Require Dose Adjustment Research Articles

Use of antibiotics in patients with chronic kidney disease: evidence from the real world.

Most antibiotics require dose adjustments in patients with chronic kidney disease (CKD) to avoid accumulation and toxicity. The aim was to characterize the use of systemic antibiotics in a group of patients with CKD and to adjust the dose according to the glomerular filtration rate (GFR). Observational study of patients with a diagnosis of CKD who received antibiotics between January-2021 July 2022. The Lexicomp® database was used to determine the dose adjustment according to the GFR. A total of 473 patients were included, average age of 72.6 years. Patients with CKD were in stage 3 (38.5%), stage 4 (23.5%), or stage 5 (38.1%). Cephalosporins (56.2%), penicillins (43.3%), and glycopeptides (20.3%) were the most widely used antibiotics. A total of 914 antibiotics were used, of which 39.5% did not require dose adjustment, 30.4% had no dose adjustment, and 30.1% had dose adjustment. Treatment with glycopeptides (adjusted Odds Ratio [aOR]:3.86; 95%CI:1.57-9.47), treatment with carbapenems (aOR:4.59; 95%CI:1.75-12.07), stage-4 CKD (aOR:31.61; 95%CI:9.77-102.29), and stage-5 CKD (aOR:21.29; 95%CI:3.66-123.61) increased the probability of receiving antibiotics without dose adjustment according to the GFR. Almost one-third of the antibiotics used in this group of patients had no dose adjustment, which generates a significant risk of toxicity and the need to identify CKD in a timely manner and the appropriate use of antibiotics.

Pharmacogenomic profiling of the South Korean population: Insights and implications for personalized medicine.

Adverse drug reactions (ADRs) pose substantial public health issues, necessitating population-specific characterization due to variations in pharmacogenes. This study delineates the pharmacogenomic (PGx) landscape of the South Korean (SKR) population, focusing on 21 core pharmacogenes. Whole genome sequencing (WGS) was conducted on 396 individuals, including 99 healthy volunteers, 95 patients with chronic diseases, 81 with colon cancer, 81 with breast cancer, and 40 with gastric cancer, to identify genotype-specific drug dosing recommendations. Our detailed analysis, utilizing high-throughput genotyping (HTG) of CYP2D6 and comparative data from the 1,000 Genomes Project (1KG) and the US National Marrow Donor Program (NMDP), revealed significant pharmacogenetic diversity in core pharmacogenes such as CYP2B6, CYP2C19, CYP4F2, NUDT15, and CYP2D6. Notably, intermediate metabolizer frequencies for CYP2B6 in SKR (3.28%) were comparable to Europeans (5.77%) and East Asians (5.36%) but significantly differed from other global populations (p < 0.01). For CYP2C19, 48.74% of SKR individuals were classified as intermediate metabolizers, with the *35 allele (2.02%) being unique to SKR, the allele not observed in other East Asian populations. Additionally, the high-risk *3 allele in CYP4F2 was significantly more frequent in SKR (34.72%) than in other East Asian populations (p < 0.01). NUDT15 poor metabolizers were found in 0.76% of SKR, aligning closely with other East Asians (1.59%), while TPMT poor metabolizers were predominantly observed in Europeans and Africans, with one case in SKR. We identified significant allele frequency differences in CYP2D6 variants rs1065852 and rs1135840. Among the 72 drugs analyzed, 93.43% (n = 370) of patients required dosage adjustments for at least one drug, with an average of 4.5 drugs per patient. Moreover, 31.31% (n = 124) required adjustments for more than five drugs. These findings reveal the substantial pharmacogenetic diversity of the SKR population within the global population, emphasizing the urgency of integrating population-specific PGx data into clinical practice to ensure safe and effective drug therapies. This comprehensive PGx profiling in SKR not only advances personalized medicine but also holds the potential to significantly improve healthcare outcomes on a broader scale.

Pharmacokinetics and safety of pirfenidone in individuals with chronic kidney disease (CKD) stage G2 and G3a: a single-dose, Phase I, Bridging study.

