Arzerra 1,000 mg concentrate for solution for infusion

Arzerra contains ofatumumab, which belongs to a group of medicines called monoclonal antibodies.

Arzerra is used to treat chronic lymphocytic leukaemia (CLL). CLL is a cancer of the blood which affects a type of white blood cell called lymphocytes. The lymphocytes multiply too quickly and live too long, so there are too many of them circulating in your blood. The disease can also affect other organs in your body. The antibody in Arzerra recognises a substance on the surface of lymphocytes and causes the lymphocyte to die.

Arzerra is used to treat CLL in patients who have not responded to other types of chemotherapy or treatments.

You must not receive Arzerra:

• if you are allergic(hypersensitive) to ofatumumab or to any of the other ingredients of Arzerra (listed in Section 6 ?Further information?)Check with your doctor if you think this may apply to you.

Take special care with Arzerra

Before you are given Arzerra your doctor needs to know:

• if you have had heart problems,
• if you have lung disease,
• if you have had hepatitis B (a liver disease). Arzerra could cause your hepatitis B to become active again. Your doctor may treat you with a suitable anti-viral medicine to help prevent this. Check with your doctor if you think any of these may apply to you . You may need extra check-ups while you are being treated with Arzerra.

Vaccination and Arzerra

If you are having any vaccinations tell your doctor, or the person giving you the vaccine, that you are being treated with Arzerra. Your response to the vaccine may be weakened and you may not be fully protected.

Infusion reactions

Medicines of this type ( monoclonal antibodies) can cause infusion reactions when they are injected into the body. You will be given medicines such as anti-histamines, steroids or pain relievers to help reduce any reaction. See also Section 4, ?Possible side effects?.

If you think you have had a similar reaction before, tell your doctor before you are given Arzerra.

Progressive multifocal leukoencephalopathy (PML)

Progressive multifocal leukoencephalopathy (PML), a serious and life threatening brain condition, has been reported with medicines like Arzerra. Tell your doctor immediately if you have memory loss, trouble thinking, difficulty with walking or loss of vision. If you had these symptoms prior to treatment with Arzerra, tell your doctor immediately about any changes in these symptoms.

Other medicines and Arzerra

Tell your doctor if you are taking any other medicines, if you?ve taken any recently, or if you start taking new ones. This includes herbal medicines and other medicines you can obtain without a prescription.

Pregnancy and breast-feeding

Arzerra is not usually recommended for use during pregnancy. There is no information about the safety of Arzerra in pregnant women.

• Tell your doctor if you are pregnant or planning to become pregnant. Your doctor will weigh up the benefit to you against the risk to your baby of taking Arzerra while you're pregnant.
• Use a reliable method of contraception to avoid becomingpregnant while you?re being treated with Arzerra, and for 12 months after your last treatment.
• If you do become pregnant during treatment with Arzerra, tell your doctor

It is not known whether the ingredients in Arzerra pass into human milk. Breast-feeding is not recommended during treatment with Arzerraand for 12 months after the last time you were treated with Arzerra.

Driving and using machines
Arzerra is unlikely to affect your ability to drive or use machines

Arzerra contains sodium

Arzerra contains 34.8 mg sodium in each 300 mg dose and 232 mg sodium in each 2,000 mg dose. You need to take this into account if you are on a controlled sodium diet.

If you have any questions on the use of Arzerra, ask the doctor who is giving you the infusion.

The usual dose

The usual dose of Arzerra for the first infusion is 300 mg. This dose will be increased, usually to 2,000 mg, for the remaining infusions.

How it is given

Arzerra is given into a vein ( intravenously) as an infusion (a drip) over several hours.

You will usually have a course of 12 infusions. You will be given an infusion once a week for eight weeks. This is followed by a four- to five-week gap. The remaining infusions will then be given once a month for four months.

Medicines given before each infusion

Before each infusion of Arzerra, you will be given pre-medication - medicines which help to reduce any infusion reactions. These may include anti-histamines, steroids and pain relievers. You will be checked closely and if you do have any reactions these will be treated.

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

Infusion reactionsMedicines of this type ( monoclonal antibodies) can cause infusion reactions, which are occasionally severe. They are more likely during the first treatment.

Very common symptoms of an infusion reaction (may affect more than 1 in 10 people):

• skin rash

Common symptoms of an infusion reaction (may affect up to 1 in 10 people):

• allergic reactions, sometimes severe with swelling of face or mouth causing difficulty in breathing ( anaphylactoid reactions)
• difficulty in breathing, shortness of breath, chest tightness, cough
• low blood pressure (can cause light-headedness when you stand up)
• flushing, high temperature
• excessive sweating
• shaking or shivering
• rapid heart beat
• feeling sick ( nausea)
• diarrhoea
• back pain
• high blood pressure
• itchy, bumpy rash ( hives)
• throat pain or irritation
• lack of energy
• blocked nose.

