PGY1 Pharmacy Residency

Retrospective Study on the Efficacy and Tolerability of Dose Modification of PD-1 and PD-L1 Inhibitors in Hospital-Based Outpatient Cancer Clinics: Continued Review

Emily Allen, PharmD; Erika N. Brown, PharmD, BCOP; Rodrigo De La Torre, PharmD; Asha Murthy, MD

PURPOSE Programmed cell death (PD-1) is a transmembrane receptor protein expressed on T cells, B cells, and NK cells that interacts with its ligand, PD-L1. Anti-PD-1 and anti-PD-L1 medications inhibit that PD-1 and PD-L1 interaction and have been shown to be effective in treating several forms of advanced cancers. Since the approval of these agents, standard dosing protocols have been utilized. However, a small population of patients in the community setting have received dose modified PD-1 and PD-L1 inhibitors secondary to adverse events. The purpose of this retrospective study is to assess the efficacy and tolerability of dose modified PD-1 and PD-L1 inhibitors compared to standard dosing.

METHODS

This retrospective observational study includes data collected from 221 patients initiated on a PD-1 or PD-L1 inhibitor between September 1, 2017 and September 31, 2019 in the outpatient community setting of the Houston Methodist Hospital System. Patients were 18 years or older, received outpatient immunotherapy, and had a diagnosis of an FDA-labeled indication for immunotherapy. The primary endpoints included incidence of adverse effects (defined by the common terminology criteria for adverse events) and time to progression.

RESULTS

of the 221 patients that received PD-1 and PD-L1 inhibitors, 200 patients have been reviewed. Patients received either nivolumab (n=81), pembrolizumab (n=93), atezolizumab (n=21) or durvalumab (n=26). Patients observed to have a dose modification included: nivolumab (n=40, 49%), pembrolizumab (n=24, 26%), and durvalumab (n=9, 35%). The most common side effects that lead to immunotherapy dose modification were pneumonitis (16%, n=21), musculoskeletal pain (15%, n=20), and diarrhea (14%, n=19). There was a median time to progression of 204 days for patients with an immunotherapy time delay, and for patients with an immunotherapy dose reduction; median time to progression was 299 days. Overall, approximately 40% of the patients included in the study had either a dose modification or delay in treatment with continued response to treatment.

CONCLUSION

Further large studies are needed to assess dose modifications of immunotherapy on both clinical outcomes and adverse events.

PGY1 PHARMACY RESIDENCY

Emily Allen, PharmD

Emily earned her PharmD from The University of Texas at Austin in 2021. Following completion of her PGY1, Emily will continue her residency training as a PGY2 Oncology Resident at Houston Methodist Hospital. Primary project preceptor: Erika N. Brown, PharmD, BCOP

Presented at 2021 Virtual Vizient Pharmacy Network, 2022 Midwest Pharmacy Residents Conference, and HOPA 2022 Annual Conference.

Evaluation of Voriconazole Dosing for Prevention of Aspergillus in Lung Transplant Recipients

Alyssa Chaplain, PharmD; Brett J. Pierce, PharmD, BCPS; Christine Pham, PharmD; Aaron Hutchins, PharmD; Will L. Musick, PharmD, BCIDP; Duc T. Nguyen, MD; Edward A. Graviss, PhD; Simon W. Yau, MD; Ahmad Goodarzi, MD; Jihad G. Youssef, MD; Howard J. Huang, MD

PURPOSE Aspergillus (ASP) infections are a known complication seen in lung transplant (LT) recipients and are associated with an increased risk in mortality. Guidance published by the American Society of Transplantation suggests the use of universal prophylaxis or preemptive therapy for these patients. However, there is currently no consensus regarding the ideal anti-fungal agent or prophylaxis strategy due to limited randomized control trials. In addition, voriconazole (VCZ) prophylaxis dosing recommendations have not been fully established. We sought to evaluate the efficacy of VCZ 200 mg twice a day (BID) for three months post LT in preventing ASP.

METHODS

A single-center, retrospective review was conducted on LT recipients who were initiated on VCZ 200 mg BID for three months between 2016 - 2020. Patients were excluded if transplanted for cystic fibrosis, received an azole other than VCZ, received an alternative VCZ dose, had prophylaxis started >14 days post-transplant, or death occurred within 30 days of transplant. The primary endpoint was defined as the incidence of (+) ASP cultures after receiving at least five days of VCZ. Secondary endpoints included classification of ASP infection, patient specific-characteristics associated with ASP infection, weight-based dose of VCZ, and time to ASP clearance.

