NAV

Anacaulase

Identification

Summary

Anacaulase is a mix of proteolytic enzymes indicated for eschar removal in adults with deep partial thickness and/or full-thickness thermal burns.

Brand Names
NexoBrid
Generic Name
Anacaulase
DrugBank Accession Number
DB17449
Background

Anacaulase (anacaulase-bcdb) is a mixture of proteolytic enzymes extracted from the stems of pineapple plants (Ananas comosus [L.] Merr.). It is mostly composed (80-95% w/w) of proteins such as stem bromelain, ananain, jacalin-like lectin, bromelain inhibitors, and phytocystatin inhibitor, as well as saccharides, as both free monosaccharides and the N-linked glycan of stem bromelain and small molecule metabolites.4 Anacaulase is indicated for eschar removal in patients with deep partial thickness and/or full-thickness thermal burns. Removing eschar (a process also known as debridement) through surgical procedures can lead to significant trauma, major blood and heat loss and adjacent tissue damage. They also require specialized surgical personnel and facilities, and autologous skin grafting may be needed. Therefore, enzymatic alternatives such as anacaulase can lead to better clinical outcomes.1,2,3 The EMA approved the use of anacaulase in 2013,1,2 and in January 2023, anacaulase received FDA approval.4

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Other protein based therapies
Protein Chemical Formula
Not Available
Protein Average Weight
23000.0 Da (average weight of proteolitic enzymes in mix)
Sequences
Not Available
Synonyms
  • Anacaulase-bcdb
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Pharmacology

Indication

Anacaulase is indicated for eschar removal in adults with deep partial thickness and/or full-thickness thermal burns.4

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Associated Therapies
Contraindications & Blackbox Warnings
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Pharmacodynamics

A study in hospitalized adult subjects with deep partial thickness and/or full-thickness thermal burns found that the use of anacaulase significantly reduced the incidence of surgical eschar removal, the time to complete eschar removal, and the blood loss related to eschar removal.5 The use of anacaulase does not induce a clinically significant prolongation of the QT interval at the recommended doses. Patients treated with anacaulase may develop serious hypersensitivity reactions, including anaphylaxis. In addition, anacaulase may lead to coagulopathy in patients with uncontrolled coagulation disorders.4

Mechanism of action

The mechanism of action of anacaulase is not clear. The mixture of enzymes in anacaulase dissolves burn wound eschar; however, the components responsible for this effect have not been identified.4

TargetActionsOrganism
UAlpha-1-antichymotrypsin
binder
Humans
UAlpha-2-macroglobulin
binder
Humans
Absorption

Anacaulase that is applied topically to deep partial and full thickness burn wounds is rapidly absorbed, with a Tmax of 4 hours. After 72 hours, most patients had no quantifiable concentrations of this product. The AUC of bromelain, a component of anacaulase, is correlated with the anacaulase dose and the size of the treated area, but not the depth of the burn wound. The Cmax values of anacaulase after the first and second application (17 hours later) are similar. A low level of accumulation (< 2-fold difference) was detected by comparing the AUC0-4 and AUC0-4 dose‑normalized levels of the second application with those of the first application.4

Volume of distribution

Not Available

Protein binding

Approximately 50% of bromelain, a component of anacaulase, binds to the human plasma antiproteinases α2-macroglobulin and α1-antichymotrypsin.5

Metabolism

As a mixture of proteolytic enzymes, anacaulase is expected to be metabolized by proteases throughout the body.

Route of elimination

Not Available

Half-life

The mean elimination half-life of anacaulase ranges from 12 to 17 hours, and there is a low presence of this product in serum 72 hours after treatment.5

Clearance

Not Available

Adverse Effects
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Toxicity

Toxicity information regarding anacaulase is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as pain and coagulation abnormalities. Symptomatic and supportive measures are recommended. The carcinogenic effects of anacaulase have not been evaluated, and fertility studies have not been performed. A bacterial reverse mutation assay and an in vitro mammalian chromosome aberration assay showed that anacaulase was not genotoxic.4

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
No interactions found.

