CELDOXOME 2 mg /Ml Koncentrat Do Rozcieńczania Do Infuzji

Treść ulotki

1. Celdoxome pegylated liposomal 2 mg/mL concentrate for dispersion for infusion
   1. What is Celdoxome pegylated liposomal and what is it used for
   2. What you need to know before using Celdoxome pegylated liposomal
   3. How to use Celdoxome pegylated liposomal
   4. Possible side effects
   5. How to store Celdoxome pegylated liposomal
   6. Package contents and other information

Celdoxome pegylated liposomal 2 mg/mL concentrate for dispersion for infusion

doxorubicin hydrochloride

Read this leaflet carefully before you use 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 pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as you, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

• 1. What Celdoxome pegylated liposomal is and what it is used for
• 2. What you need to know before you use Celdoxome pegylated liposomal
• 3. How to use Celdoxome pegylated liposomal
• 4. Possible side effects
• 5. How to store Celdoxome pegylated liposomal
• 6. Contents of the pack and other information

1. What is Celdoxome pegylated liposomal and what is it used for

Celdoxome pegylated liposomal is an antitumoural agent.
Celdoxome pegylated liposomal is used for the treatment of breast cancer in patients at
risk of cardiac problems. Celdoxome pegylated liposomal is also used for the treatment of
ovarian cancer. It is used to kill cancer cells, reduce the size of the tumour,
delay tumour growth and prolong patient survival.
Celdoxome pegylated liposomal is also used in association with another medicine,
bortezomib, for the treatment of multiple myeloma, a blood cancer, in patients who have
received at least one previous therapy.
Celdoxome pegylated liposomal is also used to achieve an improvement of Kaposi's sarcoma,
including flattening, paling and even reducing the size of the tumour.
Other symptoms of Kaposi's sarcoma, for example swelling around the tumour, can
improve or disappear.
Celdoxome pegylated liposomal contains a substance capable of interacting with cells in such a way as to
selectively kill cancer cells. Doxorubicin hydrochloride contained in Celdoxome pegylated
liposomal is enclosed in very small spheres, called pegylated liposomes, which facilitate the transport
of the drug from the blood to the tumour tissue rather than to healthy tissue.

2. What you need to know before using Celdoxome pegylated liposomal

Do not use Celdoxomepegylated liposomal:

• if you are allergic to doxorubicin hydrochloride, peanuts or soy, or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor before receiving Celdoxome pegylated liposomal:

• if you are being treated for heart problems or liver problems
• if you suffer from diabetes, as Celdoxome pegylated liposomal contains sugar, which may require adjusting your diabetes treatment accordingly
• if you have Kaposi's sarcoma and your spleen has been removed
• if you notice ulcers, changes in colour or any discomfort in your mouth.

Cases of interstitial lung disease, sometimes fatal, have been observed in patients treated with pegylated liposomal doxorubicin. The symptoms of interstitial lung disease are cough and shortness of breath, sometimes accompanied by fever, not caused by physical activity. See a doctor immediately if you experience symptoms that may be signs of interstitial lung disease.

Children and adolescents
Celdoxome pegylated liposomal should not be used in children and adolescents because it is not known how the medicine may affect them.

Other medicines and Celdoxomepegylated liposomal
Tell your doctor or pharmacist

• if you are taking, have recently taken or might take any other medicines
• about all the cancer therapies you are undergoing or have undergone in the past, as particular attention is required for those treatments that reduce the number of white blood cells, given that this medicine can cause a further reduction in the number of white blood cells. If you are not sure about the treatments you have received or the diseases you have had, talk to your doctor.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, are planning a pregnancy or are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
Since the active ingredient of Celdoxome pegylated liposomal, doxorubicin hydrochloride, can cause birth defects, it is important that you tell your doctor if you think you may be pregnant. Avoid pregnancy if you or your partner are being treated with Celdoxome pegylated liposomal, and for six months after stopping treatment.
Since doxorubicin hydrochloride can be harmful to infants, women must stop breastfeeding before starting treatment with Celdoxome pegylated liposomal. Experts recommend that women with HIV infection should not breastfeed their babies under any circumstances to prevent transmission of HIV.

Driving and operating machinery
Do not drive or operate tools or machinery if you feel tired or drowsy following treatment with Celdoxome pegylated liposomal.

Celdoxome pegylated liposomal contains soybean oil and sodium
Celdoxome pegylated liposomal contains soybean oil. If you are allergic to peanuts or soy, do not use this medicine. See “Do not use Celdoxome pegylated liposomal”.
Celdoxome pegylated liposomal contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Celdoxome pegylated liposomal

Celdoxome pegylated liposomal is a unique formulation. It should not be used interchangeably with other doxorubicin hydrochloride formulations.

