Product Information for the User

Caelyx pegylated liposomal 2 mg/ml concentrate for infusion solutiondoxorubicin hydrochloride

Read this product information carefully before starting to use the medicine, as it contains important information for you.

• Keep this product information, as you may need to read it again.

• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed only for you and should not be given to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this product information. See section 4.

1. Possible side effects
2. Storage of Caelyx pegylated liposomal

1. Contents of the package and additional information

Caelyx pegylated liposomal is an antitumoral agent.

Caelyx pegylated liposomal is used to treat breast cancer in patients at risk of cardiac problems. Caelyx pegylated liposomal is also used to treat ovarian cancer. It is used to kill cancer cells, reduce tumor size, slow tumor growth, and increase survival.

Caelyx pegylated liposomal is also used in combination with another medication, bortezomib, for the treatment of multiple myeloma (a blood cancer) in patients who have received at least one previous treatment.

Caelyx pegylated liposomal is also used to produce an improvement in Kaposi's sarcoma, including flattening, thinning, and even reduction of cancer. It may also improve and even eliminate other symptoms of Kaposi's sarcoma, such as swelling around the tumor.

Caelyx pegylated liposomal contains a medication capable of interacting with cells, thereby selectively killing those affected by cancer. The doxorubicin hydrochloride in Caelyx pegylated liposomal is enclosed in small spheres called pegylated liposomes that facilitate the release of the medication from the bloodstream into the cancerous tissue before normal and healthy tissue.

No use Caelyx pegylated liposomal

• If you are allergic to doxorubicin hydrochloride, peanuts, or soy, or to any of the components of this medication (listed in section 6).

Warnings and precautions

Inform your doctor if you experience the following:

• If you are receiving treatment for a heart or liver disease;

• If you are diabetic, as Caelyx pegylated liposomal contains sugar and your diabetes treatment may need to be adjusted;
• If you have Kaposi's sarcoma and have had your spleen removed;

• If you notice ulcers, discoloration, or any discomfort in your mouth.

Children and adolescents

Caelyx pegylated liposomal should not be used in children and adolescents, as its effects on them are unknown.

Use of Caelyx pegylated liposomal with other medicationsInform your doctor or pharmacist

• If you are using or have recently used any other medication, including those purchased without a prescription;
• About other cancer treatments you are receiving or have received, as you need to be careful with treatments that reduce the number of white blood cells, as they may cause a further reduction in white blood cell count. If you are unsure about the treatments you have received or the diseases you have had, discuss it with your doctor.

Pregnancy and breastfeeding

Consult your doctor or pharmacist before using any medication.

Since the active ingredient doxorubicin hydrochloride in Caelyx pegylated liposomal may cause birth defects, it is essential to contact your doctor if you believe you are pregnant. You should avoid becoming pregnant while you or your partner are receiving treatment with Caelyx pegylated liposomal and for six months after stopping treatment with Caelyx pegylated liposomal.

Since doxorubicin hydrochloride may be harmful to infants, women should stop breastfeeding before starting treatment with Caelyx pegylated liposomal. Health experts recommend that HIV-infected women should not breastfeed their children under any circumstances to prevent HIV transmission.

Driving and operating machinery

Do not drive or operate tools or machines if you feel tired or drowsy due to treatment with Caelyx pegylated liposomal.

Caelyx pegylated liposomal contains soy oil and sodium

Caelyx pegylated liposomal contains soy oil. Do not use this medication if you are allergic to peanuts or soy.

Caelyx pegylated liposomal contains less than 1 mmol of sodium (23 mg) per dose; this is essentially "sodium-free."

Caelyx pegylated liposomal is a formulation with specific characteristics. Therefore, it should not be exchanged with other medications that also contain doxorubicin hydrochloride.

How much Caelyx pegylated liposomal is administered

If you are being treated for breast or ovarian cancer, you will be administered Caelyx pegylated liposomal at a dose of 50 mg per square meter of your body surface (obtained from your height and weight). The dose is repeated every 4 weeks as long as the disease does not progress and you can tolerate the treatment.