Pirfenidone is an inhibitor of transforming growth factor-beta 1 (TGF-β1) and is being developed for the treatment of diabetic kidney disease (DKD). We assessed the pharmacokinetics (PK) and safety of a single dose of pirfenidone in individuals with CKD stages G2/G3a. In this phase I bridging study, patients with CKD stages G2 or G3a, aged 18-70 years, with a body mass index of 18-26 kg/m2, and glomerular filtration rate (eGFR) ranging from 45 to 89 ml/min/1.73m2, received a single oral dose of 400 mg pirfenidone capsules 30 minutes after a standard breakfast. The pharmacokinetic parameters of the two groups were measured and compared after blood and urine collection. The co-primary endpoints were the area under the plasma concentration-time curve from time zero to 36 hours (AUC0-36) and the maximum observed plasma concentration (Cmax) of pirfenidone. Safety was a secondary endpoint. The trial has been registered on ClinicalTrials.gov (ChiCTR2300077297). A total of 20 subjects participated in this study. There were no significant differences between the control group and the patient group (CKD stages G2/G3a) in terms of plasma Cmax, the time to reach the maximum observed concentration (Tmax), and elimination half-life(t1/2). However, the Vz/F of the patient group (CKD G2 stage) was significantly higher than that of the control group. Renal accumulation rate, renal clearance rate (CLr), and urine drug concentration also showed no significant differences. No severe adverse events occurred during the trial. These results indicate that the PK and safety of pirfenidone are not influenced by renal function. Individuals with renal impairment may not require dose adjustments.

Sex and common germline variants impact the toxicity profile and pharmacokinetics of alectinib: a nation-wide cohort study in patients with ALK-positive non-small cell lung cancer

IntroductionAlectinib, a small-molecule kinase inhibitor, is used as first-line treatment for anaplastic lymphoma kinase–positive (ALK+) non-small cell lung cancer (NSCLC). Albeit generally well-tolerated, a considerable subset of patients requires dose adjustments due to drug-related toxicity. Single-nucleotide polymorphisms (SNPs) in genes related to the metabolism of alectinib may upfront identify patients at risk for toxicity. MethodsIn this multicenter observational cohort study in patients with advanced ALK+ NSCLC receiving alectinib treatment, we investigated the association between toxicity, pharmacokinetics, and key genetic variants in ABCB1, CYP3A4, PPAR-α, POR, and CYP3A5. Data on demographics, adverse events, and alectinib trough levels were collected from five hospitals. ResultsAmong 215 patients, 47% experienced severe toxicity. Women experienced more severe toxicity (female versus male: 56% versus 34%; p=0.001) and also had +35% higher alectinib trough levels (p<0.001). Homozygous carriers of the PPAR-α 209G>A variant exhibited a higher incidence of grade ≥ 3 toxicity (38%) compared to patients who carried at least one wild-type allele (11%) (p=0.004). This remained significant after Bonferroni correction. Patients who experienced severe toxicity had +18.5% (95%CI: 2.9–36.6%; p=0.019) higher trough levels. ConclusionsFemale patients encounter more severe toxicity due to higher alectinib exposure, which warrants further exploration. PPAR-α 209G>A significantly increased relevant alectinib-induced toxicity, most likely due to an increase in alectinib exposure. Pre-treatment testing for genetic variants with a subsequent dose reduction could provide a viable approach to reduce alectinib-related toxicity.

Unlocking New Therapeutic Options for Vincristine-Induced Neuropathic Pain: The Impact of Preclinical Research.

Vincristine, a vinca alkaloid, is used in chemotherapy protocols for cancers such as acute leukemia, Hodgkin's disease, neuroblastoma, cervical carcinoma, lymphomas, breast cancer, and melanoma. Among the common adverse effects of vincristine is peripheral neuropathy, with most patients receiving a cumulative dose over 4 mg/m2 who develop varying degrees of sensory neuropathy. The onset of vincristine-induced peripheral neuropathy can greatly affect patients' quality of life, often requiring dose adjustments or the discontinuation of treatment. Moreover, managing vincristine-induced peripheral neuropathy is challenging, with few effective therapeutic strategies available. In the past decade, preclinical studies have explored diverse substances aimed at preventing or alleviating VIPN. Our review consolidates these findings, focusing on the analgesic efficacy and potential mechanisms of various agents, including pharmaceutical drugs, natural compounds, and antioxidants, that show promise in reducing neuropathic pain and protecting neural integrity in preclinical models. Key novel therapeutic options, such as metabolic agents (liraglutide), enzyme inhibitors (ulinastatin), antipsychotics (aripiprazole), interleukin-1 receptor antagonists (anakinra), hormones (oxytocin), and antioxidants (thioctic acid), are highlighted for their neuroprotective, anti-inflammatory, and antioxidant effects. Through this synthesis, we aim to enhance the current understanding of VIPN management by identifying pharmacological strategies that target critical molecular pathways, laying the groundwork for future clinical studies. By clarifying these novel pharmacological approaches and elucidating their mechanisms of action, this review provides a foundation for developing more effective VIPN treatment strategies to ultimately improve patient outcomes.

