NexoBrid: Uses, Dosage & Side Effects

What Is NexoBrid and What Is It Used For?

NexoBrid contains a concentrate of proteolytic enzymes enriched in bromelain as its active ingredient. Bromelain is a mixture of proteases (protein-digesting enzymes) naturally found in the stems and fruit of the pineapple plant (Ananas comosus). In NexoBrid, these enzymes have been concentrated and formulated specifically for medical use in burn wound management. The product belongs to the pharmacological class of enzymatic debriding agents, which use biological enzymes to remove dead or damaged tissue from wounds — a process known as debridement.

Burn injuries represent a significant global health burden. According to the World Health Organization (WHO), burns are responsible for an estimated 180,000 deaths annually worldwide, with the vast majority occurring in low- and middle-income countries. Even in high-income nations, severe burns require specialized treatment in dedicated burn centers. One of the critical early steps in burn wound management is the removal of eschar — the thick, leathery, devitalized tissue that forms over deep burn wounds. Eschar removal is essential because this dead tissue serves as a barrier to wound healing and a potential breeding ground for infection. Traditionally, eschar has been removed through surgical excision (tangential or fascial excision), which is effective but can also remove some viable tissue, may require general anesthesia, and carries the risks inherent in any surgical procedure including blood loss.

NexoBrid was developed as a targeted, non-surgical alternative to conventional surgical debridement. When applied to a burn wound, the proteolytic enzymes in NexoBrid selectively break down the denatured proteins that constitute the eschar, including denatured collagen and other structural proteins in the necrotic tissue. Crucially, NexoBrid demonstrates selectivity: it preferentially digests non-viable tissue while largely sparing the underlying viable dermis, subcutaneous fat, blood vessels, nerves, and other healthy structures. This selective action is a key advantage over surgical excision, which often removes some healthy tissue along with the eschar, particularly in deep partial-thickness burns where the boundary between viable and non-viable tissue can be difficult to determine visually.

The mechanism of selectivity is related to the biochemical differences between denatured (heat-damaged) and native (healthy) proteins. Heat denaturation unfolds protein structures, exposing peptide bonds that are normally buried within the folded protein. The bromelain enzymes in NexoBrid can access and cleave these exposed bonds in denatured proteins far more readily than in intact, properly folded native proteins. This biochemical selectivity is what allows NexoBrid to distinguish between dead and living tissue at a molecular level — something that even an experienced surgeon cannot always achieve perfectly at the macroscopic level.

NexoBrid is indicated for the removal of eschar in adults and children with deep partial-thickness and/or full-thickness thermal burns. Thermal burns include injuries caused by flames, scalds (hot liquids or steam), contact with hot objects, and flash burns. The product has been approved by the European Medicines Agency (EMA) since 2012 and received U.S. Food and Drug Administration (FDA) approval in 2024 under the name anacaulase-bcdb, making it the first enzymatic burn debridement product available in the United States. It is also approved in several other countries worldwide.

What Should You Know Before Using NexoBrid?

Contraindications

There are specific clinical situations in which NexoBrid must not be used. These contraindications have been established through clinical trials and post-marketing surveillance to ensure patient safety.

• Hypersensitivity: NexoBrid must not be used in patients with known hypersensitivity to the active substance (concentrate of proteolytic enzymes enriched in bromelain), to pineapple, to papain, or to any of the excipients. Cross-reactivity between bromelain and papain has been documented, so patients allergic to either substance should avoid NexoBrid. Allergic reactions can range from mild skin reactions to severe anaphylaxis.

