OBJECTIVE: To describe the effectiveness and safety of olaparib off-label indications in patients with impaired homologous recombination genes and solid tumors different than those authorized. METHODS: A single-center, o...OBJECTIVE: To describe the effectiveness and safety of olaparib off-label indications in patients with impaired homologous recombination genes and solid tumors different than those authorized. METHODS: A single-center, observational and retrospective study including patients treated with olaparib for off-label use. The main variables were patient characteristics, prior therapies, response to therapy, progression-free survival, overall survival and adverse events. RESULTS: A total of 6 patients were included. All patients had metastases and received 3 or more lines of prior treatment. The primary tumor locations and mutations were partner and localizer of BRCA2 (PALB2) intrahepatic cholangiocarcinoma, ataxia telangiectasia mutated (ATM) non-small cell lung adenocarcinoma, somatic breast cancer gene (sBRCA2) colorectal cancer, germinal breast cancer gene 2 (gBRCA2) breast neuroendocrine tumor, gBRCA2 ampullary cancer and gBRCA2 pancreatic neuroendocrine tumor. At the end of the study, one patient was still receiving olaparib showing more than 25 months of sustained stable disease response. No novel toxicities were observed besides those included in the product information. CONCLUSIONS: There is limited published evidence on the use of olaparib in patients harboring pathogenic variants other than breast cancer genes, like PALB2 and ATM and conditions different than those authorized such as digestive tract, neuroendocrine and lung tumors. Further research is to assess the efficacy of olaparib in these patients.
The consensus between the Spanish Society of Retina and Vitreous, the Spanish Society of Hospital Pharmacy and the Spanish Society of Ophthalmology on the preparation, distribution, and administration of intraocular medi...The consensus between the Spanish Society of Retina and Vitreous, the Spanish Society of Hospital Pharmacy and the Spanish Society of Ophthalmology on the preparation, distribution, and administration of intraocular medications is presented, which expands the SEO-SEFH Consensus on recommendations for use and preparation of ophthalmic preparations achieved and published in 2018 in the journal "Farmacia Hospitalaria". Initially, each society appointed at least two members to form the working group that defined the objectives of the consensus. After that, they carried out a bibliographic search of both scientific articles and documentation from regulatory agencies and manufacturers to write a first draft by internal consensus. This draft was reviewed and corrected by members other than the three scientific societies, and was sent to the societies involved for their endorsement. It was verified that this version complied with the recommendations of the AGREE II guide. This consensus includes the review of the requirements that the medical devices used must meet to avoid complications such as the release of silicone drops or other lubricants, as well as a selection of products and suppliers that meet these characteristics, the validity periods for the most common preparations, and the techniques for their preparation, handling and administration.
PURPOSE: The aim of this study was to review and compile the available information, in an easily accessible format, regarding the stability of thermolabile drugs at room temperature (22-25 °C), according to information c...PURPOSE: The aim of this study was to review and compile the available information, in an easily accessible format, regarding the stability of thermolabile drugs at room temperature (22-25 °C), according to information contained in summary of product characteristics (SmPC), published literature, and information provided by the manufacturing pharmaceutical companies. METHODS: Drugs included in our hospital that required storage at a temperature between 2 and 8 °C were selected. Medications used in clinical trials, frozen drugs, and compounded formulations were excluded. The first source of information consulted for stability data was the SmPC. In case of no information available, published literature and gray literature were reviewed. If information was not found through these sources, the manufacturing laboratory was contacted. The results are shown in table format to make the information more manageable. The table contains the following information: Drug product, trade name, brand name (manufacturer), maximum stability at room temperature, and information source. Stability data from SmPC were included for all medications, and for those with additional information obtained through the sources used in the study, this was included in a separate column. RESULTS: A total of 203 thermolabile drugs were selected. Thirty seven (18.2%) had a stability of 24 h at room temperature, 36 (17.7%) had a stability of 48 h-1 week, 63 (31%) had a stability of 1 week-1 month, and 52 (25.6%) had a stability of more than 1 month. However, 12 drugs (6.3%) had a stability of less than 24 h, and 3 drugs (1.4%) had other stability data at room temperature. Stability information for 95 (46.7%) drugs was obtained from the SmPC, 56 (27.5%) from published literature, and 36 (26.2%) from manufacturers. In 21 of these cases, the stability information was valid exclusively for a specific case, with particular storage conditions and for a specific batch of the product. CONCLUSION: The number and impact of thermolabile drugs have increased exponentially in recent years. The vast majority of these drugs maintain adequate stability at room temperature for an acceptable period of time, with some remaining stable for relatively long periods. To date, our study presents the largest dataset on the stability of these drugs. Therefore, the results of our study constitute a highly useful and up-to-date tool for saving time and money in hospital pharmacy units. Pharmaceutical manufacturers should consider publishing stability study results under non-recommended storage conditions in the SmPC.