RESULTS

Three hundred twenty patients were transplanted during this time, 143 patients met inclusion criteria, and 12 patients (7.7%) experienced a breakthrough (+) ASP culture. Of patients who developed a (+) culture, 1 (0.65%) had a proven invasive infection, 9 (5.8%) had a probable invasive infection, and 2 (1.3%) were classified as colonized based off the ISHLT consensus definitions. Most (+) ASP culture patients were designated as Lung Diagnosis Group D (restrictive). The median weight-base dose of VCZ at the time of the positive ASP culture was 2.6 mg/kg twice daily for both cohorts. More rapid clearance in days, median (IQR), was seen in patients who switched agents, 13.0 (11.0, 35.0), compared to the patients who were continued on the same VCZ dose, 57.5 (34.0, 117.0), or increased VCZ dose, 150 (98, 203), p=0.12.

CONCLUSION

Patients who received 200 mg BID of VCZ for three months resulted in a low percentage of breakthrough (+) ASP cultures with only one patient developing a proven invasive ASP infection. This retrospective chart review suggests VCZ 200 mg BID is effective at preventing ASP in LT recipients.

PGY1 PHARMACY RESIDENCY

Alyssa Chaplain, PharmD

Alyssa earned her PharmD degree from the University of Houston College of Pharmacy in 2021. Following the completion of her PGY1 Residency, Alyssa will continue her postgraduate training as a PGY2 Solid Organ Transplant Pharmacy Resident at Houston Methodist Hospital. Primary project preceptor: Brett J. Pierce, PharmD, BCPS

Presented at 2021 Virtual Vizient Pharmacy Network, 2022 Midwest Pharmacy Residents Conference, and 2022 American Transplant Congress.

Descriptive Analysis of Direct Oral Anticoagulants in Heart and Lung Transplant

Eric Rubido, PharmD; Megan Cooper, PharmD; Kevin Donahue, PharmD, BCPS; Jill Krisl, PharmD, BCPS, BCTXP

PURPOSE Direct oral anticoagulants (DOACs) are widely utilized following cardiothoracic transplantation due to complications such as atrial fibrillation and venous thromboembolism. Given the lack of published evidence describing the use of DOACs in the cardiothoracic transplant population, we aim to describe the prescribing patterns of DOACs in relation to DDIs, renal dysfunction, and periprocedural management, as well as explore the use of DOAC-specific anti-xa monitoring.

METHODS

This was a single-center, retrospective, descriptive analysis of adult cardiothoracic transplant recipients initiated on ≥3 consecutive days of DOAC therapy between May 2016 and July 2021. Patients were excluded if DOAC therapy was initiated prior to transplant or at an outside institution. The primary endpoint for this analysis was the percentage of patients dosed per package labeling. Secondary endpoints included DOAC prescribing in the context of drugdrug interactions, renal dysfunction, and periprocedural management, thromboembolism and major bleeding at 6 and 12 month, 90-day readmission due to bleeding or thrombosis, and need for DOAC-reversal.

RESULTS

A total of 125 patients were included in this analysis with a median age of 62 years. At initiation, 61.6% of patients were dosed according to package labeling. The most common reason for non-labeled dosing was concomitant azole antifungal therapy. DOAC therapy was held for 82 procedures with no reported thrombotic events and 1 major bleed in the setting of AKI. Deviation from package labeling, concomitant azole antifungal therapy, and hemodialysisdependence were not associated with increased risk of thromboembolism or major bleeding. DOAC-specific anti-xa guided dosing was associated with a reduced risk of major bleeding (0% vs. 8.9%, P = 0.05).

CONCLUSION

Deviation from package labeling is common following cardiothoracic transplantation with azole antifungal therapy as the leading cause. Additionally, DOAC therapy appears safe and effective in the setting of upcoming procedures, with further studies necessary to establish an optimal anticoagulation strategy. Furthermore, DOACspecific anti-xa monitoring has been associated with a reduction in the risk for major bleeding when used to guide long-term dosing.