Tell your doctor or a nurse immediately if you get any of these symptoms.

Very common side effects

These may affect more than 1 in 10 people:

• infections of the lungs or airways ( respiratory tract) such as pneumonia
• infections of the ear, nose or throat

Very common side effects that may show up in your blood tests:

• low levels of white blood cells
• low levels of red blood cells (anaemia) 42

Common side effects

These may affect up to 1 in 10 people:

• a fever due to an infection and low levels of white blood cells
• blood infections
• urinary tract infections
• shingles
• cold sores
• blockage in the gut ( intestine), which may feel like stomach pain. If you have persistent stomach pain, see your doctor as soon as possible.

Common side effects that may show up in your blood tests:

• low levels of platelets in the blood (cells that help blood to clot)

Uncommon side effects

These may affect up to 1 in 100 people:

• increase in potassium, phosphate and uric acid in the blood that can cause kidney problems ( tumour lysis syndrome)

The symptoms of this condition include:

• producing less urine than normal
• muscle spasms. If you notice these symptoms, contact your doctor as soon as possible.

Uncommon side effects that may show up in your blood tests:

• problems with blood clotting
• the bone marrow failing to produce enough red or white blood cells

If you get side effectsTell your doctor if any of the side effects you experience becomesevere or troublesome, or if you notice any side effects not listed in this leaflet.

Keep out of the reach and sight of children.

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

Store and transport refrigerated (2 °C ? 8 °C).
Do not freeze.
Keep the vial in the outer carton in order to protect from light.

Store the diluted infusion solution between 2 °C and 8 °C and use within 24 hours. Any unused infusion solution should be discarded 24 hours after it was prepared.

Medicines should not be disposed of via wastewater or household waste. Your doctor or nurse will dispose of any medicine that is no longer required. These measures will help to protect the environment.

What Arzerra contains

• The active substance is ofatumumab. One ml of concentrate contains 20 mg of ofatumumab.
• The other ingredients are arginine, sodium acetate (E262), sodium chloride, polysorbate 80 (E433), edetate disodium (E386), hydrochloric acid (E507) (for pH-adjustment), water for injections..

What Arzerra looks like and contents of the pack

Arzerra is a colourless concentrate for solution for infusion.

Arzerra 100 mg is available in a pack containing 3 vials and two extension sets. Each glass vial is closed with a latex-free rubber stopper and aluminium over-seal, and contains 5 ml of concentrate (100 mg of ofatumumab).

Arzerra 1,000 mg is available in a pack containing 1 vial and two extension sets. Each glass vial is closed with a latex-free rubber stopper and aluminium over-seal, and contains 50 ml of concentrate (1,000 mg of ofatumumab).

Marketing Authorisation Holder

Glaxo Group Ltd, Glaxo Wellcome House, Berkeley Avenue, Greenford, Middlesex, UB6 0NN, United Kingdom.

Manufacturer
Glaxo Operations UK Limited (Trading as Glaxo Wellcome Operations), Harmire Road, Barnard Castle, County Durham, DL12 8DT, United Kingdom.

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

BelgiëBelgiqueBelgien GlaxoSmithKline s.a.n.v. TélTel 32 02 656 21 11 LuxembourgLuxemburg GlaxoSmithKline s.a.n.v. BelgiqueBelgien TélTel 32 02 656 21 11

Te. 359 2 953 10 34 Magyarország GlaxoSmithKline Kft. Tel. 36 1 225 5300

Malta GlaxoSmithKline Malta Tel 356 21 238131 eská republika GlaxoSmithKline s.r.o. Tel 420 222 001 111 gsk.czmailgsk.com

Danmark GlaxoSmithKline Pharma AS Tlf 45 36 35 91 00 dk-infogsk.com Nederland GlaxoSmithKline BV Tel 31 030 6938100 nlinfogsk.com

Deutschland GlaxoSmithKline GmbH Co. KG Tel. 49 089 36044 8701 produkt.infogsk.com Norge GlaxoSmithKline AS Tlf 47 22 70 20 00 firmapostgsk.no

Eesti GlaxoSmithKline Eesti OÜ Tel 372 6676 900 estoniagsk.com Österreich GlaxoSmithKline Pharma GmbH Tel 43 01 97075 0 at.infogsk.com