If you are being treated for multiple myeloma, and you have received at least one previous treatment, you will be administered Caelyx pegylated liposomal at a dose of 30 mg per square meter of your body surface (measured based on your height and weight) in a 1-hour intravenous infusion on day 4 of the 3-week regimen of bortezomib, and immediately after the bortezomib infusion. The dose will be repeated as long as you respond satisfactorily and tolerate the treatment.

If you are being treated for Kaposi's sarcoma, you will be administered Caelyx pegylated liposomal at a dose of 20 mg per square meter of your body surface (obtained from your height and weight). The dose will be repeated every 2 to 3 weeks for 2 to 3 months, and then as frequently as needed to maintain the improvement of your condition.

How Caelyx pegylated liposomal is administered

Your doctor will administer Caelyx pegylated liposomal through a drip (infusion) in a vein. Depending on the dose and indication, this may take from 30 minutes to over an hour (that is, 90 minutes).

If you use more Caelyx pegylated liposomal than you should

Acute overdosing worsens adverse effects such as mouth ulcers or decreases the number of white blood cells and platelets in the blood. Treatment will include the administration of antibiotics, platelet transfusions, use of factors that stimulate white blood cell production, and symptomatic treatment of mouth ulcers.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

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

During the infusion of Caelyx 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 rash (urticaria)
• inflammation and narrowing of the airways in the lungs, causing cough, wheezing, and difficulty breathing (asthma)
• redness, sweating, chills, or fever
• chest pain or discomfort

• back pain
• increase or decrease in blood pressure

• rapid heart rate
• seizure (convulsions)

A leak of the injection fluid from the veins into the tissue under the skin may occur. If the drip stings or hurts while you are receiving a dose of Caelyx pegylated liposomal, tell your doctor immediately.

Inform your doctor immediately if you observe any of the following severe side effects:

• you have a fever, feel tired, or have signs of bruising or bleeding (very common)

• redness, swelling, peeling, or pain, mainly on the hands or feet (hand-foot syndrome). These effects have been seen very frequently and, sometimes, are severe. In severe cases, these effects may interfere with certain daily activities and may last up to 4 weeks or more before resolving completely. Your doctor may delay the start and/or reduce the dose of the next treatment (see below, Strategies for preventing and treating hand-foot syndrome)

• mouth sores, severe diarrhea, or vomiting or nausea (very common)

• infections (common), including lung infections (pneumonia) or infections that may affect your vision
• difficulty breathing (common)

• severe stomach pain (common)

• severe weakness (common)
• severe allergic reaction that may include swelling of the face, lips, mouth, tongue, or throat; difficulty swallowing or breathing; itchy rash (urticaria) (rare)
• cardiac arrest (the heart stops beating); heart failure, in which the heart does not pump enough blood to the rest of the body, which may cause difficulty breathing and may cause swelling of the legs (rare)

• formation of blood clots in the blood that reaches the lungs, causing chest pain and difficulty breathing (rare)
• swelling, heat, or pain in some area of the leg, sometimes with pain that worsens when standing or walking (rare)
• severe or potentially life-threatening rash with blisters and peeling, especially around the mouth, nose, eyes, and genitals (Stevens-Johnson syndrome) or on most of the body (toxic epidermal necrolysis) (rare)

Other side effects

Between infusions, the following may occur:

Very common side effects(may affect more than 1 in 10 patients)

• decrease in the number of white blood cells, which may increase the risk of infection. In rare cases, the decrease in white blood cells may lead to a severe infection. Anemia (decrease in red blood cells) may cause fatigue, and a decrease in platelets in the blood may increase the risk of bleeding. Due to the possible changes in your blood cells, you will be subject to regular blood tests