Evaluating Large Language Model–Supported Instructions for Medication Use: First Steps Toward a Comprehensive Model

ObjectiveTo assess the support of large language models (LLMs) in generating clearer and more personalized medication instructions to enhance e-prescription. Patients and MethodsWe established patient-centered guidelines for adequate, acceptable, and personalized directions to enhance e-prescription. A dataset comprising 104 outpatient scenarios, with an array of medications, administration routes, and patient conditions, was developed following the Brazilian national e-prescribing standard. Three prompts were submitted to a closed-source LLM. The first prompt involved a generic command, the second one was calibrated for content enhancement and personalization, and the third one requested bias mitigation. The third prompt was submitted to an open-source LLM. Outputs were assessed using automated metrics and human evaluation. We conducted the study between March and September 2024. ResultsAdequacy scores of our closed-source LLM’s output showed the third prompt outperforming the first and second one. Full and partial acceptability was achieved in 94.3% of texts with the third prompt. Personalization was rated highly, especially with the second and third prompts. The 2 LLMs showed similar adequacy results. Lack of scientific evidence and factual errors were infrequent and unrelated to a particular prompt or LLM. The frequency of hallucinations was different for each LLM and concerned prescriptions issued upon symptom manifestation and medications requiring dosage adjustment or involving intermittent use. Gender bias was found in our closed-source LLM’s output for the first and second prompts, with the third one being bias-free. The second LLM’s output was bias-free. ConclusionThis study demonstrates the potential of LLM-supported generation to produce prescription directions and improve communication between health professionals and patients within the e-prescribing system.

Population Pharmacokinetic Simulations for Dose Optimization of Tenofovir Disoproxil Fumarate in HIV-Infected Patients with Moderate-to-Severe Renal Impairment.

Tenofovir disoproxil fumarate (TDF) requires dosage adjustments from the standard 300 mg once daily to every 48-96 h for moderate-to-severe renal impairment to avoid excessive exposure. However, this extended interval can lead to variable drug exposure and inconvenience. This study aimed to utilize the population pharmacokinetic (PPK) models to optimize TDF dosing regimens for HIV-infected patients with renal impairment. A systematic literature search was conducted across PubMed, Cochrane Library, and Scopus databases to identify relevant PPK studies of TDF in HIV-infected patients. From the included studies, the PPK models and associated parameters were extracted. Monte Carlo simulations (n = 2000) were performed to generate concentration-time profiles and derive PK parameters compared against reference ranges. For moderate renal impairment, the TDF 150 mg once-daily regimen achieved cumulative exposure comparable to the approved 300 mg every-other-day regimen. In severe renal impairment, TDF 75-100 mg administered once daily provided similar cumulative exposure as 300 mg every 72-96 h regimen while maintaining daily exposure comparable to the standard dose in patients with normal renal function. The approved extended dosing intervals of 72-96 h exhibited high drug exposure variability, initially resulting in supratherapeutic levels followed by suboptimal levels preceding the subsequent dose administration. In conclusion, administering smaller once-daily doses of TDF maintains consistent daily drug exposure comparable to the standard dose in patients with normal renal function while reducing variability in drug exposure, potentially mitigating the risk of nephrotoxicity. However, additional clinical studies are required to confirm these findings.

Neurological care and outcomes in a cohort of Canadian pregnant patients with epilepsy

PurposeTo characterize anti-seizure medication (ASM) use over time, therapeutic drug monitoring, ASM dose adjustments and gestational seizure frequency among Canadian people with epilepsy of childbearing potential seen in an urban tertiary care center. MethodsParticipants were retrospectively identified from the medical records of pregnant patients with epilepsy seen at the University Health Network Comprehensive Epilepsy Program between 2014 and 2021. A descriptive analysis of outcomes, a logistic regression analysis of the odds of patients being on three ASMs associated with higher rates of teratogenicity (i.e., valproate, carbamazepine, and topiramate) over time, and a second logistic regression for predictors of seizure freedom during pregnancy were performed. Results195 pregnancies were included: 52 % had a maternal diagnosis of generalized epilepsy and 92 % were prescribed at least one ASM, with 75 % on monotherapy. The majority underwent therapeutic drug monitoring (77 %) with approximately two-thirds requiring dose adjustments (69 %), typically dosage increases (82 %). The proportion of patients on either valproate, topiramate, or carbamazepine decreased over time (OR=0.80; p<0.01). Fifty-seven percent of pregnancies maintained seizure freedom, with seizure-freedom for ≥1 year prior to conception being the strongest predictor of this outcome (OR of gestational seizure recurrence=0.04; p < 0.01). ConclusionThe proportion of patients on three ASMs associated with higher rates of teratogenicity has decreased over the duration of this study. Seizure-freedom prior to conception was associated with a decreased risk of gestational seizure recurrence.

