Caelyx pegylated liposomal 2 mg/ml concentrate for infusion solution

Patient Information Leaflet

Introduction

Patient Information Leaflet

Caelyx pegylated liposomal 2 mg/ml concentrate for solution for infusion doxorubicin hydrochloride

Read the entire leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet as 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 and must not be given to other people, even if they have the same symptoms as you. It may harm them.

• If you experience any side effects, talk to your doctor or pharmacist, even if they are side effects not listed in this leaflet. See section 4.

Leaflet Contents

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

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

3. How to use Caelyx pegylated liposomal

4. Possible side effects

5. How to store Caelyx pegylated liposomal

6. Contents of the pack and other information

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

Caelyx pegylated liposomal is an antitumour agent.

Caelyx pegylated liposomal is used to treat breast cancer in patients at risk of heart problems. Caelyx pegylated liposomal is also used to treat ovarian cancer. It works by killing cancer-affected cells, reducing tumour size, delaying tumour growth, and increasing 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 prior therapy.

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

Caelyx pegylated liposomal contains a medicine capable of interacting with cells in such a way that it selectively kills cancer-affected cells. The doxorubicin hydrochloride in Caelyx pegylated liposomal is enclosed within tiny spheres called pegylated liposomes, which help deliver the medicine from the bloodstream into cancerous tissue before reaching normal, healthy tissue.

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

Do not use Caelyx pegylated liposomal

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

Warnings and precautions

Tell your doctor if you have any of the following:

• if you are receiving treatment for heart or liver disease;

• if you have diabetes, as Caelyx pegylated liposomal contains sugar and your diabetes treatment may need to be adjusted;

• if you have Kaposi's sarcoma and your spleen has been removed;

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

Children and adolescents

Caelyx pegylated liposomal must not be used in children and adolescents, as it is unknown how the medicine will affect them.

Use of Caelyx pegylated liposomal with other medicines
Tell your doctor or pharmacist

• if you are taking or have recently taken any other medicines, including those obtained without a prescription;
• about any other anticancer treatments you are receiving or have received, as special care is needed with treatments that reduce the number of white blood cells, since they may cause a further decrease in white blood cell count. If you are unsure about the treatments you have received or the illnesses you have had, discuss this with your doctor.

Pregnancy and breastfeeding

Consult your doctor or pharmacist before using 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 may be pregnant. You must avoid becoming pregnant while you or your partner are being treated 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 women infected with HIV should not breastfeed their infants under any circumstances to avoid transmission of HIV.

Driving and use of machines

Do not drive or operate tools or machinery if you feel tired or drowsy 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 peanut 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 formulation with specific characteristics. Therefore, it must not be interchanged with other medications containing doxorubicin hydrochloride.

How much Caelyx pegylated liposomal is administered

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 meter of your body surface area (calculated based on your height and weight). This 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 have received at least one prior treatment, you will be given Caelyx pegylated liposomal at a dose of 30 mg per square meter of your body surface area (calculated based on your height and weight) administered as a 1-hour intravenous infusion on day 4 of the 3-week bortezomib regimen, 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 given Caelyx pegylated liposomal at a dose of 20 mg per square meter of your body surface area (calculated based on your height and weight). This dose is repeated every 2 to 3 weeks for 2–3 months, and then as frequently as necessary to maintain improvement.

How Caelyx pegylated liposomal is administered

Your doctor will administer Caelyx pegylated liposomal to you by intravenous infusion (drip) into a vein. Depending on the dose and indication, the infusion may last from 30 minutes to more than one hour (i.e., 90 minutes).

If you use more Caelyx pegylated liposomal than you should

Acute overdosage worsens adverse effects such as mouth ulcers or reduces the number 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 further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible adverse effects

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

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

• 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, 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 heartbeat
• Seizures (convulsions)

Leakage of the injection fluid from the veins into the tissue beneath the skin may occur. If the infusion site stings or hurts while you are receiving a dose of Caelyx pegylated liposomal, inform your doctor immediately.

