Ivosidenib significantly reduces triazole levels in patients with acute myeloid leukemia and myelodysplastic syndrome.

BACKGROUND: Ivosidenib is primarily metabolized by CYP3A4; however, it induces CYP450 isozymes, including CYP3A4 and CYP2C9, whereas it inhibits drug transporters, including P-glycoprotein. Patients with acute myeloid leukemia are at risk of invasive fungal infections, and therefore posaconazole and voriconazole are commonly used in this population. Voriconazole is a substrate of CYP2C9, CYP2C19, and CYP3A4; therefore, concomitant ivosidenib may result in decreased serum concentrations. Although posaconazole is a substrate of P-glycoprotein, it is metabolized primarily via UDP glucuronidation; thus, the impact of ivosidenib on posaconazole exposure is unknown. METHODS: Patients treated with ivosidenib and concomitant triazole with at least one serum trough level were included. Subtherapeutic levels were defined as posaconazole <700 ng/mL and voriconazole <1.0 µg/mL. The incidences of breakthrough invasive fungal infections and QTc prolongation were identified at least 5 days after initiation of ivosidenib with concomitant triazole. RESULTS: Seventy-eight serum triazole levels from 31 patients receiving ivosidenib-containing therapy and concomitant triazole were evaluated. Of the 78 concomitant levels, 47 (60%) were subtherapeutic (posaconazole: n = 20 of 43 [47%]; voriconazole: n = 27 of 35 [77%]). Compared to levels drawn while patients were off ivosidenib, median triazole serum levels during concomitant ivosidenib were significantly reduced. There was no apparent increase in incidence of grade 3 QTc prolongation with concomitant azole antifungal and ivosidenib 500 mg daily. CONCLUSIONS: This study demonstrated that concomitant ivosidenib significantly reduced posaconazole and voriconazole levels. Voriconazole should be avoided, empiric high-dose posaconazole (>300 mg/day) may be considered, and therapeutic drug monitoring is recommended in all patients receiving concomitant ivosidenib.

Impact of a near-peer teaching program within a college of pharmacy on interest in mentoring roles.

BACKGROUND AND PURPOSE: Near-peer teaching within healthcare education has numerous benefits, but there is limited literature to assess the impact that these experiences have on skill development and future teaching roles. This study describes the impact of serving as a near-peer teaching assistant on both former and current pharmacy students. EDUCATIONAL ACTIVITY AND SETTING: The University of Texas at Austin College of Pharmacy implemented the Academic Assistant (AA) program in 2009 to provide an opportunity for students to participate as near-peer educators in a variety of courses. To determine the impact of these AA positions on current and former students, participants from five years of the program were surveyed regarding the impact of the program on skill development and current or future interest in teaching/mentoring. FINDINGS: Current students in the AA program reported that participation increased the likelihood of pursuing a career with teaching/mentoring roles. A majority (65%) of alumni who participated in the program reported being in a current teaching/mentoring role with 42% responding that the AA program was impactful to their career choice. The qualitative analysis showed that direct impact to respondents included validating career goals and increasing interests in teaching/mentoring roles. Those who reported no direct impact on their career still gained valuable professional skills that included: public speaking, time management, broadened perspectives, and increased understanding of academia career expectations. SUMMARY: Providing opportunities for pharmacy students to serve in near-peer teaching roles increased students' interest in pursuing teaching/mentoring roles and offered valuable professional experiences.

Apixaban and rivaroxaban anti-Xa level utilization and associated bleeding events within an academic health system.

BACKGROUND: Oral factor Xa inhibitors (FXaI) can be administered in fixed doses without the need for routine laboratory monitoring. Anti-Xa assays can estimate anticoagulant effect for specific FXaI's. The aim of this study was to characterize anti-Xa levels in patients taking apixaban or rivaroxaban with major bleeding events. METHODS: Apixaban and rivaroxaban anti-Xa assays ordered within our hospital system from May 2016 to September 2019 were evaluated. The primary outcome was major bleeding events defined by International Society of Thrombosis and Haemostasis criteria. Median anti-Xa levels for each FXaI were calculated for those with and without major bleeding, as well as those who did and did not receive reversal agents. RESULTS: A total of 606 anti-Xa levels were analyzed. There were 146 major bleeding events documented, with the most common site being intracranial (63%). Median anti-Xa levels in patients with and without major bleeding were similar, whereas those on apixaban therapy who received reversal agents typically had higher anti-Xa levels (73 ng/mL vs. 153 ng/mL, p = 0.0019). Factors significantly associated with increased odds of bleeding were an age > 80 years, inappropriately high dosing regimens, and modest anti-Xa levels (100-300 ng/mL) for rivaroxaban specifically. CONCLUSIONS: Older age and inappropriately high dosing regimens were associated with major bleeding in patients taking apixaban and rivaroxaban. Further investigation into the utility of anti-Xa levels for FXaI is warranted.