can help provide more informati on on the safety of this medicine.

🌡️ 5. How to store Naveruclif

43 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 refers to the last day of that month.

Unopened vials: Keep the vial in the outer carton in order to p rotect from light.

After first reconstitution the di spersion should be used immedi ately. If not used immediately, the dispersion may be stored in a refrigerator (2°C-8°C) for up to 24 hours in the vial when kept in the outer carton in order to protect it from light.

The reconstituted dispersion in the intravenous drip may be sto red in a refrigerator (2°C-8°C) for up to 24 hours protected from light.

Chemical and physical in-use stability has been demonstrated fo r 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 u nused Naveruclif correctly.

📦 6. Contents of the pack and other information

What Naveruclif contains

 The active substance(s) is paclitaxel. Each vial contains 100 mg of paclitaxel formulated as albumin bound nanopar ticles. After recons titution, each ml of d ispersion contains 5 mg of paclitaxel formulated as albumin bound nanoparticles.  The other ingredient is albumin (human) (containing sodium capr ylate and N-acetyl-L- tryptophan), see section 2 “Naveruclif contains sodium”.

What Naveruclif looks like and contents of the pack

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 formul ated as albumin bound nanoparticles.

Each pack contains 1 vial.

Marketing Authorisation Holder and Manufacturer

Marketing Authorization Holder Accord Healthcare S.L.U.

World Trade Center, Moll De Barcelona s/n, Edifici Est, 6a Planta, Barcelona, 08039, 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 Or 44 Accord Healthcare Single Member S.A., 64th Km National Road, Athens, Lamia, Schimatari, 32009, Greece For any information about this m edicine, please contact the loc al representative of the Marketing Authorisation Holder:

AT / BE / BG / CY / CZ / DE / DK / EE / ES / FI / FR / HR / HU / IE / IS / IT / LT / LV / LU / MT / NL / NO / PL / PT / RO / SE / SI / SK Accord Healthcare S.L.U.

Tel: +34 93 301 00 64 EL Win Medica Α.Ε.

Τηλ: +30 210 74 88 821

This leaflet was last revised in

Detailed information on this medi cine is available on the Europ ean Medicines Agency web site: http://www.ema.europa.eu 45 ————————————————————————————————————————— Medical or healthcare professionals The following information is int ended for medical or healthcare professionals only:

Instructions for use, handling and disposal Preparation and administration precautions Paclitaxel is a cytotoxic anticancer medicinal product and, as with other potentially toxic compounds, caution should be exercised in handling Naveruclif. Gloves, goggles and protective clothing should be used. If Naveruclif dispersion contacts the skin, the skin shou ld be washed immediately and thoroughly with soap and water. If Naveruclif contacts mucous m embranes, the membranes should be flushed thoroughly with water. Naveruclif should only be prepar ed and administered by personnel appropriately trained in the handling of cytotoxic agents. Preg nant staff should not handle Naveruclif.

Given the possibility of extrava sation, it is advisable to clos ely monitor the infusion site for possible infiltration during administratio n of the medicinal product. Limiting the infusion of Naveruclif to 30 minutes, as directed, reduces the likelihood of infusion-relate d reactions.

Reconstitution of the product and administration Naveruclif should be administered under the supervision of a qu alified oncologist in units specialised in the administration of cytotoxic agents.

Naveruclif is supplied as a ster ile lyophilised powder for reco nstitution before use. After reconstitution, each ml of disp ersion contains 5 mg of paclitax el formulated as albumin bound nanoparticles. Reconstituted Naveruclif dispersion is administe red intravenously using an infusion set incorporating a 15 μm filter.

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

The solution should be directed onto the inside wall of the via l. The solution should not be injected directly onto the powder as this will result in foaming.

Once the addition is complete, the vial should be allowed to st and for a minimum of 5 minutes to ensure proper wetting of the solid . Then, the vial should gentl y and slowly be swirled and/or inverted for at least 2 minutes until complete redispersion of any powder occurs. The generation of foam must be avoided. If foaming or clumping occurs, the dispersion must stand for at least 15 minutes until foam subsides.

The reconstituted dispersion should be milky and homogenous wit hout visible precipitates. Some settling of the reconstituted disp ersion may occur. If precipit ates or settling are visible, the vial should be gently inverted again to ensure complete redispersion prior to use.

Inspect the dispersion in the vial for particulate matter. Do n ot administer the reco nstituted dispersion if particulate matter is observed in the vial.

The exact total dosing volume of 5 mg/ml dispersion required fo r the patient should be calculated and the appropriate amount of reconstituted Naveruclif should be in jected into an empty, sterile, PVC or non-PVC type intravenous bag.

The use of medical devices cont aining silicone oil as a lubrica nt (i.e. syringes and IV bags) to reconstitute and administer Naveruclif may result in the format ion of proteinaceous strands.

Administer Naveruclif using an infusion set incorporating a 15 µm filter to avoid administration of these strands. Use of a 15 µm filter removes strands and does n ot change the physical or chemical properties of the reconstituted product.

Use of filters with a pore size le ss than 15 µm may result in b lockage of the filter.

The use of specialized di(2-ethylhexyl)phthalate (DEHP)-free so lution containers or administration sets is not necessary to prepare or administer Naveruclif infus ions.

Following administration, it is r ecommended that the intravenou s line be flushed with sodium chloride 9 mg/ml (0.9%) solution for injection to ensure administration of the complete dose.

Any unused product or waste material should be disposed of in a ccordance with local requirements.

Stability Unopened vials of Naveruclif a re stable until the date indicated on the package when the vial is kept in the outer carton in order to protect from light. Neither freezing nor refrigeration adversely affects the stability of the product. This medicinal product does not requi re any special temperature storage conditions.

Stability of the reconstituted dispersion in the vial Chemical and physical in-use stability has been demonstrated fo r 24 hours at 2°C-8°C in the original carton, protected from light.

Stability of the reconstituted di spersion in the infusion bag Chemical and physical in-use stability has been demonstrated fo r 24 hours at 2°C-8°C when protected from light followed by 4 hours at 25°C, when not protected from light.

However, from a microbiological point of view, unless the metho d of reconstituting and filling of the infusion bags precludes the risks of microbial contamination, t he product should be used immediately after reconstitution and filli ng of the infusion bags.

If not used immediately, in-use storage times and conditions ar e the responsibility of the user.

The total combined storage time of reconstituted medicinal prod uct in the vial and in the infusion bag when refrigerated and protected from light is 24 hours. This ma y be followed by storage in the infusion bag for 4 hours below 25°C.

📄 Package Leaflet – official source

This article reproduces the information in the official package leaflet, as authorised in the European Union. You can consult the original document here: Product information Naveruclif (PDF, ec.europa.eu).

You can check this medicine at any time in the Union Register of medicinal products (EU number EU/1/23/1778).

⚠️ Important: This article is for information purposes only and does not replace medical advice or the package leaflet inside the medicine box. Read the leaflet carefully before use. For any questions about your treatment, talk to your doctor or pharmacist. If you experience side effects, tell your doctor or pharmacist and report them through your national reporting system.