How much Celdoxome pegylated liposomal will be administered
For the treatment of breast cancer or ovarian cancer, Celdoxome pegylated liposomal will be administered to you at a dose of 50 mg per each square meter of your body surface area (based on your height and body weight). The dose will be repeated every 4 weeks until the disease progresses and you are able to tolerate the treatment.
For the treatment of multiple myeloma, if you have already received at least one previous therapy, Celdoxome pegylated liposomal will be administered to you at a dose of 30 mg per square meter of your body surface area (based on your height and body weight) through an intravenous infusion of 1 hour administered immediately after the bortezomib infusion on day 4 of the 3-week bortezomib treatment regimen. The dose will be repeated until you respond satisfactorily and tolerate the treatment.
For the treatment of Kaposi's sarcoma, Celdoxome pegylated liposomal will be administered at a dose of 20 mg per each square meter of your body surface area (based on your height and body weight). The dose will be repeated every 2 or 3 weeks for 2 or 3 months; subsequently it will be repeated when necessary to maintain an improvement in your condition.

How Celdoxome pegylated liposomal is administered
Celdoxome pegylated liposomal will be administered to you by your doctor via intravenous infusion into a vein. Depending on the dose and indication, the infusion will last from 30 minutes to more than one hour (i.e. 90 minutes).

If you use more Celdoxome pegylated liposomal than you should
Acute overdose worsens undesirable effects such as mouth sores or a decrease in the number of white blood cells and platelets in the blood. Treatment will consist of the administration of antibiotics, platelet transfusions, the use of factors that stimulate the production of white blood cells, and symptomatic treatment of mouth sores.
If you have any doubts about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

During the infusion
During the infusion of Celdoxome pegylated liposomal, the following reactions may occur:

• severe allergic reaction that may include swelling of the face, lips, mouth, tongue or throat; difficulty swallowing or breathing; itchy skin rash (hives)
• inflammation and narrowing of the airways in the lungs, resulting in coughing, wheezing and shortness of breath (asthma)
• hot flashes, sweating, chills or fever
• chest pain or discomfort
• back pain
• high or low blood pressure
• fast heartbeat
• convulsions (seizures)

Leakage of the injected liquid from the veins into the tissues under the skin may occur. If the infusion should
cause you discomfort or pain while you are taking a dose of Celdoxome pegylated
liposomal, inform your doctor immediately.

Serious side effects
Contact your doctor immediately if you notice any of the following serious side effects:

• develops fever, feels tired or has signs of bruising or bleeding (very common)
• redness, swelling, peeling or tenderness, mainly on the hands or feet (hand-foot syndrome). These effects have been observed very commonly and, sometimes, are serious. In severe cases, these effects may interfere with certain daily activities and may last up to 4 weeks or longer before resolving completely. Your doctor may want to delay the start and/or reduce the dose of the next treatment (see below Strategies to prevent and treat hand-foot syndrome)
• sores in the mouth, severe diarrhea or vomiting or nausea (very common)
• infections (common), including lung infections (pneumonia) or infections that can affect vision
• shortness of breath (common)
• severe stomach pain (common)
• pronounced weakness (common)
• severe allergic reaction that may include swelling of the face, lips, mouth, tongue or throat; difficulty swallowing or breathing; itchy skin rash (hives) (uncommon)
• cardiac arrest (the heart stops beating), heart failure in which the heart does not pump enough blood to the rest of the body, causing shortness of breath and possible swollen legs (uncommon)
• blood clot that moves to the lungs causing chest pain and shortness of breath (uncommon)
• swelling, warmth or tenderness in the soft tissues of the legs, sometimes with pain that worsens when standing or walking (rare)
• severe or potentially life-threatening skin rash with blisters and peeling skin, especially around the mouth, nose, eyes and genitals (Stevens-Johnson syndrome) or on most of the body (toxic epidermal necrolysis) (rare).

Other side effects
The following effects may occur during the period between infusions:

Very common(may affect more than 1 in 10 people)

• reduction in the number of white blood cells, which may increase the chances of getting infections. In rare cases, having a low number of white blood cells can cause a serious infection. Anemia (reduction of red blood cells) can cause fatigue, and a reduction in platelets in the blood may increase the risk of bleeding. Due to potential changes in blood cells, you will have regular blood tests
• decreased appetite
• constipation
• skin rashes, including skin redness, allergic skin rash, rashes with redness or bumps on the skin
• hair loss
• pain, including muscle pain and chest muscle pain, joint pain, arm or leg pain
• feeling extremely tired

Common(may affect up to 1 in 10 people)