Warnings and Precautions

Before and during treatment with NexoBrid, your healthcare team should be aware of the following important precautions:

• Burn type restrictions: NexoBrid is approved only for thermal (heat) burns. It should not be used on chemical burns, electrical burns, or radiation burns, as its safety and efficacy have not been established for these injury types. The enzymatic action may behave differently in tissue damaged by non-thermal mechanisms.
• Anatomical restrictions: NexoBrid should not be applied to the face, perineum (genital/anal area), or circumferential neck burns. These areas have specific anatomical considerations — the face has thin, cosmetically sensitive skin; the perineum has high infection risk; and circumferential neck burns carry airway compromise risks — that require specialized management approaches.
• Treatment area limits: In adults, the total wound area treated with NexoBrid in a single session should not exceed 15% of total body surface area (TBSA). In pediatric patients, treatment area limits are weight-based. Exceeding these limits may increase the risk of systemic absorption and adverse effects.
• Wound deepening: In some patients, burns that initially appear to be deep partial-thickness may be found to be full-thickness after eschar removal. Additionally, there have been reports of wound deepening (extension of burn depth) associated with NexoBrid treatment. Following eschar removal, a careful assessment of the wound bed is essential to determine whether the wound will heal spontaneously or requires skin grafting.
• Bleeding risk: NexoBrid can cause local bleeding at the wound site during and after eschar removal. Patients receiving anticoagulant therapy (such as warfarin, heparin, or direct oral anticoagulants) or those with coagulation disorders may be at increased risk of significant bleeding. Hemostasis measures should be readily available.
• Infection risk: Burns treated with NexoBrid are at risk of wound infection, as with any burn wound management approach. After eschar removal, the wound bed should be monitored closely for signs of infection. Appropriate antimicrobial wound care should be applied as directed by the burn care team.
• Pain management: The application and removal of NexoBrid can be painful. Adequate analgesia must be provided before, during, and after the procedure. In some patients, procedural sedation or anesthesia may be required, particularly during the removal of dissolved eschar.
• Systemic effects: Although systemic absorption of NexoBrid is minimal, monitoring for systemic effects is recommended, particularly in patients with extensive burns or impaired renal or hepatic function. Fever is a commonly reported adverse effect and may be related to the inflammatory response triggered by enzymatic debridement.

Pregnancy and Breastfeeding

There are limited data on the use of NexoBrid in pregnant women. Animal studies have not demonstrated direct reproductive toxicity, but as a precautionary measure, NexoBrid should be used during pregnancy only when the clinical benefit clearly justifies the potential risk to the fetus. Burn injuries during pregnancy are themselves associated with significant maternal and fetal morbidity, and treatment decisions should be made on an individual basis by the multidisciplinary burn care team in consultation with obstetric specialists.

It is not known whether the active substance in NexoBrid or its metabolites are excreted in human breast milk. Given the topical application and minimal systemic absorption, the risk to the breastfed infant is considered low. However, as a precaution, breastfeeding should be temporarily discontinued for 4 days after NexoBrid application to allow complete clearance of any systemically absorbed enzymes. A decision should be made whether to discontinue breastfeeding or withhold NexoBrid treatment, taking into account the clinical urgency of the burn wound management.

Use in Children

NexoBrid is approved for use in pediatric patients for the enzymatic debridement of thermal burns. Children have different pharmacokinetic profiles and burn characteristics compared to adults — their skin is thinner, their body surface area to weight ratio is higher, and they may be more susceptible to systemic effects of topically applied agents. Dosing in children is adjusted based on body weight and wound area, with maximum treatment areas calculated according to specific pediatric dosing guidelines. Pain management is particularly important in pediatric burn patients, and age-appropriate analgesic protocols should be followed.

Use in Elderly Patients

Elderly patients may have thinner skin, reduced healing capacity, and are more likely to be taking anticoagulant or antiplatelet medications that could increase bleeding risk during debridement. No specific dose adjustment is required for elderly patients, but close monitoring for adverse effects is recommended. Comorbidities common in the elderly population, such as diabetes, peripheral vascular disease, and impaired renal or hepatic function, should be considered in treatment planning. Healing after enzymatic debridement may take longer in elderly patients, and the threshold for skin grafting may need to be adjusted accordingly.

How Does NexoBrid Interact with Other Drugs?

Drug interactions with NexoBrid are primarily related to local effects at the wound site rather than systemic pharmacokinetic interactions. Because NexoBrid is applied topically and systemic absorption is minimal, the risk of classic drug-drug interactions affecting blood levels of other medications is low. However, several clinically important interactions and precautions should be considered.

