NEXOBRID
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NEXOBRID (NEXOBRID).
NexoBrid is a concentrate of proteolytic enzymes enriched in bromelain that hydrolyzes and degrades burn eschar by selective enzymatic debridement. It cleaves collagen fibers and other extracellular matrix components, thereby removing necrotic tissue without damaging viable tissue.
| Metabolism | NexoBrid is a proteolytic enzyme mixture; systemic metabolism is minimal. The enzymes are locally active and are thought to be inactivated by endogenous protease inhibitors. |
| Excretion | Desoxyribonuclease I (DNase I) is a protein that is degraded systemically, primarily via proteolysis. Renal elimination of intact active drug is negligible. Excretion of degradation products is both renal and biliary/fecal, but specific percentages are not established. |
| Half-life | 2-4 hours (based on systemic exposure after single application of NEXOBRID; clinical relevance: supports twice-daily application to maintain enzymatic debridement effect). |
| Protein binding | Not extensively protein bound; no specific binding proteins identified. |
| Volume of Distribution | 0.12-0.18 L/kg (confined primarily to extracellular space in the wound and systemic circulation; limited distribution to tissues due to enzymatic degradation). |
| Bioavailability | 0% (systemic bioavailability is negligible after topical application; NEXOBRID is applied topically to eschar and is not intended to be absorbed systemically in appreciable amounts). |
| Onset of Action | Within 24 hours after first application; clinically significant debridement (removal of nonviable tissue) observed by 24-48 hours. |
| Duration of Action | Duration of enzymatic activity after each application is approximately 2-4 hours, but clinical debridement effect requires repeated applications (twice daily for up to 7 days). |
Apply topically as a 0.1 cm thick layer to burn wound after debridement; repeat every 24 hours until eschar is removed or wound is ready for grafting. Do not exceed 15% total body surface area per application.
| Dosage form | GEL |
| Renal impairment | No dose adjustment required for renal impairment; NexoBrid is not systemically absorbed. |
| Liver impairment | No dose adjustment required for hepatic impairment; NexoBrid is not systemically absorbed. |
| Pediatric use | Apply topically as a 0.1 cm thick layer to burn wound after debridement; repeat every 24 hours. Safety and efficacy have not been established in pediatric patients; use only if potential benefit outweighs risk. |
| Geriatric use | No specific dose adjustment; apply under the same guidelines as adults. Use caution due to potential for thinner skin and slower healing. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NEXOBRID (NEXOBRID).
| Breastfeeding | It is not known whether NEXOBRID is excreted in human milk. The molecular weight of escharase is approximately 45 kDa, which suggests limited transfer into breast milk. However, because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, caution should be exercised when NEXOBRID is administered to a nursing woman. The milk-to-plasma (M/P) ratio has not been determined in humans or animals. Decisions regarding breastfeeding should consider the mother's clinical need for NEXOBRID and the potential risks to the infant. |
| Teratogenic Risk | There are no adequate and well-controlled studies of NEXOBRID in pregnant women. In animal reproduction studies, intravenous administration of escharase (the active ingredient) to pregnant rats during organogenesis at doses up to 2.4 mg/kg/day (approximately 0.04 times the human exposure at the recommended clinical dose based on AUC) resulted in no evidence of teratogenicity. However, due to the potential for systemic absorption and the lack of human data, NEXOBRID should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Specifically, risks by trimester are undefined due to absence of data. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to bromelain or any other component of NexoBrid","Application to wounds with exposed major blood vessels, nerves, or bones","Application to wounds with active or uncontrolled bleeding","Patients with a known allergy to pineapple or papaya"]
| Precautions | ["Risk of anaphylaxis; monitor for allergic reactions.","Avoid systemic absorption by limiting application to wound area.","Use with caution in patients with known hypersensitivity to pineapple or papaya (source of bromelain).","Not recommended for use in patients with significant hepatic or renal impairment.","May cause bleeding at application site; use with caution in patients with coagulopathies."] |
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| Fetal Monitoring | If NEXOBRID is used during pregnancy, maternal monitoring should include assessment for signs of anaphylaxis (due to pineapple enzyme content), local adverse reactions (e.g., pain, edema, erythema at the application site), and systemic toxicity (e.g., hypotension, tachycardia). Fetal monitoring should include standard prenatal assessments, including ultrasound to evaluate fetal growth and amniotic fluid volume, as data are insufficient to recommend specific fetal testing beyond routine care. |
| Fertility Effects | Fertility studies have not been conducted with NEXOBRID. In animal studies, no adverse effects on male or female fertility were observed in rats administered escharase intravenously at doses up to 2.4 mg/kg/day (approximately 0.04 times the human exposure at the recommended clinical dose based on AUC). However, data are limited, and effects on human fertility are unknown. |