Migraine and headache:
Indications for: UBRELVY
Acute treatment of migraine with or without aura.
Limitations of Use:
Not for preventive treatment of migraine.
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%
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.
Concomitant use with strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin).
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.
Calcitonin gene-related peptide (CGRP) receptor antagonist.
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).
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.
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.
Generic Drug Availability:
Packets—6, 8, 10, 12, 30