APEXELSIN 5 mg/ml POWDER FOR DISPERSION FOR INFUSION

Introduction

Package Leaflet: Information for the Patient

Apexelsin 5 mg/ml powder for dispersion for infusion EFG

Paclitaxel

Read all of this leaflet carefully before this medicine is administered to you, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• If you experience side effects, consult your doctor or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the Package Leaflet

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

1. What is Apexelsin and what is it used for

What is Apexelsin

Apexelsin contains, as an active substance, paclitaxel bound to the human protein albumin, in the form of tiny particles called nanoparticles. Paclitaxel belongs to a group of medicines called "taxanes" 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 dissolve in the blood and cross the walls of blood vessels to reach the tumor. This means that other chemical agents that can cause life-threatening side effects are not needed. Such side effects occur much less frequently with Apexelsin.

What Apexelsin is used for

Apexelsin 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).
• Apexelsin 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 paclitaxel bound to human protein albumin when another treatment had failed had a higher chance of experiencing a reduction in tumor size and lived longer than people who received an alternative treatment.

• Pancreatic cancer

• Apexelsin 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 paclitaxel bound to human protein albumin with gemcitabine in a clinical trial lived longer than people who only received gemcitabine.

• Lung cancer

• Apexelsin 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".

• Apexelsin 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 Apexelsin is administered to you

Apexelsin must not be administered

• 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 less than 1500 cells/mm3 before starting treatment. Your doctor will advise you).

Warnings and precautions

Consult your doctor or nurse before starting to receive Apexelsin

• 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 receiving treatment with Apexelsin, inform your doctor or nurse. Your doctor may decide to interrupt 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, pinching, sensitivity to touch, or muscle weakness;
• if you experience respiratory problems, such as difficulty breathing or dry cough.

Children and adolescents

This medicine is only intended for adults and must not be administered to children or adolescents under 18 years of age.

Other medicines and Apexelsin

Tell your doctor if you are using or have recently used any other medicines. This is because Apexelsin may affect how some medicines work.

Similarly, some medicines may affect how Apexelsin works.

Be careful and consult your doctor when Apexelsin is administered at the same time as any of the following:

• medicines to treat 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 to treat fungal infections (such as ketoconazole)
• medicines used to help stabilize mood, also called antidepressants (such as fluoxetine)
• medicines used to treat seizure disorders (epilepsy) (such as carbamazepine, phenytoin)
• medicines used to help reduce lipid levels in the blood (such as gemfibrozil)
• medicines used to treat stomach acid or stomach ulcers (such as cimetidine)
• medicines used to treat HIV and AIDS (such as 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 you to have a pregnancy test before starting treatment with Apexelsin.

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

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

Men treated with Apexelsin are advised to use effective contraceptive methods and avoid having children during treatment and for six months after finishing it, as well as to inform themselves about the possibility of preserving their sperm before starting treatment, given the possibility that treatment with this medicine may cause irreversible infertility.

Consult your doctor before using this medicine.

Driving and using machines

Some people may feel tired or dizzy after receiving this medicine. 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, consult your doctor about your ability to drive and use machines.

Apexelsin contains sodium

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

3. How to take Apexelsin

A doctor or nurse will administer this medicine to you through a vein using 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 administered Apexelsin?

• For the treatment of metastatic breast cancer, Apexelsin is usually administered once every three weeks (on day 1 of a 21-day cycle).
• For the treatment of metastatic pancreatic cancer, Apexelsin is administered on days 1, 8, and 15 of each 28-day cycle, with gemcitabine administered immediately after Apexelsin.
• For the treatment of non-small cell lung cancer, Apexelsin 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 Apexelsin dose.

If you have any further questions about 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.