GlaxoSmithKline A.E.B.E. 30 210 68 82 100 Polska GSK Commercial Sp. z o.o. Tel. 48 022 576 9000

España GlaxoSmithKline, S.A. Tel 34 902 202 700 es-cigsk.com Portugal GlaxoSmithKline Produtos Farmacêuticos, Lda. Tel 351 21 412 95 00 FI.PTgsk.com

România GlaxoSmithKline GSK S.R.L. Tel 4021 3028 208 France Laboratoire GlaxoSmithKline Tél. 33 01 39 17 84 44 diamgsk.com

Ireland GlaxoSmithKline Ireland Limited Tel 353 01 4955000 Slovenija GlaxoSmithKline d.o.o. Tel 386 01 280 25 00 medical.x.sigsk.com

Ísland GlaxoSmithKline ehf. Sími 354 530 3700 Slovenská republika GlaxoSmithKline Slovakia s. r. o. Tel 421 02 48 26 11 11 recepcia.skgsk.com

Italia GlaxoSmithKline S.p.A. Tel 39 045 9218 111 SuomiFinland GlaxoSmithKline Oy PuhTel 358 010 30 30 30 Finland.tuoteinfogsk.com

GlaxoSmithKline Cyprus Ltd 357 22 39 70 00 Sverige GlaxoSmithKline AB Tel 46 08 638 93 00 info.produktgsk.com

Latvija GlaxoSmithKline Latvia SIA Tel 371 67312687 lv-epastsgsk.com United Kingdom GlaxoSmithKline UK Tel 44 0800 221441 customercontactukgsk.com

Lietuva

GlaxoSmithKline Lietuva UAB
Tel: + 370 5 264 90 00
info.lt@gsk.com

This leaflet was last approved in {MM/YYYY}.

This medicine has been given ?conditional approval?.
This means that there is more evidence to come about this medicine. The European Medicines Agency (EMA) will review new information on the medicine every year and this leaflet will be updated as necessary.

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

1 Before diluting Arzerra Check the Arzerra concentrate for particulate matter and discoloration prior to dilution. Ofatumumab should be a colourless solution. Do not use the Arzerra concentrate if there is discolouration.

Do not shake the ofatumumab vial for this inspection. The concentrate may contain a small amount of visible translucent-to-white, amorphous, ofatumumab particles. The filters provided as part of the extension set will remove these particles. 2 How to dilute the solution for infusion The Arzerra concentrate must be diluted in sodium chloride 9 mgml 0.9 solution for injection prior to administration, using aseptic technique.

300 mg dose - Use 3 x 100 mg/5 ml vials (15 ml total, 5 ml per vial):

• withdraw and discard 15 ml from a 1,000 ml bag of sodium chloride 9 mg/ml (0.9%) solution for injection
• withdraw 5 ml of ofatumumab from each of 3 x 100 mg vials and inject into the 1,000 ml bag
• do not shake, mix diluted solution bygentle inversion.

2,000 mg dose ? Use 2 x 1,000 mg/50 ml vials (100 ml total, 50 ml per vial):

• withdraw and discard 100 ml from a 1,000 ml bag of sodium chloride 9 mg/ml (0.9%) solution for injection
• withdraw 50 ml of ofatumumab from each of 2 x 1,000 mg vials and inject into the 1,000 ml bag
• do not shake, mix diluted solution by gentle inversion.

3 How to administer the diluted solution

Arzerra must not be administered as an intravenous push or bolus. Administer using an intravenous infusion pump, using the 0.2 micron in-line filter extension sets provided. The in-line filter must be used during the entire infusion.

The infusion must be completed within 24 hours after preparation. Discard any unused solution after this time.

Arzerra must not be mixed with, or administered as an infusion with other medicinal products or intravenous solutions. Flush line before and after ofatumumab administration with sodium chloride 9 mg/ml (0.9%) solution for injection to avoid this.

For the first and second infusion, administer over 6.5 hours (see section 4.2 of the SmPC), through a peripheral line or indwelling catheter, according to the schedule below:

Infusions 1 and 2: schedule

Time minutes mlhour 0 30 12 31 60 25 61 90 50 91 120 100 121 200

If the second infusion has been completed without a severe adverse reaction, the remaining infusions (3-12) should be administered over 4 hours (see section 4.2 of the SmPC), through a peripheral line or indwelling catheter, according to the schedule below:

Infusions 3 to 12: schedule

Time minutes mlhour 0 30 25 31 60 50 61 90 100 91 120 200 121 400

If any adverse reactions are observed, infusion rates should be reduced, according to section 4.2 of the Summary of Product Characteristics.

Any unused product or waste material should be disposed of in accordance with local requirements.