Icatibant

Icatibant
Names
Trade namesFirazyr
Other namesHoe 140, JE 049[1]
IUPAC name
  • (2S)-2-[[(3aS,7aS)-1-[2-[(2S)-2-[[(2S)-
    2-[[2-[[(4R)-1-[1-[2-[[(2R)-2-amino-5-(diaminomethylideneamino)
    pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-
    2-carbonyl]-4-hydroxypyrrolidine-2-carbonyl]amino]acetyl]amino]-
    3-thiophen-2-ylpropanoyl]amino]-3-hydroxypropanoyl]
    3,4-dihydro-1H-isoquinoline-3-carbonyl]
    2,3,3a,4,5,6,7,7a-octahydroindole-2-carbonyl]amino]-
    5-(diaminomethylideneamino)pentanoic acid
Clinical data
Drug classBradykinin B2 receptors inhibitor[2]
Main usesHereditary angioedema (HAE) with insufficient C1-esterase inhibitor[2]
Side effectsRedness, itching, and pain at the site of injection[3]
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Pregnancy
category
  • AU: C
    Routes of
    use    		Subcutaneous
    Typical dose30 mg[2]
    External links
    AHFS/Drugs.comMonograph
    Legal
    License data
    Legal status
    • AU: S4 (Prescription only)
    • US: ℞-only [2]
    • EU: Rx-only [3]
    • In general: ℞ (Prescription only)
    Chemical and physical data
    FormulaC59H89N19O13S
    Molar mass1304.54 g·mol−1
    3D model (JSmol)
    SMILES
    • C1CC[C@H]2[C@@H](C1)CC(N2C(=O)C3CC4=CC=CC=C4CN3C(=O)[C@H](CO)NC(=O)[C@H](CC5=CC=CS5)NC(=O)CNC(=O)C6C[C@H](CN6C(=O)C7CCCN7C(=O)C(CCCN=C(N)N)NC(=O)[C@@H](CCCN=C(N)N)N)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O
    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 checkY
    • Key:QURWXBZNHXJZBE-OVZQYVDUSA-N checkY

    Icatibant, sold under the brand name Firazyr, is a medication used to treat attacks of hereditary angioedema (HAE) in people with insufficient C1-esterase inhibitor.[2][3] It does not appear effective for angioedema due to ACE inhibitors.[4][5] It is given by injection under the skin.[3]

    Common side effects include redness, itching, and pain at the site of injection.[3] Other side effects may include fever, headache, and nausea.[6] Safety in pregnancy is unclear.[7] It is a bradykinin B2 receptors inhibitor.[2]

    Icatibant was approved for medical use in Europe in 2008 and the United States in 2011.[3][8] In the United Kingdom it costs the NHS about £1,400 per dose.[6] In the United States this amount costs about 3,600 USD.[9]

    Medical uses

    Dosage

    It is given as a 30 mg injection under the skin.[2] This may be repeated after 6 hours if needed.[2]

    Mechanism of action

    Bradykinin is a peptide-based hormone that is formed locally in tissues, very often in response to a trauma. It increases vessel permeability, dilates blood vessels and causes smooth muscle cells to contract. Bradykinin plays an important role as the mediator of pain. Surplus bradykinin is responsible for the typical symptoms of inflammation, such as swelling, redness, overheating and pain. These symptoms are mediated by activation of bradykinin B2 receptors. Icatibant acts as a bradykinin inhibitor by blocking the binding of native bradykinin to the bradykinin B2 receptor. Little is known about the effects of icatibant on the bradykinin B1 receptor.

    Society and culture

    Icatibant received orphan drug status in Australia, the EU, Switzerland, and the US for the treatment of hereditary angioedema (HAE).[10]

    In the EU, the approval by the European Commission (July 2008) allows Jerini to market Firazyr in the European Union's 27 member states, as well as Switzerland, Liechtenstein and Iceland, making it the first product to be approved in all EU countries for the treatment of HAE.[11] In the US, the drug was granted FDA approval on August 25, 2011.[12]

    References

    1. ↑ "Icatibant: HOE 140, JE 049, JE049". Drugs in R&D. 5 (6): 343–8. 2004. doi:10.2165/00126839-200405060-00006. PMID 15563238.
    2. 1 2 3 4 5 6 7 8 "Firazyr- icatibant acetate injection, solution". DailyMed. 16 December 2019. Archived from the original on 3 August 2020. Retrieved 17 April 2020.
    3. 1 2 3 4 5 6 "Firazyr EPAR". European Medicines Agency (EMA). Archived from the original on 12 April 2020. Retrieved 17 April 2020.
    4. ↑ Jeon, J; Lee, YJ; Lee, SY (October 2019). "Effect of icatibant on angiotensin-converting enzyme inhibitor-induced angioedema: A meta-analysis of randomized controlled trials". Journal of clinical pharmacy and therapeutics. 44 (5): 685–692. doi:10.1111/jcpt.12997. PMID 31290163.
    5. ↑ Sinert R, Levy P, Bernstein JA, Body R, Sivilotti ML, Moellman J, et al. (September–October 2017). "Randomized Trial of Icatibant for Angiotensin-Converting Enzyme Inhibitor-Induced Upper Airway Angioedema". The Journal of Allergy and Clinical Immunology. In Practice. 5 (5): 1402–1409.e3. doi:10.1016/j.jaip.2017.03.003. PMID 28552382.
    6. 1 2 BNF 81: March-September 2021. BMJ Group and the Pharmaceutical Press. 2021. p. 306. ISBN 978-0857114105.
    7. ↑ "Icatibant (Firazyr) Use During Pregnancy". Drugs.com. Archived from the original on 4 December 2020. Retrieved 25 November 2021.
    8. ↑ "Icatibant Monograph for Professionals". Drugs.com. Archived from the original on 23 January 2021. Retrieved 25 November 2021.
    9. ↑ "Icatibant Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 24 January 2021. Retrieved 25 November 2021.
    10. ↑ Longhurst HJ (September 2010). "Management of acute attacks of hereditary angioedema: potential role of icatibant". Vascular Health and Risk Management. 6: 795–802. doi:10.2147/vhrm.s4332. PMC 2941790. PMID 20859548.
    11. ↑ "Jerini Receives European Commission Approval for Firazyr (Icatibant) in the Treatment of HAE" (Press release). Jerini AG. 15 July 2008. Retrieved 22 July 2008.
    12. ↑ "FDA Approves Shire's Firazyr (icatibant injection) for Acute Attacks of Hereditary Angioedema (HAE)" (Press release). Shire. Archived from the original on 29 March 2012. Retrieved 28 August 2011.
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