Blood concentration monitoring and renal function changes during gentamicin administration for infective endocarditis: a retrospective observational study

BackgroundEstablished guidelines for monitoring gentamicin blood concentration are lacking; therefore, we focused on improving pharmacological interventions and ensuring their safety. We aimed to optimize gentamicin administration for infective endocarditis (IE) treatment.MethodsThe study involved adult patients diagnosed with IE and treated with gentamicin from January 2014 to December 2022. Clinical presentation and drug therapy regimen were comprehensively evaluated. We performed a retrospective chart review of the frequency of gentamicin dose adjustments and changes in renal function while on gentamicin. In addition, we attempted to extract risk factors for renal impairment using univariate analysis.ResultsOn average, a 7.1% decline [changed to − 6.7 ± 20.4 (standard deviation) mL/min/1.73 m2] in the estimated glomerular filtration rate was observed after gentamicin administration, but it was statistically insignificant. Notably, 58% of patients required dosage adjustments, with a subset requiring multiple adjustments. Among the cases in which dosage adjustments were made, 61% were within the first week of treatment. There were no patients with gentamicin levels below the target peak concentration. Furthermore, no independent risk factors were identified in patients requiring dose reduction.ConclusionsDose adjustment was necessary in many cases after treatment initiation. The time to dose adjustment varied widely. These findings highlight the importance of consistent blood concentration monitoring in patients of all demographics, at least weekly, and underscore that routine peak concentration assessments may not be essential when a 3 μg/mL target is maintained. This study provides information on monitoring gentamicin blood level, which can improve IE treatment safety.

8716 Late Onset of Temozolomide in Aggressive Pituitary Tumors: Insights From a Leading Oncology Center in Latin America

Abstract Disclosure: C.R. de Macedo: None. I.P. de Magalhães: None. A. Glezer: None. M. Berardo Carneiro da Cunha Neto: None. N.R. de Castro Musolino: None. O. Feher: None. R.L. Batista: None. Introduction: Temozolomide (TMZ) is an oral alkylating agent used in management of glioblastoma multiforme. Since 2006, TMZ is used in patients with pituitary tumors (PITNets) with yielded promising outcomes as an alternative for aggressive PITNets. Objective: To evaluate the response to TMZ in patients with aggressive or metastatic PITNets within the largest tertiary oncology service in Latin America. Patients and Methods: We screened all cases that received TMZ at our institution between 2008-2023 (n=661, primarily glioblastoma cases). We identified 7 cases that TMZ was employed for treating PITNets. We assessed for PITNet characteristics, functionality, timelines of treatment initiation, correlation with radiotherapy, duration of TMZ usage and treatment response utilizing the RECIST criteria. Results: At the time of diagnosis, all patients presented with macro-PITNets and 6 were giant (size greater than 4 cm). In terms of hormonal production, 4 cases were prolactinomas and 3 were non-functioning PITNets. Over the follow-up period, these tumors exhibited an aggressive behavior, manifesting rapid tumor growth despite optimized treatments and one case was recategorized as metastatic PitNET. All cases demonstrated a Ki-67 index greater than or equal to 3%. The initiation of TMZ occurred on average 9.48 years after diagnosis and subsequent to multiple surgical interventions (average of 1.8 surgeries). In 5 cases, TMZ followed radiotherapy. Among the cohort, 3 of 7 patients underwent 6 cycles of TMZ, one underwent 5 cycles, another had an extended treatment of 10 cycles and 2 patients received only 3 cycles due to adverse effects. In terms of treatment response, 4 patients exhibited stable disease, one achieved a partial response (PR) and 2 had disease progression. The most commonly side effect was mild nausea and vomiting and one patient required dose adjustment due to thrombocytopenia. A second course of TMZ was warranted in 2 cases that previously demonstrated a PR (on average one year after the initial treatment). While one case sustained the PR, the other experienced disease progression. Conclusion: The administration of this treatment was often postponed, potentially attributed to the significant disparities in opinions regarding the optimal timing of treatment initiation and the most suitable duration of usage. However, TMZ demonstrated its efficacy in maintaining disease stability for the majority of cases, with good tolerability and safety, even when used later, after multiple surgical procedures, and in patients with high Ki67 levels. Presentation: 6/2/2024

Coadministration of Cariprazine with a Moderate CYP3A4 Inhibitor in Patients with Schizophrenia: Implications for Dose Adjustment and Safety Monitoring.