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

• You have fever, feel tired, or show signs of bruising or bleeding (very common)
• Redness, swelling, peeling or tenderness, mainly in the hands or feet (hand-foot syndrome). These effects are very common and sometimes 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 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 diarrhoea, 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 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, which may cause difficulty breathing and may lead to leg swelling (uncommon)
• Blood clots forming in the blood vessels going to the lungs, causing chest pain and difficulty breathing (uncommon)
• Swelling, warmth or tenderness in an 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 over most of the body (toxic epidermal necrolysis) (rare)

Other adverse effects

Between infusions, the following may occur:

Very common adverse 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, a decrease in white blood cells may lead to a serious infection. Anaemia (decrease in red blood cells) may cause tiredness, and a decrease in blood platelets may increase the risk of bleeding. Due to possible changes in your blood cells, you will have regular blood tests
• Loss of appetite
• Constipation
• Skin rashes, including skin redness, allergic skin rash, raised or red rash on the skin
• Hair loss
• Pain, including muscle, chest, joint, arm or leg pain
• Feeling very tired

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

• Infections, including serious body-wide infection (sepsis), lung infections, infection by the herpes zoster virus (shingles), a type of bacterial infection (infection by Mycobacterium avium complex), urinary tract infection, fungal infections (including thrush and oral thrush in the mouth), infection of hair follicles, infection or irritation of the throat, infection of the nose, nasal passages or throat (common cold)
• Low number of a type of white blood cells (neutrophils), with fever
• Severe weight loss and muscle weakness, insufficient body water (dehydration), low levels of potassium, sodium or calcium in the blood
• Feeling confused, anxious, depressed, or having difficulty sleeping
• Nerve damage which may cause tingling, numbness, pain or loss of pain sensation, nerve pain, unusual skin sensations (such as tingling or prickling), decreased sensitivity, especially in the skin
• Change in taste sensation, headache, feeling very sleepy with low energy, feeling dizzy
• Inflammation of the eyes (conjunctivitis)
• Rapid heartbeat
• Increase or decrease in blood pressure, facial flushing
• Difficulty breathing which may occur after physical activity, nosebleeds, cough
• Inflammation of the stomach lining or oesophagus, ulcers (sores) in the mouth, indigestion, difficulty swallowing, mouth pain, dry mouth
• Skin problems, including dry or scaly skin, erythema, blisters or ulcers (sores) on the skin, itching, dark spots on the skin
• Excessive sweating
• Muscle spasms or muscle pain
• Pain affecting 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 various body cavities and ducts, such as nose, mouth or trachea, feeling of weakness, general feeling of discomfort, swelling due to fluid retention, sensation of swelling in hands, ankles or feet
• Weight loss

When Caelyx pegylated liposomal is used as a single medicine, some of these adverse effects are less likely to occur, and some have never been reported.

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

• Infections by the herpes simplex virus (cold sores or genital herpes), fungal infection
• 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
• Nerve damage affecting more than one area of the body
• Seizures (convulsions), fainting
• Unpleasant or painful sensation, especially on touch, drowsiness
• Blurred vision, watery eyes
• Sensation of rapid or irregular 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 dry or scaly skin, allergic rash, ulcers (sores) 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 swelling, redness or pain) in body parts previously treated with radiotherapy or damaged as a result of intravenous chemotherapy injection

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

• Infection occurring in people with a weakened immune system
• Low number of blood cells produced in the bone marrow
• Inflammation of the retina, which may cause changes in vision or blindness
• Abnormal heart rhythm, abnormal ECG (electrocardiogram) trace which may occur with low heart rate, heart condition affecting heart rate and rhythm, bluish discolouration of the skin and mucous membranes due to low oxygen concentration in the blood
• Dilation of blood vessels
• Sensation of tightness in the throat
• Sores and swelling of the tongue, ulcers (sores) on the lips
• Skin rash with fluid-filled blisters
• Vaginal infection, redness of the scrotum
• Problems with the mucous membranes of various body cavities and ducts, such as nose, mouth or trachea
• Abnormal results in liver blood tests, increased level of "creatinine" in the blood

Adverse effects with unknown 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), cancer of the mouth or lips

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

Strategies for preventing and treating hand-foot syndrome include:

• Soaking hands and/or feet in containers of cold water whenever possible (e.g., while watching television, reading or listening to the radio);
• Keeping hands and feet uncovered (without gloves, socks, etc.);
• Staying in cool environments;
• Taking cold baths when it is hot;
• Avoiding vigorous exercise that may cause trauma to the feet (e.g., jogging);
• Avoiding exposing the skin to very hot water (e.g., hot tubs, saunas);
• Avoiding tight-fitting footwear or high-heeled shoes.

Pyridoxine (Vitamin B6):

• Vitamin B6 is available without a prescription;
• Take 50–150 mg daily 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:

Chemical and physical stability has been demonstrated for 24 hours at 2°C to 8°C during use.

