CAELYX PEGYLATED LIPOSOMAL 2 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Caelyx pegylated liposomal 2 mg/ml concentrate for solution for infusiondoxorubicin hydrochloride

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.

• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What Caelyx pegylated liposomal is and what it is used for
2. What you need to know before you use Caelyx pegylated liposomal
3. How to use Caelyx pegylated liposomal

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

1. Contents of the pack and further information

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

Caelyx pegylated liposomal is an anti-tumour agent.

Caelyx pegylated liposomal is used to treat breast cancer in patients with a risk of heart problems. Caelyx pegylated liposomal is also used to treat ovarian cancer. It is used to kill the cells affected by cancer, reduce the size of the tumour, slow down the growth of the tumour and increase survival.

Caelyx pegylated liposomal is also used in combination with another medicine, 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 the cancer. Other symptoms of Kaposi's sarcoma, such as swelling around the tumour, may also improve or disappear.

Caelyx pegylated liposomal contains a medicine that interacts with cells in such a way that it selectively kills the cells affected by cancer. The doxorubicin hydrochloride in Caelyx pegylated liposomal is enclosed in tiny spheres called pegylated liposomes that facilitate the release of the medicine from the bloodstream into the cancerous tissue before it reaches normal, healthy tissue.

2. What you need to know before you use Caelyx pegylated liposomal

Do not use Caelyx pegylated liposomal

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

Warnings and precautions

Tell your doctor if you have:

• if you are receiving any treatment for 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, discolouration or any discomfort in your mouth.

Children and adolescents

Caelyx pegylated liposomal should not be used in children and adolescents because it is not known how this medicine affects them.

Using Caelyx pegylated liposomal with other medicinesTell your doctor or pharmacist

• if you are using or have recently used any other medicines, including those obtained without a prescription;
• about any other anti-cancer treatments you are receiving or have received, as special care needs to be taken with treatments that reduce the number of white blood cells, as they can cause an even greater reduction in the number of white blood cells. If you are not sure about the treatments you have received or the illnesses you have had, discuss this with your doctor.

Pregnancy and breast-feeding

Ask your doctor or pharmacist for advice before taking any medicine.

Since the active substance doxorubicin hydrochloride in Caelyx pegylated liposomal may cause birth defects, it is important that you contact your doctor if you think you are pregnant. You should avoid becoming pregnant while you or your partner are being treated with Caelyx pegylated liposomal and for 6 months after stopping treatment with Caelyx pegylated liposomal.

Since doxorubicin hydrochloride can be harmful to breast-fed babies, women must stop breast-feeding before starting treatment with Caelyx pegylated liposomal. Health experts recommend that HIV-infected women should not breast-feed their babies under any circumstances to avoid transmitting HIV.

Driving and using machines

Do not drive or use tools or machines if you feel tired or sleepy as a result of treatment with Caelyx pegylated liposomal.

Caelyx pegylated liposomal contains soya oil and sodium

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

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

3. How to use Caelyx pegylated liposomal

Caelyx pegylated liposomal is a special formulation. Therefore, it must not be exchanged with other medicines that also contain doxorubicin hydrochloride.

How much Caelyx pegylated liposomal is given

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

If you are being treated for multiple myeloma and have received at least one previous treatment, you will be given Caelyx pegylated liposomal at a dose of 30 mg per square metre of your body surface area (based on your height and weight) in a 1-hour intravenous infusion on day 4 of a 3-week bortezomib regimen and immediately after 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 given Caelyx pegylated liposomal at a dose of 20 mg per square metre of your body surface area (which is calculated from your height and weight). The dose is repeated every 2 to 3 weeks for 2 to 3 months, and then as often as necessary to maintain improvement of your condition.

How Caelyx pegylated liposomal is given

Your doctor will give you Caelyx pegylated liposomal through a drip (infusion) into a vein. Depending on the dose and indication, this can take from 30 minutes to over an hour (i.e. 90 minutes).

If you use more Caelyx pegylated liposomal than you should

Acute overdosing worsens side 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 the production of white blood cells and symptomatic treatment of mouth ulcers.

If you have any other questions 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 everybody gets them.

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

• severe allergic reaction which can include swelling of the face, lips, mouth, tongue or throat; difficulty swallowing or breathing; itchy rash (hives)
• inflammation and narrowing of the airways, causing coughing, wheezing and difficulty breathing (asthma)
• flushing, sweating, chills or fever
• chest pain or discomfort

• back pain
• increase or decrease in blood pressure

• rapid heart rate
• seizures (convulsions)

A leak of the injection liquid from the veins into the tissue under the skin can occur. If the drip hurts or is painful when you are receiving a dose of Caelyx pegylated liposomal, tell your doctor immediately.