Major Interactions

Minor Interactions

Healthcare providers should ensure that all topical agents are removed from the burn wound and the area is thoroughly cleansed with a sterile saline solution before NexoBrid application. Any residual topical antimicrobial cream, ointment, or solution may interfere with the enzymatic action of NexoBrid and reduce its effectiveness. After NexoBrid has been removed and the wound bed is clean, appropriate topical antimicrobial dressings can be reapplied as part of the ongoing burn wound management plan.

What Is the Correct Dosage of NexoBrid?

NexoBrid dosing is determined by the size of the burn wound area to be treated rather than by patient body weight (except in pediatric dose-limit calculations). The product is supplied as a powder (2 g) that must be mixed with the accompanying gel (20 g) immediately before use to create the active topical preparation. This freshly prepared gel is then applied directly to the burn wound after appropriate wound preparation.

Adults

Children

Elderly

Application Procedure

The correct application of NexoBrid is critical for its effectiveness and safety. The procedure is performed by healthcare professionals experienced in burn wound management and follows a specific protocol:

1. Wound preparation: Clean the burn wound thoroughly. Remove all topical agents (creams, ointments, antimicrobial solutions) and any loose eschar or debris. Cleanse with sterile saline or a mild antiseptic solution, then rinse with saline. Pat dry gently.
2. Skin protection: Apply a protective moisturizing cream or petroleum-based ointment to the intact skin surrounding the burn wound (approximately 2–3 cm border) to prevent the NexoBrid gel from contacting healthy unburned skin.
3. Gel preparation: Mix the NexoBrid powder with the gel immediately before use according to the instructions. The prepared gel should be used within 15 minutes of mixing.
4. Application: Apply the freshly mixed gel in a uniform layer (1.5–3 mm thick) over the entire burn wound surface. Ensure complete coverage with no gaps.
5. Occlusive dressing: Cover the treated area with an adhesive film dressing to create an occlusive seal. This prevents the gel from drying out and maintains contact with the wound surface.
6. Soaking period: Leave the dressing in place for exactly 4 hours. Do not leave NexoBrid on the wound for longer or shorter than 4 hours, as this affects both efficacy and safety.
7. Removal: After 4 hours, remove the dressing and gently remove the dissolved eschar and residual gel from the wound using a blunt instrument (such as a tongue depressor) and damp gauze. This step may require adequate analgesia or sedation.
8. Post-debridement care: After removal of all dissolved material, cleanse the wound thoroughly. Assess the wound bed to determine whether it will heal spontaneously or requires skin grafting. Apply an appropriate temporary wound dressing as directed by the burn care team.

Missed Dose

NexoBrid is a single-application treatment performed in a hospital setting under direct medical supervision. There is no concept of a “missed dose” in the traditional sense. If treatment is postponed or not completed, the decision to reschedule should be made by the burn care team based on the clinical condition of the wound and the patient. If NexoBrid fails to completely remove all eschar in a single application, the remaining eschar may be addressed through surgical excision or other debridement methods as clinically appropriate. NexoBrid should not be reapplied to the same wound area.

Overdose

Because NexoBrid is applied topically in a controlled hospital setting, overdose in the traditional pharmacological sense is unlikely. However, applying NexoBrid to an area exceeding the recommended maximum treatment area (15% TBSA in adults) or leaving it in place for longer than 4 hours may increase the risk of adverse effects, including excessive wound deepening, increased bleeding, or enhanced systemic absorption of the proteolytic enzymes. If overexposure is suspected, the gel should be removed immediately, the wound cleansed thoroughly with saline, and the patient monitored for systemic adverse effects. Treatment is supportive and symptom-directed, as there is no specific antidote for NexoBrid.

What Are the Side Effects of NexoBrid?

Like all medicines, NexoBrid can cause side effects, although not everybody gets them. The side effects associated with NexoBrid are primarily related to its local action on the burn wound. It is important to understand that some symptoms commonly observed after NexoBrid treatment — such as fever, wound pain, and changes in wound appearance — may also be part of the normal burn wound healing process and inflammatory response, making it sometimes difficult to distinguish drug-related effects from the natural course of burn wound evolution.

