APEXELSIN 5 mg /Ml Powder For Dispersion For Infusion

Зміст інструкції

1. Apexelsin 5 mg/mL powder for dispersion for infusion
   1. What is Apexelsin and what is it used for
   2. What you need to know before you receive Apexelsin
   3. How Apexelsin is administered
   4. Possible side effects
   5. How to store Apexelsin
   6. Contents of the pack and other information

Apexelsin 5 mg/mL powder for dispersion for infusion

paclitaxel

Read this leaflet carefully before you receive this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet

• 1. What Apexelsin is and what it is used for
• 2. What you need to know before you receive 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 is Apexelsin and what is it used for

What is Apexelsin
Apexelsin contains, as the active ingredient, paclitaxel bound to albumin, a human protein, in the form of tiny particles known as nanoparticles. Paclitaxel belongs to a group of medicines called taxanes, which are used in cancer therapy.

• Paclitaxel is the part of the medicine that has an effect on the tumor, it works by stopping the division of tumor cells, which for this reason 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 no other chemical substances are needed that can cause undesirable effects, which can be life-threatening. Some undesirable effects are much less frequent with Apexelsin.

What is Apexelsin used for
Apexelsin is used for the treatment of 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 attempted, but has not had an effect and if the patient is not eligible for treatments containing a group of medicines called “anthracyclines”.
• People with metastatic breast cancer who have received paclitaxel bound to the human protein called albumin, in cases where another therapy had not been successful, have had a greater probability of observing a reduction in tumor size and have lived longer compared to people who have taken an alternative therapy.
• Pancreatic cancer
• Apexelsin is used together with a medicine called gemcitabine in case of metastatic pancreatic cancer. People with metastatic pancreatic cancer (pancreatic cancer that has spread to other parts of the body) treated with paclitaxel bound to the human protein called albumin and gemcitabine in a clinical study have lived longer compared to people who have received only gemcitabine.
• Lung cancer
• Apexelsin is used together with a medicine called carboplatin in the treatment of the most common type of lung cancer, called “non-small cell lung cancer”.
• Apexelsin is used in non-small cell lung cancer in cases where surgery or radiotherapy are not suitable for the treatment of the disease.

2. What you need to know before you receive Apexelsin

Apexelsin should 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 breastfeeding;
• if you have a low number of white blood cells (initial neutrophil count less than
• 1,500 cells/mm - information on this will be provided by your doctor).

Warnings and precautions
Talk to your doctor or nurse before you receive Apexelsin

• if your kidney function is reduced;
• if you have severe liver problems;
• if you have heart disorders.

Consult your doctor or nurse if you experience any of these conditions during treatment
with Apexelsin; your doctor may decide to stop treatment or reduce the dose:

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

Children and adolescents
This medicine is only for adults and should not be given to children and adolescents under the age of
18 years.

Other medicines and Apexelsin
Tell your doctor if you are taking or have recently taken any other medicines, including
those available without a prescription and herbal medicines. This is because Apexelsin can
affect the action of other medicines and other medicines can affect the action of Apexelsin.
Be careful and consult your doctor when taking Apexelsin together with any of the following:

• medicines for the treatment of infections (antibiotics such as erythromycin, rifampicin, etc.; ask your doctor, nurse or pharmacist if you are not sure whether the medicine you are taking is an antibiotic), including medicines for the treatment of fungal infections (such as ketoconazole)
• medicines used to stabilize mood, sometimes also called antidepressants (such as fluoxetine)
• medicines used to treat seizures (epilepsy) (such as carbamazepine, phenytoin)
• medicines used to lower lipid levels in the blood (such as gemfibrozil)
• medicines used for heartburn or stomach ulcers (such as cimetidine)
• medicines used to treat HIV and AIDS (such as ritonavir, saquinavir, indinavir, nelfinavir, efavirenz, nevirapine)
• a medicine called clopidogrel used for the prevention of blood clots.

Pregnancy, breastfeeding and fertility
Paclitaxel can cause serious birth defects (at birth) and therefore should not be used during
pregnancy. Your doctor will arrange a pregnancy test before starting treatment with this
medicine.
Women of childbearing potential must use effective contraceptive methods during therapy with Apexelsin and
for at least 6 months after stopping therapy.
Do not breastfeed during treatment with this medicine, as it is not known whether the active ingredient
paclitaxel passes into breast milk.
Male patients are advised to use effective contraceptive measures and to avoid
conceiving children during therapy and for at least 3 months after stopping it, and to
seek information about semen preservation before treatment, due to the possibility that therapy with
this medicine may cause permanent infertility.
Ask your doctor for advice before taking this medicine.