Cariprazine is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6. This study aimed to evaluate the effects of erythromycin, a moderate cytochrome P450 (CYP)3A4 inhibitor, on the pharmacokinetics of cariprazine in male patients with schizophrenia, and to assess the influence of CYP2D6 phenotypes on cariprazine metabolism. Forty-two patients received oral doses of 1.5 mg cariprazine alone for 28 days (to reach steady state), followed by a co-administration of cariprazine 1.5 mg daily with erythromycin 500 mg twice daily (BID) and Enterol 250 mg BID for 21 days, followed by a 14-day post-treatment period. Blood samples were collected at predefined time points and analysed for cariprazine, its two active metabolites: desmethyl cariprazine (DCAR) and didesmethyl cariprazine (DDCAR), and erythromycin using validated high performance liquid chromatography-tandem mass spectrometry methods. CYP2D6 phenotypes were determined by genotyping. The pharmacokinetic parameters were calculated using non-compartmental analysis. Erythromycin increased the area under the curve (AUCτ) and peak concentration (Cmax) of Total cariprazine (cariprazine + DCAR + DDCAR) by about 40-50% but did not affect the time to peak concentration (Tmax). The CYP2D6 phenotypes had no substantial effect on the pharmacokinetics of cariprazine and its metabolites, either alone or in combination with erythromycin. Cariprazine was well tolerated and safe. The findings suggest that co-administration of cariprazine with moderate CYP3A4 inhibitors may require dose adjustment or monitoring; however, pharmacogenetic testing for CYP2D6 is not necessary for optimising cariprazine therapy. Trial registration number (EudraCT Number): 2018-003721-28. Date of registration: 21-SEP-2018.

Nearly complete hair re-pigmentation in an older patient treated with hydroxyurea for essential thrombocytosis

Introduction Employed in the treatment of malignancies and non-neoplastic conditions, hydroxyurea is associated with integumentary adverse effects, including skin discoloration, xerosis, pruritus, cutaneous atrophy, chronic leg ulcers, oral ulcerations, alopecia, and some nail abnormalities. Case Report A 77-year-old woman was diagnosed with essential thrombocytosis and started on low dose hydroxyurea. After 20 weeks of treatment, she experienced an unexpected change in hair color from gray to dark brown, without using hair dye or supplements. She later developed bilateral dorsal hand melanoderma, melanonychia, and onychodystrophy. Management and outcome It was decided to monitor the patient with no action taken as she was happy with this side effect of hydroxyurea. The platelet count has remained in excellent control. The dark brown hair color persisted over time. Discussion/Conclusion Hair hyperpigmentation likely occurred through melanocyte activation via hydroxyurea. Severe side effects may require dosage adjustments, while milder effects can be monitored closely. The newly observed hair color restoration in this case highlights potential dual (therapeutic and aesthetic) applications of this class of agents.

Study of Medicine Dosage Adjustments in Inpatients with Chronic Kidney Disease

Background: Decreased kidney function in patients with Chronic Kidney Disease (CKD) necessitates dose adjustment, especially for medicines that have a narrow therapeutic index to avoid unwanted medicine effects.Objectives: The purpose of this study was to determine the medicine dosage adjustments in CKD patients and their therapy outcomes.Methods: This type of research is descriptive with a retrospective approach. The sample in this study is the medical records of inpatient CKD patients at Abdoel Wahab Sjahranie Samarinda Hospital for the period May to November 2022. Calculation of GFR (Glomerular Filtration Rate) uses the MDRD (Modification of Diet in Renal Disease) formula.Results: The results showed that the sex of most patients was male as many as 56.25%. The age of most patients in the range of 53-59 years old as many as 33.75%. Most CKD severity level is stage 5 as many as 91.25%. The most common comorbidities were hypertension (61 patients), diabetes mellitus (15 patients), and edema or pulmonary edema (11 patients). There were 77 patients requiring dose adjustment out of a total of 80 patients. There were 149 (34.89%) medicines requiring dose adjustment out of a total of 427 medicines, with the 5 most medicines being calcium carbonate (24.16%), furosemide (24.16%), metoclopramide (10.74%), paracetamol (10.74%), and ranitidine (7.39%). There were 128 (85.91%) medicines with doses appropriate to the Lexicomp 2023 or Renal Pharmacotherapy 2013. The therapy outcome improved in patients who required dose adjustments by 90.91%.Conclusion: It is recommended to calculate GFR using a new formula such as eGFR using CKD-EPI, and collecting data with a larger number of samples.

Nanomedicine Therapies for Pediatric Diseases.

