Impact of Delayed-Dose Administration of USL255, Qudexy™ XR (Topiramate) Extended-Release Capsules

Authors: Anders B, Ludwig EA, Clark AM
Conference: American Academy of Neurology (AAN)
Keywords: AED, anticholinergics antispasmodics, neurology, Qudexy, seizures
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Introduction

  • Despite the importance of medication adherence for successful management of seizure disorders, nonadherence continues to be a significant problem in patients with epilepsy
  • Nonadherence to treatment, including delayed or missed antiepileptic drug (AED) dosing, can lead to increased seizure occurrence, reduced quality of life, frequent hospitalization and emergency room visits, and higher rates of morbidity/mortality 1-3
  • As use of extended-release (XR) AEDs has been shown to improve drug adherence,4 Upsher-Smith Laboratories, Inc. developed USL255, Qudexy™ XR (topiramate) extended-release capsules, as a once-daily (QD) treatment for epilepsy5
    USL255 was approved by the FDA (11 March 2014) as initial monotherapy for partial-onset seizures (POS) or primary generalized tonic-clonic (PGTC) seizures (patients aged ≥10 years) and adjunctive therapy for POS, PGTC, or seizures associated with Lennox-Gastaut syndrome (patients aged ≥2 years)5 The efficacy and safety of USL255 as adjunctive treatment for POS was recently evaluated in a multinational phase 3 study (PREVAIL; NCT01142193)6
  • Delayed administration of XR AEDs, taken less frequently than immediate-release formulations, may lead to a decrease in plasma concentrations from steady-state values to below minimum therapeutic concentrations4
  • The objective of these analyses was to predict the impact of delayed-dose administration of USL255 QD (taken 6, 12, 18, or 24 hours later than scheduled) in a simulated steady-state pharmacokinetic (PK) profile

Annual American Academy of Neurology (AAN), Philadelphia, Pennsylvania, April 2014

By Bob Anders, Elizabeth A Ludwig, Annie M. Clark