• loss of appetite

• constipation
• skin rash, including redness of the skin, allergic skin rash, hives, or red and swollen skin
• hair loss
• pain, including muscle and chest pain, joint pain, arm or leg pain

• feeling extremely tired

Common side effects(may affect up to 1 in 10 patients)

• infections, including severe infection throughout the body (sepsis), lung infections, herpes virus infections (herpes), a type of bacterial infection (infection by mycobacterium avium complex), urinary tract infections, fungal infections (including impetigo and oral impetigo in the mouth), folliculitis, throat or mouth infection, nasal, nasal passages, or throat infection (cold)

• low number of a type of white blood cell (neutrophils), with fever
• severe weight loss and muscle weakness, dehydration, low levels of potassium, sodium, or calcium in the blood
• feeling confused, anxious, depressed, difficulty sleeping

• nervous system damage that may cause tingling, numbness, pain, or loss of sensation of pain, pain in nerves, strange sensation in the skin (such as tingling or prickling), decreased sensitivity, especially in the skin

• change in sense of taste, headache, feeling extremely sleepy with little energy, feeling dizzy;
• inflammation of the eyes (conjunctivitis)
• rapid heart rate
• increase or decrease in blood pressure, red face

• difficulty breathing that may occur after physical activity, nasal bleeding, cough
• inflammation of the stomach lining or esophagus, ulcers (sores) in the mouth, indigestion, difficulty swallowing, pain in the mouth, dry mouth
• skin problems, including dry or scaly skin, redness of the skin, blisters or ulcers (sores) in the skin, itching, dark spots on the skin
• excessive sweating

• muscle spasms or muscle pain

• pain affecting muscles, bones, or back
• pain while urinating

• allergic reaction to the infusion of the medicine, illness similar to the flu, chills, inflammation of the mucous membranes of different cavities and channels of the body, such as the nose, mouth, or trachea, feeling weak, feeling generally unwell, swelling caused by fluid retention, feeling swelling in the hands, ankles, or feet

• weight loss

When Caelyx pegylated liposomal is used as the only medicine, it is less likely that some of these side effects will occur, and some of them have never occurred.

Uncommon side effects(may affect up to 1 in 100 patients)

• herpes simplex virus infections (herpes labial or herpes genital), fungal infections
• low number of all types of blood cells, increase in the 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

• nervous system damage that affects more than one area of the body
• seizure (convulsions), fainting

• unpleasant or painful sensation, especially to the touch, drowsiness
• blurred vision, watery eyes
• feeling of rapid or irregular heartbeat (palpitations), heart muscle disease, cardiac damage
• damage to tissues (necrosis) at the injection site, inflammation of the veins that causes swelling and pain, feeling dizzy when sitting or standing
• chest pain

• flatulence, inflamed gums (gingivitis)
• skin problems or rashes, including dry or scaly skin, allergic rash, ulcers (sores) or blisters in the skin, skin discoloration, change in natural skin color (pigmentation), small red or purple spots caused by bleeding under the skin, nail problems, acne
• muscle weakness
• pain in the breasts
• irritation or pain at the injection site

• swollen face, elevated body temperature
• symptoms (such as inflammation, redness, or pain) in areas of the body that have been previously treated with radiation or that have been damaged as a result of an intravenous chemotherapy injection

Rare side effects(may affect up to 1 in 1,000 patients)

• infection that occurs in people with a weakened immune system

• low number of blood cells generated in the bone marrow
• inflammation of the retina, which may cause changes in vision or blindness
• abnormal heart rhythm, abnormal ECG tracing that may occur with low heart rate, heart problem that affects heart rate and rhythm, blue discoloration of the skin and mucous membranes caused by low oxygen levels in the blood
• dilation of blood vessels
• feeling of constriction in the throat

• sores and swelling on the tongue, ulcers (sores) on the lips
• skin rash with blisters filled with fluid

• vaginal infection, redness of the scrotum
• problems with the mucous membranes of different cavities and channels of the body, such as the nose, mouth, or trachea
• abnormal results in blood tests of the liver, increased level of ‘creatinine’ in the blood

Side effects of unknown 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), cancer of the mouth or lips

Reporting 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.

