Label: Information for the Patient

Apexelsin 5 mg/ml Powder for Solution for Infusion EFG

Paclitaxel

Read this label carefully before this medicine is administered to you, as it contains important information for you.

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

What isApexelsin

Apexelsin contains, as the active ingredient, paclitaxel bound to human albumin, in the form ofsmallparticles called nanoparticles. Paclitaxel belongsto a group of medications known as “taxanes” that are used in cancer.

• 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 produce life-threatening side effects are not needed. These side effects occur much less frequently with Apexelsin.

What is Apexelsin used for

Apexelsin is used to treat the following types of cancer:

• Breast cancer

• Metastatic breast cancer (cancer that has spread to other parts of the body).
• Apexelsin is used in metastatic breast cancer when at least one other therapy has been tried but did not work and the case is not suitable for treatment with a group of medications called “anthracyclines”.
• People with metastatic breast cancer who received paclitaxel bound to human albumin 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

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

• Lung cancer

• Apexelsin 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”.

• Apexelsin is used in non-small cell lung cancer when surgery or radiation therapyare not suitable for treating the disease.

Apexelin should not be administered

• if you are allergic to paclitaxel or any of the other components of this medication (listed in section 6);
• if you have breast cancer;
• if you have a low white blood cell count (a neutrophil count of less than
• 1500 cells/mm3before starting treatment. Your doctor will advise you accordingly).

Warnings and precautions

Consult your doctor or nurse before starting to receive Apexelin

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

If you experience any of these disorders while receiving treatment with Apexelin, 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

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

Other medications and Apexelin

Inform your doctor if you are using or have recently used any other medication. This is because Apexelin may affect the way some medications work.

Similarly, some medications may affect the way Apexelin works.

Be careful and consult your doctor when you are administered Apexelin at the same time as any of the following:

• medications to treat infections (such as antibiotics like 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 (such as ketoconazole)
• medications used to help stabilize mood, also called antidepressants (such as fluoxetine)
• medications used to treat seizures (epilepsy) (such as carbamazepine, phenytoin)
• medications used to help reduce the level oflipids in the blood(such as gemfibrozil)
• medications used to treat stomach acid or stomach ulcers (such as cimetidine)
• medications used to treat HIV and AIDS (such as 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 Apexelin.

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

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

Men treated with Apexelin should use effective contraceptive methods andavoid fathering children during treatment and for six months after completing it, as well asinform themselves about the possibility of preserving their sperm before starting treatment, given the possibility of irreversible infertility.

Consult your doctor before using this medication.

Driving and operating machinery

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

If you are taking other medications as part of your treatment, consult your doctor about your ability to drive and use machinery.

Apexelin contains sodium

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

A healthcare professional will administer this medication 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 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 receive 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 (on days 1, 8, and 15 of a 21-day cycle), with carboplatin administered once every three weeks (only on day 1 of each 21-day cycle), immediately after the Apexelsin dose is administered.

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.

Very common:may affect more than 1 in 10 people

• Loss of hair (most cases of hair lossoccurred in less than a monthafter starting treatment with paclitaxel. 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 orleukocytes) 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)
• Joint 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 extremities
• Cough
• Abdominal pain
• Nasal bleeding

Common:may 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) inblood, redness, cold sores, severe blood infection that may be due to a decrease in white blood cells
• Decrease in all blood cell values
• Chest or throat pain
• Indigestion, abdominal discomfort
• Stuffy nose
• Back or bone pain
• Decreased muscle coordination or difficulty reading, increased or decreased tear production,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 kidney failure
• Increased bilirubin in the blood
• Coughing up blood
• Dry mouth, difficulty swallowing
• Weakness of the muscles
• Blurred vision