From a microbiological standpoint, the product should be used immediately. If not used immediately, the storage periods during use and the conditions prior to use are the responsibility of the user and should not exceed 24 hours at 2°C to 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 precipitation or particulate matter is observed.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the container and other 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)phospho- oxy]ethylcarbamoyl)-?-methoxypoly(ethylene glycol)-40 sodium salt (MPEG-DSPE), fully hydrogenated soybean phosphatidylcholine (HSPC), cholesterol, ammonium sulfate, sucrose, histidine, water for injections, 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 of the product and contents of the pack

Caelyx pegylated liposomal is sterile, translucent and red in colour. Caelyx pegylated liposomal is available in single packs or packs of ten vials, made of glass. Only certain 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

More information about this medicinal product is available upon request to 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
[email protected] [email protected]

????????Luxembourg/Luxemburg
„??????? & ??????? ????????” ???? Janssen-Cilag NV
???.: +359 2 489 94 00 Tél/Tel: +32 14 64 94 11
[email protected] [email protected]

Ceská republikaMagyarország
Janssen-Cilag s.r.o. Janssen-Cilag Kft.
Tel: +420 227 012 227 Tel.: +36 1 884 2858
[email protected]

DanmarkMalta
Janssen-Cilag A/S AM MANGION LTD.
Tlf: +45 4594 8282 Tel: +356 2397 6000
[email protected]

DeutschlandNederland
Janssen-Cilag GmbH Janssen-Cilag B.V.
Tel: +49 2137 955 955 Tel: +31 76 711 1111
[email protected] [email protected]

EestiNorge
UAB "JOHNSON & JOHNSON" Eesti filiaal Janssen-Cilag AS
Tel: +372 617 7410 Tlf: +47 24 12 65 00
[email protected] [email protected]

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
[email protected]

FrancePortugal
Janssen-Cilag Janssen-Cilag Farmacêutica, Lda.
Tél: 0 800 25 50 75 / +33 1 55 00 40 03 Tel: +351 214 368 600
[email protected]

HrvatskaRomânia
Johnson & Johnson S.E. d.o.o. Johnson & Johnson România SRL
Tel: +385 1 6610 700 Tel: +40 21 207 1800
[email protected]

IrelandSlovenija
Janssen Sciences Ireland UC Johnson & Johnson d.o.o.
Tel: +353 1 800 709 122 Tel: +386 1 401 18 00
[email protected]

ÍslandSlovenská republika
Janssen-Cilag AB Johnson & Johnson, s.r.o.
c/o Vistor hf. Tel: +421 232 408 400
Sími: +354 535 7000
[email protected]

ItaliaSuomi/Finland
Janssen-Cilag SpA Janssen-Cilag Oy
Tel: 800.688.777 /+39 02 2510 1 Puh/Tel: +358 207 531 300
[email protected] [email protected]

Κ?προςSverige
Βαρν?βας Χατζηπαναγ?ς Λτδ Janssen-Cilag AB
Τηλ: +357 22 207 700 Tfn: +46 8 626 50 00
[email protected]

LatvijaUnited Kingdom
UAB "JOHNSON & JOHNSON" filiale Latvija Janssen-Cilag Ltd.
Tel: +371 678 93561 Tel: +44 1 494 567 444
[email protected]

Date of latest revision of this leaflet:

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 for medical or healthcare professionals only (see section 3):

Care must be taken when handling a dispersion of Caelyx pegylated liposomal. Gloves must be worn. If Caelyx pegylated liposomal comes into contact with skin or mucous membranes, wash the affected area immediately with water and soap. Caelyx pegylated liposomal must be handled and disposed of as other anticancer medicines.

Determine the dose of Caelyx pegylated liposomal to be administered (based on the recommended dose and the patient's body surface area). Withdraw the appropriate volume of Caelyx pegylated liposomal into a sterile syringe. Strict aseptic techniques must be followed since Caelyx pegylated liposomal contains no preservative or bacteriostatic agent. The appropriate dose of Caelyx pegylated liposomal must be diluted in 5% glucose infusion solution (50 mg/ml) prior to administration. For doses < 90 mg, dilute Caelyx pegylated liposomal in 250 ml; and for doses ≥ 90 mg, dilute Caelyx pegylated liposomal in 500 ml.

To minimise 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 infusions of Caelyx pegylated liposomal may be given over a 60-minute period.

In the clinical trial programme for breast cancer, modification of the infusion regimen was permitted 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 following hour, for a total infusion time of 90 minutes.

If the patient experiences early symptoms or signs of an infusion reaction, stop 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 infusion solution (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 set be connected side-by-side to an intravenous line containing 5% glucose (50 mg/ml). The infusion may be administered via a peripheral vein. Do not use filters in the infusion line.

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