Driving and operating machinery
Some people may feel tired or dizzy after receiving this
medicine. If this happens, do not drive vehicles and do not use tools or machinery.
If other medicines are prescribed as part of the therapy, consult your doctor about the possibility of
driving and using machinery.

Apexelsin contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per vial, i.e. essentially
‘sodium-free’.

3. How Apexelsin is administered

This medicine will be administered intravenously via intravenous infusion by a doctor or a nurse.
The amount administered depends on the 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 is Apexelsin administered?

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

If you have any doubts 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 everyone will experience them.

Very common:may affect more than 1 in 10 people

• Hair loss (most cases of hair loss occurred within one month of starting treatment with paclitaxel. When it occurs, hair loss is pronounced (more than 50%) in most patients)
• Skin rash
• Abnormally low number of certain types of white blood cells (neutrophils, lymphocytes, or leukocytes) in the blood
• Red blood cell deficiency (erythrocytes)
• Reduced 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 irritation, loss of appetite
• Vomiting
• Weakness and fatigue, fever
• Dehydration, altered taste, weight loss
• Low potassium levels in the blood
• Depression, sleep disorders
• Headache
• Chills
• Difficulty breathing
• Dizziness
• Swelling of the mucous membranes and soft tissues
• Increased liver function values
• Pain in the extremities
• Cough
• Abdominal pain
• Nosebleeds

Common:may affect up to 1 in 10 people

• Itching, dry skin, changes in nails
• Infection, fever with a reduction in the number of a type of white blood cells (neutrophils) in the blood, hot flashes, oral candidiasis, serious blood infection that may be caused by a reduction in white blood cells
• Reduction in the number of all types of blood cells
• Chest pain or sore throat
• Indigestion, abdominal problems
• Nasal congestion
• Back pain, bone pain
• Reduced muscle coordination or difficulty reading, increased or decreased tearing, eyelash loss
• Changes in heart rate or rhythm, heart failure
• Decreased or increased blood pressure
• Redness or swelling at the injection site
• Anxiety
• Lung infection
• Urinary tract infection
• Blockage in the intestine, inflammation of the colon, inflammation of the bile duct
• Acute renal 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 (an enzyme) in the blood, decreased kidney function, increased blood sugar, increased phosphorus in the blood
• Decreased or absent reflexes, involuntary movements, neuralgia, fainting, dizziness upon standing, tremor, facial nerve paralysis
• Eye irritation, eye pain, eye redness, eye itching, double vision, reduced visual acuity or seeing flashing lights, blurred vision due to swelling of the retina (cystoid macular edema)
• Ear pain, tinnitus
• Cough with mucus, shortness of breath when walking or climbing stairs, runny or dry nose, decreased breath sounds, water in the lungs, hoarseness, blood clot in the lung, sore throat
• Flatulence (intestinal gas), stomach cramps, gum pain, blood in the stool
• Painful urination, frequent urination, blood in the urine, urinary incontinence
• Nail pain, painful nail sensitivity, nail loss, hives, skin pain, photosensitivity reaction, pigment disorders, increased sweating, night sweats, white spots on the skin, skin lesions, facial swelling
• Decreased phosphorus in the blood, fluid retention, low albumin levels in the blood, increased thirst, decreased calcium in the blood, decreased blood sugar, decreased sodium in the blood
• Pain and congestion of the nose, skin infections, catheter infection
• Bruising
• Pain at the site of the tumor, tumor necrosis
• Decreased blood pressure in the upright position, cold extremities (hands and feet)
• Difficulty walking, swelling
• Allergic reaction
• Decreased liver function, enlarged liver
• Chest pain
• Restlessness
• Small blood leaks in the skin due to blood clots
• A condition involving the destruction of red blood cells and acute renal failure

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

• Skin reaction to another agent or pulmonary inflammation following radiation
• Formation of blood clots
• Very slow pulse, heart attack
• Leakage of the medicine from the vein
• A disorder of the heart's electrical conduction system (atrioventricular block)