OBJECTIVE: To analyse the differences in pharmacokinetic and clinical parameters (bleeding rates and joint health) before and after switching from standard half-life factor VIII (FVIII) to extended half-life pegylated FV...OBJECTIVE: To analyse the differences in pharmacokinetic and clinical parameters (bleeding rates and joint health) before and after switching from standard half-life factor VIII (FVIII) to extended half-life pegylated FVIII in patients with severe/moderate haemophilia A on prophylaxis, 1 year before and after the switch in real-life. METHOD: This is a single-centre, comparative, observational, sequential, retrospective, and multidisciplinary study. Population pharmacokinetic models from the WAPPS-Hemo® application were used to calculate pharmacokinetic parameters and individualise prophylaxis. The annual rate of total and joint bleeds, joint health (Haemophilia Joint Health Score), plasma half-life and area under the curve ratios, FVIII consumption, administration frequency, and cost were analysed. RESULTS: Thirty-eight adult patients with haemophilia A who switched from standard half-life FVIII to extended half-life pegylated FVIII were analysed. Significant improvements (P < .05) were observed in all pharmacokinetic parameters, with plasma half-life and area under the curve improvement ratios of 1.5 and 1.9, respectively, as well as reductions in annual total and joint bleeding rates. A higher number of patients with zero total (16.0 vs. 29.0) and joint bleeds (23.0 vs. 33.0) was also observed. The median reductions in administration frequency and dose/kg/week were 30.0% and 19.7%, respectively, avoiding 44.3 infusions/patient/year, resulting in savings of 20,843 €/patient/year. Furthermore, joint health improved (23.0 vs. 21.0; P = .017), and target joints resolved after the switch. CONCLUSIONS: The pharmacokinetically guided switch from standard half-life FVIII to pegylated FVIII demonstrated significant clinical benefits with reduced bleeding rates and improvements in joint health. Additionally, improvements in pharmacokinetic parameters were observed, allowing for reduced treatment burden by decreasing administration frequency, as well as lower consumption and costs.
OBJECTIVE: The expression level of programmed death ligand 1 (PD-L1) is the only approved biomarker for predicting response to immunotherapy, yet its efficacy is not always consistent. Lactate dehydrogenase (LDH) has bee...OBJECTIVE: The expression level of programmed death ligand 1 (PD-L1) is the only approved biomarker for predicting response to immunotherapy, yet its efficacy is not always consistent. Lactate dehydrogenase (LDH) has been associated with tumor aggressiveness and poorer prognosis across various cancer types and may serve as a useful biomarker for monitoring treatment response. The objective of this study is to analyze the relationship between LDH levels prior to the start of treatment with immune checkpoint inhibitors (ICIs) and clinical outcomes in patients with non-small cell lung cancer (NSCLC). METHOD: A retrospective study was conducted including patients diagnosed with NSCLC who were treated with at least 3 cycles of immunotherapy. Data on demographics, clinical and pathological characteristics, treatment received, pretreatment LDH levels, and clinical outcomes such as treatment response and overall survival (OS) were analyzed. RESULTS: A total of 181 patients diagnosed with NSCLC were included. Elevated pretreatment LDH levels (>244 U/L) were associated with significantly reduced OS. The median survival was 548 days in patients with LDH ≤ 244 U/L, compared to 332 days in those with LDH > 244 U/L (P = .037). Among men, OS was greater in the LDH ≤ 244 U/L group (623 days) versus 332 days in the LDH > 244 U/L group (P = 0.043). In patients with metastatic disease, OS was higher in those with LDH ≤ 244 U/L (474 days) compared to 249 days in those with LDH > 244 U/L (P = .023). In patients receiving both immunotherapy and chemotherapy, OS was greater in those with LDH ≤ 244 U/L (623 days) compared to 281 days in the LDH > 244 U/L group (P = .042). CONCLUSIONS: High levels of LDH prior to the start of treatment with ICIs are associated with lower treatment efficacy and a worse prognosis of the disease, especially in male, metastatic patients with a PD-L1 expression level <1%.
