Celdoxome pegylated liposomal: detailed information

Patient Information Leaflet: Information for the User

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

doxorubicin hydrochloride
Please read this leaflet carefully before using this medicine because 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 give it to other people, even if their symptoms are the same as yours, as it may be harmful.
If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

What Celdoxome pegylated liposomal is and what it is used for
What you need to know before using Celdoxome pegylated liposomal
How to use Celdoxome pegylated liposomal
Possible side effects
How to store Celdoxome pegylated liposomal
Contents of the pack and other information

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

Celdoxome pegylated liposomal is an antitumour agent.
Celdoxome pegylated liposomal is used to treat breast cancer in patients at
risk of heart problems. Celdoxome pegylated liposomal is also used to treat
ovarian cancer. It is used to kill tumour cells, reduce tumour size,
delay tumour growth, and prolong patient survival.
Celdoxome pegylated liposomal is also used in combination with another medicine,
bortezomib, for the treatment of multiple myeloma, a type of blood cancer, in patients who have
received at least one prior therapy.
Celdoxome pegylated liposomal is also used to improve Kaposi's sarcoma, including flattening, fading, and even reduction in tumour size.
Other symptoms of Kaposi's sarcoma, such as swelling around the tumour, may also
improve or disappear.
Celdoxome pegylated liposomal contains a substance capable of interacting with cells in order to selectively kill tumour cells. The doxorubicin hydrochloride contained in Celdoxome pegylated liposomal is enclosed within tiny spheres called pegylated liposomes, which help deliver the medicine from the bloodstream to tumour tissue rather than to healthy tissue.

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

Do not use Celdoxome pegylated 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 or liver problems
if you have diabetes, because Celdoxome pegylated liposomal contains sugar, which may require adjustment of your diabetes treatment
if you have Kaposi's sarcoma and your spleen has been removed
if you notice mouth ulcers, color changes, or any other problems in your mouth.

Interstitial lung disease, including fatal cases, has been observed in patients treated with pegylated liposomal doxorubicin. Symptoms of interstitial lung disease include cough and shortness of breath, sometimes accompanied by fever, not caused by physical activity. Contact your doctor immediately if you experience symptoms that could indicate interstitial lung disease.

Children and adolescents
Celdoxome pegylated liposomal must not be used in children and adolescents, as it is not known how the medicine affects them.

Other medicines and Celdoxome pegylated liposomal
Inform your doctor or pharmacist:

if you are taking, have recently taken, or might take any other medicines
about all cancer treatments you are currently receiving or have previously received, as particular caution is required with therapies that reduce the number of white blood cells, since this medicine may further decrease white blood cell counts. If you are unsure about the treatments you have received or illnesses you have had, discuss this with your doctor.

Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Since the active substance in Celdoxome pegylated liposomal, doxorubicin hydrochloride, may cause birth defects, it is important to inform 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.
Because doxorubicin hydrochloride may harm infants, women must stop breastfeeding before starting treatment with Celdoxome pegylated liposomal. Experts recommend that women with HIV infection should not breastfeed under any circumstances to prevent transmission of HIV.

Driving and using machines
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 and is therefore essentially ‘sodium-free’.

3. How to use Celdoxome pegylated liposomal

Celdoxome pegylated liposomal is a unique formulation. It must not be used interchangeably with other formulations of doxorubicin hydrochloride.
How much Celdoxome pegylated liposomal is administered
For the treatment of breast cancer or ovarian cancer, you will be given Celdoxome pegylated liposomal at a dose of 50 mg per square metre of your body surface area (based on height and body weight). This dose will be repeated every 4 weeks until the disease progresses or you are no longer able to tolerate the treatment.
For the treatment of multiple myeloma, if you have already received at least one prior therapy, Celdoxome pegylated liposomal will be administered at a dose of 30 mg per square metre of your body surface area (based on height and body weight) via a 1-hour intravenous infusion given immediately after bortezomib infusion on day 4 of the 3-week bortezomib treatment regimen. The dose will be repeated as long as you continue to 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 square metre of your body surface area (based on height and body weight). The dose will be repeated every 2 or 3 weeks for 2 or 3 months; thereafter, it will be repeated as needed to maintain improvement in your condition.
How Celdoxome pegylated liposomal is administered
Celdoxome pegylated liposomal will be administered by your doctor via intravenous infusion (drip) 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 adverse effects such as mouth ulcers or reduced numbers of white blood cells and platelets in the blood. Treatment will include administration of antibiotics, platelet transfusions, use of factors that stimulate white blood cell production, and symptomatic treatment of mouth ulcers.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

