NEXOBRID
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kosar Doraghi, M.D. [2]
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Black Box Warning
|
Warning: Hypersensitivity reactions
See full prescribing information for complete Boxed Warning.
The prevalent adverse reactions, observed in over 10% of instances, included pruritus (itching) and pyrexia (fever).
Serious hypersensitivity reactions, including anaphylaxis, have been reported with the postmarketing use of anacaulase-bcdb. It is not advisable to use NEXOBRID for the treatment of burn wounds in situations where medical devices or vital structures could be exposed during eschar removal. To prevent potential exposure to NEXOBRID, open wounds should be protected with skin-protectant ointments or ointment gauze. NEXOBRID should be avoided in patients with uncontrolled coagulation disorders. Additionally, it is not recommended for wounds contaminated with radioactive or other hazardous substances. |
Overview
NEXOBRID is a {{{drugClass}}} that is FDA approved for the treatment of eschar in adults with deep partial thickness or full thickness thermal burns. The safety and effectiveness of NEXOBRID have not been established for treatment of: Chemical or electrical burns, burns on the face, perineum, or genitalia, burns on the feet of patients with diabetes mellitus or on the feet of patients with occlusive vascular disease, circumferential burns, and burns in patients with significant cardiopulmonary disease, including inhalation injury. NEXOBRID is not recommended for wounds contaminated with radioactive and other hazardous substances to avoid unforeseeable reactions with the product and an increased risk of spreading the noxious substance.. There is a Black Box Warning for this drug as shown here. Common adverse reactions include The most common adverse reactions (>10%) were pruritus and pyrexia..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
It is available for topical use only: • NEXOBRID may be applied in up to two applications of 4 hours each. • A first application may be applied to an area of up to 15% body surface area (BSA). • A second application may be applied 24 hours later. The total treated area for both applications must not exceed 20% BSA. • Use 1.94 g of anacaulase-bcdb in 2 g powder mixed with 20 g gel per 1% BSA, or 4.85 g of anacaulase-bcdb in 5 g powder mixed with 50 g gel per 2.5% BSA. • Prepare NEXOBRID at patient’s bedside within 15 minutes of intended application. • Apply NEXOBRID to a clean, moist wound bed free of burned epidermis layer and blisters, and cover with an occlusive film dressing for 4 hours.
Off-Label Use and Dosage (Adult)
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Required Pediatric Assessment.
Off-Label Use and Dosage (Pediatric)
Contraindications
NEXOBRID is contraindicated in patients with known hypersensitivity to anacaulase- bcdb, bromelain, pineapples, or any other NEXOBRID component. NEXOBRID is also contraindicated in patients with known hypersensitivity to papayas or papain because of cross-sensitivity risk. NEXOBRID is not recommended to treat burn wounds where medical devices (e.g., implants, pacemakers, shunts) or vital structures (e.g., large vessels) could become exposed during eschar removal. NEXOBRID is not recommended for use in patients with uncontrolled disorders of coagulation.
Warnings
|
Warning: Hypersensitivity reactions
See full prescribing information for complete Boxed Warning.
The prevalent adverse reactions, observed in over 10% of instances, included pruritus (itching) and pyrexia (fever).
Serious hypersensitivity reactions, including anaphylaxis, have been reported with the postmarketing use of anacaulase-bcdb. It is not advisable to use NEXOBRID for the treatment of burn wounds in situations where medical devices or vital structures could be exposed during eschar removal. To prevent potential exposure to NEXOBRID, open wounds should be protected with skin-protectant ointments or ointment gauze. NEXOBRID should be avoided in patients with uncontrolled coagulation disorders. Additionally, it is not recommended for wounds contaminated with radioactive or other hazardous substances. |
Hypersensitivity reactions: Serious hypersensitivity reactions, including anaphylaxis, have been reported with postmarketing use of anacaulase-bcdb. If a hypersensitivity reaction occurs, remove NEXOBRID (if applicable) and initiate appropriate therapy. Pain: Manage pain as appropriate for an extensive dressing change of burn wounds. At least 15 minutes before NEXOBRID-related procedures ensure adequate pain control measures are in place. Proteolytic Injury to Non-Target Tissues: NEXOBRID is not recommended for treatment of burn wounds where medical devices or vital structures could become exposed during eschar removal. Protect any open wounds with skin protectant ointments or ointment gauze to prevent possible exposure to NEXOBRID. Coagulopathy: Avoid use of NEXOBRID should not use in patients with uncontrolled disorders of coagulation. Use with caution in patients on anticoagulant therapy or other drugs affecting coagulation, and in patients with low platelet counts and increased risk of bleeding from other causes. Monitor patients for possible signs of coagulation abnormalities and signs of bleeding.
