Caelyx 2 mg/ml concentrate for solution for infusion

Caelyx is an antitumour agent.

Caelyx is used to treat cancer of the breast in patients at risk for heart problems. Caelyx is also used to treat cancer of the ovary. It is used to kill cancer cells, shrink the size of the tumour, delay the growth of the tumour, and extend your survival.

Caelyx is also used in combination with another medicine, bortezomib, to treat multiple myeloma, a cancer of the blood in patients who have received at least 1 prior therapy.

Caelyx is also used to produce an improvement in your Kaposi?s sarcoma including flattening, lightening and even shrinkage of the cancer. Other symptoms of Kaposi?s sarcoma, such as swelling around the tumour, may also improve or disappear.

Caelyx contains a medicine which is able to interact with cells in such a way as to selectively kill cancer cells. The doxorubicin hydrochloride in Caelyx is enclosed in tiny spheres called pegylated liposomes which help to deliver the medicinal product from the blood stream to the cancerous tissue rather than healthy normal tissue.

Do not use Caelyx

• if you are allergic (hypersensitive) to doxorubicinhydrochloride or any of the other ingredients of Caelyx.

Take special care with Caelyx

• if you are receiving any treatment for heart disease or liver disease;
• if you are diabetic, because Caelyx contains sugar which may require an adjustment to the treatment of your diabetes;
• if you have Kaposi?s sarcoma and have had your spleen removed.

Taking other medicines

Please tell your doctor or pharmacist

• if you are taking or have recently taken any other medicines, including medicines obtained without a prescription,
• about any other cancer treatments you are on or have been taking,as particular care needs to be taken with treatments which reduce the number of white blood cells, as this may cause further reduction in the number of white blood cells. If you are unsure about what treatments you have received or any illnesses you have had, discuss these with your doctor.

Pregnancy and breast-feeding
Ask your doctor or pharmacist for advice before taking any medicine.
Because the active ingredient doxorubicin hydrochloride in Caelyx may cause birth defects, it is important to tell your doctor if you think you are pregnant. Avoid becoming pregnant while you or your partner are taking Caelyx and in the six months following discontinuation of Caelyx treatment.

Because doxorubicin hydrochloride may be harmful to nursing infants, women must discontinue breast-feeding before starting treatment with Caelyx. Health experts recommend that HIV infected women do not breast-feed their infants under any circumstances in order to avoid transmission of HIV.

Driving and using machines
Do not drive or use any tools or machines if you feel tired or sleepy from treatment with Caelyx.

Caelyx is a unique formulation. It must not be used interchangeably with other formulations of doxorubicin hydrochloride.

Caelyx will be given to you by your doctor in a drip (infusion) into a vein. Depending on the dose and indication, this may take from 30 minutes to more than one hour (i.e., 90 minutes).

If you are being treated for breast cancer or ovarian cancer, Caelyx will be administered at a dose of 50 mg per square metre of your body surface area (based on your height and weight). The dose is repeated every 4 weeks for as long as the disease does not progress and you are able to tolerate the treatment.

If you are being treated for multiple myeloma, and have already received at least 1 prior therapy, Caelyx will be administered at a dose of 30 mg per square metre of your body surface area (based on your height and weight) as a 1 hour intravenous infusion on Day 4 of the bortezomib 3 week regimen immediately after the bortezomib infusion. The dose is repeated as long as you respond satisfactorily and tolerate treatment.

If you are being treated for Kaposi?sarcoma, Caelyx will be administered at a dose of 20 mg per square metre of your body surface area (based on your height and weight). The dose is repeated every 2 to 3 weeks for 2 - 3 months, then as often as necessary to maintain an improvement in your condition.

If you use more Caelyx than you should

Acute overdosing worsens side effects like sores in the mouth or decreases the number of white blood cells and platelets in the blood. Treatment will include administration of antibiotics, platelet cell transfusions, use of factors which stimulate production of white blood cells and symptomatic treatment of mouth sores.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

Like all medicines, Caelyx can cause side effects, although not everybody gets them.

During the infusion of Caelyx, the following reactions may occur: flushing of the face, shortness of breath, headache, chills, back pain, tightness in the chest and/or throat, sore throat, low or increase in blood pressure, rapid heart beat, puffing of the face, fever, dizziness, nausea, indigestion, itching, rash and sweating. In very rare cases, seizures (convulsions) have occurredStinging or swelling of the skin at the site of injection may also occur. If the drip stings or hurts while you are receiving a dose of Caelyx, tell your doctor immediately.

Contact your doctor immediately if:

• you get reddening painful skin on your hands and feet,
• you get painful reddening of the skin and/or blisters on the body or in the mouth,
• you get heart problems,
• you get mouth sores,
• you develop a fever or any other sign of an infection,
• you get sudden shortness of breath or sharp chest pain that may worsen with deep breathing or coughing,
• you get swelling, warmth, or tenderness in the soft tissues of your leg, sometimes with pain which gets worse when you stand or walk.