OBJECTIVE: Standard treatment of metastatic colorectal cancer includes oxaliplatin and 5-fluorouracil in continuous infusion. Although FOLFOX-6 is the reference combination, it is aggressive and has high toxicity. Varian...OBJECTIVE: Standard treatment of metastatic colorectal cancer includes oxaliplatin and 5-fluorouracil in continuous infusion. Although FOLFOX-6 is the reference combination, it is aggressive and has high toxicity. Variants such as the TTD regimen, which does not include folinic acid or 5-fluorouracil bolus, are used. This study evaluates the toxicity of FOLFOX-6 and TTD in first line treatment for metastatic colorectal cancer and its effectiveness. METHOD: Retrospective observational study with patients who started treatment with FOLFOX-6 and TTD, for 3 years. Demographic and clinical data were collected (age, sex, chronic pathologies, molecular profile, laterality, Eastern Cooperative Oncology Group classification, and stage), as well as treatment variables (previous adjuvant chemotherapy, intentionality, number of cycles, duration, and pharmacogenetic aspects) and toxicity. Objective response rate and progression-free survival were calculated. RESULTS: The study included 71 patients, 35 treated with FOLFOX-6, and 36 with TTD. Both groups showed similar overall toxicity profiles. FOLFOX-6 had a higher incidence of neutropenia (46% vs 8%; P < .01) and mucositis (51% vs 22%; P < .013). In addition, there were more treatment delays (40% vs 11%; P < .05) and 5-fluorouracil dose reductions (22% vs 14%; P < .05) in the FOLFOX-6 group. Deaths due to toxicity were only recorded in the FOLFOX-6 group. Effectiveness was similar in both groups. CONCLUSIONS: The TTD regimen could be a beneficial first-line option for metastatic colorectal cancer, with lower toxicity and effectiveness comparable to FOLFOX-6. It is a safe alternative for elderly or frail patients, suitable for reduced-dose 5-fluorouracil regimen with oxaliplatin.
Becerril-Moreno F, Valera-Rubio M, Aquerreta-González I
… +5 more, Domingo-Chiva E, Doménech-Moral L, Martín-Cerezuela M, Fernández de Gamarra-Martínez E, Cobo-Sacristán S
The main objective of the activity carried out in an intensive care unit (ICU) and in general, in all hospitalization units, is to provide all the human and material resources to offer the best therapeutic care to admitt...The main objective of the activity carried out in an intensive care unit (ICU) and in general, in all hospitalization units, is to provide all the human and material resources to offer the best therapeutic care to admitted patients. Work in multidisciplinary teams, made up of specialists in intensive care medicine as those responsible for the patients, doctors from other specialties, specialized nursing, physiotherapists, nutritionists, and clinical pharmacists is an optimal approach to achieve the proposed objective. The activities of the clinical pharmacist can be developed at different levels (basic, intermediate, and excellent) depending on the degree of involvement, the time dedicated, the training, and the available resources. This article aims to establish an initial work guide, through recommendations aimed at the activity to be developed by the clinical pharmacist in the ICU in relation to critical patient care and quality improvement, which serves as a reference for those pharmacists who go to develop pharmaceutical care activities in critical patients.
