BEROMUN 1 mg POWDER FOR SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the User

Beromun 1mg powder for solution for perfusion

Tasonermin

Read all of this leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor.
• If you experience any side effects, talk to your doctor, even if they are not listed in this leaflet.

Contents of the package leaflet

1. What is Beromun and what is it used for
2. What you need to know before you use Beromun
3. How to use Beromun
4. Possible side effects
5. Storage of Beromun
6. Contents of the pack and other information

1. What is Beromun and what is it used for

Beromun contains the active substance tasonermin (tumour necrosis factor alpha-1a), produced by recombinant DNA technology. It belongs to a group of medicines known as immunostimulants, which help the immune system to fight cancer cells.

Beromun is used, together with medicines containing melfalan, for the treatment of soft tissue sarcomas of the arms and legs. The treatment aims, by reducing the size of the tumour, to facilitate the removal of the tumour by surgery or to prevent serious damage to the surrounding healthy tissue and thus to delay or prevent the need to amputate the arm or leg.

2. What you need to know before you use Beromun

Do not use Beromun

• if you are allergic to tasonermin or any of the other ingredients of this medicine (listed in section 6).
• if you have serious heart problems
• if you have severe lung disease
• if you have or have recently had a stomach ulcer
• if you have a very low blood cell count or bleeding problems
• if you have moderate or severe liver or kidney disease
• if you cannot use vasopressors (used to increase low blood pressure), anticoagulants (used to prevent blood clotting) or radioactive markers
• if you are also using heart-toxic medicines
• if you have high levels of calcium in your blood
• if you have certain infections that do not respond to antibiotics
• if you have severe swelling of the affected arm or leg due to local fluid formation, or significant fluid accumulation in the abdomen
• if you are pregnant or planning to become pregnant
  • if you are breast-feeding, you must interrupt it for at least seven days after administration of Beromun

Warnings and precautions

Beromun will be administered by an expert doctor, specialized in the technique of isolated limb perfusion (ILP). This technique ensures that Beromun remains limited to the affected arm or leg. It is essential that it does not reach other parts of your body, because so-called systemic leakage can cause serious side effects in the major organs of the body.

During the ILP technique and the period of seven to ten days thereafter, during which you will have to stay in the hospital, your doctor will closely monitor your blood pressure, circulation, and any side effects. You may need to stay in an intensive care unit (ICU) for a short period immediately after ILP.

During the first three days after administration of Beromun, a disease called "compartment syndrome" may develop. Symptoms of muscle deterioration in the perfused limb include pain, swelling, and neurological symptoms (e.g., paresthesia, paralysis), and should be reported immediately to the doctor treating you.

Other medicines and Beromun

Tell your doctor if you are using, have recently used, or might use any other medicines. In particular, you should tell your doctor if you are using medicines to lower blood pressure (for the treatment of hypertension).

During ILP, you will be given other medicines to control pain, fever, blood pressure, and blood clotting, as well as general anesthesia.

Pregnancy and breast-feeding

You must not use Beromun if you are pregnant.

You must not breast-feed your child for at least seven days after receiving treatment with Beromun.

Driving and using machines

Not applicable.

Beromun contains sodium

The reconstituted medicinal product contains up to 151.27 mg (6.58 mmol) of sodium per recommended dose. This should be taken into account for patients on a low-sodium diet.

The container contains latex

The container of this medicinal product contains latex. It may cause severe allergic reactions.

3. How to use Beromun

Beromun will be administered through the technique of isolated limb perfusion (ILP), together with the anti-tumour medicine melfalan. This will happen while you are unconscious, under the influence of general anesthesia.

The blood flow entering and leaving your affected limb will be interrupted using a tourniquet. The blood, supplied with oxygen by a heart-lung machine, will be pumped into the affected limb through a catheter inserted into the main artery, while it is drained (pumped out) from the main vein. Beromun and then melfalan will be injected into this circuit, and in this way, the affected limb will be exposed to Beromun for a total of 90 minutes.

The recommended dose of Beromun depends on the affected limb and is usually 3 mg for the arm and 4 mg for the leg. The Beromun powder must be dissolved before use. The resulting solution will be administered into an artery of your affected arm or leg, through the ILP technique, over an initial period of 30 minutes.

Then, melfalan will be added, and the ILP technique will continue for another 60 minutes.