PGY1 PHARMACY RESIDENCY

Eric Rubido, PharmD

Eric earned his PharmD from the University of Florida College of Pharmacy in 2021. Following completion of his PGY1 residency, Eric will complete a PGY2 in Solid Organ Transplant at Houston Methodist Hospital. Primary project preceptor: Jill Krisl, PharmD, BCPS, BCTXP

Presented at 2021 Virtual Vizient Pharmacy Network and 2022 Midwest Pharmacy Residents Conference.

Comparison of Sedation and Analgesia Requirements in Patients with SARS-CoV-2 versus Non-SARS-CoV-2 Acute Respiratory Distress Syndrome on Veno-venous ECMO

Mariah I. Sigala, PharmD; Diane Dreucean, PharmD, BCCCP; Jesse E. Harris, PharmD, BCCCP; Kevin R. Donahue, PharmD, BCPS; Fariedeh Bostan, PharmD; Prakruthi Voore, MD; Jose Francisco Saille Cuevas, MD; Celia Morton, PharmD, BCCCP

PURPOSE

increased sedation and analgesia requirements have been described in patients with acute respiratory distress syndrome (ARDS) on veno-venous (VV) extracorporeal membrane oxygenation (ECMO) support due to unique pharmacokinetic challenges. However, there is a paucity of data comparing sedation requirements in patients on VV ECMO for ARDS secondary to SARS-CoV-2 vs other etiologies of ARDS. The objective of this study is to compare sedation and analgesia requirements in adult patients with SARS-CoV-2 ARDS versus other etiologies of ARDS requiring VV-ECMO support.

METHODS

We performed a retrospective cohort study of adult patients receiving sedation and analgesia on VV-ECMO support for ARDS. Patients were excluded if cannulated at an outside hospital for greater than 24 hours, expired within 48 hours of ECMO cannulation, or received neuromuscular blocking agents for greater than 7 consecutive days following ECMO cannulation.

RESULTS

We evaluated 108 patients on VV-ECMO support, including 44 with non-SARS-CoV-2 ARDS and 64 with SARS-CoV-2 ARDS. The median daily dexmedetomidine requirements were significantly higher in the SARS-CoV-2 cohort (16.7 vs. 13.4 mcg/kg/day, p=0.03), while the median propofol daily requirements were significantly higher in the non-SARS-CoV-2 cohort (40.3 vs. 53.5 mg/kg/day, p <0.01). There was no difference in daily requirements of opioids, benzodiazepines, and ketamine between groups. Use of adjunct agents to facilitate weaning was significantly higher in the SARS-CoV-2 cohort (78.1% vs. 43.2%, p<0.01).

CONCLUSION

We found that patients with ARDS on VV-ECMO support require multiple analgesic and sedative agents with concomitant use of adjunct agents to facilitate analgesia and sedation weaning in both SARS-CoV-2 and nonSARS-CoV-2 ARDS cohorts. To circumvent these challenges, ECMO centers should consider implementation of ECMO-specific analgosedation protocols to optimize patient outcomes.

PGY1 PHARMACY RESIDENCY

Mariah Sigala, PharmD

Mariah Sigala earned both her BSA in Biochemistry and PharmD from The University of Texas at Austin in 2021. Following completion of PGY1, Mariah will continue her postgraduate training as a PGY2 Critical Care Pharmacy Resident at Houston Methodist Hospital. Primary project preceptor: Celia Morton, PharmD, BCCCP

Presented at 2021 Virtual Vizient Pharmacy Network and 2022 Midwest Pharmacy Residents Conference.

Impact of Hypoalbuminemia on Ceftriaxone Treatment Failure in Patients with Enterobacterales Bacteremia

Evan L. Steere, PharmD, MS; Taryn A. Eubank, PharmD, BCIDP; Megan H. Cooper, PharmD; Sage B. Greenlee, PharmD; Ty C. Drake, PharmD, BCIDP

PURPOSE

Ceftriaxone is a frequently used antibiotic among hospitalized patients in the United States due to convenient dosing and robust Gram-negative activity. However, patients with hypoalbuminemia may experience a greater degree of drug clearance and suboptimal exposure due to its high protein binding affinity. The aim of this study was to assess the impact of hypoalbuminemia on clinical outcomes among hospitalized patients treated with ceftriaxone for Enterobacterales bacteremia

METHODS

We performed a retrospective cohort study to assess the impact of hypoalbuminemia (plasma albumin ≤ 2.5 g/dL) on treatment failure among hospitalized adults with monomicrobial Enterobacterales bacteremia that received at least 72 hours of CRO therapy. Secondary outcomes included hospital length of stay, total duration of antibiotic therapy, and time to infection resolution. Propensity score matching was performed based on the probability of hypoalbuminemia.