The objective of regulatory authorities is to ensure a favourable risk-benefit balance for medicines in their licenced indication, without seeking to establish their place in the therapeutic armamentarium beyond that. Th...The objective of regulatory authorities is to ensure a favourable risk-benefit balance for medicines in their licenced indication, without seeking to establish their place in the therapeutic armamentarium beyond that. The licenced indication covers heterogeneous subpopulations and often does not sufficiently specify the characteristics of the patients who may benefit. The regulatory information does not always show the benefit over the standard treatment(s); moreover, it only reacts to the conditions specified in the developer's application, and lacks an assessment of the clinical relevance of the benefit and its uncertainties. Many cases highlight the need to establish a more specific therapeutic benefit scenario than the licenced indication. For example, abemaciclib was approved in the adjuvant setting for high-risk patients with early breast cancer, but the appropriate level of risk and how to assess it needs to be specified. Also, pembrolizumab is approved for neoadjuvant plus adjuvant treatment in lung cancer; but it remains to be analysed whether it is superior to nivolumab in neoadjuvant treatment alone, which involves less treatment and economic burden. As therapeutic positioning is always a necessary decision, whether made at a national, regional, local, or individual level, it must be made in the most appropriate way. The absence of a multidisciplinary discussion and consensus, relying only on individual decisions to determine positioning from the outset, underestimates information gaps, inter-individual variability, and the influence of drug promotion. It can be harmful and costly. To properly manage the introduction of new medicines, it is essential to establish their benefit scenario in a multidisciplinary way. This, together with consideration of the clinical benefit provided versus the appropriate alternatives and the uncertainties of the benefit, constitutes the objective of the clinical assessment and the basis for designing a well-focused economic analysis. This allows policy-makers to make the most appropriate decisions on pricing and funding new treatments. In an ideal situation, the benefit scenario considered for the new medicine would coincide with the one established for funding, but costs that are difficult to bear may lead to restrictions and affect the final positioning after the economic and budgetary impact assessment.
INTRODUCTION: The Community Pharmacy Survey on Patient Safety Culture (CPSOPSC) is a tool created by the Agency for Healthcare Research and Quality and used in the United States to assess the patient safety culture among...INTRODUCTION: The Community Pharmacy Survey on Patient Safety Culture (CPSOPSC) is a tool created by the Agency for Healthcare Research and Quality and used in the United States to assess the patient safety culture among community pharmacy workers. This survey has been adapted for use in hospital pharmacies in other countries. However, it has not yet been implemented in Spanish hospital pharmacies due to the lack of an applicable version in Spain. This project aims to adapt and reach a consensus on the CPSOPSC for its subsequent use as a tool to improve patient safety in hospital pharmacies in Spain. METHODS: This non-clinical study will be developed in different phases: obtaining the necessary permissions, reviewing the literature to identify studies on the use of the CPSOPSC in hospital pharmacies, adapting the survey's questions to the sociocultural context, reaching a consensus on the questions using the Delphi-Rand/UCLA methodology with a panel of patient safety experts. These experts, who are hospital pharmacists, will evaluate the adapted survey in several rounds, using a Likert scale and telematic workshops to adjust the questions. Finally, a software application will be developed for the implementation, completion, and data management of the survey. DISCUSSION: Adapting the CPSOPSC to hospital pharmacies in Spain may be a useful tool for measuring the patient safety culture in this context. Through the Delphi-Rand/UCLA methodology, expert consensus and the relevance of the survey are ensured. Additionally, the creation of a computer application will facilitate data collection and analysis, promoting its use among professionals. The resulting survey from this project can identify specific needs and areas for improvement in Spanish hospital pharmacies, being useful for future actions aimed at improving patient safety.
OBJECTIVE: The treatment and prevention of delirium in the intensive care unit (ICU) have gained significant importance in patient care in recent years. Some studies have linked delirium with increased risks of mortality...OBJECTIVE: The treatment and prevention of delirium in the intensive care unit (ICU) have gained significant importance in patient care in recent years. Some studies have linked delirium with increased risks of mortality, prolonged hospital stay, and more days of mechanical ventilation. This study aims to analyse the use of psychotropic drugs initiated in the ICU and their continuation upon hospital discharge, as well as to evaluate their contribution to polypharmacy and associated adverse clinical effects. METHOD: A multicentre prospective observational case study was designed, focusing on patients over 18 years old admitted to the ICU and treated with psychotropic drugs. Data on demographics, variables related to admission and psychotropic drug treatment, as well as clinical outcomes and adverse effects, will be collected. Among other variables, the frequency of psychotropic treatments initiated in the ICU and continued upon discharge from the ICU and the hospital will be measured. Data collection will be performed through review of electronic medical records and prescription programmes, and IBM SPSS 20.0 statistical package will be used for analysis. DISCUSSION: Delirium is common in ICU patients and is associated with long-term negative consequences. Although antipsychotics are used to treat delirium, their prolonged use can have adverse effects, and their continuation after ICU discharge contributes to polypharmacy. This study aims to provide information on the use of psychotropic drugs initiated in the ICU and their continuation upon discharge, with the goal of identifying opportunities for intervention and reducing unnecessary use of these medications.