Finally, your limb will be washed to remove any remaining Beromun and melfalan.

The ILP technique allows the tumour cells in your limb to be exposed to a very high dose of Beromun and melfalan, enhancing their anti-tumour effect, but without reaching the rest of your body, where it could cause serious side effects.

Normally, you will not receive a second ILP with Beromun. If it happens, it will not take place until at least six weeks after the first ILP.

If you use more Beromunthan you should

Because Beromun is always administered by expert hospital doctors, accidental overdose is extremely unlikely. Nevertheless, if it were to happen, your doctor will immediately wash the affected limb to remove Beromun and interrupt the ILP technique. In case of risk of serious side effects, your doctor will immediately transfer you to an intensive care unit (ICU) to closely monitor you and initiate appropriate treatment.

In case of severe systemic leakage of Beromun

If more than 10% of your dose of Beromun reaches the main part of your body, your doctor will take similar measures to those described for the treatment of an overdose.

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

4. Possible side effects

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

Side effects can be caused by Beromun, melfalan, the ILP technique, or a combination of these factors. Some side effects can be serious, especially if Beromun reaches other parts of your body (systemic leakage). In approximately 2% of cases, Beromun can cause tissue damage in the affected arm or leg, which may be severe enough to require amputation. 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 initiate appropriate treatment.

During treatment with this medicine, the following side effects were observed (grouped by frequency of occurrence).

Very common (may affect more than 1 in 10 people)

• heart rhythm disorders (arrhythmia)
• feeling of dizziness, vomiting
• liver damage
• blisters on the skin
• fever (usually mild to moderate), chills
• pain in the affected arm and leg
• fatigue (tiredness)

Common (may affect up to 1 in 10 people)

• infections
• local wound infections
• decrease in the number of certain white blood cells and platelets
• hypersensitivity reactions (allergy)
• nerve damage
• decreased consciousness
• headache
• heart problems that can cause shortness of breath or swelling of the ankles
• formation of blood clots in the arteries or veins of the affected arm or leg (thrombosis)
• low blood pressure, shock
• severe respiratory problems
• constipation, diarrhoea
• skin necrosis (death of skin cells) of the affected arm or leg
• swelling of the ankles, feet, or toes caused by fluid accumulation in the affected arm or leg
• "compartment syndrome", a disease characterized by pain, swelling, and neurological symptoms, as well as muscle damage in the affected arm or leg
• muscle pain
• protein in the urine
• night sweats
• tissue necrosis (death of tissue cells) of the affected arm or leg, which may be severe enough to require amputation

Uncommon (may affect up to 1 in 100 people)

• blood infection (sepsis)
• fluid in the lungs
• stomach pain
• gastritis (inflammation of the stomach lining)
• temporary loss of fingernails or toenails of the affected arm or leg
• kidney failure
• blood tests showing changes in kidney function
• narrowing or closure of the blood vessels in the limbs that carry blood from the heart

Reporting of side effects

If you experience any side effects, talk to your doctor, even if they are not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Beromun

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and on the label of the vial after EXP. The expiry date is the last day of the month shown.

Store in a refrigerator (2°C - 8°C). The reconstituted product should be used immediately.

6. Contents of the pack and other information

Composition of Beromun

• The active substance is tasonermin. Each vial contains 1 mg of tasonermin. The contents of one vial of Beromun powder must be reconstituted with 5.3 ml of sterile sodium chloride 0.9% injection solution.
• The other ingredients (excipients) are sodium dihydrogen phosphate dihydrate, disodium phosphate dodecahydrate, and human serum albumin.

Appearance and pack contents

Beromun is a white to almost white powder for solution for perfusion (powder for perfusion), provided in a glass vial with a rubber stopper and sealed with an aluminium flip-off cap.

Each pack contains 4 vials of powder.

Marketing authorisation holder

Boehringer Ingelheim International GmbH

Binger Strasse 173

55216 Ingelheim am Rhein

Germany

Manufacturer

Boehringer Ingelheim RCV GmbH & Co KG

Dr. Boehringer-Gasse 5-11

1121 Vienna

Austria

You can obtain further information on this medicine from the representative of the marketing authorisation holder:

Date of last revision of this leaflet:

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu

The leaflet for this medicine can be found on the European Medicines Agency website in all languages of the European Union/European Economic Area.