Uncommon:may affect up to 1 in 100 people

• Weight gain, increased lactate dehydrogenase in blood, renal function alteration, increased glucose in blood, increased phosphorus in blood
• Decreased or absent reflexes, involuntary movements, nerve pain, fainting, dizziness when standing, tremors, facial nerve paralysis
• Irritated eyes, eye pain, red eyes, itching in the eyes, double vision, reduced vision, or flashing lights, blurred vision due to inflammation of the retina (macular cystoid edema)
• Ears pain, ringing in the ears
• Coughing up mucus, shortness of breath when walking or climbing stairs, nasal congestion, decreased respiratory sounds,fluid in the lungs, loss of voice, blood clots in the lungs, dry throat
• Gas, stomach cramps, mouth pain, rectal bleeding
• Painful urination (dysuria), frequent urination, blood in the urine, involuntary loss of urine (urinary incontinence)
• Nail pain, nail discomfort, nail loss, hives, skin pain, photosensitivity reaction, skin pigmentation disorders, increased sweating, night sweats, white spots on the skin, sores, facial swelling
• Decreased phosphorus in blood, fluid retention,low albumin in blood, increased thirst,decreased calcium in blood, decreased blood sugar, decreased sodium in blood
• Nasal pain, skin infections, catheter-related infection
• Contusion
• Tumor pain, tumor necrosis
• Decreased blood pressure when standing, cold extremities
• Difficulty walking, swelling
• Allergic reaction
• Decreased liver function, enlarged liver
• Chest pain
• Nervousness
• Small skin bleeding 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

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

Very rare:may affect up to 1 in 10,000 people

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

Frequency not known: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 leaflet. You can also report them directly through thenational notification system included in theAppendix 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 on the vial after CAD. 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) fora maximum of 24 hours protected from light.

The total combined conservation time of 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.

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

Composition of Apexelsin

• The active principle 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”.

Appearance of the product and contents of the pack

Apexelsin is a powder or lyophilisate 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 pack contains 1 vial.

Marketing Authorization Holder

WhiteOak Pharmaceutical B.V.

Teleportboulevard 130,

Amsterdam, 1043 EJ,

Netherlands

Responsible Person

SciencePharma Sp. z o.o.

Chelmska 30/34

00-725 Warsaw

Poland

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

Last update of this leaflet:

The detailed information on this medicinal product is available on the website of the European Medicines Agency:https://www.ema.europa.eu/.

This leaflet is available in all languages of the European Union/European Economic Area on the website of the European Medicines Agency.

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This information is intended for healthcare professionals only:

Instructions for use, preparation and disposal

Precautions for preparation and administration

Paclitaxel is a cytotoxic anticancer drug, so Apexelsin must be handled with caution, as with other potentially toxic substances. 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 experienced personnel in the handling of cytotoxic agents. Pregnant women should not handle Apexelsin.

Due to the possibility of extravasation, it is recommended to closely monitor the infusion site for any signs of extravasation during administration of the drug. Limiting the infusion time of Apexelsin to 30 minutes, as instructed, reduces the likelihood of reactions associated with infusion.

Reconstitution and administration of the medicinal product

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 lyophilisate for reconstitution before use. After reconstitution, each ml of dispersion contains 5 mg of paclitaxel bound to albumin in a nanoparticle formulation. The reconstituted dispersion of Apexelsin is administered by intravenous infusion 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%) solution for infusion into the 100 mg Apexelsin vial 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 this will produce foam.

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 fully redispersed. Foam formation should be avoided. 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. A certain degree of sedimentation of the reconstituted dispersion may occur. If there are signs of precipitation or sedimentation, the vial should be gently inverted to achieve complete redispersion before use.

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

The exact volume of the 5 mg/ml dispersion required for the patient should be calculated, and the appropriate amount of reconstituted Apexelsin should be injected into a sterile, empty intravenous infusion bag, type PVC or non-PVC.

The use of medical devices containing silicone oil as a lubricant (i.e., IV administration sets) for reconstituting and administering Apexelsin may lead to the formation of protein filaments. Apexelsin 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 affecting the physical or chemical properties of the reconstituted medicinal product.

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

No special containers or equipment without DEHP are required for preparing or administering Apexelsin infusions.

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

The disposal of unused medicinal product and all materials that have come into contact with it should be carried out in accordance with local regulations.

Stability

Unopened vials of Apexelsin 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 affect the stability of the medicinal product. This medicinal product 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 ºC-8 ºC 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 ºC-8 ºC followed by 4 hours at 25 ºC, 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 combined storage time of the reconstituted medicinal product 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 ºC.