Identification
- Summary
Icatibant is a bradykinin B2 receptor antagonist used to treat acute episodes of swelling and inflammation associated with hereditary angioedema (HAE).
- Brand Names
- Firazyr, Sajazir
- Generic Name
- Icatibant
- DrugBank Accession Number
- DB06196
- Background
Icatibant (Firazyr) is a synthetic peptidomimetic drug consisting of ten amino acids, and acts as an effective and specific antagonist of bradykinin B2 receptors. It has been approved in the EU for use in hereditary angioedema, and is under investigation for a number of other conditions in which bradykinin is thought to play a significant role. Icatibant currently has orphan drug status in the United States and FDA approved on August 25, 2011.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Icatibant (DB06196)
- Weight
- Average: 1304.54
Monoisotopic: 1303.660795176 - Chemical Formula
- C59H89N19O13S
- Synonyms
- Icatibant
- External IDs
- HOE 140
- HOE-140
- HOE140
- Hoechst 140
- JE 049
Pharmacology
- Indication
Approved for use in acute attacks of hereditary angioedema (HAE). Investigated for use/treatment in angioedema, liver disease, and burns and burn infections.
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- Contraindications & Blackbox Warnings
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Icatibant is a potent, specific, competitive, and selective peptidomimetic bradykinin beta2-receptor antagonist (pA2 = 9.04). It has a modified peptide structure, and is the first bradykinin receptor antagonist to act on the guinea-pig trachea without demonstrating agonist effects. It also inhibits aminopeptidase N (Ki = 9.1 μM). If an IV dose of 0.4 and 0.8 mg/kg was infused over 4 hours, one may observe an inhibited response to bradykinin challenge for 6 - 8 hours following completion of infusion.
- Mechanism of action
Bradykinin is a peptide-based hormone that is formed locally in tissues in response to a trauma and acts to increases vessel permeability, dilates blood vessels and causes smooth muscle cells to contract. Bradykinin plays an important role in the mediation of pain as surplus bradykinin is partly responsible for producing signs of inflammation by activating bradykinin B2 receptors. In patients with HAE, they have an absent or dysfunctional C1-esterase inhibitor. This inhibitor is responsible for the production of bradykinin in which displacement of bradykinin from B2 receptors by icatibant has an inhibitory effect on the receptor for a relatively long time.
Target Actions Organism AB2 bradykinin receptor antagonistHumans UAminopeptidase N inhibitorHumans - Absorption
The absolute bioavailability of icatibant following a 30 mg subcutaneous dose is approximately 97%. Maximum plasma concentrations (Cmax) of 974 ± 280 ng/mL was reached when a single subcutaneous dose of 30 mg was administered. The AUC was 2165 ± 568 ng∙hr/mL. Icatibant did not accumulate following multiple doses.
- Volume of distribution
Vdss, subcutaneous injection = 29.0 ± 8.7 L.
- Protein binding
Not Available
- Metabolism
Icatibant is metabolized by proteolytic enzymes into inactive metabolites. The cytochrome P450 enzyme system is not involved with the metabolism of icatibant.
- Route of elimination
Urine (<10% unchanged)
- Half-life
After subcutaneous administration, mean elimination half-life was 1.4 ± 0.4 hours.
- Clearance
Plasma clearance following subcutaneous administration was 245 ± 58 mL/min.
- Adverse Effects
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Not Available
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Icatibant which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Icatibant which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Icatibant which could result in a higher serum level. Acetaminophen Acetaminophen may decrease the excretion rate of Icatibant which could result in a higher serum level. Acetazolamide Acetazolamide may increase the excretion rate of Icatibant which could result in a lower serum level and potentially a reduction in efficacy. Acetylsalicylic acid The risk or severity of angioedema can be increased when Acetylsalicylic acid is combined with Icatibant. Aclidinium Icatibant may decrease the excretion rate of Aclidinium which could result in a higher serum level. Acrivastine Icatibant may decrease the excretion rate of Acrivastine which could result in a higher serum level. Acyclovir Acyclovir may decrease the excretion rate of Icatibant which could result in a higher serum level. Adefovir dipivoxil Adefovir dipivoxil may decrease the excretion rate of Icatibant which could result in a higher serum level. 
