The effect of multiple doses of ubrogepant on the pharmacokinetics of an oral contraceptive in healthy women: Results of an open-label, single-center, two-period, fixed-sequence study

Abstract

Background: Ubrogepant is a novel, oral calcitonin gene–related peptide receptor antagonist for acute treatment of migraine. This study evaluated potential drug–drug interactions between ubrogepant and an oral contraceptive containing ethinyl estradiol (EE) and norgestimate (NGM). Methods: This open-label, single-center, two-period, fixed-sequence study enrolled healthy, postmenopausal or oophorectomized, adult women. In period 1, participants received a single oral dose of EE 0.035 mg/NGM 0.25 mg (EE-NGM) followed by a 7-day washout. In period 2, participants received oral ubrogepant 50 mg daily on days 1–14; single-dose EE-NGM was coadministered with ubrogepant on day 10. Pharmacokinetic parameters for plasma EE and norelgestromin (NGMN) were compared with and without ubrogepant. Results: Twenty-two participants aged 46–66 years were enrolled; 21 completed the study. Geometric mean ratios and 90% confidence intervals for the comparison of EE-NGM + ubrogepant to EE-NGM alone were contained within 0.80 and 1.25 for area under the plasma drug concentration–time curve (AUC) from time zero to infinity (AUC0–∞; 0.96 [0.91, 1.01]) and C max (0.91 [0.82, 1.004]) of NGMN and AUC0–∞ (0.97 [0.93, 1.01]) of EE, but not C max of EE (0.74 [0.69, 0.79]). Median t max of EE was delayed following EE-NGM + ubrogepant (3.0 h) versus EE-NGM alone (median of 1.5 h), whereas median t max of NGMN was unchanged (1.5 h). Geometric mean apparent terminal half-life ( t ½) was similar with and without ubrogepant for EE (23 vs. 21 h) and NGMN (36 h both conditions). All ubrogepant-related adverse events were mild or moderate. Conclusion: Ubrogepant did not demonstrate potential for clinically meaningful drug–drug interactions with an EE-NGM oral contraceptive. Trial registration: Not applicable (phase 1 trial)

Ubrogepant Is Safe and Efficacious in Participants Taking Concomitant Preventive Medication for Migraine: A Pooled Analysis of Phase 3 Trials

“…In addition, pharmacokinetic data on the impact of ubrogepant on CGRP-targeted monoclonal antibodies (mAbs) have not shown any interactions [ 28 ]. Consistent with the safety results reported here, ubrogepant has minimal pharmacokinetic drug–drug interactions overall [ 13 , 29 , 30 ]. The results of this study indicate that ubrogepant is safe to use with the preventive medications for migraine and can be applied when being used in real-world practice.…”

Safety and Risk of Medication Overuse Headache in Lasmiditan and Second-Generation Gepants: A Rapid Review

“…Ubrogepant showed no clinically relevant signal of hepatotoxicity following intermittent, high- frequency dosing, or clinically significant drug-drug interactions with erenumab, galcanezumab, paracetamol, naproxen, sumatriptan and components of an oral contraceptive. [38][39][40][41][42]…”

Novel Therapies in Acute Migraine Management: Small-Molecule Calcitonin Gene-Receptor Antagonists and Serotonin 1F Receptor Agonist

“…In phase I studies, ubrogepant was not associated with any clinically significant pharmacokinetic interactions when coadministered with sumatriptan, naproxen, acetaminophen, and oral contraceptives. 24-26…”

“…In phase I studies, ubrogepant was not associated with any clinically significant pharmacokinetic interactions when coadministered with sumatriptan, naproxen, acetaminophen, and oral contraceptives. [24][25][26] Ubrogepant is administered as a 50-or 100-mg dose, which can be repeated at least 2 hours after the initial dose with a 24-hour maximum dose of 200 mg. 18 Rimegepant is dosed as 75 mg once at the onset of migraine pain, with a maximum 24-hour dose of 75 mg. 19 The safety of using ubrogepant to treat more than 8 migraines and rimegepant to treat more than 15 migraines in a 30-day period has not been established. 18,19 Additional pharmacokinetic and dosing information for ubrogepant and rimegepant are located in Table 2.…”