Between infusions, the following may occur:

• redness, swelling and sores on the palms of your hands and feet. These effects have been seen frequently, and are sometimes severe. In severe cases, these effects may interfere with certain daily activities, and may last for 4 weeks or longer before resolving completely. The doctor may wish to delay the start and/or reduce the dose of the next treatment (see Strategies to prevent and treat hand-foot syndrome, below);
• pain or sores in mouth or throat, nausea, vomiting, stomach pains, diarrhoea, constipation, oral thrush (a fungal infection in the mouth), sores in nose, bleeding from your nose, cold sores, loss of appetite, weight loss and tongue inflammation;
• decrease in the number of white blood cells, which can increase the chances of infections. Anaemia (reduction in red blood cells) may cause tiredness, and decreased platelets in the blood may increase the risk of bleeding. In rare cases, having low white blood cells may lead to severe infection. Laboratory values related to the function of the liver may either increase or decrease while on Caelyx. It is because of the potential changes in your blood cells that you will have regular blood tests . From a clinical study in patients with AIDS-KS comparing Caelyx against another treatment (bleomycin/vincristine), there may be a higher chance of some infections with Caelyx. However, in contrast to the experience with patients with AIDS-KS, when Caelyx was compared to a standard treatment for advanced ovarian cancer (topotecan), the risk of infections was substantially lower in the Caelyx-treated patients. The risk of low blood counts and infections was similarly low in breast cancer studies. Some of these effects may be related to your disease and not to Caelyx;
• general feeling of tiredness, sleepiness, confusion, dizziness, weakness, bone pain, breast pain, muscle pain, leg cramps or swelling, general swelling, inflammation of the retina (the light-detecting membrane of the eye), increased tear production, blurred vision, feeling of pins and needles or pain in hands and feet;
• hair loss, inflammation of hair follicles, scaly skin, inflammation or rash, abnormal skin pigmentation (colouring), and nail disorder ;
• heart problems, e.g., irregular heart beat, enlarged blood vessels;
• fever, increased temperature or any other sign of infection which may be related to your disease;
• respiratory problems, i.e., difficulty in breathing or coughing which may be linked to infections you have caught as a result of your disease;
• if you have previously had skin reactions, i.e., pain, redness and dryness of skin, during treatment with radiotherapy, this may also happen with Caelyx.

Other side effects that may occur with a combination of Caelyx and bortezomib include:

• joint pain, decreased or abnormal sensation to stimulation, inflammation of the cornea, redness of the eye, redness of the scrotum.

When Caelyx is used alone, some of these effects are less likely to occur, and some have not occurred at all.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Strategies to prevent and treat hand-foot syndrome:
Every day for 4-7 days beginning immediately after you have received Caelyx:

• soak hands and/or feet in basins of cold water when possible (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 cool baths during hot weather;
• avoid vigorous exercise that might cause trauma to the feet (e.g. jogging);
• avoid exposure of skin to very hot water (e.g. jacuzzis, saunas);
• avoid tight fitting footwear or high-heeled shoes.

Pyridoxine (Vitamin B6):

• Vitamin B6 is available without prescription.
• Take 50-150 mg daily beginning at the first signs of redness or tingling.

Keep out of the reach and sight of children.

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

After dilution:
Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C to 8°C. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and should not be longer than 24 hours at 2°C to 8°C. Partially used vials must be discarded.

Do not use Caelyx after the expiry date which is stated on the label and carton.

Do not use Caelyx if you notice that it shows evidence of precipitation or any other particulate matter.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

What Caelyx contains

• The active substance is doxorubicin hydrochloride. One ml of Caelyx contains 2 mg of doxorubicin hydrochloride in a pegylated liposomal formulation.
• The other ingredients are?-(2-[1,2-distearoyl- sn-glycero(3)phosphooxy]ethylcarbamoyl)-?-methoxypoly(oxyethylen)-40 sodium salt (MPEG-DSPE), fully hydrogenated soy phosphatidylcholine (HSPC), cholesterol, ammonium sulphate, sucrose, histidine, water for injections, hydrochloric acid and sodium hydroxide.

Caelyx concentrate for solution for infusion: vials which provide 10 ml (20 mg) or 25 ml (50 mg).

What Caelyx looks like and contents of the pack

The solution for infusion is sterile, translucent and red. Caelyx is available in glass vials as a single pack or packs of ten vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder: Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse

Manufacturer: Janssen Pharmaceutica NV, Turnhoutseweg 30, B-2340 Beerse, Belgium

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

BelgiëBelgiqueBelgien Janssen-Cilag NVSA Antwerpseweg 15-17 B-2340 Beerse TélTel 32 14 64 94 11 LuxembourgLuxemburg Janssen-Cilag NVSA Antwerpseweg 15-17 B-2340 Beerse TélTel 32 14 64 94 11

Magyarország Janssen-Cilag Kft., Tó Park H-2045 Törökbalint Tel 36 23 513 858 Johnson Johnson, d.o.o. .. 4 , 4 1766 . 359 2 489 94 00

eská republika Janssen-Cilag s.r.o. Karla Englie 32016 CZ-150 00 Praha 5 Tel. 420 227 012 222 Malta Am Mangion Ltd. Mangion Building, Triq dida fi Triq Valletta MT-LQA 6000 Luqa Tel 356 2397 6000