• infections, including serious infection throughout the body (sepsis), lung infections, viral herpes zoster infections (shingles), a type of bacterial infection (Mycobacterium aviumcomplex infection), urinary tract infections, fungal infections (including candidiasis and oral thrush), hair root infection, infection or irritation of the nose, throat or sinuses (common cold)
• low number of a type of white blood cells (neutrophils) with fever
• severe weight loss and muscle wasting, insufficient amount of water in the body (dehydration), low levels of potassium, sodium or calcium in the blood
• feeling confused, anxious, depressed, difficulty sleeping
• nerve damage, which can cause tingling, numbness, pain or loss of pain sensation, nerve pain, unusual skin sensation (such as a tingling or

something crawling on the skin), reduced sensations and sensitivity, especially at the
skin level

• altered sense of taste, headache, feeling extremely sleepy with low energy, feeling dizzy
• eye inflammation (conjunctivitis)
• fast heartbeat
• high or low blood pressure, hot flashes
• shortness of breath, which may be caused by physical activity, nosebleeds, coughing
• inflammation of the lining of the stomach and esophagus, ulcers (painful) in the mouth, indigestion, difficulty swallowing, pain in the mouth, dry mouth
• skin problems, including scaly or dry skin, skin redness, blisters or ulcers (painful) on the skin, itching, dark spots on the skin
• excessive sweating
• muscle spasms or pain
• pain, including muscle, bone or back pain
• pain during urination
• allergic reaction to the infusion of the medicine, flu-like illness, chills, inflammation of the lining of cavities and passages inside the body such as nose, mouth or trachea, feeling weak, general feeling of being unwell, swelling caused by fluid accumulation in the body, swollen hands, ankles or feet
• weight loss.

When Celdoxome pegylated liposomal is used alone, some of these effects are less likely, and
some do not occur at all.

Uncommon(may affect up to 1 in 100 people)

• herpes simplex virus infections (cold sores or genital herpes), fungal infection
• low number of all types of blood cells, increased number of “platelets” (cells that help blood to clot)
• allergic reaction
• high level of potassium in the blood, low level of magnesium in the blood
• nerve damage, which affects more than one part of the body
• convulsions (seizures), fainting
• uncomfortable or painful sensation, especially to the touch, feeling sleepy
• blurred vision, watery eyes
• feeling of speed or irregularity of the heartbeat (palpitations), heart muscle disease, heart damage
• tissue damage (necrosis) where the injection was given, inflammation of the veins causing swelling and pain, feeling dizzy when sitting or standing up
• chest discomfort
• flatulence, inflamed gums (gingivitis)
• problems or rashes on the skin, including skin that cracks or peels, allergic skin rash, ulcers (painful) or hives on the skin, skin depigmentation, changes in the natural color (pigmentation) of the skin, small red or purple spots caused by bleeding under the skin, nail problems, acne
• muscle weakness
• chest pain
• irritation or pain where the injection was given
• swelling of the face, high body temperature
• return of symptoms (such as inflammation, redness or pain) in a part of the body previously treated with radiation therapy or previously damaged by a chemotherapy injection into a vein.

Rare(may affect up to 1 in 1,000 people)

• infection, which occurs in people with a weakened immune system
• low number of blood cells produced in the bone marrow
• inflamed retina, which can cause changes in vision or blindness
• abnormal heart rhythm, abnormal heart tracing on an ECG (electrocardiogram) and with possible slow heartbeat, heart problem that affects the heartbeat and heart rhythm, blue color of the skin and mucous membranes caused by low oxygen levels in the blood
• dilation of blood vessels
• feeling of constriction in the throat
• swollen and painful tongue, ulcers (painful) on the lips
• skin rash with blisters filled with liquid
• vaginal infection, redness of the scrotum
• problems with the linings of cavities and passages inside the body, such as nose, mouth or trachea
• abnormal results in liver tests, increased level of “creatinine” in the blood.

Not known(frequency cannot be estimated from available data)

• blood cancer that develops rapidly and affects blood cells (acute myeloid leukemia), bone marrow disease that affects blood cells (myelodysplastic syndrome), tumor of the mouth or lips.
• cough and shortness of breath, sometimes accompanied by fever, not caused by physical activity (interstitial lung disease)

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor or nurse. You can also report side effects directly through the national reporting system listed in
Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.
Strategies to prevent and treat hand-foot syndrome include:

• when possible, immerse hands and/or feet in a basin of cold water (e.g. while watching television, reading or listening to the radio)
• keep hands and feet uncovered (no gloves, socks etc.)
• stay in cool places
• take cold baths during warm periods
• avoid vigorous exercise that can cause trauma to the feet (e.g. running)
• avoid exposure of the skin to very hot water (e.g. hot tub, sauna)
• avoid tight or high-heeled shoes.