Adverse Reactions
Clinical Trials Experience
The most common adverse reactions (>10%) were pruritus and pyrexia.
Postmarketing Experience
The following adverse reactions have been identified during postapproval use of anacaulase-bcdb outside of the United States. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Immune system disorders: Hypersensitivity, including anaphylaxis and urticaria.
Drug Interactions
Use with caution in patients on anticoagulant therapy or other drugs affecting coagulation.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA): There are no available data on NEXOBRID use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% an 15 to 20%, respectively.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of NEXOBRID in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of NEXOBRID during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of NEXOBRID in women who are nursing.
Pediatric Use
The safety and effectiveness of NEXOBRID in pediatric patients have not been established.
Geriatic Use
Out of 177 subjects treated with NEXOBRID for eschar removal in deep partial thickness (DPT) and/or full thickness (FT) thermal burns, only 3% were 65 years or older, with less than 1% being 75 years or older. Clinical studies lacked sufficient representation of individuals aged 65 and older, making it unclear if they respond differently to NEXOBRID compared to younger adults.
Gender
There is no FDA guidance on the use of NEXOBRID with respect to specific gender populations.
Race
There is no FDA guidance on the use of NEXOBRID with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of NEXOBRID in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of NEXOBRID in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of NEXOBRID in women of reproductive potentials and males.
Immunocompromised Patients
The following adverse reactions have been identified during postapproval use of anacaulase-bcdb outside of the United States. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Immune system disorders: Hypersensitivity, including anaphylaxis and urticaria
Administration and Monitoring
Administration
1. Dosage and Administration Overview: NEXOBRID is only to be administered by a healthcare provider. Healthcare providers should take precautions to avoid exposure to NEXOBRID during preparation and handling (e.g., use of gloves, surgical masks, and other protective coverings, as needed). NEXOBRID lyophilized powder and gel vehicle must be mixed before administration. Each vial of lyophilized powder, jar of gel vehicle, and the mixed NEXOBRID are for use for only one patient and one application NEXOBRID is available as: 2 g of lyophilized powder (containing 1.94 grams of anacaulase-bcdb) mixed in 20 g gel vehicle per 1% body surface area (BSA), or 5 g lyophilized powder (containing 4.85 grams of anacaulase-bcdb) mixed in 50 g gel vehicle per 2.5% BSA. NEXOBRID is for topical use only. Apply an ointment skin protectant around the treatment area to create an ointment barrier. Apply a 3 mm thick layer (approximate thickness of a tongue depressor) of NEXOBRID to an area of up to 15% body surface area (BSA) in one application. If the wound area is more than 15% BSA, apply NEXOBRID in 2 separate sessions (e.g., treat up to 15% BSA in one session and up to 5% BSA in a second session). Apply the second application of NEXOBRID twenty-four (24) hours after the first application to the same or new burn wound area. The total treatment area must not exceed 20% BSA (40 grams of NEXOBRID lyophilized powder) across two treatment sessions.
2. Preparation of Patient and Burn Wound Treatment Area: Use pain management as practiced for an extensive dressing change of burn wounds 15 minutes before all NEXOBRID-related procedures. Prepare the wound area as follows: 1. Thoroughly clean the wound to remove any charred tissue, blisters, and any topical products. 2. Apply a dressing soaked with an antibacterial solution to the treatment area for at least 2 hours. 3. Ensure the wound bed is clear of any remnants of topical agents (e.g. silver sulfadiazine or povidone iodine). 4. Apply an ointment skin protectant (e.g., petrolatum) 2 to 3 cm outside of the treatment area to create an ointment barrier. 5. Protect any open wounds (e.g., laceration, abraded skin, and escharotomy incision) with skin-protectant ointments or ointment gauze to prevent possible exposure to NEXOBRID. 6. Avoid applying the ointment to the treatment area itself, as this would impede direct contact of NEXOBRID with the eschar.
