Prospect: information for the user

NexoBrid 2 g powder and gel for gel

concentrated enriched proteolytic enzymes bromelain

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

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor.
• If you or your child experience adverse effects, consult your doctor, even if they are not listed in this prospect. See section 4.

What is NexoBrid

NexoBrid contains a mixture of enzymes called "concentrated proteolytic enzyme enriched bromelain concentrate", which is produced from an extract of the pineapple plant stem.

What is NexoBrid used for

NexoBrid is used to remove burned tissue from deep or partially deep skin burns in adults, adolescents, and children of all ages.

The use of NexoBrid may reduce the need or extent of surgical removal of burned tissue and/or skin transplants.

No use NexoBrid:

• If you or your child are allergic to bromelain
• If you or your child are allergic to pineapple
• If you or your child are allergic to papaya/papain
• If you or your child are allergic to any of the other components of the powder or gel (listed in section 6).

Warnings and precautions

Consult your doctor or nurse before starting to use NexoBrid if:

• You or your child have a heart condition;
• You or your child have diabetes;
• You or your child have an active stomach ulcer;
• You or your child have a vascular disease (with or without vascular occlusion);
• You or your child have enlarged veins in the area near the burn;
• You or your child have implants or pacemakers or a vascular shunt;
• You or your child have bleeding problems or are taking anticoagulant medications;
• Your wounds or your child's wounds have been in contact with chemicals and other hazardous substances;
• You or your child have a lung disease;
• You or your child present or may present lung damage due to smoke inhalation;
• You or your child are allergic to latex, bee stings, or olive pollen. In this case, you or your child may also experience allergic reactions to NexoBrid.

Allergic reactions can cause, for example, breathing difficulties, skin swelling, hives, other skin reactions, skin redness, low blood pressure, rapid heart rate, and abdominal discomfort, or a combination of these effects. If you or your child notice any of these signs or symptoms, inform your doctor or caregiver immediately.

Allergic reactions can be severe and require medical treatment.

In case of skin contact, rinse NexoBrid off with water. This is intended to reduce the likelihood of an allergic reaction to NexoBrid.

The use of NexoBrid to remove burned tissue may cause fever and inflammation or wound infection, and possibly a general infection. You and your child may be periodically examined for these possible problems and may receive medications to prevent or treat infections.

NexoBrid may reduce the blood's ability to form clots, increasing the risk of bleeding. NexoBrid should be used with caution if you or your child are taking medications that reduce the blood's ability to form clots (called anticoagulants) or if you or your child have a tendency to bleed, a stomach ulcer, a blood intoxication, or another condition that may cause bleeding. After treatment with NexoBrid, your doctor may check your blood coagulation levels.

Avoid direct contact of NexoBrid with the eyes. If NexoBrid enters the eyes, rinse them with plenty of water for at least 15 minutes.

To prevent wound healing problems, the treated burn will be covered as soon as possible with dressings or temporary or permanent skin substitutes.

NexoBrid should not be used on chemical burns, electrical burns, burns on the foot in patients with diabetes or vascular occlusive disease, contaminated burns, or burns that may come into contact with foreign materials (such as implants, pacemakers, and shunts) or large-caliber blood vessels, the eyes, or other important parts of the body. NexoBrid should be used with caution in areas with varicose veins to prevent the risk of bleeding from them.

Use of NexoBrid with other medications

Inform your doctor if you or your child are using, have used recently, or may need to use any other medications.

Your doctor will exercise caution and monitor for signs of decreased blood coagulation or bleeding when prescribing other medications that affect blood coagulation, as NexoBrid may reduce it.

NexoBrid may:

• increase the effects of certain medications whose inactivation is performed by liver enzymes called CYP2C8 and CYP2C9. This is because NexoBrid can be absorbed from the burn wound into the bloodstream. Some examples of such medications are:

• amiodarone (used to treat certain types of irregular heartbeat),
• amodiaquine and chloroquine (used to treat malaria and some forms of inflammation),
• fluvastatin (used to treat high cholesterol),
• pioglitazone, repaglinide, tolbutamide, and glipizide (used to treat diabetes),
• paclitaxel (used to treat cancer),
• torsemide (used to increase urine flow),
• ibuprofen (used to treat fever, pain, and some forms of inflammation),
• losartan (used to treat high blood pressure (hypertension)),

• celecoxib (used to treat some forms of inflammation),
• warfarin (used to reduce blood coagulation),
• phenytoin (used to treat epilepsy).

