Advise patients to inform their healthcare provider of grapefruit juice intake because a dosage modification is recommended with co administration

 ADVERSE REACTIONS

The most common adverse reaction resulting in discontinuation in the long-term safety study was nausea, Somnolence, Dry Mouth

UBRELVY is contraindicated with concomitant use of strong CYP3A4 inhibitor

PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Drug Interactions-                                                                                                       Inform patients that UBRELVY may interact with certain other drugs; therefore, advise patients to report to their healthcare provider the use of any other prescription medications, over-the-counter medications, or herbal product

Advise patients to inform their healthcare provider of grapefruit juice intake because a dosage modification is recommended with co administration.

Pregnancy- pregnancy ant during treatment or plan to become pregnant 

Lactation-

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

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CLINICAL PHARMACOLOGY

1. Mechanism of Action-

Ubrogepant is a calcitonin gene-related peptide receptor antagonist.

2. Pharmacodynamics Cardiac Electrophysiology-                                                            At a dose 2 times the maximum recommended daily dose, UBRELVY does not prolong the QT interval to any clinically relevant extent.

3 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.

Elimination-                                                                                                            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.

Excretion -                                                                                                                    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.

Specific Populations-                                                                                             Patients with Renal Impairment Population pharmacokinetic analysis based on pooled data from clinical

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 [see Dosage and Administration (2.5)].

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.

USE IN SPECIFIC POPULATIONS

8.1 Pregnancy 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.

2. Lactation-                                                                                                                 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.

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

4.Geriatric Use In pharmacokinetic studies, no clinically significant pharmacokinetic differences were 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.

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range

5. 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.

No dose adjustment is recommended for patients with mild or moderate hepatic impairment. Dose adjustment for UBRELVY is recommended for patients with severe hepatic impairment [see Dosage and Administration (2.2)].

6. Renal Impairment-                                                                                                    The renal route of elimination plays a minor role in the clearance of ubrogepant [see Clinical Pharmacology (12.3)].

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)