In 2020, the top 10 causes of death among children and adolescents between the ages of 1 and 19 years old included cancer, congenital anomalies, heart disease, and chronic respiratory disease; all these conditions are potentially treatable with medical intervention. However, children exhibit specific physiological and developmental characteristics that can significantly impact drug pharmacokinetics, pharmacodynamics, and safety profile. These factors illustrate the importance of a heightened focus on pediatric drug development. Traditional drugs lack proper circulation, permeability, targeting, accumulation, and release, and they often require dose adjustments or modifications, which can result in suboptimal therapeutic outcomes and increased risks of adverse effects in pediatric patients. Nanomedicines have emerged as efficient drug delivery systems because of their unique properties, which can improve the solubility and stability of drugs by encapsulating them in different forms of nanoparticles. This review discusses the challenges of pediatric therapy, and the current state of nanomedicines for pediatric diseases in terms of Food and Drug Administration-approved nanomedicines, the types of diseases treated or diagnosed, and preclinical studies that have the potential to be translated to the clinic. In summary, nanomedicine holds significant potential for addressing the unique and pressing challenges associated with diagnosing and treating pediatric diseases.

Tailored Treatment Strategies in First Line Therapy for Ovarian Cancer Patients: A Critical Review of the Literature.

Ovarian cancer (OC) is a significant cause of cancer-related mortality in women globally, with a five-year survival rate of approximately 49%. Standard therapy involves cytoreductive surgery followed by chemotherapy. Its poor prognosis has driven interest in alternative therapies such as targeted molecular agents like bevacizumab and poly (ADP-ribose) polymerase inhibitors (PARPi). This review systematically searched PubMed from January 2018 to December 2023 for studies on PARPi in OC. Emphasis was on identifying relevant Phase III trials, extracting data on study design, patient demographics, and outcomes. Special focus was on assessing PARPi efficacy, safety, impact on quality of life, and ongoing trials, including those on Clinicaltrials.gov. The efficacy of PARPi in first-line therapy for OC has been extensively studied. Trials like SOLO-1, PRIMA, and ATHENA-MONO have demonstrated significant improvements in progression-free survival (PFS) and overall survival (OS), particularly in patients with BRCA mutations. Additionally, the combination of PARPi with other agents like bevacizumab has shown promising results in extending PFS. However, PARPi treatment is associated with various adverse effects, including hematologic toxicities like anemia, thrombocytopenia, and neutropenia. While most adverse events are manageable, some patients may require dose adjustments or discontinuation of treatment. Importantly, PARPi maintenance therapy has not adversely affected health-related quality of life (HRQoL), with studies reporting similar HRQoL scores between PARPi-treated and placebo-treated patients. PARPi offer effective treatment with manageable side effects, suitable even for medically fragile patients. Individualized dosing can optimize benefits while minimizing adverse events. Exploring diverse treatment approaches, particularly in patients with limited life expectancy or high disease burden, could improve outcomes. Ongoing research is investigating alternative therapies and combinations to broaden treatment options. Combining bevacizumab with PARPi may be justified for first-line and recurrent maintenance therapy. Regardless of mutational status, PARPi should be considered for maintenance therapy in newly diagnosed advanced OC. Platinum sensitivity remains crucial for treatment decisions and predicting survival outcomes.

Using a rule‐based decision tool for medication dose selection to improve patient safety and the need for pharmacist intervention

AbstractIntroductionAn assortment of alerts has been employed to influence provider order entry, yet many medication orders still require dose adjustment by pharmacists upon order verification.ObjectivesThe primary goals of this study were to evaluate the impact of adding rule‐based decision support to the computerized provider order entry system on the need for medication dose adjustment by a pharmacist and the occurrence of acute kidney injury (AKI) among patients.MethodsThis was a retrospective, pre‐ and post‐implementation observational study on the integration of rule‐based logic into the computerized provider order entry system to automatically select default doses and frequencies for weight‐based or renally‐cleared medications in alignment with health system guidelines. The primary end points were the proportion of medication orders that required pharmacist intervention for dose adjustment and the number of times the AKI pop‐up alert was triggered.ResultsAfter inclusion and exclusion criteria were applied to all available orders, there were 47 393 and 45 767 orders included for final analysis in the pre‐ and post‐implementation periods, respectively. The post‐implementation period showed a significant reduction in pharmacist dosing interventions, with a relative risk of 0.42 (95% confidence interval [CI]: 0.40–0.43; p &lt; 0.0001) and a reduction in AKI (relative risk = 0.58 [95% CI: 0.53–0.64; p &lt; 0.0001]).ConclusionThis study demonstrates the potential of rule‐based decision support to improve initial medication dose selection, reduce the occurrence of AKI, and reduce pharmacist workload, all without increasing alert fatigue.