3. Preparation and Application of NEXOBRID Gather the following supplies before NEXOBRID preparation and application. All supplies should be sterile: • Instrument for mixing (e.g., spatula or tongue depressor) • Tongue depressor for NEXOBRID application • 0.9% Sodium Chloride Irrigation • Occlusive film dressing • Loose, thick fluffy dressing and bandage Maintain pain management throughout the application as practiced for an extensive dressing change of burn wounds. At least 15 minutes before NEXOBRID application, ensure adequate pain control measures are in place to address NEXOBRID-related pain. Preparation: Prepare NEXOBRID at the patient’s bedside within 15 minutes of the intended application. Using an aseptic technique, mix NEXOBRID lyophilized powder and gel vehicle as follows: 1. Pour the NEXOBRID lyophilized powder into the gel vehicle jar. 2. Thoroughly mix the NEXOBRID lyophilized powder and gel vehicle using a sterile instrument (e.g., tongue depressor or spatula) until the mixture is uniform. The mixed lyophilized powder and gel vehicle produce NEXOBRID in a final concentration of 8.8% w/w. Discard NEXOBRID if not used within 15 minutes of preparation, as the enzymatic activity of the product decreases progressively following mixing. Application: Apply NEXOBRID within 15 minutes of preparation as follows: 1. Moisten the treatment area by sprinkling sterile 0.9% Sodium Chloride Irrigation onto the burn wound. 2. Using a sterile tongue depressor, completely cover the moistened treatment area with the mixed NEXOBRID in a 3 mm thick layer (approximate thickness of a tongue depressor) that completely covers the burn wound area. 3. Cover the treated wound with a sterile occlusive film dressing. 4. Gently press the occlusive film dressing at the area of contact with the ointment barrier to ensure adherence between the occlusive film dressing and the sterile ointment barrier and to achieve complete containment of NEXOBRID on the treatment area. NEXOBRID gel should fill the entire volume of the treatment area, and there should be no visible air under the occlusive film dressing. 5. Cover the dressed wound with a sterile loose, thick, fluffy dressing and secure with a sterile bandage. 6. Leave the dressing and NEXOBRID in place for 4 hours. 7. Discard any unused portions of NEXOBRID.
Monitoring
4. Removal of NEXOBRID Remove NEXOBRID after 4 hours. Gather the following supplies before NEXOBRID removal. All supplies should be sterile: • Blunt-edged instruments (e.g., tongue depressor) • Large dry gauze • Gauze soaked with 0.9% Sodium Chloride Irrigation • Dressing soaked with an antibacterial solution Implement and maintain pain management as practiced for an extensive dressing change of burn wounds throughout the following removal procedure: 1. Remove the occlusive film dressing using an aseptic technique. 2. Remove the ointment barrier using a sterile blunt-edged instrument. 3. Remove the dissolved eschar from the wound by scraping it away with a sterile bluntedged instrument. 4. Wipe the wound thoroughly with a large sterile dry gauze, then wipe with a sterile gauze that has been soaked with sterile 0.9% Sodium Chloride Irrigation. Rub the treated area until the appearance of a clean dermis or subcutaneous tissues with pinpoint bleeding. 5. To remove remnants of dissolved eschar, apply a dressing soaked with an antibacterial solution for at least 2 hours.
5. Second Application of NEXOBRID: A second application of NEXOBRID may be applied 24 hours following the first application to either the same area previously treated with NEXOBRID or to a new area. A second application may be considered if: • The wound area is more than 15% BSA, or • Multiple wound areas on different body surfaces require two treatments for logistical reasons such as body position, or • The first application’s eschar removal was not complete, The total treated area must not exceed 20% BSA, inclusive of both applications.
6. Wound Care after Eschar Removal Wound care following eschar removal should be based on the healthcare provider’s clinical judgment (e.g., observe for spontaneous reepithelization or proceed with autograft). 7. Monitoring Monitor patients for signs of local or systemic allergic reactions. If a hypersensitivity reaction occurs, remove NEXOBRID (if applicable) from the treatment area and initiate appropriate therapy.
DOSAGE FORMS AND STRENGTHS For topical gel: 8.8%; off-white to light tan lyophilized powder in a glass vial to be mixed in a clear and colorless gel vehicle in a glass jar.
IV Compatibility
There is limited information regarding the compatibility of NEXOBRID and IV administrations.
Overdosage
There is limited information regarding NEXOBRID overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding NEXOBRID Pharmacology in the drug label.
Mechanism of Action
NEXOBRID contains a blend of enzymes that effectively breaks down the eschar in burn wounds. However, the precise elements responsible for this action have not been identified.
Structure
The drug substance in NEXOBRID, anacaulase-bcdb, is a mixture of proteolytic enzymes extracted from the stems of pineapple plants that have been sterile-filtered and lyophilized. The drug substance, anacaulase-bcdb, is composed mainly (80% to 95% w/w) of the proteins: stem bromelain, ananain, jacalin-like lectin, bromelain inhibitors, and phytocystatin inhibitor; and saccharides, as both free monosaccharides and the N-linked glycan of stem bromelain, and small molecule metabolites. The drug substance includes inactive buffer components containing acetic acid, ammonium sulfate, and Water for Injection. Each gram of lyophilized powder contains 0.97 grams of anacaulase-bcdb. NEXOBRID (anacaulase-bcdb) for topical gel is a botanical drug product supplied as a sterile, preservative-free, lyophilized powder in a single-dose glass vial that must be mixed in a gel vehicle supplied in a single-dose glass jar before application.
