Apexelsin 5 mg/ml powder for perfusion dispersion EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Apexelsin 5 mg/ml powder for perfusion solution for concentrate for dispersion EFG

Paclitaxel

Read the entire leaflet carefully before you are given 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, ask your doctor or nurse.
• If you experience any side effects, talk to your doctor or nurse, including any side effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Apexelsin is and what it is used for

What Apexelsin is

Apexelsin contains, as its active substance, paclitaxel bound to the human protein albumin, in the form of tiny particles called nanoparticles. Paclitaxel belongs to a group of medicines known as “taxanes” used in cancer treatment.

• Paclitaxel is the part of the medicine that acts on cancer; it works by preventing cancer cells from dividing, which causes them to die.
• Albumin is the part of the medicine that helps paclitaxel dissolve in the blood and pass through blood vessel walls to reach the tumor. This means that it is not necessary to use other chemical agents that may cause adverse reactions which could be life-threatening. Such adverse reactions occur much less frequently with Apexelsin.

What Apexelsin is used for

Apexelsin is used to treat the following types of cancer:

• Breast cancer

• Metastatic breast cancer (breast 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 has not worked, and when your condition is not suitable for treatment with a group of medicines called “anthracyclines”.

• Patients with metastatic breast cancer who received paclitaxel bound to human albumin protein after another treatment had failed experienced a greater likelihood of tumor shrinkage and lived longer than patients who received an alternative treatment.

• Pancreatic cancer

• Apexelsin is used in combination with a medicine called gemcitabine if you have metastatic pancreatic cancer. In a clinical trial, patients with metastatic pancreatic cancer (pancreatic cancer that has spread to other parts of the body) who received paclitaxel bound to human albumin protein together with gemcitabine lived longer than those who received gemcitabine alone.

• Lung cancer

• Apexelsin is also used in combination with a medicine called carboplatin if you have the most common type of lung cancer, known as “non-small cell lung cancer”.

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

2. What you need to know before starting to take Apexelsin

Apexelsin must not be administered

• if you are allergic to paclitaxel or to any of the other ingredients of this medicine (listed in section 6);
• if you are breastfeeding;
• if you have a low white blood cell count (neutrophil count less than 1500 cells/mm³) before starting treatment. Your doctor will advise you on this.

Warnings and precautions

Talk to your doctor or nurse before receiving Apexelsin

• if you have impaired kidney function;
• if you have severe liver problems;
• if you have heart conditions.

If you experience any of the following conditions during treatment with Apexelsin, inform your doctor or nurse. Your doctor may decide to interrupt treatment or reduce the dose:

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

Children and adolescents

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

Other medicines and Apexelsin

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

Likewise, some medicines may affect how Apexelsin works.

Be cautious and consult your doctor when receiving Apexelsin at the same time as any of the following:

• medicines used to treat infections (i.e., antibiotics such as erythromycin, rifampicin, etc.; if in doubt whether your medicine is an antibiotic, ask your doctor, nurse, or pharmacist), and medicines used to treat fungal infections (such as ketoconazole);
• medicines used to help stabilize mood, also known as antidepressants (such as fluoxetine);
• medicines used to treat seizures (epilepsy) (such as carbamazepine, phenytoin);
• medicines used to help reduce lipid levels in the blood (such as gemfibrozil);
• medicines used for stomach acidity 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, breastfeeding, and fertility

Paclitaxel may cause severe birth defects and therefore must not be used if you are pregnant. Your doctor will request a pregnancy test before starting treatment with Apexelsin.

Women of childbearing potential must use effective contraceptive methods during treatment and for one month after completion of treatment with Apexelsin.

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

Men treated with Apexelsin are advised to use effective contraception and avoid fathering a child during treatment and for six months after treatment ends. Men should also seek advice on the possibility of sperm preservation before starting treatment, due to the risk 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 operate any tools or machinery.

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

Apexelsin contains sodium

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

3. How to take Apexelsin

A doctor or nurse will administer this medicine into your vein through an intravenous infusion system.

Your dose 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 Apexelsin be administered?

• For the treatment of metastatic breast cancer, Apexelsin is usually given once every three weeks (on day 1 of a 21-day cycle).
• For the treatment of metastatic pancreatic cancer, Apexelsin is given 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 given 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 dose of Apexelsin.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone gets them.