RESULTS

A total of 448 patients met study criteria and 260 patients were included in the propensity score matched analysis. The majority of patients developed bacteremia from a urinary source (71.5%), and Escherichia coli was the most common pathogen identified (72.3%). Compared to patients with normoalbuminemia, those with hypoalbuminemia experienced numerically higher rates of treatment failure although this difference did not reach statistical significance (12.3% vs. 7.7%, P = 0.21). Among the subgroup of patients receiving care in the intensive care unit, the impact of hypoalbuminemia on treatment failure was more pronounced (24.4% vs. 7.3%, P = 0.07).

CONCLUSION

Hypoalbuminemia may increase the risk of CRO treatment failure in patients with Enterobacterales bacteremia especially in those that are critically ill.

PGY1 PHARMACY RESIDENCY

Evan L. Steere, PharmD

Evan earned his PharmD from the University of Kansas in 2021. Following the completion of his PGY1 residency, Evan will continue his postgraduate training as a PGY2 infectious Diseases Pharmacy Resident at Houston Methodist Hospital. Primary project preceptor: Ty Drake, PharmD, BCIDP

Presented at 2021 Virtual Vizient Pharmacy Network and 2022 Midwest Pharmacy Residents Conference.

Comparison of the Efficacy and Safety of Sodium Polystyrene Sulfonate and Sodium Zirconium Cyclosilicate for the Treatment of Hyperkalemia in Hospitalized Patients

Eileen Sullivan, PharmD; Melanie Ruegger, PharmD, BCPS; Ian Dunne, PharmD, BCPS; Neil Sutaria, MD; William Towers, PharmD, BCPS

PURPOSE

Hyperkalemia is a common electrolyte abnormality that has been associated with life-threatening arrhythmias and increased mortality. Due to the ability to exchange potassium for other electrolytes in the gastrointestinal tract, potassium binders are a mainstay of treatment in the acute care setting. The purpose of this study was to compare the efficacy and safety of two commonly utilized potassium binders ¬- sodium polystyrene sulfonate (SPS) and sodium zirconium cyclosilicate (SZC) - for the treatment of hyperkalemia in hospitalized patients.

RESULTS

The mean reduction in serum potassium 4-24 hours after potassium binder administration was 0.96 mEq/L with SPS and 0.78 mEq/L with SZC. The mean total dose of SPS and SZC leading to these reductions was 25 g SPS and 10 g SZC respectively. The rate of hyperkalemia resolution within 24 hours was higher in patients who received SPS (74.9%) compared with SZC (68.8%). Overall, other electrolyte derangements were rare, but there was a greater incidence of hypomagnesemia with SPS. No events of intestinal necrosis were noted in this study.

METHODS

This retrospective cohort study included 3,903 patients with a potassium level greater than 5 mEq/L who received either SPS or SZC for the treatment of hyperkalemia between May 2018 and August 2021. Patients who received dialysis prior to SPS/SZC administration or a repeat potassium level and those who received other potassium lowering medications for treating hyperkalemia were excluded.

CONCLUSION

Both SPS and SZC effectively lowered potassium within 24 hours of administration in hospitalized patients and demonstrated favorable safety profiles. While a statistically greater reduction in potassium was seen with SPS compared to SZC, most patients receiving SZC received only a single 10 g dose. Further dosing comparisons between both agents are needed to optimize the potassium lowering effects for the treatment of acute hyperkalemia.

PGY1 PHARMACY RESIDENCY

Eileen Sullivan, PharmD

Eileen earned her BS in Biochemistry and PharmD from the University of Texas at Austin in 2021. Following completion of her PGY1, Eileen will be completing a PGY2 in internal Medicine at Houston Methodist.

Primary project preceptor: Melanie Ruegger, PharmD, BCPS

Presented at 2021 Virtual Vizient Pharmacy Network and 2022 Midwest Pharmacy Residents Conference.