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- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Icatibant acetate 325O8467XK 138614-30-9 HKMZRZUEADSZDQ-DZJWSCHMSA-N - International/Other Brands
- Firazyr
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Firazyr Injection, solution 30.0 mg/3mL Subcutaneous Takeda Pharmaceuticals America, Inc. 2011-08-25 Not applicable US 
Firazyr Injection, solution 30 mg Subcutaneous Takeda Pharmaceuticals International Ag 2020-12-16 Not applicable EU 
Firazyr Injection, solution 30 mg Subcutaneous Takeda Pharmaceuticals International Ag 2020-12-16 Not applicable EU Firazyr Solution 10 mg / mL Subcutaneous Takeda 2014-07-14 Not applicable Canada 
Icatibant Accord Injection, solution 30 mg Subcutaneous Accord Healthcare S.L.U. 2021-10-07 Not applicable EU Icatibant Accord Injection, solution 30 mg Subcutaneous Accord Healthcare S.L.U. 2021-10-07 Not applicable EU Icatibant Injection Solution 10 mg / mL Subcutaneous Juno Pharmaceuticals Corp. Not applicable Not applicable Canada Icatibant Injection Solution 30 mg / 3 mL Subcutaneous Accord Healthcare Inc Not applicable Not applicable Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Icatibant Injection, solution 30 mg/3mL Subcutaneous Apotex Corp. 2021-04-15 Not applicable US Icatibant Injection 30 mg/3mL Subcutaneous Cipla USA Inc. 2020-07-13 Not applicable US Icatibant Injection, solution 30 mg/3mL Subcutaneous Takeda Pharmaceuticals America, Inc. 2019-07-30 Not applicable US Icatibant Injection, solution 10 mg/1mL Subcutaneous Fresenius Kabi USA, LLC 2020-11-15 Not applicable US Icatibant Injection, solution 30 mg/3mL Subcutaneous Hikma Pharmaceuticals USA Inc. 2020-03-09 Not applicable US Icatibant Injection, solution 30 mg/3mL Subcutaneous bryant ranch prepack 2021-04-15 Not applicable US Icatibant Injection, solution 30.0 mg/3mL Subcutaneous Glenmark Pharmaceuticals Inc., USA 2021-05-21 Not applicable US Icatibant Injection 30 mg/3mL Subcutaneous Slayback Pharma LLC 2021-01-28 Not applicable US Icatibant Injection, solution 30 mg/3mL Subcutaneous Eugia US LLC 2023-08-14 Not applicable US Icatibant Injection, solution 10 mg/1mL Subcutaneous Teva Pharmaceuticals USA, Inc. 2019-07-15 Not applicable US
Categories
- ATC Codes
- B06AC02 — Icatibant
- Drug Categories
- Agents causing angioedema
- Amino Acids, Peptides, and Proteins
- Analgesics
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Autacoids
- Biological Factors
- Blood and Blood Forming Organs
- Bradykinin B2 Receptor Antagonists
- Bradykinin Receptor Antagonists
- Complement Inactivating Agents
- Drugs that are Mainly Renally Excreted
- Drugs Used in Hereditary Angioedema
- Immunologic Factors
- Inflammation Mediators
- Intercellular Signaling Peptides and Proteins
- Kinins
- Nerve Tissue Proteins
- Neuropeptides
- Oligopeptides
- Peptides
- Peripheral Nervous System Agents
- Proteins
- Sensory System Agents
- Classification
- Not classified
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 7PG89G35Q7
- CAS number
- 130308-48-4
- InChI Key
- QURWXBZNHXJZBE-SKXRKSCCSA-N
