Ubrogepant

Ubrogepant, sold under the brand name Ubrelvy, is a medication used for the acute (immediate) treatment of migraine with or without aura (a sensory phenomenon or visual disturbance) in adults.^[4][5] It is not indicated for the preventive treatment of migraine.^[6] Ubrogepant is a small-molecule calcitonin gene-related peptide receptor antagonist.^[7][8] It is the first drug in this class approved for the acute treatment of migraine.

Ubrogepant

Clinical data
Trade names	Ubrelvy
Other names	MK-1602
AHFS/Drugs.com	Monograph
MedlinePlus	a620016
License data	US DailyMed: Ubrogepant
Routes of administration	By mouth
ATC code	N02CD04 (WHO)
Legal status
Legal status	CA: ℞-only[1][2][3] US: ℞-only[4]
Pharmacokinetic data
Protein binding	87% (in vitro)
Elimination half-life	5-7 hrs
Excretion	fecal/biliary
Identifiers
IUPAC name (6S)-N-[(3S,5S,6R)-6-Methyl-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-3-piperidinyl]-2'-oxo-1',2',5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridine]-3-carboxamide
CAS Number	1374248-77-7
PubChem CID	68748835
DrugBank	DB15328
ChemSpider	28536135
UNII	AD0O8X2QJR
KEGG	D10673
ChEMBL	ChEMBL2364638
CompTox Dashboard (EPA)	DTXSID00160178
Chemical and physical data
Formula	C29H26F3N5O3
Molar mass	549.554 g·mol−1
3D model (JSmol)	Interactive image
SMILES C[C@@H]1[C@H](c2ccccc2)C[C@H](NC(=O)c2cnc3c(c2)C[C@@]2(C3)C(=O)Nc3ncccc32)C(=O)N1CC(F)(F)F
InChI InChI=1S/C29H26F3N5O3/c1-16-20(17-6-3-2-4-7-17)11-22(26(39)37(16)15-29(30,31)32)35-25(38)19-10-18-12-28(13-23(18)34-14-19)21-8-5-9-33-24(21)36-27(28)40/h2-10,14,16,20,22H,11-13,15H2,1H3,(H,35,38)(H,33,36,40)/t16-,20-,22+,28+/m1/s1 Key:DDOOFTLHJSMHLN-ZQHRPCGSSA-N

The most common side effects are nausea, tiredness and dry mouth.^[6] Ubrogepant is contraindicated for co-administration with strong CYP3A4 inhibitors.^[6]

History

Ubrogepant, also known as MK-1602, was discovered by scientists at Merck.^[9]

The effectiveness of ubrogepant for the acute treatment of migraine was demonstrated in two randomized, double-blind, placebo-controlled trials.^[6] In these studies, 1,439 adult patients with a history of migraine, with and without aura, received the approved doses of ubrogepant to treat an ongoing migraine.^[6][10] In both studies, the percentages of patients achieving pain relief two hours after treatment (defined as a reduction in headache severity from moderate or severe pain to no pain) and whose most bothersome migraine symptom (nausea, light sensitivity or sound sensitivity) stopped two hours after treatment were significantly greater among patients receiving ubrogepant (19–21% depending on the dose) compared to those receiving placebo (12%).^[6][11] Patients were allowed to take their usual acute treatment of migraine at least two hours after taking ubrogepant.^[6] 23% of patients were taking a preventive medication for migraine.^[6]

In December 2019, the US Food and Drug Administration approved Ubrelvy produced by Allergan USA, Inc. for treatment of migraine after onset.^[6][12]

References

1. "Ubrelvy Product information". Health Canada. Retrieved 2 January 2023.
2. "Summary Basis of Decision - Ubrelvy". Health Canada. 30 March 2023. Retrieved 24 April 2023.
3. "Details for: Ubrelvy". Health Canada. 11 May 2023. Retrieved 3 March 2024.
4. "Ubrelvy- ubrogepant tablet". DailyMed. Retrieved 4 June 2021.
5. "Ubrogepant Prescribing Information" (PDF). FDA.gov. U.S. Food and Drug Administration. 2019.
6. "FDA approves new treatment for adults with migraine". U.S. Food and Drug Administration (FDA) (Press release). 23 December 2019. Archived from the original on 23 December 2019. Retrieved 23 December 2019. This article incorporates text from this source, which is in the public domain.
7. Tfelt-Hansen P, Olesen J (April 2011). "Possible site of action of CGRP antagonists in migraine". Cephalalgia. 31 (6): 748–750. doi:10.1177/0333102411398403. PMID 21383046. S2CID 22049557.
8. Spreitzer H (22 May 2018). "Neue Wirkstoffe: Ubrogepant". Österreichische Apotheker-Zeitung (in German) (11/2018).
9. Moore E, Fraley ME, Bell IM, Burgey CS, White RB, Li CC, et al. (January 2020). "Characterization of Ubrogepant: A Potent and Selective Antagonist of the Human Calcitonin Gene‒Related Peptide Receptor". The Journal of Pharmacology and Experimental Therapeutics: jpet.119.261065. doi:10.1124/jpet.119.261065. PMID 31992609. S2CID 210946813.
10. "Drug Trials Snapshots: Ubrelvy". U.S. Food and Drug Administration (FDA). 13 January 2020.
11. Dodick DW, Lipton RB, Ailani J, Lu K, Finnegan M, Trugman JM, Szegedi A (December 2019). "Ubrogepant for the Treatment of Migraine". The New England Journal of Medicine. 381 (23): 2230–2241. doi:10.1056/NEJMoa1813049. PMID 31800988. S2CID 208645302.
12. Maddipatla M (23 December 2019). "Allergan's acute migraine treatment wins U.S. FDA approval". Reuters. Retrieved 24 December 2019.