Novel Drug-Drug Interaction of Potential Rifabutin-Induced Edoxaban Failure: A Case Report.

Purpose: To report an incident of a breakthrough deep vein thrombosis (DVT) and potential example of a drug-drug interaction in a patient treated with edoxaban and rifabutin who was being treated for respiratory tuberculosis. Case: A 76-year-old male presented with anemia requiring transfusion and subsequent shortness of breath that was later diagnosed to be respiratory tuberculosis. He experienced a prolonged hospital stay due to persistently positive Mycobacterium tuberculosis respiratory samples and a complicated social situation that required continuous hospitalization for approximately five months. During his treatment the patient was transitioned from apixaban to edoxaban due to a drug-drug interaction with rifabutin. He subsequently had a DVT while on edoxaban after two months of therapy that would require him to transition to warfarin. Conclusion: This case represents an example of a potentially significant drug-drug interaction between edoxaban and rifabutin. Other direct oral anticoagulants (DOACs) exhibit a potential drug-drug interaction that limit their effectiveness when used with rifamycins. This report describes the first known case of a patient experiencing a DVT after prolonged edoxaban use in combination with rifabutin. Treatment with DOACs for patients taking concomitant cytochrome P450 (CYP) inducers such as rifabutin may be more complicated than previously believed.

Optimization of Vancomycin Dosing to Achieve Target Area Under the Curve in Pediatrics.

OBJECTIVE: Vancomycin dosing requirements to achieve a target area under curve/minimum inhibitory concentration (AUC/MIC) of 400 to 600 mg•hr/L have not been established in pediatrics. Dose modeling studies and recent guidelines suggest dosing higher than historical recommendations. This study examines dosing requirements to achieve target AUC/MIC in human pediatric patients. METHODS: This retrospective study includes 77 patients, aged 1 month to 18 years, at a single center, who received at least 2 days of intravenous vancomycin with a pharmacokinetic monitoring note and calculated AUC/MIC. Dosing to achieve target AUC/MIC was evaluated by age and indication. Nephrotoxicity was also assessed. RESULTS: The mean dose required to achieve target AUC/MIC for all patients was 67.7 mg/kg/day. Adjusting for age, the mean dose required to achieve target AUC/MIC of 400 to 600 mg•hr/L was found to be statistically significantly different among 3 age cohorts: 1 month to 5 years, 6 to 12 years, and 13 to 18 years [F(2,74) = 15.32, p < 0.001], with mean requirements of 79 ± 14.1, 65.6 ± 21.1, and 53.9 ± 17.1 mg/kg/day, respectively. Dosing requirements were also found to be statistically significantly different across indications [F(6,70) = 4.84, p < 0.001]. Acute kidney injury was identified in 5 patients (6.5%). CONCLUSIONS: The vancomycin dose required to achieve target AUC/MIC in pediatrics was significantly higher in younger pediatric patients and ranged from 53.9 to 79 mg/kg/day, confirming recent guideline recommendations. Doses can be further adjusted for indication. Nephrotoxicity rates remain low compared with historical rates with single trough monitoring.

An Investigation of Prevalence and Predictors of Disengagement and Exhaustion in Pharmacy Students.

Objective. To determine the prevalence of burnout in first, second, and third professional year (P1, P2, and P3) pharmacy students at a single institution and identify predictors of higher burnout scores. Methods. A 31-question anonymous online survey was developed and administered to a total of 390 P1, P2, and P3 students at the University of Kentucky College of Pharmacy. The survey consisted of a modified version of the 16-question Oldenburg Burnout Inventory (OLBI) and 14 additional questions related to demographic and co-curricular and extracurricular related questions. Descriptive and inferential statistical analyses were conducted as appropriate to determine differences among the variables studied and to identify predictive variables of disengagement and emotional exhaustion. Results. Seventy-five percent of invited students participated in the study. Results of the analyses showed that P1 students had significantly lower engagement scores than both P2 and P3 students, and that P2 students were significantly less exhausted than P1 and P3 students. There was a lack of correlation between burnout scores and students' postgraduate goals, curricular involvement, and work responsibilities. Married students reported being significantly less exhausted than unmarried students. Conclusion. This study added to the growing evidence that pharmacy students have relatively high rates of disengagement and emotional exhaustion. Because the variables expected to contribute to burnout were not found to be predictive in this study, further analyses examining the positive and negative predictive factors associated with burnout scores in pharmacy students are needed. Identifying these factors would allow targeted interventions to be made early in the academic careers of students most susceptible to burnout.