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. |
| Molecular Weight | 527.6 |
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 | Limited human data; animal studies show no evidence of harm. Caution advised. |
| 2nd trimester | No adequate studies; use only if potential benefit justifies risk. |
| 3rd trimester | No adequate studies; potential for uterine effects and fetal harm; avoid near term. |
Clinical note
Comprehensive clinical and safety monograph for UBROGEPANT (UBROGEPANT).
| Placental transfer | Unknown; likely crosses placenta due to molecular weight and lipophilicity. |
| Breastfeeding | Not recommended; excreted in animal milk; unknown effects on infant. |
| Lactation Rating | L4 - Possibly Hazardous |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to ubrogepant or any componentConcomitant use with strong CYP3A4 inhibitors
| 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. |
| Food/Dietary | No specific food interactions known. However, avoid grapefruit juice as it may inhibit CYP3A4 and increase ubrogepant exposure. Take with or without food. |
Loading safety data…
| 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 | 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. |
| Clinical Pearls | First-in-class calcitonin gene-related peptide (CGRP) receptor antagonist indicated for acute migraine treatment. Does not cause vasoconstriction, safe in patients with cardiovascular disease. Maximum two doses per 24 hours, not for prevention. Onset within 2 hours. Avoid concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole) as they increase ubrogepant exposure; reduce dose if moderate CYP3A4 inhibitors are used. Not recommended in severe hepatic impairment (Child-Pugh C) or end-stage renal disease. |
| Patient Advice | Take one tablet at the first sign of migraine headache. · If symptoms improve but return, a second dose may be taken at least 2 hours after the first dose. Do not exceed 2 doses in 24 hours. · Do not use this medicine to prevent migraines. · Tell your healthcare provider if you have liver or kidney problems, or are pregnant or breastfeeding. · Inform your doctor about all medications you take, especially antifungal or antibiotic drugs, as they may affect ubrogepant levels. · This medicine may cause drowsiness; avoid driving or operating machinery until you know how it affects you. |