Prescription Drug Information: UBRELVY

UBRELVY- ubrogepant tablet
Allergan, Inc.

1 INDICATIONS AND USAGE

UBRELVY 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.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage

The recommended dose of UBRELVY is 50 mg or 100 mg taken orally with or without food.

If needed, a second dose may be taken at least 2 hours after the initial dose. The maximum dose in a 24-hour period is 200 mg. The safety of treating more than 8 migraines in a 30-day period has not been established.

2.2 Dosage Modification s

Dosing modifications for concomitant use of specific drugs and for patients with hepatic or renal impairment are provided in Table 1.

Table 1: Dose Modifications for Drug Interactions and for Specific Populations
Dosage Modifications Initial Dose Second Dose a (if needed)
Concomitant Drug [see Drug Interactions ( 7 )]
Moderate CYP3A4 Inhibitors ( 7.1) 50 mg Avoid within 24 hours
Weak CYP3A4 Inhibitors ( 7.1) 50 mg 50 mg
Strong CYP3A4 Inducers ( 7.2) Avoid concomitant use
Weak & Moderate CYP3A4 Inducers ( 7.2) 100 mg 100 mg
BCRP and/or P-gp only Inhibitors ( 7.3) 50 mg 50 mg
Spec i fic Populations [see Use in Specific Populations ( 8 )]
Severe Hepatic Impairment (Child-Pugh Class C) ( 8.6) 50 mg 50 mg
Severe Renal Impairment (CLcr 15-29 mL/min) ( 8.7) 50 mg 50 mg
End-Stage Renal Disease (CLcr <15 mL/min) ( 8.7) Avoid use

a Second dose may be taken at least 2 hours after the initial dose

3 DOSAGE FORMS AND STRENGTHS

UBRELVY 50 mg is supplied as white to off-white, capsule-shaped, biconvex tablets debossed with “U50” on one side.

UBRELVY 100 mg is supplied as white to off-white, capsule-shaped, biconvex tablets debossed with “U100” on one side.

4 CONTRAINDICATIONS

UBRELVY is contraindicated with concomitant use of strong CYP3A4 inhibitors [see Drug Interactions ( 7.1)].

6 ADVERSE REACTIONS

6.1 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 [see Clinical Studies ( 14)] . 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.

7 DRUG INTERACTIONS

7.1 CYP3A4 I nhibitors

Co-administration of UBRELVY with ketoconazole, a strong CYP3A4 inhibitor, resulted in a significant increase in exposure of ubrogepant [see Clinical Pharmacology ( 12.3) ]. UBRELVY should not be used with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin) [see Contraindication s ( 4)].

Co-administration of UBRELVY with verapamil, a moderate CYP3A4 inhibitor, resulted in an increase in ubrogepant exposure [see Clinical Pharmacology ( 12.3) ]. Dose adjustment is recommended with concomitant use of UBRELVY and moderate CYP3A4 inhibitors (e.g., cyclosporine, ciprofloxacin, fluconazole, fluvoxamine, grapefruit juice) [see Dosage and Administration ( 2.2)].

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 [see Dosage and Administration ( 2.2)].

7.2 CYP3A4 I nducers

Co-administration of UBRELVY with rifampin, a strong CYP3A4 inducer, resulted in a significant reduction in ubrogepant exposure [ s ee Clinical Pharmacology ( 12.3) ]. 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 [see Dosage and Administration ( 2.2)].

7 .3 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 [ s ee Clinical Pharmacology ( 12.3) ]. Clinical drug interaction studies with inhibitors of these transporters were not conducted. Dose adjustment is recommended with BCRP and/or P-gp only inhibitors [see Dosage and Administration ( 2.2) ].

8 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 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.

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