UBROGEPANT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for UBROGEPANT (UBROGEPANT).
Ubrogepant is a calcitonin gene-related peptide (CGRP) receptor antagonist. It binds to CGRP receptors, blocking the vasodilatory and pro-inflammatory effects of CGRP, thereby aborting migraine attacks without causing vasoconstriction.
| Metabolism | Primarily metabolized by CYP3A4; minor contributions from CYP2C8 and CYP3A5. Excreted mainly as metabolites in feces (42%) and urine (27%) with less than 1% unchanged in urine. |
| Excretion | Primarily eliminated via biliary/fecal excretion (approximately 70% of dose recovered in feces) with ~30% renal excretion (mostly as unchanged drug). |
| Half-life | Terminal elimination half-life is ~5-7 hours, supporting twice-daily dosing for migraine prevention. |
| Protein binding | ~87% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Vd is approximately 1.0 L/kg, indicating extensive tissue distribution beyond plasma volume. |
| Bioavailability | Oral bioavailability is approximately 24% due to P-glycoprotein-mediated efflux and first-pass metabolism. |
| Onset of Action | Oral: Onset of effect for acute migraine treatment observed as early as 2 hours post-dose (2-hour pain freedom endpoint in clinical trials). |
| Duration of Action | Clinical effect duration for acute migraine is 24-48 hours; for prevention, sustained effect with BID dosing. |
50 mg or 100 mg orally once daily as needed for acute treatment of migraine attacks; maximum daily dose: 200 mg. Not for prophylactic use.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min). Severe renal impairment (eGFR <30 mL/min): Not recommended due to lack of data. |
| Liver impairment | Child-Pugh A: No dose adjustment. Child-Pugh B: Not recommended. Child-Pugh C: Contraindicated. |
| Pediatric use | Safety and efficacy in pediatric patients (<18 years) have not been established; no recommended dose. |
| Geriatric use | No specific dose adjustment required; limited data in patients ≥65 years, use with caution due to potential for decreased renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for UBROGEPANT (UBROGEPANT).
| Breastfeeding | No data on presence in human milk; effect on infant unknown. Consider benefits of breastfeeding and maternal need for ubrogepant, and potential infant exposure. |
| Teratogenic Risk | No human data on fetal risk; animal studies show no teratogenic effects at exposures up to 10 times the human AUC at the MRHD. Avoid in pregnancy unless benefit outweighs potential risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
None
| Serious Effects |
["Concurrent use with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir) is contraindicated due to risk of elevated ubrogepant levels."]
| Precautions | ["Hypersensitivity reactions (including dyspnea, rash, urticaria, and facial swelling) have been reported; discontinue use if serious hypersensitivity occurs.","Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) is not recommended due to increased ubrogepant exposure.","Concomitant use with moderate CYP3A4 inducers (e.g., efavirenz) or strong inducers (e.g., rifampin) may reduce efficacy.","Use with caution in patients with severe hepatic impairment (Child-Pugh C) as safety and efficacy have not been established."] |
Loading safety data…
| No specific monitoring required; standard prenatal care. |
| Fertility Effects | No human data; animal studies show no adverse effects on fertility at exposures up to 10 times the human AUC. |