Journal of pharmacy practice最新文献

The promising results seen in the treatment of refractory hematologic malignancies with tisagenlecleucel (Kymriah), the pioneering Chimeric Antigen Receptor (CAR) T-cell immunotherapy, has stimulated a fast growth in research and clinical testing of novel CAR-T constructs, targets, and various generations of CAR T-cells. Pharmacists may receive inquiries about active clinical trials or may be contributing to the care of patients participating in these studies. This briefing discusses the on-going clinical trials that explore novel CAR T-cell immunotherapies in pediatric refractory malignancies of hematologic and solid organ origins. It can be valuable in assisting practitioners in navigating the rapidly evolving field of CAR T-cell immunotherapies.

Background: Several studies have examined INR fluctuations using pharmacokinetic (PK) models or post-hoc INR values after completing nirmatrelvir/ritonavir, but further study of the effects of the drug interaction with warfarin during treatment is necessary. Case Summary: Nirmatrelvir/ritonavir is largely utilized in the outpatient setting so data regarding INR trends in hospitalized patients on warfarin is limited. However, many who receive nirmatrelvir/ritonavir outpatient experience difficulty with presenting to clinic for INR checks due to feeling acutely ill along with isolation precautions. We present the case of a patient receiving warfarin and utilizing home INR testing for monitoring. After diagnosis of coronavirus disease of 2019 (COVID-19), she was started on nirmatrelvir/ritonavir on day five after testing positive. Most recent INR prior to the start of therapy was 2.7 and had been stable on the same dose for months prior to infection. On day two of nirmatrelvir/ritonavir, her INR rose to 4.0 on home point of care INR testing. Despite reducing her dose of warfarin by 15%, her INR remained supratherapeutic the day after completing nirmatrelvir/ritonavir (4.0) and for several checks after. One month after completion of therapy, her INR returned to therapeutic levels. Practice Implications: While PK models and case series have hypothesized both potential increases or decreases in INR with the nirmatrelvir/ritonavir and warfarin interaction, COVID-19 infection itself can cause several pharmacodynamic changes which can increase INR, including decreased appetite and, in severe cases, organ dysfunction. This case provides real-world insight into the drug interaction between nirmatrelvir/ritonavir and the drug-disease state interaction between warfarin and COVID-19.

Background: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) help manage type 2 diabetes (T2DM) and may have efficacy in steatotic liver disease. Objective: To determine the prevalence and clinical impact of GLP-1 RA use in patients with T2DM and liver disease. Methods: This was a retrospective study of adult patients with T2DM and nonalcoholic fatty liver disease (NAFLD), nonalcoholic fatty liver (NAFL), or nonalcoholic steatohepatitis (NASH) between 1/1/21-12/31/21. Patients with hepatitis B or C, or on pioglitazone were excluded. Eligible patients treated with a GLP-1 RA were compared to controls. The primary outcome was change in Fibrosis-4 (FIB-4) score, with NAFLD Fibrosis Score (NFS) as a secondary outcome. Follow-up scores were calculated from labs within 3 to 15 months after baseline. Results: Of 242 eligible patients, 79 patients (32.6%) were treated with a GLP-1 RA. At baseline, FIB-4 score was lower and NFS was higher in the GLP-1 RA group vs controls (1.80 vs 2.33; P = .101, .36 vs -.47, P < .001; respectively). At follow up, FIB-4 score decreased to 1.77 in the GLP-1 RA group and increased to 2.71 in controls (P = .045). Follow up NFS was stable in the GLP-1 RA group and increased in the control group (.36 vs -.43; P = .308). Conclusion: Patients treated with GLP-1 RAs had less evidence of liver fibrosis progression compared to no treatment, although the differences were small. These results suggest that treatment with GLP-1 RAs may have clinical impact on slowing liver fibrosis, however results should be confirmed in a larger, more diverse sample.

Background: Opioid overdoses decrease when communities have access to naloxone. Clinicians play a key role in offering naloxone to high-risk chronic opioid patients. Managed care pharmacists within our health plan noted disproportionate processing for claims of opioid utilizers compared to claims of naloxone prescriptions. Objective: To increase naloxone access and prescribing to members who classify at a dosage with a higher risk for opioid overdose, defined as over 90 morphine milligram equivalents (MME). Methods: Multiple system-wide initiatives were implemented to improve naloxone access. A claims file was pulled monthly to identify members on opioids meeting MME criteria >90 MME per day excluding members with cancer, sickle cell disease, or on hospice. A separate report was then matched to naloxone claims and prescribing percentages calculated. Results: 12 444 utilizing members on opioids were identified from June 2019 prescription claims data. Of these, 131 were on opioids exceeding 90 MME per day, or 1.05% of utilizers, and the percentage of members exceeding 90 MME per day prescribed naloxone was 6.87%. By May 2023, the percentage of opioid utilizers exceeding 90 MME per day decreased to 0.58%. Naloxone prescribing increased to 41.18%. Conclusion: A multi-pronged approach to improve access to naloxone and continued educational efforts by our health plan increased naloxone prescribing in members on opioids exceeding 90 MME per day.