Real-world treatment patterns and clinical outcomes among patients with HR+/HER2- advanced/metastatic breast cancer receiving palbociclib in Brazil: IRIS study.

e13088 Background: Palbociclib was approved for hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) advanced/metastatic breast cancer (aBC/mBC) in Brazil in 2018. Worldwide studies explore palbociclib's real-world use and outcomes; however, this data is not available for Brazilian patients. IRIS Brazil study aimed to describe demographic/clinical characteristics, treatment and clinical outcomes of adult female patients who have received palbociclib as first-line treatment for HR+/HER2- aBC/mBC in private healthcare institutions in Brazil. Methods: This retrospective descriptive study included females aged 18 years or older diagnosed with HR+/HER2- aBC/mBC and those who had received palbociclib as their initial line of therapy. The study analyzed variables such as demographics, clinical characteristics, treatment history, palbociclib combinations, and clinical outcomes. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier estimates at 6- and 12-month time points. Results: A total of 121 patients were included in the study. The mean age was 54.4 years, and 82 (67.7%) were menopausal at diagnosis. A total of 51 patients (42.1%) were treated with palbociclib + fulvestrant, while 67 (55.8%) were treated with palbociclib + aromatase inhibitors. The majority of patients (n = 79; 65.3%) did not require any dose adjustments. Among the 40 patients (33.1%) who required dose adjustments, the main reason was adverse events/toxicity (n = 36; 90%). The PFS rates at 6 and 12 months were 78% and 60%, respectively. The OS rates at 6 and 12 months were 86% and 70%, respectively. Conclusions: Results from this initial real-world assessment of clinical outcomes in Brazil suggest that Palbociclib combinations exhibit favorable effectiveness in treating HR+/HER2- aBC/mBC disease, as measured by PFS and OS rates.

A real-world, patient-reported outcomes study in patients with platinum-sensitive recurrent ovarian cancer receiving long-term maintenance therapy with niraparib.

e23164 Background: Niraparib has been approved for the maintenance treatment of newly diagnosed advanced and platinum-sensitive recurrent ovarian cancer (PSR OC). The phase 3 PRIMA and NOVA studies showed that maintenance niraparib did not worsen quality of life (QoL) compared with placebo. However, no QoL data have been reported for Asian OC patients treated with niraparib. Here, we report patient-reported outcomes (PROs) for PSR OC patients who received niraparib as maintenance therapy for more than two years in a real-world setting. Methods: This prospective, real-world study included OC patients participating in the Niraparib Patient Assistance Program (PAP) in China (NCT06037213). Eligible patients had histologically confirmed PSR epithelial OC, fallopian tube, or primary peritoneal cancer, had been maintained on niraparib for more than two years without disease progression and were still receiving niraparib within 28 days. PROs were assessed every 4-6 weeks for three times using the EQ-5D-5L questionnaire and the FOSI. In addition, a 6-question niraparib medication questionnaire including starting dose, adaptive dose, dose adjustments and reasons, missed doses, concomitant medications was administered at baseline. Results: The PAP enrolled 3154 PSR OC patients, 1151 had been on niraparib for more than two years and could be followed up. From August 2023 to January 2024, 604 eligible patients were recruited and completed at least one assessment. The median age was 58 years (range, 27-82 years). The median duration of treatment with niraparib was 34.8 months (range, 30.5-46.7 months). Among 445 patients with BRCAm status, 104 were BRCAm (23.4%) and 341 were BRCAwt (76.6%). A total of 491 patients (81.3%) received niraparib 200 mg as a starting dose, while 107 (17.7%) required dose adjustments in clinical practice. Presently, 503 (83.3%) were on 200mg. 523 (86.6%) were compliant with the daily oral dose of niraparib, without missing any doses in the previous 6 months. 193 patients (32.0%) had common chronic disease, and 176 (29.1%) were taking concomitant medications during maintenance. The EQ-5D-5L HUI and VAS scores remained stable across the three assessments. The baseline mean EQ-5D-5L HUI and VAS scores were 0.98 (SD 0.05) and 84.31 (SD 10.50), respectively, and the least squares (LS) mean changes from baseline to the third assessment were -0.004 (SE 0.001) and -0.609 (SE 0.248), respectively. A similar situation was observed for the FOSI score. The baseline mean FOSI score was 31.13 (SD 1.37), and the LS mean change from baseline to the third assessment was -0.359 (SE 0.033). Conclusions: In the real world, patients with PSR OC who underwent long-term maintenance treatment with niraparib exhibited a consistently stable QoL. This finding highlights the significant clinical value of niraparib in maintaining QoL in these populations.