• intensify your reaction or your child's reaction to cancer chemotherapy fluorouracil and vincristine.
• cause an unwanted drop in blood pressure when you or your child are treated with medications called IECA, which are used to treat high blood pressure (hypertension) and other conditions.
• increase drowsiness when used together with medications that can cause drowsiness. These medications include, for example, sedatives, tranquilizers, some pain relievers, and antidepressants.
• The silver sulfadiazine or povidone-iodine at the wound site may reduce the effectiveness of the medication.

If you have doubts about whether you or your child are taking any of the previously mentioned medications, speak with your doctor before using NexoBrid.

Pregnancy and breastfeeding

NexoBrid is not recommended during pregnancy.

As a precaution, do not breastfeed for at least 4 days after applying NexoBrid.

If you are pregnant or breastfeeding, think you may be pregnant, or intend to become pregnant, consult your doctor or pharmacist before using this medication.

NexoBrid application is performed only by specialists in burn clinics. It must be prepared directly before use and applied by a doctor or other healthcare professional.

2 g of NexoBrid powder mixed with 20 g of gel with a thickness of 1.5 to 3 millimeters per burned area of 1% of the body surface area of an adult patient is applied.

It should be left for 4 hours, to be removed afterwards. A subsequent second application is not recommended.

• NexoBrid should not be applied to more than 15% of the total body surface area in adults and children/adolescents aged 4 to 18 years.
• This medication should not be applied to more than 10% of the total body surface area in children aged 0 to 3 years.

At the end of this leaflet, in the section for medical or healthcare professionals, instructions for preparing the NexoBrid gel are included.

Before its application on a burn, NexoBrid powder is mixed to form a gel. It must be used within a maximum of 15 minutes after mixing.

• NexoBrid will be applied to a clean, moist, and blister-free lesion area.

• Other medications (such as silver sulfadiazine or povidone-iodine) will be removed from the wound before NexoBrid application.

• A dressing impregnated with an antibacterial solution will be applied before NexoBrid application for 2 hours.

• You and your child will be given an appropriate medication to prevent and treat pain at least 15 minutes before applying NexoBrid and before extraction.

• After NexoBrid and dead tissue extraction from the wound, a dressing impregnated with an antibacterial solution will be applied for another 2 hours.

• The vial containing the powder, the gel bottle, and the prepared gel mixture must be used for single use only.

If too much NexoBrid is used

If too much NexoBrid gel is applied to a burn, the excess gel must be cleaned.

If you have any other questions about the use of this medication, ask your doctor.

Like all medications, NexoBrid can produce adverse effects, although not all people will experience them.

Reactions to NexoBrid can occur, which may cause, for example, respiratory difficulties, skin swelling, rashes, skin redness, low blood pressure, rapid heart rate, and nausea/vomiting/abdominal cramps, or a combination of these effects. If you or your child notice any of these symptoms or signs, inform your doctor or caregiver immediately.

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

• Fever

Frequent(may affect up to 1 in 10 people)

• Pain in the treated area of the burn (even though medications are used to prevent or reduce pain caused by the removal of burned tissue)
• Burn wound infection, including skin infection around the wound (cellulitis)
• Wound complications, including wound deepening, wound opening, wound drying or dehiscence, and failure of proper healing of skin grafts
• Rash or redness in the area around the burn
• Mild allergic reactions such as rash
• Fast heart rate
• Itching in the burned area, which is very frequent as part of the normal healing process of the burn

Infrequent

• Bruising in the wound area

Unknown Frequency(frequency cannot be estimated from available data)

• Severe allergic reactions, including anaphylaxis

Reporting Adverse Effects

If you or your child experience any type of adverse effect, consult your doctor or nurse, even if it is a possible adverse effect not listed in this prospectus. You can also report them directly through thenational notification system included in theAppendix V. By reporting adverse effects, you can contribute to providing more information about the safety of this medication.

