Topiramate Extended Release: A Review in Epilepsy

Once-daily oral topiramate extended release (USL255; hereafter referred to as topiramate XR) [QUDEXY(®) XR] is approved in the USA for use as initial monotherapy and adjunctive therapy in patients aged ≥2 years with partial-onset seizures (POS) or primary generalized tonic-clonic seizures and as adjunctive therapy in patients aged ≥2 years with seizures associated with Lennox-Gastaut syndrome. Compared with twice-daily topiramate immediate release at the same total daily dose, topiramate XR provided bioequivalent exposure, an extended absorption rate (permitting convenient once-daily dosing) and more constant therapeutic plasma concentrations (potentially minimizing topiramate-associated adverse events). Switching between the two formulations did not affect the maintenance of topiramate concentrations. Moreover, the contents of a topiramate XR capsule may be sprinkled on to soft food for patients who have difficulty swallowing. In a multinational phase III study in adults with refractory POS, adjunctive topiramate XR was associated with significantly greater improvements from baseline in weekly median seizure frequency and the proportion of patients achieving a ≥50 % reduction in seizure frequency compared with placebo. These benefits were sustained during a 55-week open-label extension study. Adjunctive topiramate XR was generally well tolerated in these studies, with the majority of treatment-emergent adverse events being mild or moderate in intensity. In conclusion, current evidence suggests once-daily topiramate XR extends the treatment options currently available for patients aged ≥2 years with epilepsy, with its dosing regimen potentially delivering tolerability and adherence advantages over AEDs that require more frequent administration.