Pyridoxine (vitamin B6):

• vitamin B6 can be purchased without a prescription
• take 50-150 mg per day starting at the first signs of redness or tingling.

5. How to store Celdoxome pegylated liposomal

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 label and the packaging.
Closed vial
Store in a refrigerator (2 °C - 8 °C). Do not freeze.
After dilution
The chemical and physical stability during use has been demonstrated for 24 hours at temperatures between 2 °C
and 8 °C.
From a microbiological point of view, the product must be used immediately. If not
used immediately, the storage times and conditions of the diluted solution before its
use are the responsibility of the user and must not exceed 24 hours when stored at
temperatures between 2 °C and 8 °C. Partially used vials must be discarded.
Do not use this medicine if you notice precipitate or other types of particles.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Celdoxome containspegylated liposomal

• The active substance is doxorubicin hydrochloride. Each mL of Celdoxome pegylated liposomal contains 2 mg of doxorubicin hydrochloride in a formulation of pegylated liposomes.
• The other components are N-(carbonyl-methoxypolyethylene glycol-2000)-1,2-distearoyl- sn-glycero-3-phosphoethanolamine sodium salt (MPEG-DSPE), hydrogenated phosphatidylcholine (from soy) (HSPC), cholest-5-en-3 β -ol, ammonium sulfate, sucrose, histidine, water for injections, hydrochloric acid (for pH adjustment) and sodium hydroxide (for pH adjustment). See section 2 “Celdoxome pegylated liposomal contains soy oil and sodium”.

Description of the appearance of Celdoxome pegylated liposomal and package contents
The concentrate for dispersion for infusion is sterile, translucent and red, with a pH of 6.5. Celdoxome
pegylated liposomal is available in glass vials of 10 mL (20 mg) or 25 mL (50 mg).
Each pack contains 1 vial or 10 vials.
Not all pack sizes may be marketed.

Marketing authorisation holder
Baxter Holding B.V.
Kobaltweg 49,
3542 CE Utrecht,
Netherlands

Manufacturer
Baxter Oncology GmbH
Kantstrasse 2
33790 Halle/Westfalen
Germany

Other sources of information
More detailed information on this medicine is available on the website of the European
Medicines Agency, https://www.ema.europa.eu .
This leaflet is available in all the languages of the European Union/European Economic Area on the
website of the European Medicines Agency.
------------------------------------------------------------------------------------------------------------------------
The following information is intended exclusively for physicians and healthcare professionals
(see section 3):
Celdoxome pegylated liposomal should be handled with caution. The use of gloves is necessary. If
Celdoxome pegylated liposomal comes into contact with skin or mucous membranes, wash immediately and
thoroughly with water and soap. Celdoxome pegylated liposomal should be handled and disposed of in
accordance with the precautions indicated for other antineoplastic drugs.
Determine the dose of Celdoxome pegylated liposomal to be administered (depending on the recommended
dose and the patient's body surface area). Withdraw the correct volume of Celdoxome
pegylated liposomal using a sterile syringe. Strict aseptic conditions must be maintained, as
Celdoxome pegylated liposomal does not contain preservatives or bacteriostatic agents. Before
administration, the correct dose of Celdoxome pegylated liposomal must be diluted in
5% glucose solution (50 mg/mL) for intravenous infusion. For doses < 90 mg dilute
Celdoxome pegylated liposomal in 250 mL and for doses ≥ 90 mg dilute Celdoxome pegylated liposomal
in 500 mL.
To reduce the risk of infusion reactions, the initial dose should be administered at a
rate not exceeding 1 mg/min. If no infusion reaction is observed, subsequent
infusions of Celdoxome pegylated liposomal may be administered over 60 minutes.
In clinical studies on breast cancer, a modification of the infusion was permitted in patients who had a reaction following administration: 5% of the total dose was administered slowly during the first 15 minutes. If tolerated without
reactions, the infusion rate was doubled for the next 15 minutes. If tolerated, the infusion
was completed over the following hour for a total injection time of 90 minutes.
If the patient exhibits early symptoms or signs of an infusion reaction, immediately stop the
infusion, administer appropriate premedication (antihistamines and/or
short-acting corticosteroids) and resume the infusion at a slower rate.
The use of diluents other than 5% glucose solution (50 mg/mL) for intravenous infusion or the
presence of any bacteriostatic agent, such as benzyl alcohol, may cause
precipitation of Celdoxome pegylated liposomal.
It is recommended to connect the infusion line containing Celdoxome pegylated liposomal
to the lateral port of an intravenous infusion of 5% glucose solution (50 mg/mL).
The infusion can be administered through a peripheral vein. Do not use with in-line filters.