Berotralstat
{{Short description|Medication}}
{{Use American English|date=July 2021}}
{{Use dmy dates|date=August 2021}}
{{Infobox drug
| drug_name =
| INN =
| image = Berotralstat Structure.svg
| width =
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| pronounce =
| tradename = Orladeyo
| Drugs.com =
| MedlinePlus =
| licence_CA =
| licence_EU = yes
| DailyMedID = Berotralstat
| licence_US =
| pregnancy_AU =
| pregnancy_AU_comment =
| pregnancy_category=
| routes_of_administration = By mouth
| class = Plasma kallikrein inhibitor
| ATCvet =
| ATC_prefix = B06
| ATC_suffix = AC06
| ATC_supplemental =
| legal_AU =
| legal_AU_comment =
| legal_BR =
| legal_BR_comment =
| legal_CA = Rx-only
| legal_CA_comment = {{cite web | title=Summary Basis of Decision - Orladeyo | website=Health Canada | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00610&lang=en | access-date=28 November 2022}}[https://pdf.hres.ca/dpd_pm/00066149.PDF Product monograph] hres.ca
| legal_DE =
| legal_DE_comment =
| legal_NZ =
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| legal_UK =
| legal_UK_comment =
| legal_US = Rx-only
| legal_US_comment = {{cite web | title=Orladeyo- berotralstat hydrochloride capsule | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3527ece1-e7e0-40b1-b0c5-6baeb0deabeb | access-date=25 December 2020}}{{cite web | title=Drug Trials Snapshot: Orladeyo | website=U.S. Food and Drug Administration | date=3 December 2020 | url=https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshot-orladeyo | archive-url=https://web.archive.org/web/20201218144319/https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshot-orladeyo | url-status=dead | archive-date=18 December 2020 | access-date=25 December 2020}} {{PD-notice}}
| legal_EU = Rx-only
| legal_EU_comment = {{cite web | title=Orladeyo EPAR | website=European Medicines Agency (EMA) | date=24 February 2021 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/orladeyo | access-date=12 July 2021}}{{cite web | title=Orladeyo Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1544.htm | access-date=3 March 2023}}
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| bioavailability =
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| index2_label = as HCl
| CAS_number_Ref =
| CAS_number = 1809010-50-1
| CAS_number2 = 1809010-52-3
| CAS_supplemental =
| PubChem = 137528262
| IUPHAR_ligand =
| DrugBank_Ref =
| DrugBank = DB15982
| ChemSpiderID_Ref =
| ChemSpiderID = 81368516
| UNII_Ref =
| UNII = XZA0KB1BDQ
| UNII2 = 88SH1NBL2B
| KEGG_Ref =
| KEGG = D11673
| KEGG2_Ref =
| KEGG2 = D11674
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| NIAID_ChemDB =
| PDB_ligand =
| synonyms = BCX7353, BCX-7353
| IUPAC_name = 2-[3-(aminomethyl)phenyl]-N-[5-[(R)-(3-cyanophenyl)-(cyclopropylmethylamino)methyl]-2-fluorophenyl]-5-(trifluoromethyl)pyrazole-3-carboxamide
| C = 30 | H = 26 | F = 4 | N = 6 | O = 1
| SMILES = NCC1=CC(=CC=C1)N1N=C(C=C1C(=O)NC1=CC(=CC=C1F)[C@H](NCC1CC1)C1=CC=CC(=C1)C#N)C(F)(F)F
| StdInChI = 1S/C30H26F4N6O/c31-24-10-9-22(28(37-17-18-7-8-18)21-5-1-3-19(11-21)15-35)13-25(24)38-29(41)26-14-27(30(32,33)34)39-40(26)23-6-2-4-20(12-23)16-36/h1-6,9-14,18,28,37H,7-8,16-17,36H2,(H,38,41)/t28-/m1/s1
| StdInChI_comment =
| StdInChIKey = UXNXMBYCBRBRFD-MUUNZHRXSA-N
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}}
Berotralstat, sold under the brand name Orladeyo, is a medication used to prevent attacks of hereditary angioedema (HAE) in people aged twelve years and older.{{cite journal | vauthors = Hwang JR, Hwang G, Johri A, Craig T | title = Oral plasma kallikrein inhibitor BCX7353 for treatment of hereditary angioedema | journal = Immunotherapy | volume = 11 | issue = 17 | pages = 1439–1444 | date = December 2019 | pmid = 31635497 | doi = 10.2217/imt-2019-0128 | doi-access = free }}{{cite journal | vauthors = Zuraw B, Lumry WR, Johnston DT, Aygören-Pürsün E, Banerji A, Bernstein JA, Christiansen SC, Jacobs JS, Sitz KV, Gower RG, Gagnon R, Wedner HJ, Kinaciyan T, Hakl R, Hanzlíková J, Anderson JT, McNeil DL, Fritz SB, Yang WH, Tachdjian R, Busse PJ, Craig TJ, Li HH, Farkas H, Best JM, Clemons D, Cornpropst M, Dobo SM, Iocca HA, Kargl D, Nagy E, Murray SC, Collis P, Sheridan WP, Maurer M, Riedl MA | display-authors = 6 | title = Oral once-daily berotralstat for the prevention of hereditary angioedema attacks: A randomized, double-blind, placebo-controlled phase 3 trial | journal = The Journal of Allergy and Clinical Immunology | date = October 2020 | volume = 148 | issue = 1 | pages = 164–172.e9 | pmid = 33098856 | doi = 10.1016/j.jaci.2020.10.015 | doi-access = free }}
The most common side effects include abdominal pain, vomiting, diarrhea, back pain, and heartburn.
Berotralstat was approved for medical use in the United States in December 2020,{{cite web | title=Orladeyo: FDA-Approved Drugs | website=U.S. Food and Drug Administration (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=214094 | access-date=25 December 2020}} and in the European Union in April 2021.
History
Berotralstat was approved based on evidence from one clinical trial (Trial 1 /NCT03485911) of 120 participants with hereditary angioedema. The trial was conducted at 40 sites in the United States, the European Union, and Canada. Trial investigators evaluated participants 12 years and older{{Cite web|title=Berotralstat (Oral Route) Side Effects - Mayo Clinic|url=https://www.mayoclinic.org/drugs-supplements/berotralstat-oral-route/side-effects/drg-20506380?p=1|access-date=3 March 2021|website=www.mayoclinic.org}} with hereditary angioedema for eight weeks to determine the number of attacks for each participant. The trial enrolled only participants who had at least two attacks during the eight-week period. Participants were assigned to receive one of two doses of berotralstat or placebo once every day for 24 weeks. Neither the participants nor the investigators knew which treatment was being given until after the trial was completed. All participants could use other medications for treatment of attacks.
References
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External links
- {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/berotralstat | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Berotralstat }}
- {{ClinicalTrialsGov|NCT03485911|Efficacy and Safety Study of BCX7353 as an Oral Treatment for the Prevention of Attacks in HAE (APeX-2)}}
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