Icatibant

Compound Name:IcatibantMolecular Target:Bradykinin B2 receptorMolecular Structure:Synthetic decapeptide with five non-proteinogenic amino acidsLicensed Indication:Acute attacks of hereditary angioedema affecting any body part in patients 18 years of age and olderManufacturer and/or Distributor:Shire Human Genetic Therapies, IncInitial FDA Approval2011SummaryIcatibant (Firazyr) is a synthetic peptidomimetic drug consisting of ten amino acids which is a selective and specific bradykinin B2 receptor antagonist. Bradykinin is a key effector peptide in hereditary angioedema (HAE). Binding of bradykinin to the bradykinin B2 receptor leads to the responses characteristic of HAE, including vasodilation, edema, and stimulation of pain fibers. Icatibant is administered subcutaneously. In 2011, icatibant was approved by the FDA for the treatment of acute attacks of hereditary angioedema in patients 18 years of age and older. It has been shown to lead to a more rapid improvement in symptoms compared to placebo and tranexamic acid and to a decreased need for other medical interventions during acute attacks. ̈ More recent studies suggest possible efficacy in non-histaminergic episodic angioedema including those associated with administration of angiotensin converting enzyme inhibitors. Localized injection site reactions of pain, erythema, swelling, or bruising occur in 97% of treated patients. Icatibant is classified as Pregnancy Category C. Other adverse reactions are pyrexia, transaminase elevations, dizziness and rash.References

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1. 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):1497-1503.
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2. Cicardi M, Banerji A, Bracho F, Malbran A, Rosenkranz B, Riedl M, et al. Icatibant, a new bradykinin- receptor antagonist, in hereditary angioedema. N Engl J Med. 2010 Aug 5;363(6):532-541. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20818888

3. Deeks ED. Icatibant. Drugs. 2010;70(1):73-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20030426

4. Maurer M, Longhurst HJ, Fabien V, Li HH, Lumry WR. Treatment of hereditary angioedema with icatibant: efficacy in clinical trials versus effectiveness in the real-world setting. Allergy Asthma Proc. 2014 Sep-Oct;35(5):377-81.
 http://www.ncbi.nlm.nih.gov/pubmed/25198193

5. Egan M, Wang J. Icatibant Use in Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema. J Allergy Clin Immunol Pract. 2015 Sep-Oct;3(5):824-5. http://www.ncbi.nlm.nih.gov/pubmed/26613106

6. Icatibant for Patients with Type III Hereditary Angioedema: A Review of Clinical Effectiveness and Harms [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2014 Feb. http://www.ncbi.nlm.nih.gov/pubmed/25654149

7. Vaheri A, Strandin T, Jääskeläinen AJ, Vapalahti O, Jarva H et al. Pathophysiology of a severe case of Puumala hantavirus infection successfully treated with bradykinin receptor antagonist icatibant. Antiviral Res. 2014 Nov;111:23-5.
 http://www.ncbi.nlm.nih.gov/pubmed/25194993

8. Medjadba W, Martin-Eauclaire MF, Laraba-Djebari F. Involvement of Kallikrein-Kinin System on Cardiopulmonary Alterations and Inflammatory Response Induced by Purified Aah I Toxin from Scorpion Venom. Inflammation. 2015 Sep 11.
 http://www.ncbi.nlm.nih.gov/pubmed/26361946

9. Lumry WR, Farkas H, Moldovan D, Toubi E, Baptista J et al. Icatibant for Multiple Hereditary Angioedema Attacks across the Controlled and Open-Label Extension Phases of FAST-3. Int Arch Allergy Immunol. 2015;168(1):44-55.
 http://www.ncbi.nlm.nih.gov/pubmed/26556097

10. J Allergy Clin Immunol. 2016 Nov 29. pii: S0091-6749(16)31376-8. doi: 10.1016/j.jaci.2016.09.051. [Epub ahead of print] Effect of bradykinin receptor antagonism on ACE inhibitor-associated angioedema. Straka BT1, Ramirez CE1, Byrd JB1, Stone E1, Woodard-Grice A1, Nian H2, Yu C2, Banerji A3, Brown NJ4.

11. Clin Exp Immunol. 2016 Dec 9. doi: 10.1111/cei.12910. [Epub ahead of print] Comparing acquired angioedema with hereditary angioedema (type I/II): Findings from the Icatibant Outcome Survey. Longhurst HJ1, Zanichelli A2, Caballero T3, Bouillet L4, Aberer W5, Maurer M6, Fain O7, Fabien V8, Andresen I8; for the IOS Study Group.

12. Immunol Allergy Clin North Am. 2017 Feb;37(1):183-200. doi: 10.1016/j.iac.2016.08.011. The Angiotensin-Converting-Enzyme-Induced Angioedema. Bas M1.

13. Ann Pharmacother. 2016 Jan;50(1):47-59. doi: 10.1177/1060028015607037. Epub 2015 Sep 28. Off-Label Use of Agents for Management of Serious or Life-threatening Angiotensin Converting Enzyme Inhibitor-Induced Angioedema. Culley CM1, DiBridge JN2, Wilson GL Jr3.

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