Ubrelvy Drug Information

is indicated for the acute treatment of migraine with or without aura in adults. Limitations of Use UBRELVY is not indicated for the preventive treatment of migraine. UBRELVY is a calcitonin gene-related peptide receptor antagonist indicated for the acute treatment of migraine with or without aura in adults.

Limitations of Use UBRELVY is not indicated for the preventive treatment of migraine.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of UBRELVY was evaluated in 3,624 subjects who received at least one dose of UBRELVY. In two randomized, double-blind, placebo-controlled, Phase 3 trials in adult patients with migraine (Studies 1 and 2), a total of 1,439 patients received UBRELVY 50 mg or 100 mg . Of the UBRELVY-treated patients in these 2 studies, approximately 89% were female, 82% were White, 15% were Black, and 17% were of Hispanic or Latino ethnicity. The mean age at study entry was 41 years (range of 18-75 years). Long-term safety was assessed in 813 patients, dosing intermittently for up to 1 year in an open-label extension study.

Patients were permitted to treat up to 8 migraines per month with UBRELVY. Of these 813 patients, 421 patients were exposed to 50 mg or 100 mg for at least 6 months, and 364 patients were exposed to these doses for at least one year, all of whom treated at least two migraine attacks per month, on average. In that study, 2.5% of patients were withdrawn from UBRELVY because of an adverse reaction. The most common adverse reaction resulting in discontinuation in the long-term safety study was nausea.

Adverse reactions in Studies 1 and 2 are shown in Table 2. Table 2: Adverse Reactions Occurring in At Least 2% and at a Frequency Greater than Placebo in Studies 1 and 2 Placebo (N= 984) % UBRELVY 50 mg (N=954) % UBRELVY 100 mg (N=485) % Nausea 2 2 4 Somnolence* 1 2 3 Dry Mouth 1 <1 2 *Somnolence includes the adverse reaction-related terms sedation and fatigue. 6. 2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of UBRELVY. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Immune System Disorders: Hypersensitivity (e.g., anaphylaxis, dyspnea, facial or throat edema, rash, urticaria, and pruritus) Vascular Disorders: Hypertension , Raynaud’s phenomenon

CYP3A4 I nhibitors Co-administration of

UBRELVY with ketoconazole, a strong CYP3A4 inhibitor, resulted in a significant increase in exposure of ubrogepant . UBRELVY should not be used with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin) . Co-administration of UBRELVY with verapamil, a moderate CYP3A4 inhibitor, resulted in an increase in ubrogepant exposure . Dose adjustment is recommended with concomitant use of UBRELVY and moderate CYP3A4 inhibitors (e.g., cyclosporine, ciprofloxacin, fluconazole, fluvoxamine, grapefruit juice) . No dedicated drug interaction study was conducted with ubrogepant and weak CYP3A4 inhibitors. Dose adjustment is recommended with concomitant use of UBRELVY with weak CYP3A4 inhibitors .

CYP3A4 I nducers Co-administration of

UBRELVY with rifampin, a strong CYP3A4 inducer, resulted in a significant reduction in ubrogepant exposure . In patients taking strong CYP3A4 inducers (e.g., phenytoin, barbiturates, rifampin, St. John’s Wort), loss of ubrogepant efficacy is expected, and concomitant use should be avoided. Co-administration of UBRELVY with moderate or weak CYP3A4 inducers was not evaluated in a clinical study.

Dose adjustment is recommended with concomitant use of UBRELVY and moderate or weak CYP3A4 inducers .

BCRP and / or P-gp Only Inhibitors Ubrogepant is a substrate of

BCRP and P-gp efflux transporters. Use of BCRP and/or P-gp only inhibitors (e.g., quinidine, carvedilol, eltrombopag, curcumin) may increase the exposure of ubrogepant . Clinical drug interaction studies with inhibitors of these transporters were not conducted. Dose adjustment is recommended with BCRP and/or P-gp only inhibitors .

Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors outcomes in women who become pregnant while taking UBRELVY. Patients should be encouraged to enroll by calling 1-833-277-0206 or visiting http://empresspregnancyregistry.com. Risk Summary There are no adequate data on the developmental risk associated with the use of UBRELVY in pregnant women. In animal studies, adverse effects on embryofetal development were observed following administration of ubrogepant during pregnancy (increased embryofetal mortality in rabbits) or during pregnancy and lactation (decreased body weight in offspring in rats) at doses greater than those used clinically and which were associated with maternal toxicity ( see Data ). 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. Data Animal Data Oral administration of ubrogepant (0, 1.5, 5, 25, 125 mg/kg/day) to pregnant rats during the period of organogenesis resulted in no adverse effects on embryofetal development.

Plasma exposure (AUC) at the highest dose tested is approximately 45 times that in humans at the maximum recommended human dose (MRHD) of 200 mg/day. In pregnant rabbits, ubrogepant (0, 15, 45, 75, or 250 mg/kg/day) was administered orally throughout organogenesis in two separate studies. In both studies, the highest dose tested (250 mg/kg/day) was associated with maternal toxicity.

In the first study, ubrogepant produced abortion and increased embryofetal mortality in surviving litters at the high dose (250 mg/kg/day). In the second study, excessive maternal toxicity at the high dose (250 mg/kg/day) resulted in early termination and lack of fetal data for that dose group. Plasma exposure (AUC) at the highest no-effect dose (75 mg/kg/day) for adverse effects on embryofetal development in rabbit is approximately 8 times that in humans at the MRHD. Oral administration of ubrogepant (0, 25, 60, or 160 mg/kg/day) to rats throughout gestation and lactation resulted in decreased body weight in offspring at birth and during the lactation period at the mid and high doses, which were associated with maternal toxicity. Plasma exposure (AUC) at the no-effect dose for adverse effects on pre- and postnatal development in rats (25 mg/kg/day) is approximately 15 times that in humans at the MRHD.

Pediatric Use Safety and effectiveness in pediatric patients have not been established.

is contraindicated: With concomitant use of strong CYP3A4 inhibitors In patients with a history of serious hypersensitivity to ubrogepant or any component of UBRELVY. Reactions have included anaphylaxis, dyspnea, and facial or throat edema Concomitant use with strong CYP3A4 inhibitors. History of serious hypersensitivity to ubrogepant or any component of UBRELVY.

E The elimination half-life of ubrogepant is approximately 5 to 7 hours; therefore, monitoring of patients after overdose with UBRELVY should continue for at least 24 hours, or while symptoms or signs persist.