Beromun 1 mg powder for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Beromun 1 mg powder for solution for infusion

Tasonermin

Read the entire leaflet carefully before you start using this medicine, because 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.
• If you experience any adverse reactions, consult your doctor, even if they are not listed in this leaflet.

Leaflet contents

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

1. What Beromun is and what it is used for

Beromun contains the active substance tasonermin (tumor necrosis factor alfa-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, in combination with medications containing melphalan, for the treatment of soft tissue sarcomas in the arms and legs. The treatment aims to reduce tumor size, thereby facilitating surgical removal of the tumor or preventing severe damage to nearby healthy tissue, and thus delaying or avoiding the need for amputation of the arm or leg.

2. What you need to know before using 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 significant heart problems
• if you have severe lung disorder
• if you have or have recently had a stomach ulcer
• if you have too low a 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 tracers
• if you are also using medicines that are toxic to the heart
• 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 accumulation, or significant fluid accumulation in the abdomen
• if you are pregnant or plan to become pregnant
  • if you are breastfeeding, you must stop breastfeeding for at least seven days after administration of Beromun

Warnings and precautions

Beromun will be administered by an experienced physician specialized in the technique of isolated limb perfusion (ILP). This technique ensures that Beromun remains confined to the affected arm or leg. It is important that the drug does not reach other parts of your body, as so-called systemic leakage can cause serious adverse effects in major organs.

During the ILP procedure and the seven to ten days following it, during which you will need to remain in hospital, your doctor will carefully monitor your blood pressure, circulation, and any adverse effects. You may need to stay in an intensive care unit (ICU) for a short period of time immediately after the ILP.

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

Other medicines and Beromun

Inform your doctor if you are taking, have recently taken, or might need to take any other medicines. In particular, you should inform your doctor if you are taking medicines to lower blood pressure (for treatment of hypertension).

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

Pregnancy and breastfeeding

You must not use Beromun if you are pregnant.

You must not breastfeed for at least seven days after receiving treatment with Beromun.

Driving and use of machines

Not applicable.

Beromun contains sodium

The reconstituted medicine contains up to 151.27 mg (6.58 mmol) of sodium per recommended dose. This should be taken into account in patients on low-sodium diets.

The container contains latex rubber

The container of this medicine contains latex rubber. It may cause severe allergic reactions.

3. How to use Beromun

Beromun will be administered using the isolated limb perfusion (ILP) technique, together with the antitumour medicinal product melphalan. This will occur while you are unconscious under general anaesthesia.

The blood flow into and out of your affected limb will be interrupted using a tourniquet. Blood, oxygenated by a cardio-pulmonary machine, will be pumped into the affected limb through a catheter inserted into the main artery, while simultaneously being drained (pumped out) through the main vein. Beromun and subsequently melphalan will be injected into this circuit, thereby exposing the affected limb 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. Beromun powder must be dissolved before use. The resulting solution will be administered into an artery of your affected arm or leg via the isolated limb perfusion (ILP) technique over an initial period of 30 minutes.

Melphalan will then be added, and the ILP technique will continue for another 60 minutes.

Finally, your limb will be flushed to remove any remaining Beromun and melphalan.

The ILP technique allows tumour cells in your limb to be exposed to a very high dose of Beromun and melphalan, enhancing their antitumour effect, while preventing these substances from reaching the rest of your body, where they could cause serious adverse effects.

Generally, you will not receive a second ILP with Beromun. If a second procedure is performed, it will not occur earlier than six weeks after the first ILP.

If you are given more Beromun than you should

Because Beromun is always administered by experienced and qualified hospital doctors, accidental overdose is extremely unlikely. However, if it were to occur, your doctor would immediately flush the affected limb to remove Beromun and discontinue the ILP procedure. In case of risk of serious adverse effects, your doctor would immediately transfer you to an intensive care unit (ICU) for close monitoring and initiation of 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 as described for the treatment of an overdose.

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

4. Possible adverse effects

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

Adverse effects may be caused by Beromun, melphalan, the PEA technique, or a combination of these factors. Some adverse effects may be serious, especially if Beromun reaches other parts of your body (systemic leakage). In approximately 2% of cases, Beromun may cause tissue damage in the affected arm or leg, which is severe enough to require amputation. If there is any risk of serious adverse effects, your doctor will immediately transfer you to an intensive care unit for closer monitoring and to initiate appropriate treatment.

The following adverse effects have been observed during treatment with this medicine (grouped according to the likelihood of occurrence).

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

• heart rhythm disorders (arrhythmia)
• dizziness, vomiting
• liver injury
• skin blisters
• fever (usually mild to moderate), chills
• pain in the affected arm or leg
• tiredness (fatigue)

Common (may affect up to 1 in 10 people)

• infections
• local wound infections
• decreased number of certain white blood cells and platelets
• hypersensitivity reactions (allergy)
• nerve injury
• decreased consciousness
• headache
• heart problems that may cause shortness of breath or swelling of the ankles
• blood clot formation in the arteries or veins of the affected arm or leg (thrombosis)
• low blood pressure, shock
• serious breathing problems
• constipation, diarrhea
• skin necrosis (death of skin cells) in the affected arm or leg
• swelling of the ankles, feet, or fingers due to fluid accumulation in the affected arm or leg
• "compartment syndrome", a condition 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) in 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
• inflammation of the gastric mucosa (gastritis)
• temporary loss of fingernails or toenails in the affected arm or leg
• kidney failure
• blood tests showing changes in kidney function
• narrowing or blockage of blood vessels in the limbs that carry blood away from the heart

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, even if it is a possible adverse effect not listed in this leaflet. You may 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.

5. Storage of Beromun

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

Do not use this medicine after the expiry date stated on the carton and on the label of the vial after EXP. The expiry date refers to the last day of the month indicated.

Store in a refrigerator (between 2°C and 8°C). Once reconstituted, the 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 0.9% sodium chloride injection solution.
• The other components (excipients) are disodium hydrogen phosphate dodecahydrate, sodium dihydrogen phosphate dihydrate, and human serum albumin.

Appearance of the product and contents of the pack

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

Each pack contains 4 powder vials.

Marketing Authorization 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

Further information on this medicinal product is available upon request by contacting the local representative of the Marketing Authorization Holder:

Date of the most recent review of this leaflet:

Other sources of information

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

This leaflet can be found on the website of the European Medicines Agency in all languages of the European Union/European Economic Area.