Very common: may affect more than 1 in 10 people

• Hair loss (most cases of hair loss occurred within less than one month after starting treatment with paclitaxel. When it occurs, hair loss is severe (more than 50%) in most patients)
• Skin rash
• Abnormally low levels of certain types of white blood cells (neutrophils, lymphocytes or leucocytes) in the blood
• Reduction in red blood cells
• Decreased number of platelets in the blood
• Effects 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 levels of potassium in the blood
• Depression, sleep problems
• Headache
• Chills
• Difficulty breathing
• Dizziness
• Swelling of 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 low levels of a type of white blood cell (neutrophils) in the blood, flushing, mouth ulcers, severe blood infection possibly due to reduced white blood cells
• Reduction in all blood cell values
• Chest or throat pain
• Indigestion, abdominal discomfort
• Nasal congestion
• Back pain, 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
• 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, impaired kidney function, increased blood glucose, increased blood phosphorus
• Reduced or absent reflexes, involuntary movements, nerve pain, fainting, dizziness upon standing, tremors, facial nerve paralysis
• Irritated eyes, eye pain, red eyes, itchy eyes, double vision, reduced vision, flashing lights, blurred vision due to retinal inflammation (cystoid macular edema)
• Ear pain, ringing in the ears
• Cough with phlegm, shortness of breath when walking or climbing stairs, runny or dry nose, decreased breath sounds, fluid in the lungs, loss of voice, blood clot in the lungs, dry throat
• Gas, stomach cramps, gum pain, rectal bleeding
• Painful urination (dysuria), need to urinate more often than normal (frequent urination), blood in the urine, involuntary loss of urine (urinary incontinence)
• Nail pain, nail discomfort, nail loss, hives, skin pain, photosensitivity reaction, pigmentation disorders, increased sweating, night sweats, white spots on the skin, sores, facial swelling
• Low blood phosphorus, fluid retention, low albumin in blood, increased thirst, low blood calcium, low blood sugar, low blood sodium
• Pain and swelling in the nose, skin infections, catheter-related infection
• Bruising
• Pain at tumor site, tumor necrosis
• Drop in blood pressure upon standing, cold extremities
• Difficulty walking, swelling
• Allergic reaction
• Decreased liver function, enlarged liver
• Chest pain
• Nervousness
• Small skin bleeds due to blood clots
• A condition involving 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 lung inflammation following radiation
• Blood clots
• Very slow pulse, heart attack
• Leakage of medicine from the vein (extravasation)
• Heart conduction system disorder (atrioventricular block)

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

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

Frequency not known: cannot be estimated from available data

• Hardening/thickening of the skin (scleroderma)

Reporting of adverse effects

If you experience any adverse effects, consult your doctor or nurse, even if they are possible adverse effects not listed in this leaflet. You may also report them directly through the national reporting system detailed in Appendix V. By reporting adverse 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 refers to 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 should be used immediately. If not used immediately, the vial containing the dispersion must be kept inside 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 may be stored in the refrigerator (2 °C–8 °C) for up to 24 hours, protected from light.

The total combined storage time of the reconstituted medicine in the vial and in the infusion bag, when refrigerated and protected from light, is 24 hours. After this, it may be kept in the infusion bag for up to 4 hours at a temperature below 25 °C.

Your doctor or pharmacist is responsible for the proper disposal of any unused portion of Apexelsin.

6. Contents of the container and other information

Composition of Apexelsin

• 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 component is human albumin solution (containing sodium caprylate and N-acetyl-L-tryptophan), see section 2 “Apexelsin contains sodium”.

Appearance of the product and contents of the container

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 pack contains 1 vial.

Marketing Authorization Holder

WhiteOak Pharmaceutical B.V.

Teleportboulevard 130,

Amsterdam, 1043 EJ,

The Netherlands

Manufacturer

SciencePharma Sp. z o.o.

Chelmska 30/34

00-725 Warsaw

Poland

Further information on this medicinal product is available upon request by contacting the local representative of the Marketing Authorization Holder:

Date of the most recent review of this summary:

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

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

This information is intended for healthcare professionals only:

Instructions for use, preparation and disposal

Precautions for preparation and administration

Paclitaxel is a cytotoxic antineoplastic agent; therefore, Apexelsin must be handled with care, as with other potentially toxic drugs. Gloves, safety goggles, and protective clothing should be used. In case of skin contact, the affected area must be washed immediately and thoroughly with water and soap. In case of contact with mucous membranes, these should be thoroughly rinsed with copious amounts 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, the infusion site should be closely monitored for signs of extravasation during administration of the drug. Limiting the infusion time of Apexelsin to 30 minutes, as per instructions, reduces the likelihood of infusion-related reactions.

Reconstitution and administration of the medicine

Apexelsin must 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 incorporating 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 onto the inner wall of the vial. The solution must not be injected directly onto the powder, as this will cause foaming.

After adding the solution, allow the vial to stand for at least 5 minutes to ensure proper wetting of the solute. Then gently and carefully shake and/or slowly invert the vial for at least 2 minutes until complete redispersion of the powder. Foaming should be avoided. If foam or clumps form, allow the dispersion to stand for at least 15 minutes until the foam disappears.

The reconstituted dispersion should appear milky and homogeneous without visible precipitates. Some sedimentation of the reconstituted dispersion may occur. If precipitate or sedimentation is observed, gently invert the vial 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 required for the patient should be calculated, and the appropriate amount of reconstituted Apexelsin should be injected into an empty, sterile intravenous infusion bag made of PVC or non-PVC material.

The use of medical devices containing silicone oil as lubricant (e.g., syringes and IV administration bags) for reconstituting and administering Apexelsin may lead to the formation of protein filaments. Apexelsin should be administered using an infusion set incorporating a 15 µm filter to prevent administration of these filaments. The use of a 15 µm filter removes the filaments and does not alter the physical or chemical properties of the reconstituted medicine.

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

There is no need for DEHP-free containers or administration sets specifically for the preparation or administration of Apexelsin infusions.

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

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

Stability

Unopened vials of Apexelsin remain stable until the date indicated on the container when stored in the outer packaging to protect from light. Freezing or refrigeration does not adversely affect the stability of the medicine. This medicine 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 standpoint, unless the reconstitution and filling method for 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 medicine in the vial and in the infusion bag, when refrigerated and protected from light, is 24 hours. It may then be stored in the infusion bag for up to 4 hours at a temperature below 25°C.