Clinical trials have evaluated the safety of NexoBrid in controlled settings. The pivotal trials compared NexoBrid with the standard of care (surgical debridement and/or Polyhexanide gel) and documented the frequency and severity of adverse events. The following side effects have been reported in clinical trials and post-marketing surveillance:

It is important to report any suspected side effects to your healthcare provider. Healthcare professionals are encouraged to report adverse reactions through their national adverse drug reaction reporting system. In the EU, reports can be submitted to the national competent authority or through the EMA. In the US, adverse reactions should be reported to the FDA MedWatch program.

Many of the common side effects, such as wound pain, fever, and local bleeding, are expected consequences of the debridement process itself and are manageable with appropriate supportive care. Wound deepening, while concerning, occurs in a minority of patients and is carefully assessed by the burn team to determine whether additional interventions (such as skin grafting) are needed. The overall safety profile of NexoBrid in clinical trials has been considered acceptable given the clinical benefits of faster eschar removal and potential reduction in surgical procedures.

How Should You Store NexoBrid?

Proper storage of NexoBrid is essential to maintain the activity and safety of the proteolytic enzymes. As a biological product containing active enzymes, NexoBrid is sensitive to temperature and light, which can degrade the enzymatic activity over time. The following storage conditions must be strictly maintained:

• Temperature: Store in a refrigerator at 2°C to 8°C (36°F to 46°F). The cold chain must be maintained from manufacturing through to the point of use in the hospital pharmacy or burn unit.
• Light protection: Keep in the original outer packaging to protect from light. Exposure to light can degrade the bromelain enzymes.
• Do not freeze: Freezing can damage the protein structure of the enzymes and the physical properties of the gel carrier, rendering the product ineffective.
• Shelf life: The shelf life of NexoBrid when stored under the recommended conditions is indicated on the packaging. Do not use after the expiry date printed on the carton and vial label.
• After mixing: Once the powder has been mixed with the gel, the prepared product must be used immediately — within 15 minutes of mixing. The mixed gel cannot be stored, refrigerated, or saved for later use. Any unused mixed gel must be discarded according to local pharmaceutical waste disposal regulations.
• Keep out of reach of children: As with all medications, NexoBrid should be stored securely and kept out of the sight and reach of children, although in practice it is stored in hospital pharmacies and burn unit medication rooms.

Do not use NexoBrid if the packaging is damaged, if the powder appears discolored or has an unusual appearance, or if the gel has separated or changed consistency. Healthcare professionals should inspect the product before preparation and use. Any product that does not meet the expected appearance criteria should be returned to the pharmacy and not administered to patients.

What Does NexoBrid Contain?

NexoBrid is a two-component product consisting of a powder and a gel that are mixed together immediately before application. Understanding the composition of each component is important for identifying potential allergens and ensuring safe use.

Active Ingredient

• Concentrate of proteolytic enzymes enriched in bromelain (also known as anacaulase-bcdb): 2 g of powder per unit. This is a mixture of stem bromelain and related proteolytic enzymes extracted from the stems of the pineapple plant (Ananas comosus). The enzyme concentrate is standardized by its proteolytic activity to ensure consistent potency between batches.

Inactive Ingredients (Excipients)

The powder component contains no additional excipients — it consists solely of the lyophilized (freeze-dried) enzyme concentrate.

The gel component (20 g) contains the following inactive ingredients:

• Carbomer 980: A high-molecular-weight polymer used as a gelling agent to provide the viscous gel consistency necessary for the product to remain in contact with the wound surface during the 4-hour application period.
• Isopropyl palmitate: An emollient that helps maintain the gel’s texture and consistency.
• Sodium hydroxide: Used for pH adjustment to ensure the gel is at the optimal pH for enzymatic activity.
• Purified water: The vehicle for the gel formulation.

The product does not contain preservatives, artificial colors, or fragrances. As a biologically derived product, each batch undergoes quality control testing to verify enzymatic potency, sterility, endotoxin levels, and other quality parameters before release for clinical use.