Products
Ubrogepant was approved in the United States in 2019 in tablet form (Ubrelvy).
Structure and properties
Ubrogepant (C29H26F3N5O3, Mr = 549.6 g/mol) exists as a white powder that is practically insoluble in water.
Effects
Ubrogepant has analgesic properties and is effective against other symptoms of migraine such as photophobia (sensitivity to light), phonophobia (sensitivity to sound), and nausea. The effects are due to antagonism at the CGRP receptor. The half-life is in the range of 5 to 7 hours. CGRP (Calcitonin Gene-Related Peptide) is a neuropeptide that plays an important role in triggering migraine attacks. It consists of 37 amino acids and is expressed in the peripheral and central nervous systems. Two isoforms exist, CGRP-α (Figure) and CGRP-β, which differ in three amino acids. Both are agonists at the CGRP receptor. CGRP has potent vasodilatory properties and plays a central role in pain initiation as well as neurogenic inflammation. Migraineurs have been found to have elevated levels of CGRP during an attack, and intravenous administration of the peptide can induce attacks in migraine patients.
Indications
For acute therapy of migraine in adults, with or without aura.
Dosage
According to the SmPC. The drug is taken perorally and only as needed, unlike CGRP inhibitors (monoclonal antibodies). The tablets are administered independently of meals. If needed, another dose can be taken after at least two hours.
Contraindications
- Hypersensitivity
- Concurrent therapy with potent CYP3A4 inhibitors.
For complete precautions, see the drug label.
Interactions
Ubrogepant is metabolized primarily by CYP3A4 and interactions are possible with both inhibitors and inducers. Combination with strong CYP3A4 inhibitors is contraindicated (see above). Furthermore, ubrogepant is also a substrate of P-glycoprotein and BCRP.
Adverse effects
The most common potential adverse effects include nausea and drowsiness. Liver toxicity has not been observed. This is in contrast to other CGRP receptor antagonists. Unlike the triptans, ubrogepant does not cause vasoconstriction.