- InChI
- InChI=1S/C59H89N19O13S/c60-37(14-5-19-67-57(61)62)48(82)72-38(15-6-20-68-58(63)64)52(86)75-22-8-18-43(75)54(88)77-30-35(80)26-44(77)50(84)70-28-47(81)71-40(27-36-13-9-23-92-36)49(83)74-41(31-79)53(87)76-29-34-12-2-1-10-32(34)24-46(76)55(89)78-42-17-4-3-11-33(42)25-45(78)51(85)73-39(56(90)91)16-7-21-69-59(65)66/h1-2,9-10,12-13,23,33,35,37-46,79-80H,3-8,11,14-22,24-31,60H2,(H,70,84)(H,71,81)(H,72,82)(H,73,85)(H,74,83)(H,90,91)(H4,61,62,67)(H4,63,64,68)(H4,65,66,69)/t33-,35+,37+,38-,39-,40-,41-,42-,43-,44-,45-,46+/m0/s1
- IUPAC Name
- (2S)-2-{[(2S,3aS,7aS)-1-[(3R)-2-[(2S)-2-[(2S)-2-(2-{[(2S,4R)-1-[(2S)-1-[(2S)-2-[(2R)-2-amino-5-carbamimidamidopentanamido]-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]-4-hydroxypyrrolidin-2-yl]formamido}acetamido)-3-(thiophen-2-yl)propanamido]-3-hydroxypropanoyl]-1,2,3,4-tetrahydroisoquinoline-3-carbonyl]-octahydro-1H-indol-2-yl]formamido}-5-carbamimidamidopentanoic acid
- SMILES
- [H][C@]12C[C@]([H])(N(C(=O)[C@@]3([H])CC4=C(CN3C(=O)[C@H](CO)NC(=O)[C@H](CC3=CC=CS3)NC(=O)CNC(=O)[C@]3([H])C[C@@H](O)CN3C(=O)[C@@H]3CCCN3C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](N)CCCNC(N)=N)C=CC=C4)[C@@]1([H])CCCC2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O
References
- General References
- Cockcroft JR, Chowienczyk PJ, Brett SE, Bender N, Ritter JM: Inhibition of bradykinin-induced vasodilation in human forearm vasculature by icatibant, a potent B2-receptor antagonist. Br J Clin Pharmacol. 1994 Oct;38(4):317-21. [Article]
- Bork K, Frank J, Grundt B, Schlattmann P, Nussberger J, Kreuz W: Treatment of acute edema attacks in hereditary angioedema with a bradykinin receptor-2 antagonist (Icatibant). J Allergy Clin Immunol. 2007 Jun;119(6):1497-503. Epub 2007 Apr 5. [Article]
- FDA Approved Drug Products: FIRAZYR (icatibant) injection [Link]
- External Links
- Human Metabolome Database
- HMDB0015624
- KEGG Drug
- D04492
- PubChem Compound
- 71364
- PubChem Substance
- 99443237
- ChemSpider
- 5293384
- BindingDB
- 50406750
- 1148138
- ChEBI
- 68556
- ChEMBL
- CHEMBL2028850
- Therapeutic Targets Database
- DCL000131
- PharmGKB
- PA164749185
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Icatibant
- FDA label
- Download (543 KB)
- MSDS
- Download (87.6 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Hereditary Angioedema (HAE) 1 4 Recruiting Basic Science Heart Failure 1 4 Terminated Treatment ACE Inhibitor-associated Angioedema 1 3 Completed Treatment ACE Inhibitor-associated Angioedema 1 3 Completed Treatment Angioedema 1 3 Completed Treatment Hereditary Angioedema (HAE) 6 3 Not Yet Recruiting Health Services Research Intradialytic Hypotension 1 2 Completed Prevention Hemodialysis-Induced Symptoms / Mitochondrial Disorders 1 2 Completed Treatment Angioedema 1 2 Completed Treatment Coronavirus Disease 2019 (COVID‑19) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Parenteral; Subcutaneous 30 MG Injection, solution Subcutaneous 30.0 mg/3mL Solution Subcutaneous 10 mg / mL Solution Subcutaneous 30 mg Injection Subcutaneous 30 mg/3mL Injection, solution Subcutaneous 10 mg/1mL Injection, solution Subcutaneous 30 mg/3mL Injection, solution Subcutaneous 30 MG Injection, solution 30 MG/3ML Solution Subcutaneous 30 mg / 3 mL Injection, solution 30 MG Injection, solution Parenteral 30 mg/3ml - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5648333 No 1997-07-15 2019-07-15 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility 1 mg/mL MSDS - Predicted Properties
