Ubrelvy

— THERAPEUTIC CATEGORIES —
  • Migraine and headache
PAGE CONTENTS
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Ubrelvy Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Ubrogepant 50mg, 100mg; tabs.

    Pharmacological Class

    Calcitonin gene-related peptide (CGRP) receptor antagonist.

    How Supplied

    Packets—6, 8, 10, 12, 30

    How Supplied

    Ubrelvy 50 mg is supplied as white to off-white, capsule-shaped, biconvex tablets debossed with “U50” on one side in unit-dose packets (each packet contains 1 tablet):  

    • Box of 10 Packets  

    • Box of 16 Packets  

    • Box of 30 Packets 

    Ubrelvy 100 mg is supplied as white to off-white capsule-shaped, biconvex tablets debossed with “U100” on one side in unit-dose packets (each packet contains 1 tablet):  

    • Box of 10 Packets

    • Box of 16 Packets

    • Box of 30 Packets

    Storage

    Store between 20°C and 25°C (68°F and 77°F): excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature].

    Manufacturer

    AbbVie

    Generic Availability

    NO

    Mechanism of Action

    Ubrogepant is a calcitonin gene-related peptide receptor antagonist.

    Ubrelvy Indications

    Indications

    Acute treatment of migraine with or without aura.

    Limitations of Use

    Not for preventive treatment of migraine.

    Ubrelvy Dosage and Administration

    Adult

    Initially 50mg or 100mg; may give a second dose at least 2hrs after initial dose (max 200mg/day). Concomitant use with moderate CYP3A4 inhibitors: initially 50mg, avoid second dose within 24hrs. Concomitant use with BCRP and/or P-gp only inhibitors or weak CYP3A4 inhibitors: initially 50mg; may give second dose after 2hrs (if needed). Concomitant use with moderate or weak CYP3A4 inducers: initially 100mg; may give second dose after 2hrs (if needed). Severe hepatic (Child-Pugh Class C) or renal (CrCl 15–29mL/min) impairment: initially 50mg; may give second dose after 2hrs (if needed). The safety of treating more than 8 migraines in a 30-day period has not been established.

    Children

    Not established.

    Ubrelvy Contraindications

    Contraindications

    Concomitant use with strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin).

    Ubrelvy Boxed Warnings

    Not Applicable

    Ubrelvy Warnings/Precautions

    Warnings/Precautions

    Discontinue if a severe hypersensitivity reaction occurs; treat appropriately. Severe hepatic (Child-Pugh Class C) or severe renal (CrCl 15–29mL/min) impairment: See Adults. ESRD (CrCl <15mL/min): avoid. Elderly. Pregnancy. Nursing mothers.

    Pregnancy Considerations

    Risk Summary

    • There are no adequate data on the developmental risk associated with the use of Ubrelvy in pregnant women. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The estimated rate of major birth defects (2.2% -2.9%) and miscarriage (17%) among deliveries to women with migraine are similar to rates reported in women without migraine. 

    Clinical Considerations

    • Disease-Associated Maternal and/or Embryo/Fetal Risk: Published data have suggested that women with migraine may be at increased risk of preeclampsia and gestational hypertension during pregnancy. 

    Nursing Mother Considerations

    There are no data on the presence of ubrogepant in human milk, the effects of ubrogepant on the breastfed infant, or the effects of ubrogepant on milk production. 

    The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Ubrelvy and any potential adverse effects on the breastfed infant from Ubrelvy or from the underlying maternal condition.

    Pediatric Considerations

    Safety and effectiveness in pediatric patients have not been established.

    Geriatric Considerations

    There were no clinically significant pharmacokinetic differences observed between elderly and younger subjects. Clinical studies of Ubrelvy did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients. 

    Use caution with dose selection for an elderly patient, usually starting at the low end of the dosing range. 