Very common:may affect more than 1 in 10 people

• Hair loss (most cases of hair loss occurred within a month after starting treatment with paclitaxel. When it occurs, hair loss is pronounced (more than 50%) in most patients)
• 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 platelet count in blood
• Effect on peripheral nerves (pain, numbness, tingling, or loss of sensitivity)
• 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 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

Common: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, redness, mouth sores, severe blood infection that may be due to a reduction in white blood cells
• Reduction in all blood cell values
• Chest pain or throat pain
• Indigestion, abdominal discomfort
• Nasal congestion
• Back pain, bone pain
• Decreased muscle coordination or difficulty reading, increased or decreased tears, eyelash loss, skin discoloration, increased sweating, night sweats, white spots on the skin, sores, facial swelling
• 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

Uncommon: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 or dry nose, decreased breath sounds, fluid in the lungs, hoarseness, blood clots in the lungs, dry throat
• Gas, stomach cramps, gum pain, rectal bleeding
• Painful urination (dysuria), frequent urination (urinary frequency), blood in the urine, involuntary loss of urine (urinary incontinence)
• Nail pain, nail disorders, nail loss, hives, skin pain, photosensitivity reaction, skin discoloration, increased sweating, night sweats, white spots on the skin, sores, facial swelling
• Decreased phosphorus in the blood, fluid retention, low albumin in the blood, increased thirst, decreased calcium in the blood, decreased sugar in the blood, decreased sodium in the blood
• Pain and swelling in the nose, skin infections, catheter-related infections
• Bruising
• Pain and swelling at the tumor site, tumor necrosis
• Decreased 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

Rare:may affect up to 1 in 1,000 people

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

Very rare: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, consult your doctor or nurse, even if they are not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Apexelsin

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

Do not use this medicine after the expiry date stated on the carton and vial after EXP. The expiry date is the last day of the month stated.

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 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 total storage time for the reconstituted medicine in the vial and 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.

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

6. Container Content and Additional Information

Apexelsin Composition

• The active ingredient 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 component is human albumin solution (contains sodium caprylate and N-acetyl-L-tryptophan), see section 2 "Apexelsin contains sodium".

Product Appearance and Container Content

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

Each container contains 1 vial.

Marketing Authorization Holder

WhiteOak Pharmaceutical B.V.

Teleportboulevard 130,

Amsterdam, 1043 EJ,

Netherlands

Manufacturer

SciencePharma Sp. z o.o.

Chelmska 30/34

00-725 Warsaw

Poland

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Prospectus:

Detailed information about this medication is available on the European Medicines Agency website: https://www.ema.europa.eu/.

This prospectus can be found on the European Medicines Agency website in all languages of the European Union/European Economic Area.

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This information is intended only for doctors or healthcare professionals:

Instructions for Use, Preparation, and Disposal

Precautions for Preparation and Administration

Paclitaxel is a cytotoxic antineoplastic medication, so Apexelsin should be handled with caution, as with other potentially toxic medications. 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. Apexelsin should only be prepared and administered by personnel experienced in handling cytotoxic agents. Pregnant women should not handle Apexelsin.

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 Apexelsin to 30 minutes, according to the instructions, reduces the likelihood of infusion-related reactions.

Reconstitution and Administration of the Medication

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

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

Using a sterile syringe, slowly inject 20 ml of sodium chloride 9 mg/ml (0.9%) solution for infusion into the 100 mg Apexelsin vial over at least 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 this will cause foaming.

After adding the solution, the vial should be allowed to stand for at least 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 Apexelsin should be injected into an empty, sterile intravenous infusion bag (PVC or non-PVC type).

The use of medical products containing silicone oil as a lubricant (i.e., syringes and IV bags) to reconstitute and administer Apexelsin may result in the formation of protein filaments. Apexelsin 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 DEHP-free infusion bags or administration equipment to prepare or administer Apexelsin infusions.

After administration, it is recommended to flush the intravenous line thoroughly 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 Apexelsin vials remain stable until the expiration 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 container, 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, followed by 4 hours at 25°C, protected from light.

However, from a microbiological point of view, unless the method of reconstitution and filling of the infusion bags precludes 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 are the responsibility of the user.

The total combined storage time of 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.