Danmark Janssen-Cilag AS Hammerbakken 19 DK-3460 Birkerød Tlf 45 45 94 82 82 Nederland Janssen-Cilag BV Dr. Paul Janssenweg 150 NL-5026 RH Tilburg Tel 31 13 583 73 73

Deutschland Janssen-Cilag GmbH Johnson Johnson Platz 1 D-41470 Neuss Tel 49 2137 955 955 Norge Janssen-Cilag A.S. Drammensveien 288 N-0283 Oslo Tlf 47 24 12 65 00

Österreich Janssen-Cilag Pharma GmbH Vorgartenstraße 206b A-1020 Wien Tel 43 1 610 300 Eesti Janssen-Cilag Polska Sp z o.o. Eesti filiaal Lõõtsa 2 EE-11415 Tallinn Tel 372 617 7410

Janssen-Cilag .... 56 GR-151 21 , Polska Janssen-Cilag Polska Sp. z o.o. ul. Iecka 24 PL - 02-135 Warszawa

T 30 210 80 90 000 Tel.48 22 237 60 00

España Janssen-Cilag, S.A. Paseo de las Doce Estrellas, 5-7 E-28042 Madrid Tel 34 91 722 81 00 Portugal Janssen-Cilag Farmacêutica, LDA. Estrada Consiglieri Pedroso, 69 A Queluz de Baixo P-2734-503 Barcarena Tel 351 21 43 68 835

France Janssen-Cilag 1, rue Camille Desmoulins, TSA 91003 F-92787 Issy Les Moulineaux, Cedex 9 Tél 33 1 55 00 21 00 România Johnson Johnson d.o.o. Str. Tipografilor nr. 11-15, Cldirea S-Park, corp A2, etaj 5 Bucureti 013714 - RO Tel 40 21 207 18 00

Slovenija Johnson Johnson d.o.o. martinska 53 SI-1000 Ljubljana Tel 386 1 401 18 30 Ireland Janssen-Cilag Ltd. 50 100 Holmers Farm Way High Wycombe Buckinghamshire HP12 4EG - UK Tel 44 1494 567 567

Slovenská republika Janssen-Cilag Pribinova 25, 5th floor SK-811 09 Bratislava Tel 421 2 335 52 656 Ísland Janssen-Cilag co Vistor hf. Hörgatún 2 IS-210 Garðabær Sími 354 535 7000

Italia Janssen-Cilag SpA Via M.Buonarroti, 23 I-20093 Cologno Monzese MI Tel 39 02 2510 1 SuomiFinland Janssen-Cilag OY VaisalantieVaisalavägen 2 FIN-02130 EspooEsbo PuhTel 358 207 531 300

Sverige Janssen-Cilag AB Box 7073 S-192 07 Sollentuna Tel 46 8 626 50 00 , 7 CY-1060 357 22 755 214

Latvija Janssen-Cilag Polska Sp. z o.o. filile Latvij Matrou iela 15 Rga, LV 1048 Tel 371 678 93561 United Kingdom Janssen-Cilag Ltd. 50 100 Holmers Farm Way High Wycombe Buckinghamshire HP12 4EG - UK Tel 44 1494 567 567

Lietuva

UAB ?Johnson & Johnson?
Gele-inio Vilko g. 18A
LT 08104 Vilnius
Tel: +370 5 278 68 88

This leaflet was last approved on

The following information is intended for medical or healthcare professionals only (see section 3):

Caution must be exercised in handling Caelyx solution. The use of gloves is required. If Caelyx comes into contact with skin or mucosa, wash immediately and thoroughly with soap and water. Caelyx must be handled and disposed of in a manner consistent with that of other anticancer medicinal products.

Determine the dose of Caelyx to be administered (based upon the recommended dose and the patient's body surface area). Take the appropriate volume of Caelyx up into a sterile syringe. Aseptic technique must be strictly observed since no preservative or bacteriostatic agent is present in Caelyx. The appropriate dose of Caelyx must be diluted in 5 % (50 mg/ml) glucose solution for infusion prior to administration. For doses < 90 mg, dilute Caelyx in 250 ml, and for doses ? 90 mg, dilute Caelyx in 500 ml.

To minimize the risk of infusion reactions, the initial dose is administered at a rate no greater than 1 mg/minute. If no infusion reaction is observed, subsequent Caelyx infusions may be administered over a 60-minute period.

In the breast cancer trial program, modification of the infusion was permitted for those patients experiencing 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 for 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 infusion reaction, immediately discontinue the infusion, give appropriate premedications (antihistamine and/or short acting corticosteroid) and restart at a slower rate.

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

It is recommended that the Caelyx infusion line be connected through the side port of an intravenous infusion of 5 % (50 mg/ml) glucose. Infusion may be given through a peripheral vein. Do not use with in-line filters.