Package Insert: Information for the User

Beromun 1 mg Powder for Solution for Infusion

Tasonermina

Read this package insert carefully before starting to use this medication,because it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor.
• If you experience any adverse effects, consult your doctor, even if they are not listed in this package insert.

Beromuncontains the active ingredient tasonermin (alpha-1a tumor necrosis factor),produced by recombinant DNA technology. It belongs to a group of medications known as immunostimulants, which help the immune system fight cancer cells.

Beromun is used, in combination with medications containing melfalan, for the treatment of soft tissue sarcomas of arms and legs. The treatment aims to reduce the size of the tumor, making it easier to remove surgically or prevent severe damage to surrounding healthy tissue, thereby delaying or preventing the need for amputation of the arm or leg.

No use Beromunif

-you are allergic to tasonermina or any of the other components of this medication (listed in section6).

-you have serious heart problems

-you have a severe lung disorder

-you have or have had a stomach ulcer recently

-you have a low blood cell count or bleeding problems

-you have moderate or severe liver or kidney disease

-you cannot use vasopressors (used to increase low blood pressure), anticoagulants (used to prevent blood clotting) or radioactive markers

-you are also using heart toxic medications

-you have high levels of calcium in your blood

-you have certain infections that do not respond to antibiotics

-you have severe swelling of the affected arm or leg, due to local fluid formation, or significant fluid accumulation in the abdomen

-you are pregnant or plan to become pregnant

• if you are breastfeeding, you must stop for at least seven days after receiving Beromun treatment

Warnings and Precautions

Beromun will be administered by an expert and specialized doctor using the isolated limb perfusion (ILP) technique. This technique ensures that Beromun is limited to the affected arm or leg. It is essential that it does not reach other parts of your body, as systemic leakage can cause severe adverse effects on major organs.

During the ILP technique and the seven to ten-day hospital stay, your doctor will closely monitor your blood pressure, circulation, and any adverse effects. You may need to stay in an intensive care unit (ICU) for a short period immediately after the ILP.

Within the first three days after Beromun administration, 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 immediately reported to your treating doctor.

Other Medications and Beromun

Inform your doctor if you are using, have used recently, or may need to use any other medication. In particular, inform your doctor if you are using medications to lower blood pressure (for hypertension treatment).

During ILP, other medications will be administered to control pain, fever, blood pressure, and blood clotting, as well as general anesthesia.

Pregnancy and Lactation

You must not use Beromun if you are pregnant.

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

Driving and Machine Use

Not applicable.

Beromun Contains Sodium

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

The Container Contains Latex

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

Beromun will be administered using the isolated limb perfusion (ILP) technique, along with the antitumor medication melfalan. This will occur while you are unconscious, under the influence of a general anesthetic.

The blood flow into and out of your affected limb will be interrupted using a tourniquet. Blood, supplied with oxygen by a cardiopulmonary machine, will be pumped into the affected limb through a catheter inserted into the main artery while being drained (pumped out) from the main vein. Beromun and then melfalan will be injected into this circuit, and thus your 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. Beromun powder must be dissolved before use. The resulting solution will be administered into an artery of your affected arm or leg, using the isolated limb perfusion (ILP) technique for an initial period of 30 minutes.

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

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

The ILP technique allows the tumor cells in your limb to be exposed to a very high dose of Beromun and melfalan, enhancing their antitumor effect without reaching the rest of your body, where it could cause severe adverse effects.

Generally, you will not receive a second ILP with Beromun. If this occurs, it will not happen until at least six weeks after the first ILP.

If you use more Beromun than you should

Since Beromun is always administered by expert and qualified hospital doctors, an accidental overdose is extremely unlikely. Nevertheless, in the event that it occurs, your doctor will immediately wash your affected limb to eliminate Beromun and interrupt the ILP technique. In the event of a risk of severe adverse effects, your doctor will immediately transfer you to an intensive care unit (ICU) for careful monitoring and initiation of appropriate treatment.

In the event of severe systemic leakage of Beromun

If more than 10% of your Beromun dose 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 other questions about the use of this product, ask your doctor.

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

The side effects may be caused by Beromun, melfalan, the PEA 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 is severe enough to require amputation. If there is a risk of serious side effects, your doctor will immediately transfer you to an intensive care unit for closer monitoring and initiation of appropriate treatment.

During treatment with this medicine, the following side effects were observed (grouped according to the probability of their occurrence).

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

-Heart rhythm disorders (arrhythmia)

-Sensation of dizziness, vomiting

-Liver damage

-Rash

-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

-Decreased number of certain white blood cells and platelets

-Hypersensitivity reactions (allergy)

-Nerve damage

-Decreased consciousness

-Headache

-Heart problems that may 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, diarrhea

-Necrosis of the skin (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 and leg

-Muscle pain

-Protein in the urine

-Nocturnal sweating

-Necrosis of the tissues (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)

-Liquid in the lungs

-Stomach pain

-Inflammation of the gastric mucosa (gastritis)

-Temporary loss of fingernails or toenails of the affected arm or leg

-Renal failure

-Blood test showing changes in how the kidneys work

-Narrowing or closure of the blood vessels of the extremities that transport blood from the heart

Reporting of side effects

If you experience any type of side effect, consult your doctor, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through thenational notification system included in theAppendixV. By reporting side effects, you can contribute to providing more information about the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the packaging and on the vial label after CAD. The expiration date is the last day of the month indicated.

Store in a refrigerator (between 2°C and 8°C). Once the product has been reconstituted, it must be used immediately.

Composition of Beromun

-The active principle is tasonermin. Each vial contains 1 mg of tasonermin. The contents of a vial of Beromun powder must be reconstituted with 5.3 ml of sterile injectable sodium chloride solution at 0.9%.

-The other components (excipients) are dihydrogen phosphate of sodium dihydrate, dodecahydrate of disodium phosphate, and human serum albumin.

Appearance of the product and contents of the package

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

Each package contains 4 vials of powder.

Holder of the marketing authorization

Boehringer Ingelheim International GmbH

Binger Strasse 173

55216 Ingelheim am Rhein

Germany

Responsible for manufacturing

Boehringer Ingelheim RCV GmbH & Co KG

Dr. Boehringer-Gasse 5-11

1121 Vienna

Austria

For more information about this medication, please contact the local representative of the holder of the marketing authorization:

Last review date of this leaflet:

Other sources of information

The detailed information about this medication is available on the website of the European Medicines Agency:http://www.ema.europa.eu

This leaflet is available in all languages of the European Union/European Economic Area on the website of the European Medicines Agency.