Embodiment of Pharmacist Intervention in Palliative Care and Augmentation of a Curriculum for its Assessment

Background Palliative care is the care of patients who have progressive, life-threatening illnesses and who are facing death in the foreseeable future. Since there is a growing need for pharmacist’s intervention in palliative care and there is a gap in the education of palliative care for pharmacy students, this study aims to identify roles and services that have to be performed by palliative care pharmacists in medication-related areas and also to formulate an add-on course to train pharmacy graduates. Materials and Methods A prospective interventional study was done in the palliative care centre in Perinthalmanna, Kerala, India. Relevant data were pooled and analysed for drug-related problems. Necessary interventions were made. Results were interpreted and an add-on course for the training of pharmacy graduates was formulated. Results A total of 88 patients were included in the study. The most prevalent conditions in our palliative setting were kidney disease, liver disease, cancer and stroke. Notably, 38 and 10 cases were found to have drug interactions and drug duplications, respectively. Four patients required dosage adjustments. Fifty cases involved pharmacist intervention which improved the outcome by 80%. At the end of the study, a curriculum was formulated to implement a 3-month add-on course entitled ‘PALLIATIVE PHARMACY’ under the guidance of an Expert committee for training pharmacists and pharmacy students. Conclusion The study identified that there are various roles a pharmacist must undertake in a palliative setup. The involvement of pharmacists in patients’ treatment helps to prevent drug-related problems to a greater extent. The addition of an integrated course for the management of palliative care patients will help to improve the learning as well as practical skills of pharmacists. Incorporating basic and clinical sciences in the therapeutic course is an effective learning plan.

#2733 Osteoporosis and CKD-MBD in hemodialysed patients: efficacy and safety of denosumab

Abstract Background and Aims Osteoporosis is a chronic progressive disease characterized by low bone mass and deterioration of bone tissue which results in a rapid increase in fracture risk. Osteoporosis in hemodialysed patients with Chronic Kidney Disease – Mineral and Bone Disorder (CKD-MBD) is a debilitating clinical condition with complex therapeutic management. In fact, most of the drugs commonly used to counteract osteoporosis are generally contraindicated when Glomerular Filtration Rate (GFR) is lower than 35 ml/min. Denosumab is approved for the treatment of osteoporosis and does not require dose adjustment in case of impaired renal function. For this reason, since 2014 this drug has been used by nephrologists for the treatment of osteoporotic patients also in hemodialysis. Although the interest and diffusion in this specialized clinical field are growing, only few data are still available in literature. The aim of the study was to evaluate the efficacy and safety of Denosumab in long-term therapies (up to 68 months of therapy) in hemodialysed patients. Method Since December 2013, a total of 22 hemodialysed patients have been treated with Denosumab annually (4) or semi-annually (18) for up to 68 consecutive months. During the treatment, we monitored the blood levels of calcium, phosphorus, PTH, beta-CrossLaps and bone alkaline phosphatase (BALP), T-SCORE and fracture risk (FR) using Qualitative UltraSonography (QUS) or Computerized Bone Mineralometry (CBM) every 30 months and every 2 years, respectively. Results 4/22 patients completed at least 48 months of follow-up, observing a substantial stability of the mean values of blood calcium (from 9.09 mg/dl to 8.63 mg/dl) and phosphorus (from 5.2 mg/dl to 4.1 mg/dl), against a reduction in the mean values of B-CrossLaps and bone alkaline phosphatase (BALP) (respectively from 2975.32 to 1452.75 pg/ml and from 32.09 to 14.58 mcg/L). Comparison of QUS exams demonstrated improved T-score (mean values from −4.71 to −4.17) and reduced fracture risk (mean value from 13% to 8%). The results of the CBMs confirmed the improvement of the bone disease at the lumbar spine (T-score from −3.8 to 2.8 after 2 years of treatment) and the substantial stability of the T-score at the femoral level (from −3.5 to −3.2 after 2 years of treatment). It should be noted that in our samples two patients achieved the longest observation period (68-month follow-up in continuous therapy), in which we observed improvement of the bone disease also at the femoral level compared to the start of treatment (T-score from −3.9 to −2.8 after 48 months of treatment). Only one fracture has been recorded. Conclusion The results obtained confirm efficacy and safety of Denosumab in reducing the risk of fractures, with the improvement of BMD and T-score at the lumbar spine using Computerized Bone Mineralometry (CBM). We underline that close biochemistry monitoring and careful evaluation of the therapeutic procedures before and after Denosumab administration helped us to minimise and promptly correct adverse effects due to hypocalcemia. In addition we are particularly satisfied to report in most patients a significant reduction of pain and an improvement of mobility. The results collected are consistent with acceptable safety and demonstrated efficacy of Denosumab in hemodialysis patients.