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

Do not use NexoBrid after the expiration date that appears on the vial, bottle, and box label after “EXP/CAD”. The expiration date is the last day of the month indicated.

Store and transport refrigerated (between 2 °C and 8 °C).

NexoBrid must be stored in an upright position to maintain the gel at the bottom of the bottle and in the original packaging to protect it from light.

Do not freeze.

NexoBrid must be used within a maximum of 15 minutes after mixing the powder with the gel.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of NexoBrid

• The active principle (from the vial powder) is a concentrated solution of enriched proteolytic enzymes in bromelain: one vial contains 2 g, corresponding to 0.09 g/g of concentrated solution of enriched proteolytic enzymes in bromelain after mixing.
• The other components are:

• for the powder, ammonium sulfate and acetic acid
• and for the gel, carbomer 980, anhydrous sodium phosphate, sodium hydroxide, and water for injection.

Appearance of the product and contents of the package

This medicinal product is supplied in the form of powder and gel for gel (powder in a vial [2 g] and gel in a bottle [20 g]), package size 1 (one package contains a vial of powder and a bottle of gel).

The powder varies between off-white and light brown and the gel is clear and colorless.

Further information about this medicinal product can be obtained by contacting the marketing authorization holder.

Marketing authorization holder

MediWound Germany GmbH

Hans-Sachs-Strasse 100

65428 Rüsselsheim

Germany

e-mail: [email protected]

Responsible person for manufacturing

Diapharm GmbH & Co. KG

Am Mittelhafen 56

48155 Münster

Germany

Last review date of this leaflet:

Other sources of information

Detailed information on this medicinal product is available on the website of the European Medicines Agency:http://www.ema.europa.eu.There are also links to other websites on rare diseases and orphan medicinal products.

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This information is intended solely for healthcare professionals:

Preparation and administration

From a microbiological point of view and since the enzymatic activity of the product decreases progressively after mixing, the reconstituted product must be used immediately after preparation (within a maximum of 15 minutes).

NexoBrid must be applied to a moist, clean, and keratin-free lesion area (after blister removal).

Topical medications (such as silver sulfadiazine or povidone-iodine) should be removed from the lesion area and the wound should be cleaned before applying NexoBrid.

Patient and lesion area preparation

• NexoBrid cannot be used to treat a total lesion area greater than 15% of the ASCT in adults and children/adolescents >3 years; in children 0 to 3 years, no more than 10% of the ASCT can be treated.
• Debridement is a painful procedure and requires adequate analgesia or anesthesia. Pain treatment should be initiated at least 15 minutes before NexoBrid application, in accordance with standard practices for large dressing changes.
• The wound should be thoroughly cleaned and the superficial keratin layer or blisters should be removed from the lesion area, as keratin will isolate the eschar from direct contact with NexoBrid and prevent its removal by NexoBrid.
• A dressing impregnated with an antibacterial solution should be applied for 2 hours.
• All topical antibacterial medications should be removed before applying NexoBrid. Residual antibacterial medications may reduce NexoBrid activity, reducing its effectiveness.
• The area from which the eschar is to be removed should be surrounded with a sterile petroleum jelly ointment barrier, applied a few centimeters outside the treatment area (using a dispenser). The petroleum jelly layer should not come into contact with the area to be treated to prevent the eschar from being covered, as this would isolate it from direct contact with NexoBrid.

To prevent possible irritation of the abraded skin by accidental contact with NexoBrid and possible bleeding from the wound, acute lesion areas such as lacerations or incisions (tearing of the skin's scabs) should be protected with a sterile greasy ointment or a greasy dressing (e.g. vaseline gauze).

This medicinal product should be used with caution in areas with varices, in order to avoid erosion of the venous wall and the risk of bleeding.

• A 9 mg/ml (0.9%) sterile isotonic sodium chloride solution should be sprayed on the burn. The wound should be kept moist during the application procedure.

