Hemostatic efficacy of four factor prothrombin complex concentrate in intracerebral hemorrhage patients receiving warfarin vs. factor Xa inhibitors.

INTRODUCTION: 4-F PCC is administered for reversal of factor Xa inhibitor-associated coagulopathy despite a lack of quality evidence demonstrating hemostatic efficacy. The aim of this study was to evaluate the hemostatic efficacy of 4-F PCC in intracerebral hemorrhage patients who received factor Xa inhibitors versus warfarin. MATERIALS AND METHODS: This was a multi-center, retrospective, observational cohort study at a large healthcare system. Patients taking warfarin received 4-F PCC 25-50 units/kg based on the presenting INR, while patients taking a factor Xa inhibitor received 35 units/kg. The primary outcome was the percentage of patients with good or excellent hemostatic efficacy as assessed by modified Sarode scale, with neurologic outcomes assessed as a secondary endpoint. Patients were included in the primary outcome population if they had a repeat CT scan within 24 h. RESULTS: One hundred fifty-seven patients were included in the primary outcome population; [warfarin (n = 76), factor Xa inhibitors (n = 81)]. Hemostatic efficacy was 83 % in the warfarin group versus 75 % in the factor Xa inhibitor group (p = 0.24). The hemostatic efficacy risk difference between the groups was 7.6 % (95 % CI 5.1 %, 20.2 %). Good neurologic outcome (mRS 0-2) at discharge was 17 % in warfarin patients versus 12 % in the factor Xa inhibitor patients (p = 0.40). CONCLUSIONS: There was no significant difference in hemostatic efficacy or clinical outcomes between patients taking warfarin or a factor Xa inhibitor following reversal with 4-F PCC. This study provides further support that 4-F PCC can be used for the reversal of factor Xa inhibitor-associated coagulopathy.

Improving Appropriate Dosing of Intravenous dilTIAZem in Patients With Atrial Fibrillation or Flutter With Rapid Ventricular Response in the Emergency Department.

INTRODUCTION: Atrial fibrillation and atrial flutter are common supraventricular arrhythmias in patients who present to the emergency department. Under the American Heart Association guidelines, dilTIAZem is the calcium channel blocker frequently used by many practitioners for rate control. Currently, institution-specific data have identified that many patients receiving dilTIAZem for atrial fibrillation or atrial flutter are given initial doses that exceed the recommended dose by more than 10%, resulting in hypotension in some patients. METHODS: ED personnel were surveyed to determine their current knowledge of appropriate intravenous dilTIAZem dosing and methods of prescribing intravenous dilTIAZem to determine the causes of higher dosing. Based on the baseline data, an intervention of adding a text alert when withdrawing dilTIAZem from the automated medication dispensing cabinet was implemented. RESULTS: Following the intervention, 29 patients received intravenous dilTIAZem for rate control of atrial fibrillation or flutter with rapid ventricular response. For the primary outcome, the incidence of high-dose dilTIAZem decreased by 19% (P = 0.03). There was no change in the secondary outcome of a reduction in hypotension (P = 0.3). DISCUSSION: The interventions of education and medication alerts resulted in a significant increase in the percentage of patients receiving appropriate doses of dilTIAZem and a nonsignificant decrease in the incidence of hypotension. This process-oriented intervention resulted in an improvement in appropriate dilTIAZem doses at our site. Rate control was not statistically significantly different between the 2 groups. Long-term sustainability of this intervention requires further study.

Correction to: Pharmacokinetic and Tissue Distribution Profile of Long Acting Tenofovir Alafenamide and Elvitegravir Loaded Nanoparticles in Humanized Mice Model.

There are errors in the published article (Volume 34, Number 12, pp. 2749-2755). The errors occurred in pharmacokinetic study design of materials and methods section on page 2750-51.

Pharmacokinetic and Tissue Distribution Profile of Long Acting Tenofovir Alafenamide and Elvitegravir Loaded Nanoparticles in Humanized Mice Model.

PURPOSE: Non-adherence to the antiretroviral (ARV) regimen is a critical factor in determining efficacy of ARV drugs for pre-exposure prophylaxis (PrEP). A long-acting parenteral formulation may be an effective alternative to daily oral dosing. A pharmacokinetic and tissue distribution study of drug-loaded nanoparticle (NP) was performed in female humanized CD34+-NSG mice. METHODS: Mice received 200 mg/kg each of tenofovir alafenamide (TAF) and elvitegravir (EVG) as free drugs (TAF + EVG solution) or as drug loaded NP (TAF + EVG NP) formulation by subcutaneous (SubQ) administration. Plasma and tissue were collected to determine tenofovir (TFV) and EVG concentrations using LC-MS/MS. Non-compartmental analysis was performed using WinNonlin. RESULTS: SubQ administration of TAF + EVG NP formulation resulted in long residence time and exposure for both drugs. The AUC(0-72h) of TFV and EVG was 14.1 ± 2.0, 7.2 ± 1.8 µg × hr./mL from drugs in solution (free) and the AUC(0-14day) for the same drugs was 23.1 ± 4.4, 39.7 ± 6.7 µg × hr./mL from NPs. The observed elimination half-life (t1/2) for TFV of free and NPs were 14.2 h, 5.1 days and for EVG 10.8 h, 3.3 days, respectively. CONCLUSION: This study documents that a TAF + EVG NP provides sustained release, which can overcome patient non-adherence to dosing and may facilitate prediction of appropriate protective drug concentration for HIV prophylaxis.