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

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

Not known:frequency cannot be estimated based on available data

• Hardening/thickening of the skin (scleroderma)

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please tell your
doctor or nurse. You can also report side effects directly through the national reporting system detailed in
Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Apexelsin

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date which is stated on the package and vial after
Expiry./EXP. The expiry date refers to the last day of that month.
Closed vials: keep the vial in the outer packaging to protect the medicine from light.
After the first reconstitution, the dispersion must be used immediately. If not
used immediately, the dispersion can be stored in a refrigerator (2 °C – 8 °C) for up to
24 hours in the vial kept in the outer packaging that protects the medicine from light.
The dispersion reconstituted for intravenous infusion can be stored in a refrigerator (2 °C – 8 °C)
for up to 24 hours protected from light.
The total storage time of the medicine reconstituted in the vial and in the infusion bag,
if refrigerated and protected from light, is 24 hours. This can be followed by storage for 4 hours
in the infusion bag at temperatures below 25 °C.
The doctor or pharmacist is responsible for the correct disposal of unused Apexelsin.

6. Contents of the pack and other information

What Apexelsin contains

• The active substance is paclitaxel. Each vial contains 100 mg of paclitaxel bound to albumin formulated in nanoparticles. After reconstitution, each mL of dispersion contains 5 mg of paclitaxel bound to albumin formulated in nanoparticles.
• The other component is human albumin solution (containing sodium caprylate and N-acetyl-L-tryptophan), see section 2 “Apexelsin contains sodium”.

Description of the appearance of Apexelsin and contents of the pack
Apexelsin is a white to yellow lyophilized powder or tablet for infusion dispersion.
Apexelsin is available in a glass vial containing 100 mg of paclitaxel bound to albumin
formulated in nanoparticles.
Each pack contains 1 vial.

Marketing authorisation holder
WhiteOak Pharmaceutical B.V.
Teleportboulevard 130,
Amsterdam, 1043 EJ,
Netherlands

Manufacturer
SciencePharma Sp. z o.o.
Chełmska 30/34
00-725 Warsaw
Poland
For further information on this medicinal product, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
WhiteOak Pharmaceutical B.V.
Tél/Tel: +31 202255118

Lietuva
Zentiva, k.s.
Tel: +370 52152025

България
Zentiva, k.s.
Тел: + 359 24417136

Luxembourg/Luxemburg
WhiteOak Pharmaceutical B.V.
Tél/Tel: +31 202255118

Magyarország
WhiteOak Pharmaceutical B.V.
Tel: +31 202255118

Danmark
FrostPharma AB
Tlf: + 46 8243660

Česká republika
Zentiva, k.s.
Tel: +420 267241111

Malta
WhiteOak Pharmaceutical B.V.
Tel: +31 202255118

Deutschland
WhiteOak Pharmaceutical B.V.
Tel.: +49 88569039983

Nederland
WhiteOak Pharmaceutical B.V.
Tel: +31 320798100

Eesti
Zentiva, k.s.
Tel: +372 5270308

Norge
FrostPharma AB
Tlf: + 46 8243660

Ελλάδα
WhiteOak Pharmaceutical B.V.
Τηλ: +31 202255118

Österreich
IHCS Arzneimittel Vertriebs GmbH
Tel: +43 171728861

España
Zentiva, Spain S.L.U.
Tel: +34 671365828

Polska
Zentiva Polska Sp. z o.o.
Tel: + 48 22 375 92 00

France
Zentiva France
Tél: +33 800089219

Portugal
WhiteOak Pharmaceutical B.V.
Tel: +351 300505995

Hrvatska
WhiteOak Pharmaceutical B.V.
Tel: +385 17757005

Ireland
Caragen Limited
Tel : + 353 15688566

România
WhiteOak Pharmaceutical B.V.
Tel: +31 202255118

Slovenija
WhiteOak Pharmaceutical B.V.
Tel: +385 17757005

Ísland
FrostPharma AB
Sími: +46 82436 60

Slovenská republika
WhiteOak Pharmaceutical B.V.
Tel: +42 123325144

Italia
Istituto Gentili s.r.l.
Tel: +39 0289132700

Suomi/Finland
FrostPharma AB
Puh/Tel: + 46 8243660

Κύπρος
C.A.Papaellinas Ltd
Τηλ ： +357 22741741

Sverige
FrostPharma AB
Tel: + 46 8243660

Latvija
Zentiva, k.s.
Tel: +371 67893939
More 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 official languages of the European Union/European Economic Area on the
website of the European Medicines Agency.