Objectives: Tacrolimus remains the mainstay of immunosuppression in kidney transplantation. Understanding the relationship between therapeutic tacrolimus levels and outcomes of acute rejection, patient/graft survival, and tolerability are important. The relationship between time to therapeutic tacrolimus levels and outcomes has not been well established, specifically with the use of extended release tacrolimus formulation (LCP-Tac). This study investigated time to therapeutic tacrolimus levels of 2 tacrolimus formulations, LCP-Tac and immediate release tacrolimus (IR-Tac), as a predictor of clinical outcomes. Methods: This was a single-center, retrospective, cohort study of kidney transplant recipients at Duke Hospital between 2013-2021. The primary objective evaluated the difference in time to therapeutic tacrolimus levels with LCP-Tac vs IR-Tac regimens. Secondary endpoints included time within therapeutic range during the first 3 months post-transplant, incidence of biopsy-proven rejection, development of de novo donor specific antibodies, and patient and allograft survival at 12 months post-transplant. Results: 128 patients were included (63 in LCP-Tac group and 65 in IR-Tac group). The time to therapeutic tacrolimus level was similar between formulations (7.2 days with LCP-Tac compared to 6.7 days with IR-Tac, P = .63). The time within therapeutic range during the first 3 months post-transplant, via modified Rosendaal, was similar with LCP-Tac and IR-Tac (56.1% vs 64.8%, respectively). Rates of biopsy-proven acute rejection at 12 months were similar (7/63 (11.1%) compared to 4/65 (6.2%)). There was no difference in patient/graft survival between groups. Conclusions: The time to therapeutic tacrolimus levels did not differ based on tacrolimus formulation and was not correlated with clinical outcomes.

Clostridioides difficile is a toxin-producing bacteria that is a main cause of antibiotic-associated diarrhea. Clostridioides difficile infections (CDI) are associated with disruptions within the gastrointestinal (GI) microbiota which can be further exacerbated by CDI-targeted antibiotic treatment thereby causing recurrent CDI (rCDI) and compounding the burden placed on patients and the healthcare system. Treatment of rCDI consists of antibiotics which can be paired with preventative therapeutics, such as bezlotoxumab or fecal microbiota transplants (FMTs), if sustained clinical response is not obtained. Newer preventative strategies have been recently approved to assist in restoring balance within the GI system with the goal of preventing recurrent infections.

Background: Thrombocytopenia is due to multifactorial causes in critically ill patients. One etiology is continuous renal replacement therapy (CRRT); however, it is unknown if different modalities impact the incidence. Objectives: To compare the incidence of thrombocytopenia with the NxStage CRRT system using continuous venovenous hemodialysis (CVVHD) compared to the Prismaflex system using continuous venovenous hemodiafiltration (CVVHDF). Methods: This was a retrospective cohort study at a large academic medical center in the United States. Individuals aged 18 or older admitted to the cardiovascular ICU between June 1, 2016 and September 30, 2022, and received CRRT for at least 48 hours were identified. Results: One hundred and forty-seven patients met inclusion criteria. Sixty-one patients received CVVHD with the NxStage system, while 86 received CVVHDF with the Prismaflex system. Thrombocytopenia occurred in 57.4% of patients treated with NxStage vs 19.8% treated with Prismaflex (OR 5.46; 95% confidence interval [CI], 2.62-11.39). These results were consistent in an adjusted model (OR 5.57; 95% CI, 2.34-13.28). There was no difference in the time to thrombocytopenia between groups. Patients treated with the NxStage system had lower platelet nadirs, more heparin-induced thrombocytopenia testing, more direct thrombin inhibitor use, and more blood transfusions. Conclusions: A greater incidence of thrombocytopenia occurred in cardiovascular ICU patients treated with CVVHD using the NxStage system vs CVVHDF with the Prismaflex system.

Necrotizing fasciitis is a serious infection that requires prompt surgical excision and broad spectrum antibiotics. Fournier's gangrene (FG) is a type of necrotizing fasciitis that specifically affects the perineal, scrotal, and genital region. FG is a known adverse outcome of the class of medications known as sodium-glucose cotransporter 2 (SGLT2) inhibitors. This class of drugs is most commonly use to treat diabetes, but recently it's use has expanded to include those with heart failure, regardless of whether they have diabetes. With the increased use of SGLT2 inhibitors, the incidence of FG may increase as well. We present 2 case reports of patients who experienced FG while on SGLT2 inhibitor therapy.

Background: A Medicare Annual Wellness Visit (MAWV) serves Medicare patients by identifying and addressing gaps in preventive services and health screenings, often aligning with outpatient practice quality metrics. Objective: Evaluate an existing pharmacist-led MAWV telehealth service, determine the baseline quality metric satisfaction rate of telehealth MAWVs, and assess for improvement after implementing a post-MAWV follow-up protocol at a suburban, lower-income primary care clinic. Methods: This IRB-exempt, single-center retrospective chart review utilized the electronic health record at Christ Health Center, Birmingham, AL. From August 2020 through May 2022, 288 charts were assessed between 2 retrospective chart reviews that included patients 18 years or older with Medicare insurance and the ability to conduct a telehealth MAWV. The first chart review assessed metric and recommendation satisfaction within 12 months of the visit. The second chart review was performed after follow-up protocol implementation to assess for additional improvement within 3 months of the visit. Results: The percentage of MAWV recommendations completed groups after implementing a follow-up protocol. For the first chart review, 57.1% of the assessed Health Resources and Services Administration (HRSA), Uniform Data System (UDS) quality metrics, and Centers for Medicare and Medicaid Services (CMS)-required MAWV components were satisfied from the first chart review compared to 53.3% of satisfied quality metrics post-protocol implementation in spite of a substantially shorter follow-up timeframe. Conclusion: Telehealth MAWVs improve preventive care and quality metric satisfaction for Medicare patients. Post-visit follow-up protocols enhance satisfaction rates. Pharmacist-led MAWVs foster interprofessional collaboration and comprehensive patient care.