Once-Daily Valbenazine for Tardive Dyskinesia or Huntington’s Disease Chorea in Patients with Dysphagia or Swallowing Difficulties

Background: Once-daily valbenazine is approved for tardive dyskinesia (TD) and Huntington’s disease (HD) chorea. Dysphagia is common in both disorders, and alternative modes for oral medication administration are available with 2 approved valbenazine formulations.
Objectives: To report the suitability of different modes of valbenazine administration.
Methods: Three in vitro studies were conducted to assess the suitability of crushing valbenazine capsule contents (compacted powder) for addition to soft foods/liquids or delivery via gastrostomy tube (G-tube). In addition, two studies were conducted with a new approved valbenazine granules formulation: an in vitro study evaluating compatibility of granules with soft foods; and a phase 1 study analyzing bioequivalence between valbenazine formulations (granules versus compacted powder), along with bioequivalence between fed and fasted states for valbenazine granules sprinkled on applesauce. Geometric mean ratios (GMRs) for Cmax and AUC of valbenazine and its primary metabolite, [+]-α-dihydroxytetrabenazine ([+]-α-HTBZ), were analyzed, with bioequivalence defined as the GMR 90% CI falling within 80-125%.
Results: In vitro studies demonstrated that the compacted-powder contents of valbenazine capsules can be crushed and added to soft foods and liquids or delivered via G-tube. In addition, valbenazine granules were shown to be compatible with a variety of acidic and slightly acidic soft foods. Bioequivalence between valbenazine granules and intact compacted-powder capsule was demonstrated, with no overall effect on the extent of absorption (AUC for valbenazine and [+]-α-HTBZ). Bioequivalence between fed and fasted states was also demonstrated for valbenazine granules.
Conclusions: Two approved formulations of valbenazine provide oral administration options for patients with dysphagia.