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

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

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

• mouth ulcers, severe diarrhoea or vomiting or nausea (very common)

• infections (frequent), including lung infections (pneumonia) or infections that can affect your vision
• difficulty breathing (frequent)

• severe stomach pain (frequent)

• severe weakness (frequent)
• severe allergic reaction which can include swelling of the face, lips, mouth, tongue or throat; difficulty swallowing or breathing; itchy rash (hives) (uncommon)
• heart stoppage (the heart stops beating); heart failure, in which the heart does not pump enough blood to the rest of the body, which can cause difficulty breathing and can cause swelling of the legs (uncommon)

• formation of blood clots in the blood that reaches the lungs, causing chest pain and difficulty breathing (uncommon)
• swelling, warmth or pain on palpation in any area of the leg, sometimes with pain that worsens when standing or walking (rare)
• severe 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

The following may occur between infusions:

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

• decrease in the number of white blood cells, which can increase the risk of infection. In rare cases, a decrease in white blood cells can lead to a serious infection. Anaemia (decrease in red blood cells) can cause tiredness, and a decrease in platelets in the blood can increase the risk of bleeding. Due to 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, bumpy rash or redness of the skin
• hair loss
• pain, including muscle and chest pain

• feeling very tired

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

• infections, including serious infection of the whole body (sepsis), lung infections, infections caused by the herpes zoster virus (shingles), a type of bacterial infection (Mycobacterium avium complex infection), urinary tract infection, fungal infections (including thrush and oral thrush in the mouth), infection of the hair follicles, throat irritation, infection of the nose, nasal passages or throat (common cold)

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

• nerve damage that can cause tingling, numbness, pain or loss of pain sensation, nerve pain, abnormal sensation in the skin (such as tingling or prickling), decreased sensitivity, especially in the skin

• change in taste, headache, feeling very sleepy with little energy, feeling dizzy;
• eye inflammation (conjunctivitis)
• rapid heart rate
• increase or decrease in blood pressure, facial flushing

• difficulty breathing that can appear after physical activity, nosebleeds, coughing
• inflammation of the stomach lining or oesophagus, mouth ulcers, indigestion, difficulty swallowing, mouth pain, dry mouth
• skin problems, including dry or scaly skin, allergic rash, mouth ulcers or blisters on the skin, skin discoloration, change in the natural colour (pigmentation) of the skin, small red or purple spots caused by bleeding under the skin, nail problems, acne
• excessive sweating

• muscle spasms or cramps

• pain that affects muscles, bones or back
• pain when urinating

• allergic reaction to the infusion of the medicine, flu-like illness, chills, inflammation of the mucous membranes of different body cavities and passages, such as the nose, mouth or trachea, feeling of weakness, general feeling of being unwell, swelling caused by fluid retention, feeling of swelling of hands, ankles or feet

• weight loss

When Caelyx pegylated liposomal is used as a single medicine, it is less likely that some of these side effects will occur, and some of them have never been seen.

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

• infections caused by the herpes simplex virus (cold sores or genital herpes), fungal infections
• low number of all types of blood cells, increase in the number of ‘platelets’ (cells that help the blood to clot)
• allergic reaction
• high level of potassium in the blood, low level of magnesium in the blood

• nerve damage that affects more than one area of the body
• seizures (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, heart damage
• tissue damage (necrosis) at the injection site, inflammation of the veins that causes swelling and pain, feeling of dizziness when sitting or standing up
• discomfort in the chest

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

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

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

• infection that occurs in people with a weakened immune system

• low number of blood cells produced in the bone marrow
• inflammation of the retina, which can cause changes in vision or blindness
• abnormal heart rhythm, abnormal tracing on an electrocardiogram (ECG) that can occur with low heart rate, heart problem that affects heart rate and rhythm, bluish discoloration of the skin and mucous membranes caused by low oxygen levels in the blood
• dilation of blood vessels
• feeling of tightness in the throat

• mouth ulcers and swelling, ulcers on the lips
• skin rash with blisters filled with fluid

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

Side effects with unknown frequency(cannot be estimated from the available data)

• blood cancer that develops quickly and affects blood cells (acute myeloid leukaemia), bone marrow disease that affects blood cells (myelodysplastic syndrome), mouth or lip cancer

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via 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:

• soaking your hands and/or feet in cold water when possible (e.g. 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 can cause trauma to your feet (e.g. jogging);

• avoiding exposure of your skin to very hot water (e.g. hot tubs, saunas);
• avoiding tight footwear or high-heeled shoes.