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

During infusion
The following reactions may occur during infusion of Celdoxome pegylated liposomal:

severe allergic reaction which may include swelling of the face, lips, mouth, tongue or throat; difficulty swallowing or breathing; itchy rash (urticaria)
inflammation and narrowing of the lung airways, resulting in cough, wheezing and shortness of breath (asthma)
hot flushes, sweating, chills or fever
chest pain or discomfort
back pain
high or low blood pressure
rapid heartbeat
seizures (convulsions)

Leakage of the infused liquid from the vein into surrounding tissues may occur. If the infusion causes discomfort or pain while you are receiving 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:

fever, feeling of tiredness, or 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 may sometimes be severe. 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 decide to delay the start and/or reduce the dose of the next treatment (see below for strategies to prevent and treat hand-foot syndrome)
mouth sores, severe diarrhoea, vomiting or nausea (very common)
infections (common), including lung infections (pneumonia) or infections that may affect vision
shortness of breath (common)
severe stomach pain (common)
marked weakness (common)
severe allergic reaction which may include swelling of the face, lips, mouth, tongue or throat; difficulty swallowing or breathing; itchy rash (urticaria) (uncommon)
cardiac arrest (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 possibly swollen legs (uncommon)
blood clot that travels 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, particularly around the mouth, nose, eyes and genital organs (Stevens-Johnson syndrome) or over most of the body (toxic epidermal necrolysis) (rare).

Other side effects
The following side effects may occur between infusions:

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

decrease in the number of white blood cells, which may increase the risk of infections. In rare cases, low white blood cell count may lead to a serious infection. Anaemia (reduction in red blood cells) may cause tiredness, and 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
reduced appetite
constipation
skin rashes, including skin redness, allergic skin rashes, rashes with redness or bumps on the skin
hair loss
pain, including muscle pain, chest muscle pain, joint pain, pain in arms or legs
feeling of extreme tiredness

Common (may affect up to 1 in 10 people)

infections, including severe body-wide infection (sepsis), lung infections, infections from herpes zoster virus (shingles), a type of bacterial infection (Mycobacterium avium complex infection), urinary tract infections, fungal infections (including candidiasis and oral candidiasis), hair follicle infections, throat infection or irritation, infection or irritation of the nose, sinuses or throat (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, anxiety, depression, difficulty sleeping
nerve damage, which may cause tingling, numbness, pain or loss of sensitivity to pain, nerve pain, unusual skin sensations (such as tingling or a crawling sensation on the skin), reduced sensation and sensitivity, especially in the skin
altered sense of taste, headache, feeling extremely sleepy with low energy, dizziness
eye inflammation (conjunctivitis)
rapid heartbeat
high or low blood pressure, hot flushes
shortness of breath, which may be caused by physical activity, nosebleeds, cough
inflammation of the lining of the stomach and oesophagus, mouth ulcers (painful), indigestion, difficulty swallowing, mouth pain, 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 muscle pain
pain, including pain in muscles, bones or back
pain during urination
allergic reaction to the medicine infusion, flu-like illness, chills, inflammation of the lining of cavities and passages inside the body such as nose, mouth or trachea, feeling of weakness, general feeling of being unwell, swelling due to fluid accumulation in the body, swollen hands, ankles or feet
decrease in body weight.

When Celdoxome pegylated liposomal is used alone, some of these side 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 affecting more than one part of the body
seizures (convulsions), fainting
unpleasant or painful sensation, especially on touch, drowsiness
blurred vision, watery eyes
sensation of speed or irregularity of heartbeat (palpitations), heart muscle disease, heart damage
tissue damage (necrosis) at the injection site, inflammation of veins causing swelling and pain, dizziness when sitting or standing up
chest discomfort
flatulence, inflamed gums (gingivitis)
skin problems or rashes, including cracked or peeling skin, allergic skin rashes, painful ulcers or hives on the skin, skin depigmentation, changes in natural skin colour (pigmentation), small red or purple spots caused by bleeding under the skin, nail problems, acne
muscle weakness
chest pain
irritation or pain at the injection site
facial swelling, high body temperature
return of symptoms (such as inflammation, redness or pain) in an area previously treated with radiotherapy or previously damaged by a chemotherapy injection into a vein.

