BEROMUN 1 mg/5 ml powder and solvent for solution forinfusion

BEROMUN contains the active substance tasonermin (tumor necrosis factor alfa-1a), produced by recombinant DNA technology. It belongs to a class of medicines known as immunostimulants, which help your body?s immune system fight cancer cells.

Beromun is used, together with melphalan containing medicine, for the treatment of soft tissue sarcoma of the arms and legs. By reducing the size of the tumour, the treatment is intended to facilitate the removal of the tumor by surgery or to prevent severe damage to the surrounding healthy tissue and thus to delay or prevent the need for arm or leg amputation.

Do not use BEROMUN

• if you are allergic (hypersensitive) to tasonermin or any of the other ingredients of BEROMUN (such as human serum albumin).
• if you have significant heart problems
• if you have severe lung disease
• if you have or have recently had a stomach ulcer
• if you have too low numbers of blood cells or bleeding problems
• if you have moderate to severe liver or kidney disease
• if you cannot use vasopressors (used to increase low blood pressure), anticoagulants (used to prevent blood clotting) or radioactive tracers
• if you are also using medicines with heart toxicity
• if you have raised levels of calcium in your blood
• if you have certain infections which do not respond to antibiotics
• if you have severe swelling of the affected arm or leg due to local fluid build-up, or severe fluid build-up in the abdomen
• if you are pregnant or planning to become pregnant.
• if you are breast-feeding, you must stop for at least seven days after receiving BEROMUN

Take special care with BEROMUN

Beromunwill be administered by a doctor who is experienced and skilled in isolated limb perfusion (ILP). This technique ensures that BEROMUNis kept within the affected arm or leg. It is important that it does not reach other parts of your body, because this so-called systemic leakage could cause serious side effects on the main organs of the body.

During the IPL and the seven to ten day period you will need to stay in hospital afterwards, your doctor will carefully monitor your blood pressure, circulation and any side effects. You may have to stay in an intensive care unit (ICU) directly after the ILP for a short time.

A rare condition called ?compartment syndrome? may develop within the first three days after BEROMUN administration. Symptoms of muscle damage at the perfused limb include pain, swelling, as well as neurological symptoms (e. g. paraesthesia, paralysis), all of which should be reported immediately to the treating physician.

Using other medicines

Please tell your doctor if you are using or have recently used any other medicines, including medicines obtained without a prescription. In particular, you should tell your doctor if you are using medicines to lower blood pressure (to treat hypertension).

For ILP, you will also receive other medicines to control pain, fever, blood pressure and blood clotting, as well as general anaesthesia.

Pregnancy and breast-feeding

You must not use BEROMUN if you are pregnant.
You must not breast-feed for at least seven days after treatment with BEROMUN.

Important information about some of the ingredients of BEROMUN

This medicinal product contains up to 77 mg (3.3 mmol) sodium per recommended dose. To be taken into consideration by patients on a controlled sodium diet.

Beromun will be administered by isolated limb perfusion (ILP), together with the anti-tumour agent melphalan. This will occur whilst you are unconscious, under the influence of a general anaesthetic.

The blood flow to and from your affected limb will be stopped using a tourniquet. Blood, supplied with oxygen by a heart and lung machine, is pumped into your affected limb via a catheter in the main artery, while it is drained (pumped out) from the main vein. BEROMUN and then melphalan are injected into this circuit, over a total of 90 minutes the affected limb will be exposed to Beromun.

The dose of BEROMUN depends on the affected limb, usually 3 mg for the arm and 4 mg for the leg. BEROMUN powder has to be dissolved before use. The resulting solution will be administered into an artery in your affected arm or leg by ILP for an initial period of 30 minutes.
After that, melphalan will be added and the ILP continued for another 60 minutes. Finally, your limb will be washed out to remove the rest of BEROMUNand melphalan.

ILP allows that tumour cells in your limb can be exposed to a very high dose of BEROMUN and melphalan, enhancing their anti-tumour effect, but without reaching the rest of the body, where they could cause serious side effects.

You will usually not receive a second ILP with Beromun. If you do, this will not be until at least six weeks after your first ILP.

If you use more BEROMUN than you should

As BEROMUNis always administered by experienced and qualified hospital doctors, accidental overdose is extremely unlikely. However, should this occur, your doctor will immediately wash out your affected limb to remove BEROMUN, and the ILP will be stopped. If there is any risk of serious side effects, your doctor will immediately transfer you to an intensive care unit to closely monitor you and start adequate treatment.

If there is significant systemic leakage of BEROMUN

If more than 10% of your BEROMUN dosereaches the main part of your body, your doctor will take similar measures as in the case of overdose.

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

Side effects may be caused by BEROMUN, melphalan, the ILP technique or a combination of these factors. Some of the side effects can be serious, particularly if BEROMUNreaches other parts of your body (systemic leakage). In approximately 2% of cases, BEROMUNmay cause tissue damage in your affected arm or leg which is severe enough to require amputation.

