Posaconazole-digoxin drug-drug interaction mediated by inhibition of P-glycoprotein.

Drug-drug interactions between digoxin and the triazole antifungal agents, mediated via various cytochrome P450 isozymes, have been described in the literature. Posaconazole is not extensively metabolized by these isozymes but is both a p-glycoprotein (P-gp) substrate and inhibitor. To our knowledge, there have been no published cases of clinically significant posaconazole-digoxin drug-drug interactions. We report an interaction between posaconazole (300 mg by mouth daily) and digoxin (0.25 mg by mouth daily, Monday through Friday) resulting in atrial fibrillation with slow ventricular response and degenerating into polymorphic ventricular tachycardia.

Effect of single agent high-dose methotrexate-related acute kidney injury on length of hospitalization and relative dose intensity in adult patients with central nervous system lymphoma.

Purpose Grade ≥3 adverse effects prolong hospitalization and reduce chemotherapy dose intensity. The purpose of this study was to evaluate the rate and severity of high-dose methotrexate-related acute kidney injury and analyze its effect on hospital length of stay and relative chemotherapy dose intensity. Methods This was a retrospective cohort analysis. Patients receiving ≥1 dose of high-dose methotrexate were analyzed for acute kidney injury and length of stay. Patients receiving ≥6 cycles of induction therapy were included in the analysis of relative chemotherapy dose intensity. Chi squared analysis was used to determine the differences between dichotomous data; Student's t-test for parametric data and Mann-Whitney U test for non-parametric data for continuous variables. Statistical analyses were performed with IBM SPSS Statistics (version 21). Results Twenty-six patients and 194 treatment encounters were identified. Thirteen patients were evaluated for relative chemotherapy dose intensity. Grade ≥3 acute kidney injury occurred in four patients (15% of patients; 2% of encounters). There were no grade 5 adverse events. Mean length of stay for encounters with grade ≥3 acute kidney injury was almost three times longer than for those with ≤ grade 2 acute kidney injury (p = 0.041). Mean relative chemotherapy dose intensity was reduced approximately in half for patients experiencing grade ≥3 acute kidney injury (p < 0.01). The most common adverse events were hypokalemia and nausea. Proton pump inhibitors were the most frequently co-administered medications with the potential to affect high-dose methotrexate pharmacokinetics. Conclusion At our cancer program, the rate of grade ≥3 acute kidney injury with high-dose methotrexate is similar to that reported by others. Grade ≥3 acute kidney injury following high-dose methotrexate administration significantly prolonged length of stay and reduced relative chemotherapy dose intensity.

Impact of Quetiapine Treatment on Duration of Hypoactive Delirium in Critically Ill Adults: A Retrospective Analysis.

STUDY OBJECTIVE: Because delirium remains a common consequence of critical illness, and reducing its duration has been shown to have a positive impact on patient outcomes during and after an intensive care unit (ICU) stay, we sought to determine whether treatment of hypoactive delirium with quetiapine reduces the duration of delirium compared with no pharmacologic treatment. DESIGN: Retrospective cohort study. SETTING: Three medical-surgical ICUs within the two main campuses of an academic tertiary care hospital system. PATIENTS: A total of 113 adults with documented hypoactive delirium during an ICU length of stay (LOS) of at least 72 hours between August 2013 and September 2014; 52 patients received at least one dose of quetiapine during their hypoactive delirium course, and 61 patients received no pharmacologic delirium treatment. MEASUREMENTS AND MAIN RESULTS: Patients were screened for hypoactive delirium using the Confusion Assessment Method-ICU (CAM-ICU) and the Richmond Agitation Sedation Scale (RASS). The primary outcome was time to first resolution of delirium, and secondary outcomes included ICU and hospital LOS, and duration of mechanical ventilation. To assess potential adverse effects of quetiapine, the number of RASS assessments deeper than goal and the total number of RASS assessments documented during the delirium course were recorded for all patients. Daily progress notes and discharge documentation were surveyed to assess for new onset of extrapyramidal symptoms or torsade de pointes. Median duration of hypoactive delirium was shorter in the quetiapine-treated group compared with the no-quetiapine group (1.5 vs 2.0 days, p=0.04), and time to extubation after screening positive for delirium trended favorably toward quetiapine-treated patients (3 vs 5 days, p=0.08). There were no significant differences in ICU or hospital LOS, and safety outcomes were similar between groups. CONCLUSION: In this mixed ICU population, treatment of hypoactive delirium with quetiapine was safe and reduced the duration of delirium compared with standard care alone. Prospective placebo-controlled studies are needed to further assess the role of antipsychotics in hypoactive delirium.