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

infection, occurring in people with a weakened immune system
low number of blood cells produced in the bone marrow
inflamed retina, which may cause changes in vision or blindness
abnormal heart rhythm, abnormal heart tracing on ECG (electrocardiogram) and possibly slow heartbeat, heart problem affecting heartbeat and rhythm, blue colour of the skin and mucous membranes due to low oxygen levels in the blood
dilation of blood vessels
sensation of tightness in the throat
swollen and painful tongue, painful ulcers on the lips
skin rash with fluid-filled blisters
vaginal infection, redness of the scrotum
problems with the linings of cavities and passages inside the body, such as nose, mouth or trachea
abnormal liver function tests, increased level of "creatinine" in the blood.

Not known (frequency cannot be estimated from the available data)

rapidly developing blood cancer affecting blood cells (acute myeloid leukaemia), bone marrow disease affecting blood cells (myelodysplastic syndrome), tumour 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 experience any side effect, including those not listed in this leaflet, talk to your doctor or nurse. You can also report side effects directly via the national reporting system referred to in Annex 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 environments
take cold baths during hot periods
avoid vigorous exercises that may cause trauma to the feet (e.g. running)
avoid exposing the skin to very hot water (e.g. hot tubs, saunas)
avoid tight-fitting or high-heeled shoes.

Pyridoxine (vitamin B6):

vitamin B6 can be purchased without a prescription
take 50–150 mg daily, 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 stated on the label and carton.

Unopened vial
Store in the refrigerator (2 °C - 8 °C). Do not freeze.

After dilution
Chemical and physical in-use stability has been demonstrated for 24 hours at temperatures between 2 °C and 8 °C.
From a microbiological standpoint, the product should be used immediately. If not used immediately, the storage times and conditions of the diluted solution prior to 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 any precipitate or other types of particles.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package Contents and Other Information

What Celdoxome pegylated liposomal contains

The active substance is doxorubicin hydrochloride. Each mL of Celdoxome pegylated liposomal contains 2 mg of doxorubicin hydrochloride in a pegylated liposomal formulation.
The other components are N-(carbonyl-methoxypolyethylene glycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine sodium salt (MPEG-DSPE), hydrogenated soy phosphatidylcholine (HSPC), cholest-5-en-3β-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 contents of the container
The concentrate for dispersion for infusion is sterile, translucent, and red, with a pH of 6.5. Celdoxome
pegylated liposomal is available in 10 mL (20 mg) or 25 mL (50 mg) glass vials.
Each pack contains 1 vial or 10 vials.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Baxter Holding B.V.
Kobaltweg 49,
3542 CE Utrecht,
The Netherlands

Manufacturer
Baxter Oncology GmbH
Kantstrasse 2
33790 Halle/Westfalen
Germany

Other sources of information
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 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 must be handled with care. Gloves must be worn. If Celdoxome pegylated liposomal comes into contact with skin or mucous membranes, immediately wash thoroughly with soap and water. Celdoxome pegylated liposomal must be handled and disposed of according to the precautions recommended for other cytotoxic anticancer drugs.
Determine the required dose of Celdoxome pegylated liposomal (based on the recommended dose and the patient's body surface area). Withdraw the correct volume of Celdoxome pegylated liposomal using a sterile syringe. Aseptic techniques must be strictly observed, as Celdoxome pegylated liposomal contains neither preservatives nor bacteriostatic agents. Prior to 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; for doses ≥ 90 mg, dilute 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 occurs, subsequent infusions of Celdoxome pegylated liposomal may be given over 60 minutes.
In the clinical trial program for breast cancer, a modified infusion regimen was allowed for patients who experienced an infusion reaction: 5% of the total dose was administered slowly over the first 15 minutes. If tolerated without reaction, the infusion rate was doubled for the next 15 minutes. If tolerated, the infusion was completed over the following hour, resulting in a total infusion time of 90 minutes.
If the patient shows 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 side port of an intravenous infusion line containing 5% glucose solution (50 mg/mL).
The infusion may be administered through a peripheral vein. Do not use in-line filters.