Side effects may occur with certain frequencies, which are defined as follows:

• very common: affects more than 1 user in 10
• common: affects 1 to 10 users in 100
• uncommon: affects 1 to 10 users in 1,000
• rare: affects 1 to 10 users in 10,000
• very rare: affects less than 1 user in 10,000
• not known: frequency cannot be estimated from the available data.

Local effects that you may experience in your affected arm or leg shortly after BEROMUN administration include:

Very common local side effects

• pain and swelling, or infections, in the affected arm or leg
• damage to nerves of the affected arm or leg
• blistering of the skin, sometimes resulting in local wound infections
• fluid build-up in the affected arm or leg

Common local side effects

• blood clot formation in the artery or vein of the affected arm or leg
• temporary loss of finger or toe nails of the affected arm or leg - ?compartment syndrome?, a medical condition characterised by pain, swelling and neurological symptoms, as well as muscle damage in the affected arm or leg
• hypersensitivity reaction

General effects that you may experience due to leakage of BEROMUN into other parts of the body include:

Very common general side effects

• fever (usually mild to moderate), chills
• disturbances in your heart beat (cardiac arrhythmia)
• nausea, vomiting
• fatigue
• liver damage
• infections

Common general side effects

• heart disorders
• low blood pressure, shock
• headache, decreased consciousness
• muscle pain, night sweats
• protein in urine
• tiredness
• blood poisoning (sepsis)
• severe breathing problems
• constipation, diarrhoea
• reductions in numbers of certain white blood cells and platelets
• nerve damage
• hypersensitivity (allergic) reactions

Uncommon general side effects

• kidney failure

These general side effects could become more serious, particularly if the systemic leakage exceeds 10% of the administered dose. If there is any risk of serious side effects, your doctor will immediately transfer you to an intensive care unit to closely monitor you and start adequate treatment.

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.

Keep out of the reach and sight of children.

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

Store in a refrigerator (2°C - 8°C).

What BEROMUN contains

• The active substance is tasonermin. Each vial contains 1 mg tasonermin. After reconstitution, each ml solution contains 0.2 mg tasonermin.
• The other ingredients are sodium dihydrogen phosphate dihydrate, disodium phosphate dodecahydrate, sodium chloride and human serum albumin.
• The solvent contains sodium chloride and water for injections.

What BEROMUN looks like and contents of the pack

BEROMUN is a white to off-white powder for solution for infusion supplied in a glass vial with rubber stopper and sealed with aluminium flip-off cap.
Each solvent glass ampule contains 5 ml sodium chloride 9 mg/ml (0.9%) solution for injection. Each pack contains 4 vials of powder and 4 ampoules of solvent.

Marketing Authorisation Holder

Boehringer Ingelheim International GmbH
Binger Strasse 173
55216 Ingelheim am Rhein
Germany

Manufacturer

Boehringer Ingelheim Austria GmbH
Dr. Boehringer-Gasse 5-11
1121 Vienna
Austria

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

BelgiëBelgiqueBelgien SCS Boehringer Ingelheim Comm.V TélTel 32 2 773 33 11 LuxembourgLuxemburg SCS Boehringer Ingelheim Comm.V TélTel 32 2 773 33 11

359 2 958 79 98 Magyarország Boehringer Ingelheim RCV GmbH Co KG Magyarországi Fióktelepe Tel 36 1 299 8900

eská republika Boehringer Ingelheim spol. s r.o. Tel 420 234 655 111 Malta Boehringer Ingelheim Ltd. Tel 44 1344 424 600

Danmark Boehringer Ingelheim Danmark AS Tlf 45 39 15 88 88 Nederland Boehringer Ingelheim b.v. Tel 31 0 800 22 55 889

Deutschland Boehringer Ingelheim Pharma GmbH Co. KG Tel 49 0 800 77 90 900 Norge Boehringer Ingelheim Norway KS Tlf 47 66 76 13 00

Österreich Boehringer Ingelheim RCV GmbH Co KG Tel 43 1 80 105-0 Eesti Boehringer Ingelheim Pharma GmbH Eesti Filiaal Tel 372 60 80 940

Boehringer Ingelheim Ellas A.E. T 30 2 10 89 06 300 Polska Boehringer Ingelheim Sp. z o.o. Tel 48 22 699 0 699

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France Boehringer Ingelheim France S.A.S. Tél 33 3 26 50 45 33 România Boehringer Ingelheim RCV GmbH Co KG Viena - Sucursala Bucuresti Tel 40 21 330 99 63

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Boehringer Ingelheim Ellas A.E. T 30 2 10 89 06 300 Sverige Boehringer Ingelheim AB Tel 46 8 721 21 00

United Kingdom Boehringer Ingelheim Ltd. Tel 44 1344 424 600 Latvija Boehringer Ingelheim Pharma GmbH Prstvniecba Latvij Tel 371 67 240 068

Lietuva
Boehringer Ingelheim Pharma Ges mbH
Atstovyb- Lietuvoje
Tel: +370 37 473922

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