MabCampath 30 mg/ml concentrate for solution for infusion

MabCampath is used to treat patients with chronic lymphocytic leukaemia (CLL), a cancer of the lymphocytes (a type of white blood cell). It is used in patients for whom treatment combinations including fludarabine (another medicine used in leukaemia) are not appropriate.

The active substance in MabCampath, alemtuzumab, is a monoclonal antibody. A monoclonal antibody is an antibody (a type of protein) that has been designed to recognise and bind to a specific structure (called an antigen) that is found in certain cells in the body. In CLL, too many lymphocytes are produced. Alemtuzumab has been designed to bind to a glycoprotein (a protein that is coated with sugar molecules) that is found on the surface of lymphocytes. As a result of this binding, the lymphocytes die, and this helps to control the CLL.

Do not use MabCampath if you:

are allergic to alemtuzumab or to proteins of a similar origin or to any of the other ingredients of MabCampath see section 6 Further Information. Your doctor will inform you accordingly have an infection have HIV have an active second malignancy are pregnant see also Pregnancy.

Take special care with MabCampath:

When you first receive MabCampath, you may experience side effects soon after the first infusions (see section 4 ?Possible side effects?). These effects will gradually reduce as treatment is continued.

You may also be given

steroids, antihistamines or analgesics treatment for fever to help reduce some of the side effects.

The dosage of MabCampath will not be increased until the effects are reduced.

MabCampath treatment may reduce your natural resistance to infections

antibiotics and antivirals may be given to provide you with extra protection.

You will be examined for symptoms of a certain type of viral infection called CMV (cytomegalovirus) during your MabCampath therapy and for at least 2 months afterwards.

Your doctor will monitor you carefully if you

have heart disease or chest pains andor you are receiving treatment to reduce high blood pressure, as MabCampath may make these conditions worse. Patients with these conditions may be at higher risk of a heart attack.

have been treated in the past with chemotherapies or general medications that have a high risk of causing heart damage, your doctor may wish to monitor your cardiac function ECG, heart rate, body weight while receiving MabCampath.

have other side effects, most often blood disorders from taking MabCampath. Your doctor will be monitoring the effects of treatment and your progress carefully by examining you and by taking blood samples for analysis on a regular basis.

are over 65 years of age as you may be more intolerant to the medicine than other patients.

You may experience an allergic or hypersensitivity reaction to MabCampath solution, especially against the protein contained in it, while the infusion is given to you. Your doctor will treat you for this, if this happens.

Because of the potential for a fatal reaction to transfusion of any blood products following treatment with MabCampath, it is recommended that you speak to your doctor regarding the irradiation of blood products prior to receiving the transfusion. You should inform your doctor if you experience any unusual symptoms after a transfusion.

MabCampath is not recommended in children below 17 years of age or in patients who have kidney or liver disorders.

Taking other medicines

You should inform your doctor if you are taking or have recently taken any other medicines, even those not prescribed.

In particular, you should not be given MabCampath within 3 weeks of taking any other anti-cancer agents.

Also, you should not be vaccinated with live viral vaccines during treatment and for at least 12 months after you have finished your treatment. Speak to your doctor before receiving any vaccinations.

Pregnancy

MabCampath must not be administered to patients who are pregnant, therefore if you:

are pregnant or you think you may be pregnant, you should tell your doctor immediately.

are a woman of childbearing potential or a fertile man, then you should use effective contraceptive methods before you start treatment, during treatment and for 6 months after treatment.

Breast-feeding

You should stop breast-feeding when you start your treatment and you should not begin breast-feeding again until at least 4 weeks after you have finished your treatment and you have consulted your doctor on the matter.

Driving or using machines

No studies of the effects of MabCampath on the ability to drive and use machines have been performed. However you should be cautious as confusion and sleepiness have been seen. You should ask your doctor for advice.

MabCampath is administered into one of your veins via a drip (see also ?information intended for medical or healthcare professionals?).

Each time you are given MabCampath, it will take about 2 hours for all the solution to enter your blood.

MabCampath treatment may continue for up to 12 weeks depending on your progress.