Pyridoxine (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.

5. Storage of Caelyx pegylated liposomal

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

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

After dilution:

The chemical and physical stability has been demonstrated 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 not used immediately, the storage times and conditions prior to use are the responsibility of the user and should not exceed 24 hours between 2°C and 8°C. Partially used vials must be discarded.

Do not use this medicine after the expiry date stated on the label and carton.

Do not use this medicine if you notice evidence of precipitation or presence of particles.

Medicines should not be disposed of 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 additional information

Composition of Caelyx pegylated liposomal

• The active substance is doxorubicin hydrochloride. One 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)phosphoxy]ethylcarbamoyl)-?-methoxypoly(oxethylene)-40 sodium salt (MPEG-DSPE), fully hydrogenated soy phosphatidylcholine (HSPC), cholesterol, ammonium sulfate, sucrose, histidine, water for injectable preparations, hydrochloric acid (for pH adjustment), and sodium hydroxide (for pH adjustment). See section 2.

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

Appearance and package contents of the product

Caelyx pegylated liposomal is sterile, translucent, and red. Caelyx pegylated liposomal is available in individual or packs of ten vials, made of glass. Not all pack sizes may be marketed.

Marketing Authorisation Holder

Janssen-Cilag International NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

Manufacturer

Janssen Pharmaceutica NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

You can request more information about this medicine from the local representative of the Marketing Authorisation Holder:

België/Belgique/BelgienLietuva

Janssen-Cilag NV UAB "JOHNSON & JOHNSON"

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

janssen@jacbe.jnj.com lt@its.jnj.com

????????Luxembourg/Luxemburg

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

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

jjsafety@its.jnj.com janssen@jacbe.jnj.com

Ceská republikaMagyarország

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

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

janssenhu@its.jnj.com

DanmarkMalta

Janssen-Cilag A/S AM MANGION LTD.

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

jacdk@its.jnj.com

DeutschlandNederland

Janssen-Cilag GmbH Janssen-Cilag B.V.

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

jancil@its.jnj.com janssen@jacnl.jnj.com

EestiNorge

UAB "JOHNSON & JOHNSON"Eesti filiaal Janssen-Cilag AS

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

ee@its.jnj.com jacno@its.jnj.com

Ελλ?δαÖsterreich

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

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

EspañaPolska

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

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

contacto@its.jnj.com

FrancePortugal

Janssen-Cilag Janssen-Cilag Farmacêutica, Lda.

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

medisource@its.jnj.com

HrvatskaRomânia

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

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

jjsafety@JNJCR.JNJ.com

IrelandSlovenija

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

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

Janssen_safety_slo@its.jnj.com

ÍslandSlovenská republika

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

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

Sími: +354 535 7000

janssen@vistor.is

ItaliaSuomi/Finland

Janssen-Cilag SpA Janssen-Cilag Oy

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

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Κ?προςSverige

Βαρν?βας Χατζηπαναγ?ς Λτδ Janssen-Cilag AB

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

jacse@its.jnj.com

LatvijaUnited Kingdom

UAB "JOHNSON & JOHNSON"filiale Latvija Janssen-Cilag Ltd.

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

lv@its.jnj.com

Date of last revision of this leaflet:

Detailed information on this medicine is available on the European Medicines Agency (EMEA) website http://www.emea.europa.eu/.

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

Caution should be exercised when handling Caelyx pegylated liposomal. Gloves should be worn. In case Caelyx pegylated liposomal comes into contact with skin or mucous membranes, wash the affected area immediately with water and soap. Caelyx pegylated liposomal should be handled and disposed of as with other cytotoxic 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 measures 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 5% glucose solution for infusion (50 mg/ml) prior to administration. For doses <90 mg, dilute caelyx pegylated liposomal in 250 ml, and for doses< p>

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

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

In the clinical trial program in breast cancer, modification of the infusion was allowed in those 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 symptoms or signs of an infusion reaction, interrupt the infusion immediately, administer appropriate symptomatic treatment (antihistamine and/or short-acting corticosteroid), and restart at a slower rate.

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

It is recommended that the Caelyx pegylated liposomal infusion line be connected laterally to a 5% glucose solution for infusion (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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