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Valbenazine and deutetrabenazine are vesicular monoamine transporter 2 (VMAT2) inhibitors approved for tardive dyskinesia. The clinical activity of valbenazine is primarily attributed to its only dihydrotetrabenazine (HTBZ) metabolite, [+]‐α‐HTBZ. Deutetrabenazine is a deuterated form of tetrabenazine and is metabolized to four deuterated HTBZ metabolites: [+]‐α‐deuHTBZ, [+]‐β‐deuHTBZ, [−]‐α‐deuHTBZ, and [−]‐β‐deuHTBZ. An open‐label, crossover study characterized the pharmacokinetic profiles of the individual deuHBTZ metabolites, which have not been previously reported. VMAT2 inhibition and off‐target interactions of the deuHTBZ metabolites were evaluated using radioligand binding. The only valbenazine HTBZ metabolite, [+]‐α‐HTBZ, was a potent VMAT2 inhibitor, with negligible affinity for off‐target dopamine, serotonin, and adrenergic receptors. Following deutetrabenazine administration, [−]‐α‐deuHTBZ represented 66% of circulating deuHTBZ metabolites and was a relatively weak VMAT2 inhibitor with appreciable affinity for dopamine (D2S, D3) and serotonin (5‐HT1A, 5‐HT2B, 5‐HT7) receptors. [+]‐β‐deuHTBZ was the most abundant deuHTBZ metabolite that potently inhibited VMAT2, but it represented only 29% of total circulating deuHTBZ metabolites. The mean half‐life of [+]‐α‐HTBZ (22.2 hours) was ∼3× longer than that of [+]‐β‐deuHTBZ (7.7 hours). These findings are similar to studies with tetrabenazine, in that deutetrabenazine is metabolized to four deuHTBZ stereoisomers, the most abundant of which has negligible interaction with VMAT2 in vitro and appreciable affinity for several off‐target receptors. In contrast, valbenazine's single HTBZ metabolite is a potent VMAT2 inhibitor in vitro with no discernible off‐target activity. Determination of the effects of intrinsic/extrinsic variables on deutetrabenazine's safety/efficacy profile should incorporate assessment of the effects on all deuHTBZ metabolites. [ABSTRACT FROM AUTHOR]

The CP reviews hospitalized patient's medication record, Lab investigations, ensures proper medication reconciliation along with communication with healthcare providers in daily rounds, to optimize patient's pharmacotherapy plan. If the patient had been experiencing issues with the medication in question, or if there was a strong probability of the medication causing issues in the future, the pharmacist contacted the provider that prescribed the medication in question via EHR direct message. In 2021, clinical pharmacists at HJAHC developed a program to collaborate with pharmacy students to identify and intervene on those patients who were omitted treatment for the following quality measures: 1) use of antithrombotic drugs in patients 18 years or older with ischemic vascular disease (IVD) and/or, 2) use of statins for the prevention of cardiovascular events in patients 21 years or older with, or at risk for developing, cardiovascular disease. Upon review of eligible patients for empagliflozin in 2021, only 18 patients with HF and 5 patients with ischemic stroke were identified. Two clinical pharmacists determined patient eligibility for empagliflozin, performed medication reconciliation, provided medication and disease state education, obtained prior authorizations, and phoned patients to follow up on day-7 and day-21 post-discharge. [Extracted from the article]

Background: Tardive dyskinesia is a persistent movement disorder induced by chronic neuroleptic exposure. NBI-98854 is a novel, highly selective, vesicular monoamine transporter 2 inhibitor. We present results of a randomized, 6-week, double-blind, placebo-controlled, dose-titration study evaluating the safety, tolerability, and efficacy of NBI-98854 for the treatment of tardive dyskinesia.Methods: Male and female adult subjects with moderate or severe tardive dyskinesia were included. NBI-98854 or placebo was given once per day starting at 25 mg and then escalated by 25 mg to a maximum of 75 mg based on dyskinesia and tolerability assessment. The primary efficacy endpoint was the change in Abnormal Involuntary Movement Scale from baseline at week 6 scored by blinded, central video raters. The secondary endpoint was the Clinical Global Impression of Change-Tardive Dyskinesia score assessed by the blinded investigator.Results: Two hundred five potential subjects were screened, and 102 were randomized; 76% of NBI-98854 subjects and 80% of placebo subjects reached the maximum allowed dose. Abnormal Involuntary Movement Scale scores for NBI-98854 compared with placebo were significantly reduced (p = 0.0005). Active drug was also superior on the Clinical Global Impression of Change-Tardive Dyskinesia (p < 0.0001). Treatment-emergent adverse event rates were 49% in the NBI-98854 and 33% in the placebo subjects. The most common adverse events (active vs. placebo) were fatigue and headache (9.8% vs. 4.1%) and constipation and urinary tract infection (3.9% vs. 6.1%). No clinically relevant changes in safety assessments were noted.Conclusion: NBI-98854 significantly improved tardive dyskinesia and was well tolerated in patients. These results support the phase 3 clinical trials of NBI-98854 now underway. [ABSTRACT FROM AUTHOR]