During the first week, your doctor will increase the dose of MabCampath slowly to reduce the possibility of you having side effects and to allow your body to tolerate MabCampath better.

If you experience early side effects the initial smaller doses may be repeated until the effects go away or reduce. The doctor will carefully monitor you and decide what are the appropriate amounts of MabCampath to give you during your whole treatment period.

If more MabCampath is given than recommended

Your doctor will treat you, as appropriate, if you have any side effects.

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

Your doctor may give you other medicines or change your dose to help reduce any side effects (see section 2 ?Take Special care?).

Serious side effects, including difficulty in breathing, inflammation of the lungs, extreme shortness of breath, fainting, heart attack, low red blood cell and low blood platelet levels, infections, bleeding in the brain (intracranial haemorrhage) have occurred with fatal outcome. Diseases related to an overactive immune system where your immune system attacks your own body can lead to low red blood cells, low blood platelets and/or low white blood cells, and nerve disorders, and these can also be fatal. Tell your doctor immediately if you experience any of these side effects.

In addition, testing indicating the presence of antibodies that may destroy red blood cells (Coombs test) has been reported.

Very common side effects (seen in at least 1 in every 10 patients treated in clinical trials):

Usually one or more of these effects happen during the first week after the start of treatment:

fever, shiveringchills, sweating, nausea feeling sick, vomiting, low blood pressure, low whitered blood cell levels, infections including pneumonia and blood poisoning, irritation andor blistering of the mouth region, low blood platelet levels, tiredness, rash, itching, red raised lesions on the skin, shortness of breath, headache, diarrhoea and loss of appetite.

They are usually only mild or moderate problems and they gradually diminish during the course of treatment.

Common side effects (affects 1 to 10 patients in every 100 patients treated in clinical trials):

high blood pressure, fast or slow heart rate, feeling your heart racing, blood vessel spasm becoming red in the face, bruising of the skin taste changes decreased sense of touch dizziness, sensation of spinning, fainting, shaking or trembling movements, feeling restless eye inflammation e.g. conjunctivitis pins and needles or burning sensation of the skin abnormal liver function, constipation, indigestion, passing abdominal gas inflammation, irritation andor tightness of the lungs, throat andor sinuses, too little oxygen reaching the body organs, coughing, coughing up of blood abdominal bleeding e.g. in the stomach and intestine injection site reactions including redness, swelling, pain, bruising, inflammation generally feeling unwell, weakness, pain in various parts of the body muscle, back, chest, bones, joints, stomach and intestine weight loss, dehydration, thirst, swelling of the lower legs, temperature change sensation, low calcium or sodium blood levels flu-like symptoms abscess, skin redness or allergic skin reaction, blistering of the skin confusion, anxiety, depression, sleeplessness

Uncommon side effects (affects 1 to 10 in every patients in 1,000 patients treated in clinical trials):

bone marrow disorders heart disorders heart stopping, heart attack, heart congestion, irregular heart rate blood disorders abnormal clotting, decreased protein, low potassium levels high blood sugar, worsening diabetes bleeding and inflammation of the gums, blisters on the tongue, nosebleeds fluid in the lungs, difficulty breathing, harsh sound when breathing, runny nose, abnormal findings in the lungs, lymph gland disorders nervousness, abnormal thinking swelling around the eye ringing sound in the ears, deafness hiccups, burping hoarseness abnormal kidney function paralysis of the small bowel impotence unsteadiness, increased muscle tone unusual increased or altered sensitivity to touch abnormal sensationfeeling or movement pain when urinating, decreases in urine flow, increased frequency in urination, blood in urine, incontinence 58

tumour lysis syndrome a metabolic disorder, which may begin with pains in the side and blood in the urine

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 your pharmacist.

Keep out of the reach and sight of children.

Do not use MabCampath after the expiry date (EXP) which is stated on the outer carton and the vial label. The expiry date refers to the last day of that month.

Store in a refrigerator (2-C-8-C).

Do not freeze.

Store in the original packaging in order to protect from light.

MabCampath should be used within 8 hours after dilution. During that time the solution may be stored at 15°C-30°C or refrigerated.