    Renal Impairment Considerations

    The renal route of elimination plays a minor role in the clearance of ubrogepant. No dose adjustment is recommended for patients with mild or moderate renal impairment. Dose adjustment is recommended for patients with severe renal impairment (CLcr 15-29 mL/min). Avoid use of Ubrelvy in patients with end-stage renal disease (ESRD) (CLcr <15 mL/min).

    Hepatic Impairment Considerations

    In patients with pre-existing mild (Child-Pugh Class A), moderate (Child-Pugh Class B), or severe hepatic impairment (Child-Pugh Class C), ubrogepant exposure was increased by 7%, 50%, and 115%, respectively. No dose adjustment is recommended for patients with mild or moderate hepatic impairment. Adjust dose for patients with severe hepatic impairment.

    Ubrelvy Pharmacokinetics

    Absorption

    Following oral administration of Ubrelvy, ubrogepant is absorbed with peak plasma concentrations at approximately 1.5 hours. Ubrogepant displays dose-proportional pharmacokinetics within the recommended dose range. 

    Effect of Food: When Ubrelvy was administered with a high-fat meal, the time to maximum ubrogepant plasma concentration was delayed by 2 hours and resulted in a 22% reduction in Cmax with no change in AUC. Ubrelvy was administered without regard to food in clinical efficacy studies.

    Distribution

    Plasma protein binding of ubrogepant is 87% in vitro. The mean apparent central volume of distribution of ubrogepant (V/F) after single dose oral administration is approximately 350 L.

    Metabolism

    Ubrogepant is eliminated mainly through metabolism, primarily by CYP3A4. The parent compound (ubrogepant), and 2 glucuronide conjugate metabolites were the most prevalent circulating components in human plasma. The glucuronide metabolites are not expected to contribute to the pharmacological activity of ubrogepant since they were reported as about 6000-fold less potent in the CGRP receptor binding assay. 

    Elimination

    The elimination half-life of ubrogepant is approximately 5-7 hours. The mean apparent oral clearance (CL/F) of ubrogepant is approximately 87 L/hr. Ubrogepant is excreted mostly via the biliary/fecal route, while the renal route is a minor route of elimination. Following single oral dose administration of [14C]-ubrogepant to healthy male subjects, 42% and 6% of the dose was recovered as unchanged ubrogepant in feces and urine, respectively.

    Specific Populations 

    • Patients with Renal Impairment: Population pharmacokinetic analysis based on pooled data from clinical studies was used to evaluate the effect of renal impairment characterized based on estimated creatinine clearance (CLcr) using the Cockcroft-Gault (CG) equation. Renal impairment did not reveal a significant difference in the pharmacokinetics of ubrogepant in patients with mild or moderate renal impairment (CLcr 30-89 mL/min) relative to those with normal renal function (CLcr >90 mL/min). Patients with severe renal impairment or ESRD (eGFR <30 mL/min) have not been studied. Dose adjustment in patients with severe renal impairment (CLcr 15-29 mL/min) is recommended based on ADME information and a conservative assumption that severe renal impairment is unlikely to cause more than a two-fold increase in exposure of ubrogepant. No dosing recommendations can be made for patients with ESRD (CLcr<15 mL/min). 

    • Patients with Hepatic Impairment: In patients with pre-existing mild (Child-Pugh Class A), moderate (Child-Pugh Class B), or severe hepatic impairment (Child-Pugh Class C), ubrogepant exposure was increased by 7%, 50%, and 115%, respectively. Patients with severe hepatic impairment require dose adjustments. 

    • Other Specific Populations: Based on a population pharmacokinetic analysis, age, sex, race, and body weight did not have a significant effect on the pharmacokinetics (Cmax and AUC) of ubrogepant. Therefore, no dose adjustments are warranted based on these factors.

    Ubrelvy Interactions

    Interactions

    See Contraindications. Potentiated by moderate CYP3A4 inhibitors (eg, cyclosporine, ciprofloxacin, fluconazole, fluvoxamine, grapefruit juice); adjust doses (see Adults). May be potentiated by BCRP and/or P-gp only inhibitors (eg, quinidine, carvedilol, eltrombopag, curcumin); adjust doses. Antagonized by strong CYP3A4 inducers (eg, phenytoin, barbiturates, rifampin, St. John's wort); avoid. Concomitant moderate or weak CYP3A4 inducers: adjust doses (see Adults).