Property Value Source Water Solubility 0.0362 mg/mL ALOGPS logP -2.2 ALOGPS logP -7.7 Chemaxon logS -4.6 ALOGPS pKa (Strongest Acidic) 3.46 Chemaxon pKa (Strongest Basic) 12.48 Chemaxon Physiological Charge 3 Chemaxon Hydrogen Acceptor Count 23 Chemaxon Hydrogen Donor Count 18 Chemaxon Polar Surface Area 516.22 Å2 Chemaxon Rotatable Bond Count 30 Chemaxon Refractivity 363.79 m3·mol-1 Chemaxon Polarizability 135.1 Å3 Chemaxon Number of Rings 7 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.5123 Blood Brain Barrier - 0.8713 Caco-2 permeable - 0.8198 P-glycoprotein substrate Substrate 0.8421 P-glycoprotein inhibitor I Non-inhibitor 0.8961 P-glycoprotein inhibitor II Non-inhibitor 0.9801 Renal organic cation transporter Non-inhibitor 0.6176 CYP450 2C9 substrate Non-substrate 0.7753 CYP450 2D6 substrate Non-substrate 0.7828 CYP450 3A4 substrate Non-substrate 0.5958 CYP450 1A2 substrate Non-inhibitor 0.661 CYP450 2C9 inhibitor Non-inhibitor 0.8477 CYP450 2D6 inhibitor Non-inhibitor 0.876 CYP450 2C19 inhibitor Non-inhibitor 0.796 CYP450 3A4 inhibitor Non-inhibitor 0.729 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9691 Ames test Non AMES toxic 0.6483 Carcinogenicity Non-carcinogens 0.8963 Biodegradation Not ready biodegradable 0.898 Rat acute toxicity 2.4262 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9506 hERG inhibition (predictor II) Inhibitor 0.5187
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Type 1 angiotensin receptor binding
- Specific Function
- Receptor for bradykinin. It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system.
- Gene Name
- BDKRB2
- Uniprot ID
- P30411
- Uniprot Name
- B2 bradykinin receptor
- Molecular Weight
- 44460.15 Da
References
- Privitera PJ, Beckstead RM, Yates P, Walgren R: Autoradiographic localization of [125I-Tyr0]bradykinin binding sites in brains of Wistar-Kyoto and spontaneously hypertensive rats. Cell Mol Neurobiol. 2003 Oct;23(4-5):805-15. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Zinc ion binding
- Specific Function
- Broad specificity aminopeptidase. Plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. May play a critical role in the pathogen...
- Gene Name
- ANPEP
- Uniprot ID
- P15144
- Uniprot Name
- Aminopeptidase N
- Molecular Weight
- 109538.68 Da
References
- Bawolak MT, Fortin JP, Vogel LK, Adam A, Marceau F: The bradykinin B2 receptor antagonist icatibant (Hoe 140) blocks aminopeptidase N at micromolar concentrations: off-target alterations of signaling mediated by the bradykinin B1 and angiotensin receptors. Eur J Pharmacol. 2006 Dec 3;551(1-3):108-11. Epub 2006 Sep 8. [Article]
Drug created at March 19, 2008 16:16 / Updated at December 02, 2023 06:46