Impact of pharmacist-managed immune checkpoint inhibitor toxicities.

BACKGROUND: Immune checkpoint inhibitors are associated with unique autoimmune side effects that differ from traditional cytotoxic chemotherapy. Pharmacists may play an important role in providing key supportive care measures necessary to aid patients and oncologists through immune-related adverse events (irAEs). This study aims to evaluate the impact of a pharmacist-managed irAE protocol in an oncology clinic. METHODS: This study is a retrospective chart review of the implementation of a pilot irAE pharmacy protocol. Patients treated with an immune checkpoint inhibitor and subsequently identified to have dermatologic, gastrointestinal, hepatic, or thyroid toxicities and managed under the pilot irAE pharmacy protocol from 1 October 2018 to 28 February 2019 were enrolled. Study endpoints included number of pharmacist interventions and physician satisfaction. Additional endpoints included pharmacotherapy initiated, dose adjustments, and patient follow-ups. RESULTS: From 1 October 2018, to 28 February 2019, 17 patients were referred and approved by their primary oncologists for pharmacy management under the pilot irAE protocol. During the pilot period, pharmacists initiated 21 new medications for the treatment of irAEs, including thyroid hormone replacement in 7 patients (41%) and oral corticosteroids in 6 patients (35%) with a total of 28 dose adjustments. In addition, the pilot protocol included an assessment of physician satisfaction, which showed a reduced number of physician hours per month managing irAEs, increased physician confidence in irAE management, and a desire for continued pharmacist-management of irAEs. CONCLUSIONS: Oncology pharmacists had an impact on management of toxicities in our oncology clinic as indicated by the pharmacist interventions and physician satisfaction.

Population pharmacokinetic analysis of high-dose methotrexate in pediatric and adult oncology patients.

PURPOSE: High-dose methotrexate (HD-MTX) is widely used in pediatric and adult oncology treatment regimens. This study aimed to develop a population pharmacokinetic model to characterize pediatric and adult MTX exposure across various disease types and dosing regimens, and to evaluate exposure-toxicity relationships. METHODS: MTX pharmacokinetic data from pediatric and adult patients were collected. A population pharmacokinetic model was developed to determine the effects of age, liver function, renal function, and demographics on MTX disposition. The final model was used in Monte Carlo simulations to generate expected exposures for different dosing regimens. The association of toxicity, determined through chart review, and MTX area under the curve (AUC) was modeled using logistic regression. RESULTS: The analysis included 5116 MTX concentrations from 320 patients (135 adult, age 19-79 years; 185 pediatric, age 0.6-19 years). Estimated glomerular filtration rate (eGFR) and treatment cycle number were independent predictors of clearance (CL). CL varied 2.1-fold over the range of study eGFR values and increased 14% for treatment cycle numbers greater than 7. Higher MTX AUC was associated with higher risk of nephrotoxicity in adults, and neurotoxicity and hepatotoxicity in pediatrics. CONCLUSIONS: This study represents one of the most comprehensive evaluations of HD-MTX PK across a wide range of ages and disease types. After accounting for differences in renal function, age did not impact CL, although toxicity patterns differed by age. The model allows for early identification of patients with slowed MTX clearance and at higher risk of toxicity.

A Clinical Review of Surgical vs Transcatheter Aortic Valve Replacement in Geriatric Patients.

OBJECTIVE: To provide an up-to-date review of the available evidence regarding management of elderly patients after transcatheter aortic valve replacement (TAVR). DATA SOURCES: A PubMed search of articles published (September 1969-December 2016) was done using a combination of the following words: aortic valve stenosis, geriatric, elderly, transcatheter aortic valve replacement, surgical aortic valve replacement, transcatheter aortic valve implantation (TAVI), and dual antiplatelet therapy. STUDY SELECTION/DATA EXTRACTION: Relevant original research, review articles, and guidelines were assessed for the management of elderly patients after TAVR. References from the above literature were also evaluated. Articles were selected for inclusion based on relevance to the topic, detailed methods, and complete results. DATA SYNTHESIS: Aortic valve stenosis is common in the geriatric population. While patients were historically treated with surgical aortic valve replacement (AVR), more patients are now undergoing TAVR. This article reviews the current literature regarding outcomes and pharmacotherapy between surgical and TAVR in the elderly population. CONCLUSION: Appropriate management of pharmacotherapy after surgical or TAVR can help improve outcomes in elderly patients, and pharmacists can provide guidance regarding evidence-based therapy.