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The following information is intended exclusively for physicians or healthcare professionals:

Instructions for use, handling and disposal
Precautions for preparation and administration
Paclitaxel is a cytotoxic antineoplastic agent; as with other potentially toxic compounds,
certain precautions must be taken when handling Apexelsin. Wear gloves, goggles and
protective clothing. If Apexelsin dispersion comes into contact with the skin, wash the skin
immediately and thoroughly with water and soap. If Apexelsin comes into contact with mucous
membranes, they should be rinsed well with plenty of water. Apexelsin must be prepared and
administered only by personnel adequately trained in the handling of cytotoxic agents. Apexelsin
should not be handled by pregnant women.
Due to the possibility of extravasation, it is recommended to carefully monitor the infusion site for
any leakage during administration. Limiting the infusion of Apexelsin to 30 minutes, as indicated,
reduces the likelihood of infusion-related reactions.

Reconstitution and administration of the medicinal product
Apexelsin must be administered under the supervision of a qualified oncologist in specialized
departments for the administration of cytotoxic agents.
Apexelsin is supplied as a sterile lyophilized powder and must be reconstituted before use.
After reconstitution, each mL of dispersion contains 5 mg of paclitaxel bound to albumin
formulated in nanoparticles. The reconstituted Apexelsin dispersion is administered intravenously
using an infusion set equipped with a 15-micron filter.
Using a sterile syringe, slowly inject 20 mL of sodium chloride 9 mg/mL (0.9%) solution
for infusion into the 100 mg vial of Apexelsin for at least 1 minute.
The solution must be directed towards the inner wall of the vial. The solution must not be
injected directly onto the powder as this will create foam.
Once the addition of solution is complete, allow to stand for at least 5 minutes to allow the powder
to be completely permeated. Then, rotate and/or invert the vial gently and slowly for at least
2 minutes, until all the powder is completely redispersed. Avoid foam formation. If foam or
clumps form, allow 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
precipitate. Deposits may occur in the reconstituted dispersion. If precipitates or deposits are
visible, gently invert the vial again to ensure complete redispersal before use.
Examine the dispersion in the vial to check for precipitate. Do not administer the reconstituted
dispersion if precipitates are observed in the vial.
The exact total volume of the 5 mg/mL dispersion required for the patient must be calculated and
the appropriate amount of reconstituted Apexelsin must be injected into a sterile, empty PVC or
other material intravenous infusion bag.
The use of medical devices containing silicone lubricant oil (syringes and IV bags) for
reconstituting and administering Apexelsin may cause the formation of protein filaments.
Administer Apexelsin using an infusion set equipped with a 15-micron filter to prevent
administration of these filaments. The use of a 15-micron filter removes the filaments and does not
alter the physical or chemical properties of the reconstituted product.
The use of filters with a pore size less than 15 microns may cause the filter to become blocked.
Special containers or administration sets not containing DEHP are not required for the preparation
and administration of Apexelsin infusions.
After administration, it is recommended to flush the infusion line with sodium chloride 9 mg/mL
(0.9%) injectable solution to ensure complete dose administration.
Unused medicinal product and waste derived from such medicinal product must be disposed of in
accordance with local regulations.

Stability
Closed vials of Apexelsin are stable until the date indicated on the packaging, provided that
the vial is stored in the outer packaging to protect the medicinal product from light. Freezing and
refrigeration do not have any adverse effects on the stability of the medicinal product. This
medicinal product does not require any special storage temperature.

Stability of the reconstituted dispersion in the vial
The product has been shown to be chemically and physically stable for 24 hours at 2 °C – 8 °C in
the original packaging, protected from light.

Stability of the reconstituted dispersion in the infusion bag
The product has been shown to be chemically and physically stable 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
infusion bags excludes the risk of microbial contamination, the product must be
used immediately after reconstitution and filling of the infusion bags.
If the product is not used immediately, the storage times and conditions during use are the
responsibility of the user.
The total storage time of the medicinal product reconstituted in the vial and in the infusion bag,
if refrigerated and protected from light, is 24 hours. This may be followed by storage for 4 hours
in the infusion bag at temperatures below 25 °C.