Pharmacodynamics
The pharmacodynamics of NEXOBRID are unknown. Cardiac Electrophysiology: At the approved recommended dose, NEXOBRID did not prolong the QT interval in humans to any clinically relevant extent.
Pharmacokinetics
Absorption:
Topically applied NEXOBRID to deep partial and full thickness burn wounds is rapidly absorbed, with median serum Tmax of 4 hours (during the treatment application). Systemic exposure (i.e., AUC) of bromelain, a component of anacaulase-bcdb is correlated with the size of the treated area and NEXOBRID dose, but not the depth of the burn wound.
Elimination:
A majority of subjects had no quantifiable serum concentrations after 72 hours. The mean ± SD terminal half-life of bromelain, a component of anacaulase-bcdb, is 12 ± 4.4 hours. Cmax and the dose normalized Cmax values after the first and second application (mean dosing interval of 17 hours) are comparable and only slight accumulation (less than 2-fold difference) is seen in AUC0-4 and AUC0-4 dose normalized levels after the second application, compared to the first application.
Drug Interaction Studies: Effect of NEXOBRID on Other Drugs Bromelain, a component of anacaulase-bcdb, exhibited CYP2C8 time-dependent inhibition in human hepatocytes and inhibited human microsomal CYP2C9. No clinical studies have been conducted to assess the potential for systemic drug interactions.
Nonclinical Toxicology
Carcinogenicity or fertility studies have not been conducted with anacaulase-bcdb. Anacaulase-bcdb was not genotoxic in a bacterial reverse mutation assay and an in vitro mammalian chromosome aberration assay.
Clinical Studies
The efficacy of NEXOBRID for the eschar removal of deep partial thickness (DPT) and full thickness (FT) thermal burns has been investigated in two trials. Study 1: NEXOBRID, a treatment for deep partial thickness and/or full thickness thermal burns, was compared to standard of care (SOC) and a gel vehicle. The study included 175 subjects, with NEXOBRID showing a significantly higher incidence of ≥95% eschar removal compared to the gel vehicle (93% vs. 4%). In terms of surgical eschar removal, NEXOBRID had a lower incidence (4%) compared to SOC (72%). The median time to eschar removal was 1 day for NEXOBRID and 3.8 days for SOC. Additionally, the estimated median time to ≥95% wound closure was 31 days for NEXOBRID and 36 days for SOC. Frequent evaluations post ≥95% wound closure were not conducted to assess time to 100% wound closure. Study2: NEXOBRID was investigated in a multicenter, open-label, randomized, two-arm study comparing it to standard of care (SOC) treatment for subjects with deep partial thickness and/or full thickness thermal burns (5 - 24% BSA). The study enrolled 182 subjects, with the first 26 subjects at each site receiving NEXOBRID and the remaining 156 subjects randomized to NEXOBRID or SOC. Demographics were similar across both arms, with a mean age of 29.9 years and predominantly adult, male, and White subjects. The study focused on the incidence of surgical eschar removal (tangential, minor, avulsion, Versajet, and/or dermabrasion excision). The results showed that NEXOBRID had a lower incidence of excision for eschar removal compared to SOC. In terms of the estimated median time to ≥95% wound closure, NEXOBRID had a longer duration (33 days) compared to SOC (24 days) for randomized subjects. Similar to Study 1, the study did not conduct frequent evaluations after achieving ≥95% wound closure to assess time to 100% wound closure.
How Supplied
The co-packaged 20 gram or 50 gram jar of the sterile, preservative-free gel vehicle contains carbomer 980, dibasic sodium phosphate, sodium hydroxide, and Water for Injection. NEXOBRID (anacaulase-bcdb) for topical gel, 8.8%, is supplied as a package containing two components, a sterile, preservative-free, off-white to light tan lyophilized powder in a glass vial and a sterile, preservative-free, clear and colorless gel vehicle in a glass jar, that are mixed prior to application. NEXOBRID is available:
• One glass vial of 2 g lyophilized powder (containing 1.94 grams of anacaulase-bcdb) and
one glass jar of 20 g gel vehicle per carton (NDC 69866-2002-3)
• One glass vial of 5 g lyophilized powder (containing 4.85 grams of anacaulase-bcdb) and
one glass jar of 50 g gel vehicle per carton (NDC 69866-2005-3)
Storage
Store and transport NEXOBRID package upright and refrigerated at 2°C to to 8°C (36 °F to 46 °F) in the original carton to protect it from light. DO NOT FREEZE. Do not use it if the vial or jar is damaged.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
Advise patients of the risk of hypersensitivity reactions, including anaphylaxis.
Precautions with Alcohol
Alcohol-NEXOBRID interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding NEXOBRID Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding NEXOBRID Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.