Products

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International/Other Brands
NexoBrid (MediWound LTD)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
NexobridKit158 mg/1gTopicalVericel Corporation2022-12-29Not applicableUS flag
NexobridKit158 mg/1gTopicalVericel Corporation2022-12-29Not applicableUS flag

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
Not Available
CAS number
Not Available

References

Synthesis Reference

Rosenberg, L., et al. (2013). Proteolytic extract from bromelain for the treatment of connective tissue disorders (WIPO Patent No. WO 2013/011514 A1). World Intellectual Property Organization. https://patentimages.storage.googleapis.com/b2/1e/1b/400a744ebc007f/WO2013011514A1.pdf

General References
  1. Serracanta J, Baena J, Martinez-Mendez JR, Sanchez-Sanchez M, Lopez-Suso E, Galeiras R, Perez-Del-Caz MD, Vivo-Benlloch C, Monclus-Fuertes E, Casalduero-Viu J, Martin-Playa P, Ugalde-Gutierrez M, Gacto-Sanchez P, Rincon-Ferrari MD, Piqueras-Perez JM, Martin-Luengo A: Bromelain-based enzymatic burn debridement: Spanish multidisciplinary consensus. Eur J Plast Surg. 2022 Sep 29:1-9. doi: 10.1007/s00238-022-01999-2. [Article]
  2. Hirche C, Kreken Almeland S, Dheansa B, Fuchs P, Governa M, Hoeksema H, Korzeniowski T, Lumenta DB, Marinescu S, Martinez-Mendez JR, Plock JA, Sander F, Ziegler B, Kneser U: Eschar removal by bromelain based enzymatic debridement (Nexobrid(R)) in burns: European consensus guidelines update. Burns. 2020 Jun;46(4):782-796. doi: 10.1016/j.burns.2020.03.002. Epub 2020 Mar 30. [Article]
  3. Rosenberg L, Krieger Y, Bogdanov-Berezovski A, Silberstein E, Shoham Y, Singer AJ: A novel rapid and selective enzymatic debridement agent for burn wound management: a multi-center RCT. Burns. 2014 May;40(3):466-74. doi: 10.1016/j.burns.2013.08.013. Epub 2013 Sep 26. [Article]
  4. FDA Approved Drug Products: NEXOBRID (anacaulase-bcdb) for topical gel [Link]
  5. EMA Summary of Product Characteristics: NexoBrid powder and gel [Link]
RxNav
2626723
Wikipedia
Bromelain_(pharmacology)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentThermal Burns1
3CompletedTreatmentThermal Burns1
Not AvailableAvailableNot AvailableThermal Burns1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
KitTopical158 mg/1g
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Targets

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Details1. Alpha-1-antichymotrypsin
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
Curator comments
Bromelain, a component of anacaulase, binds to human alpha-1-antichymotrypsin.
General Function
Although its physiological function is unclear, it can inhibit neutrophil cathepsin G and mast cell chymase, both of which can convert angiotensin-1 to the active angiotensin-2.
Specific Function
Dna binding
Gene Name
SERPINA3
Uniprot ID
P01011
Uniprot Name
Alpha-1-antichymotrypsin
Molecular Weight
47650.36 Da
References
  1. Barrett AJ, Starkey PM: The interaction of alpha 2-macroglobulin with proteinases. Characteristics and specificity of the reaction, and a hypothesis concerning its molecular mechanism. Biochem J. 1973 Aug;133(4):709-24. doi: 10.1042/bj1330709. [Article]
  2. EMA Summary of Product Characteristics: NexoBrid powder and gel [Link]
Details2. Alpha-2-macroglobulin
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
Curator comments
Bromelain, a component of anacaulase, binds to human alpha-2-macroglobulin.
General Function
Tumor necrosis factor binding
Specific Function
Is able to inhibit all four classes of proteinases by a unique 'trapping' mechanism. This protein has a peptide stretch, called the 'bait region' which contains specific cleavage sites for differen...
Gene Name
A2M
Uniprot ID
P01023
Uniprot Name
Alpha-2-macroglobulin
Molecular Weight
163289.945 Da
References
  1. Barrett AJ, Starkey PM: The interaction of alpha 2-macroglobulin with proteinases. Characteristics and specificity of the reaction, and a hypothesis concerning its molecular mechanism. Biochem J. 1973 Aug;133(4):709-24. doi: 10.1042/bj1330709. [Article]
  2. EMA Summary of Product Characteristics: NexoBrid powder and gel [Link]

Enzymes

Details1. Cytochrome P450 2C8
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Bromelain, a component of anacaulase, inhibits CYP2C8.
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. FDA Approved Drug Products: NEXOBRID (anacaulase-bcdb) for topical gel [Link]
  2. EMA Summary of Product Characteristics: NexoBrid powder and gel [Link]
Details2. Cytochrome P450 2C9
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Bromelain, a component of anacaulase, inhibits CYP2C9.
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. FDA Approved Drug Products: NEXOBRID (anacaulase-bcdb) for topical gel [Link]
  2. EMA Summary of Product Characteristics: NexoBrid powder and gel [Link]

Drug created at January 19, 2023 18:04 / Updated at January 27, 2023 03:56