Do not use MabCampath if you notice any signs of particulate matter or discolouration prior to administration.

Medicines should not be disposed of via wastewater or household waste. Your healthcare professional will dispose of medicines no longer required. These measures will help protect the environment.

What MabCampath contains

The active substance is alemtuzumab.
One ml contains 30 mg of alemtuzumab. Each vial contains 30 mg of alemtuzumab.

The other ingredients are disodium edetate, polysorbate 80, potassium chloride, potassium dihydrogen phosphate, sodium chloride, dibasic sodium phosphate and water for injections.

What MabCampath looks like and contents of the pack

MabCampath is a concentrate for solution for infusion that comes in a glass vial.

Each pack of MabCampath contains 3 vials.

Marketing Authorisation Holder

Genzyme Europe BV, Gooimeer 10, 1411 DD Naarden, Netherlands

Manufacturer

Genzyme Ltd., 37 Hollands Road, Haverhill, Suffolk CB9 8PU, United Kingdom

Genzyme Ireland Limited., IDA Industrial Park, Old Kilmeaden Road, Waterford, Ireland

Bayer Schering Pharma AG, Müllerstrasse 178, D-13342 Berlin, Germany.

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

ItaliaMalta Genzyme Srl ItaliaItalja, Tel 39 059 349 811 BelgiëBelgiqueBelgien Luxemburg Luxembourg Genzyme Belgium N.V., TélTel 32 2 714 17 11

. 359 2 971 1001 Magyarország Genzyme Europe B.V. Képviselet Tel 36 1 310 7440

Nederland Genzyme Europe B.V., Tel 31 35 699 1200 eská RepublikaSlovenská Republika Slovenija Genzyme Czech s.r.o. Tel 420 221 722 511

Österreich Genzyme Austria GmbH, Tel 43 1 774 65 38 DanmarkNorgeSverigeSuomiFinland Ísland Genzyme AS, DanmarkTanskaDanmörk, TlfPuh.Sími 45 32712600

Deutschland Genzyme GmbH, Tel 49 610236740 PolskaEestiLatvijaLietuva Genzyme Polska Sp. z o.o. PoolaPolijaLenkija, Tel 48 22 246 0900

Genzyme Hellas Ltd. 30 210 99 49 270 Portugal Genzyme Portugal S.A. Tel 351 21 422 0100

España Genzyme, S.L.U., Tel 34 91 6591670 România Genzyme Biopharma SRL Tel 40 212 43 42 28

France Genzyme S.A.S, Tél 33 0 825 825 863 United KingdomIreland Genzyme Therapeutics Ltd. United Kingdom, Tel 44 1865 405200

This leaflet was last approved in

The following information is intended for medical or healthcare professionals only:

During the first week, 3 mg of MabCampath is given on Day 1, then 10 mg on Day 2 and then 30 mg on Day 3, depending on tolerability. MabCampath will be given at 30 mg three times per calendar week on alternate days, for up to 12 weeks.

The vial contents should be inspected for particulate matter and discolouration prior to administration. If particulate matter is present or the solution is coloured, then the vial should not be used.

MabCampath contains no antimicrobial preservatives, therefore, it is recommended that MabCampathshould be prepared for intravenous infusion using aseptic techniques and that the diluted solution for infusion should be administered within 8 hours after preparation and protected from light. The required amount of the vial contents should be added to 100 ml of sodium chloride 9 mg/ml (0.9%) solution for infusion or glucose (5%) solution for infusion. The bag should be inverted gently to mix the solution. Care should be taken to ensure the sterility of the prepared solution particularly as it contains no antimicrobial preservatives.

Other medicinal products should not be added to the MabCampath infusion solution or simultaneously infused though the same intravenous line.

Caution should be exercised in the handling and preparation of the MabCampath solution. The use of latex gloves and safety glasses is recommended to avoid exposure in case of breakage of the vial or other accidental spillage. Women who are pregnant or trying to become pregnant should not handle MabCampath.

Procedures for proper handling and disposal should be observed. Any spillage or waste material should be disposed of by incineration.