The strategies for preventing and treating hand-foot syndrome include:

• soaking your hands and/or feet in cold water when possible (for example, while watching TV, reading, or listening to the radio);
• keeping your hands and feet uncovered (without gloves, socks, etc.);
• staying in cool places;

• taking cold water baths when it is hot;
• avoiding strenuous exercise that may cause trauma to the feet (for example, jogging);

• avoiding exposure of the skin to very hot water (for example, hot tubs, saunas);
• avoiding tight-fitting shoes or high-heeled shoes.

Piridoxina (Vitamin B6):

• vitamin B6 is available without a prescription;

• take 50-150 mg per day starting when the first signs of redness or tingling appear.

Keep this medication out of the sight and reach of children.

Store in refrigerator (between 2°C and 8°C). Do not freeze.

After dilution:

The chemical and physical stability was confirmed during its use for a period of 24 hours between 2°C and 8°C.

From a microbiological point of view, the product should be used immediately. If it is not used immediately, the storage periods during its use and the conditions before using it are the responsibility of the user and should not be greater than 24 hours between 2°C and 8°C. Partially used vials should be discarded.

Do not use this medication after the expiration date that appears on the label and the box.

Do not use this medication if you observe evidence of precipitation or presence of particles.

Medications should not be thrown down the drain or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of Caelyx pegylated liposomal

• The active ingredient is doxorubicin hydrochloride. 1 ml of Caelyx pegylated liposomal contains 2 mg of doxorubicin hydrochloride in a pegylated liposomal formulation.

-The other components are?-(2-[1,2-distearoyl-sn-glycero(3)phosphooxy]ethylcarbamoyl)-?-methoxy(poly(oxirane)-40 sodium salt (MPEG-DSPE), soybean phosphatidylcholine, fully hydrogenated (HSPC), cholesterol, ammonium sulfate, sucrose, histidine, water for injection, hydrochloric acid (pH adjustment) and sodium hydroxide (pH adjustment). See section 2.

Caelyx pegylated liposomal concentrated for infusion solution: vials providing 10 ml (20 mg) or 25 ml (50 mg).

Appearance of the product and contents of the container

Caelyx pegylated liposomal is sterile, transparent and red in color. Caelyx pegylated liposomal is available in individual vials or in vials of ten, made of glass. Only some container sizes may be marketed.

Marketing Authorization Holder

Janssen-Cilag International NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

Responsible for manufacturing

Janssen Pharmaceutica NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

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

Belgium/Belgique/BelgienLithuania

Janssen-Cilag NVUAB "JOHNSON & JOHNSON"

Tel/Tél: +32 14 64 94 11Tel: +370 5 278 68 88

[email protected][email protected]

?Luxembourg/Luxemburg

„??????? & ??????? ????????” ????Janssen-Cilag NV

???.: +359 2 489 94 00Tél/Tel: +32 14 64 94 11

[email protected][email protected]

Czech RepublicHungary

Janssen-Cilag s.r.o.Janssen-Cilag Kft.

Tel: +420 227 012 227Tel.: +36 1 884 2858

[email protected]

DenmarkMalta

Janssen-Cilag A/SAM MANGION LTD.

Tlf: +45 4594 8282Tel: +356 2397 6000

[email protected]

GermanyNetherlands

Janssen-Cilag GmbHJanssen-Cilag B.V.

Tel: +49 2137 955 955Tel: +31 76 711 1111

[email protected][email protected]

EstoniaNorway

UAB "JOHNSON & JOHNSON"Eesti filiaalJanssen-Cilag AS

Tel: +372 617 7410Tlf: +47 24 12 65 00

[email protected][email protected]

GreeceAustria

Janssen-Cilag Φαρμακευτικ? Α.Ε.Β.Ε.Janssen-Cilag Pharma GmbH

Tηλ: +30 210 80 90 000Tel: +43 1 610 300

SpainPoland

Janssen-Cilag, S.A.Janssen-Cilag Polska Sp. z o.o.