Preparation of NexoBrid gel (mixing powder with gel)

• NexoBrid powder and gel are sterile. Aseptic technique should be used when mixing NexoBrid powder with the gel. The powder should not be inhaled. Gloves and protective equipment, as well as surgical masks and protective glasses, should be used.
• The vial of NexoBrid powder should be opened by carefully removing the aluminum closure cap and removing the rubber stopper.
• When opening the gel bottle, it should be confirmed that the tamper-evident ring is separating from the bottle closure. If the tamper-evident ring was already separated from the bottle closure before opening, the gel bottle should be discarded and a new gel bottle used.
• NexoBrid powder is then transferred to the corresponding gel bottle.

• NexoBrid powder and gel should be mixed thoroughly until a uniform mixture of light brown to brown color is obtained. This usually requires mixing NexoBrid powder and gel for 1 to 2 minutes.
• NexoBrid gel should be prepared at the patient's bedside.

Application of NexoBrid

• The area to be treated should be moistened by spraying a sterile saline solution around the petroleum jelly barrier.
• NexoBrid should be applied topically to the burn within 15 minutes of mixing, with a thickness of 1.5 to 3 mm.
• The burn should then be covered with a sterile occlusive dressing that adheres to the sterile petroleum jelly barrier applied in accordance with the previous instructions (seePatient and lesion area preparation). The NexoBrid gel should fill the entire occlusive dressing, and special care should be taken not to leave any air under this occlusive dressing. Gently pressing the area of contact between the occlusive dressing and the barrier ensures adherence between the occlusive dressing and the barrier, as well as complete confinement of NexoBrid in the treatment area.
• The prepared wound should be covered with a thick, loose, and padded dressing, secured with a bandage.
• The dressing should remain on the wound for 4 hours.

Removal of NexoBrid

• Removal of NexoBrid is a painful procedure and requires adequate analgesia or anesthesia. Adequate analgesic medication should be administered at least 15 minutes before NexoBrid application.
• After 4 hours of treatment with NexoBrid, the occlusive dressing should be removed using aseptic techniques.
• The petroleum jelly barrier should be removed using a sterile instrument with rounded edges (e.g., a tongue depressor).
• The dissolved eschar should be removed from the wound using a sterile instrument with rounded edges.
• The wound should be thoroughly cleaned first with a large, dry, sterile gauze or cloth and then with a sterile gauze or cloth impregnated with a 9 mg/ml (0.9%) sterile isotonic sodium chloride solution. The treated area should be rubbed until a pinkish surface with bleeding points or a white tissue appears. This rubbing maneuver will not remove the adherent eschar from areas where it persists.
• A dressing impregnated with an antibacterial solution should be applied for another 2 hours.

Wound care after debridement

• The debrided area should be covered immediately with dressings or temporary or permanent skin substitutes to prevent desiccation and/or the formation of pseudo-escars and/or infections.
• Before applying a permanent skin substitute or a temporary skin substitute to a recently debrided area using enzymatic methods, a moist-to-dry dressing should be applied.
• Before applying grafts or primary dressings, the debrided bed should be cleaned and refreshed using, for example, brushing or scraping to allow the dressings to adhere.
• Deep partial-thickness wounds and deep burns should have autografts implanted as soon as possible after debridement with NexoBrid. The suitability of permanent skin substitutes (e.g., autografts) for deep partial-thickness wounds should also be carefully evaluated shortly after debridement with NexoBrid.

Recommendations for safe handling

Each vial, gel, or reconstituted gel of NexoBrid should be used for a single patient.

There have been reports of occupational exposure to bromelain, leading to sensitization. Sensitization may have occurred due to inhalation of bromelain powder. Allergic reactions to bromelain include anaphylactic reactions and other immediate-type reactions with manifestations such as bronchospasm, angioedema, urticaria, and mucosal and gastrointestinal reactions. When mixing NexoBrid powder with the gel, adequate handling is required, including the use of gloves and protective equipment, as well as surgical masks and protective glasses. The powder should not be inhaled.

Avoid accidental eye exposure. In case of eye exposure, irrigate the exposed eyes with plenty of water for at least 15 minutes. In case of skin exposure, remove NexoBrid by rinsing it with water.

Disposal

The disposal of unused medicinal product and all materials that have come into contact with it will be carried out in accordance with local regulations.