    Ubrelvy Adverse Reactions

    Adverse Reactions

    Nausea, somnolence.

    Ubrelvy Clinical Trials

    Clinical Trials

    The efficacy of Ubrelvy for the acute treatment of migraine was demonstrated in two randomized, double-blind, placebo-controlled trials [Study 1 (NCT02828020) and Study 2 (NCT02867709)]. 

    In Study 1, patients were randomly assigned to receive placebo (n=559) or Ubrelvy 50 mg (n=556) or 100 mg (n=557); and in Study 2, patients were randomly assigned to receive placebo (n=563) or Ubrelvy 50 mg (n=562). In all studies, patients were instructed to treat a migraine with moderate to severe headache pain intensity. Patients were allowed to take a second dose of study medication (Ubrelvy or placebo), or the patient’s usual acute treatment for migraine, between 2 to 48 hours after the initial treatment for a non-responding or recurrent migraine headache. Up to 23% of patients were taking preventive medications for migraine at baseline. None of these patients were on concomitant preventive medication that act on the CGRP pathway. 

    The primary efficacy analyses were conducted in patients who treated a migraine with moderate to severe pain. The efficacy of Ubrelvy was established by an effect on pain freedom at 2 hours post-dose and most bothersome symptom (MBS) freedom at 2 hours post-dose, compared to placebo, for Studies 1 and 2. Pain freedom was defined as a reduction of moderate or severe headache pain to no pain, and MBS freedom was defined as the absence of the self-identified MBS (i.e., photophobia, phonophobia, or nausea). Among patients who selected an MBS, the most commonly selected was photophobia (56%), followed by phonophobia (24%), and nausea (19%).

    In both studies, results showed that a significantly greater percentage of patients treated with Ubrelvy achieved headache pain freedom and MBS freedom 2 hours post-dose compared with those treated with placebo. Treatment with Ubrelvy also reduced the incidence of photophobia and phonophobia at both doses (50 mg and 100 mg) compared with placebo. 

    In Study 1, the percentages of patients treated with Ubrelvy 50 mg and 100 mg achieved the following primary and secondary endpoints vs placebo, respectively:

    • Pain free at 2 hours: 19.2% (P =.002) and 21.2% (P <.001) vs 11.8%

    • MBS free at 2 hours: 38.6% (P <.001) and 37.7% (P <.001) vs 27.8%

    • Pain relief at 2 hours: 60.7% (P <.001) and 61.4% (P <.001) vs 49.1%

    • Sustained pain freedome at 2–24 hours: 12.7% (*not statistically significant) and 15.4% (P =.002) vs 8.6%

    In Study 2, the percentages of patients treated with Ubrelvy 50 mg achieved the following primary and secondary endpoints vs placebo, respectively:

    • Pain free at 2 hours: 21.8% (P =.007) vs 14.3%

    • MBS free at 2 hours: 38.9% (P <.001) vs 27.4%

    • Pain relief at 2 hours: 62.7% (P <.001) vs 48.2%

    • Sustained pain freedome at 2–24 hours: 14.4% (P =.005) vs 8.2%

    Ubrelvy Note

    Not Applicable

    Ubrelvy Patient Counseling

    Patient Counseling

    Drug Interactions 

    • Advise patients to report to their healthcare provider the use of any other prescription medications, over-the-counter medications, or herbal products. Advise patients to inform their healthcare provider of grapefruit juice intake because a dosage modification is recommended with coadministration. 

    Pregnancy 

    • Advise patients to notify their healthcare provider if they become pregnant during treatment or plan to become pregnant. 

    Lactation 

    • Inform patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed. 

    Cost Savings Program

    Ubrelvy U-Save Card: https://www.ubrelvy.com/savings

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