Tel: +34 91 722 81 00Tel.: +48 22 237 60 00

[email protected]

FrancePortugal

Janssen-CilagJanssen-Cilag Farmacêutica, Lda.

Tél: 0 800 25 50 75 / +33 1 55 00 40 03Tel: +351 214 368 600

[email protected]

CroatiaRomania

Johnson & Johnson S.E. d.o.o.Johnson & Johnson România SRL

Tel: +385 1 6610 700Tel: +40 21 207 1800

[email protected]

IrelandSlovenia

Janssen Sciences Ireland UCJohnson & Johnson d.o.o.

Tel: +353 1 800 709 122Tel: +386 1 401 18 00

[email protected]

IcelandSlovak Republic

Janssen-Cilag ABJohnson & Johnson, s.r.o.

c/o Vistor hf.Tel: +421 232 408 400

Sími: +354 535 7000

[email protected]

ItalyFinland

Janssen-Cilag SpAJanssen-Cilag Oy

Tel: 800.688.777 /+39 02 2510 1Puh/Tel: +358 207 531 300

[email protected][email protected]

CyprusSweden

Βαρν?βας Χατζηπαναγ?ς ΛτδJanssen-Cilag AB

Τηλ: +357 22 207 700Tfn: +46 8 626 50 00

[email protected]

LithuaniaUnited Kingdom

UAB "JOHNSON & JOHNSON"filiale LatvijaJanssen-Cilag Ltd.

Tel: +371 678 93561Tel: +44 1 494 567 444

[email protected].com

Last update of this leaflet:

The detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA)http://www.emea.europa.eu/.

This information is intended solely for healthcare professionals (see section 3):

Caution should be exercised when handling a Caelyx pegylated liposomal dispersion. Gloves should be used. In case Caelyx pegylated liposomal comes into contact with skin or mucous membranes, the affected area should be washed immediately with water and soap. Caelyx pegylated liposomal should be handled and disposed of as other anticancer drugs.

Determine the dose of Caelyx pegylated liposomal to be administered (based on the recommended dose and the patient's body surface area). Take the appropriate volume of Caelyx pegylated liposomal in a sterile syringe. Strict aseptic procedures should be followed since Caelyx pegylated liposomal does not contain any preservative or bacteriostatic agent. The appropriate dose of Caelyx pegylated liposomal should be diluted in a glucose 5% solution for infusion (50 mg/ml) before administration. For doses

• 90 mg, dilute Caelyx pegylated liposomal in 500 ml.

To minimize the risk of infusion reactions, the initial dose should be administered at a rate not exceeding 1 mg/minute. If no infusion reaction is observed, subsequent Caelyx pegylated liposomal infusions can be administered over a period of 60 minutes.

In the clinical trial program in breast cancer, modification of the infusion was allowed in patients who experienced an infusion reaction as follows: 5% of the total dose was infused slowly over the first 15 minutes. If tolerated without reaction, the infusion rate was doubled over the next 15 minutes. If tolerated, the infusion was completed over the next hour for a total infusion time of 90 minutes.

If the patient experiences early symptoms or signs of an infusion reaction, discontinue the infusion immediately, administer appropriate symptomatic treatment (antihistamine and/or short-acting corticosteroid) and resume at a slower rate.

The use of any diluent other than glucose 5% solution for infusion (50 mg/ml), or the presence of any bacteriostatic agent, such as benzyl alcohol, may cause Caelyx pegylated liposomal to precipitate.

It is recommended that the Caelyx pegylated liposomal syringe be connected laterally to an intravenous infusion of glucose 5% solution (50 mg/ml). The infusion can be administered through a peripheral vein. Do not use with filters in the infusion line.

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