INTRODUCTION: Pediatric patients are more likely to experience medication-related errors and serious associated harms. The identification of high-risk medications (HRM) and their study in special populations, such as chi...INTRODUCTION: Pediatric patients are more likely to experience medication-related errors and serious associated harms. The identification of high-risk medications (HRM) and their study in special populations, such as children with excess body weight (EBW), is a part of safety improvement strategies. OBJECTIVE: To generate, through a consensus technique structured by an interdisciplinary group of pediatricians and hospital pharmacists, an operational and updated list of HRM for hospital use in children over 2 years of age. The document was part of a collaboration project between the Spanish Society of Hospital Pharmacists and the Spanish Society of Pediatric Hospital Medicine. METHODS: The study was carried out in 2 sequential phases: (a) preparation of a preliminary list of HRM through bibliographic review and (b) subsequent application of the double-round Delphi method to agree on a definitive list of HRM. The results obtained were validated by calculating the probability of chance agreement and the modified Kappa statistic for each drug. RESULTS: The original list obtained by bibliographic review included 26 pharmacological classes and 96 drugs. Of the total of 37 experts, 32 (86.4%) completed both rounds of the Delphi. The final consensus list of HRM incorporated 24 pharmacological classes and 101 drugs. The modified Kappa statistic reflected a high percent agreement (94.9%) in the consensus reached by the participants. CONCLUSION: This list can establish a tool for future studies and interventions to improve the safety of medications in general pediatric population, as well as in high-risk subgroups, such as pediatric patients with EBW.
INTRODUCTION: Obesity constitutes a global public health problem, and knowledge about drug dosing in obese patients is limited. Clinical trials in critically ill patients rarely include obese individuals, resulting in a...INTRODUCTION: Obesity constitutes a global public health problem, and knowledge about drug dosing in obese patients is limited. Clinical trials in critically ill patients rarely include obese individuals, resulting in a lack of specific dosing information in product data sheets. The aim of this literature review is to provide clinicians with efficient and safe guidelines for this group of patients. METHODS: A multidisciplinary group composed of pharmacists specialised in hospital pharmacy and physicians specialised in intensive care medicine was formed. The therapeutic groups and, in depth, the most commonly used active ingredients in the intensive care unit were identified and reviewed. The bibliographic review was carried out using terms such as: "obese", "overweight", "critical illness", "drug dosification", and "therapeutic dose monitoring". All the information was evaluated by the working group, which reached a consensus on dosing recommendations for each drug in obese critically ill patients. RESULTS: Eighty three drugs belonging to the following therapeutic groups were identified: antivirals, antibacterials, antifungals, immunosuppressants, antiepileptics, vasopressors, anticoagulants, neuromuscular blocking agents, and sedatives. A table with the consensus dosing recommendation for each of these was produced after review. CONCLUSIONS: Drug dosing in obese patients, both in critical and non-critical settings, remains an area with significant uncertainties. This review provides updated and exhaustive information on the dosing of the main therapeutic groups in obese critically ill patients, and is a useful tool for both physicians in critical care units and clinical pharmacists in their practice in this setting.
INTRODUCTION: Rheumatoid arthritis (RA) is the most common chronic inflammatory rheumatic disease, its management and morbidity impose a great burden to healthcare systems. Development and rollout of biological disease m...INTRODUCTION: Rheumatoid arthritis (RA) is the most common chronic inflammatory rheumatic disease, its management and morbidity impose a great burden to healthcare systems. Development and rollout of biological disease modifying anti-rheumatic drugs has contributed to improvements for patients, however, high costs have prevented them to be widely used. This is being addressed with biosimilars, with equal benefit-risk profile and reduced costs. The objective is to analyze the cost-effectiveness of subcutaneous biosimilar tocilizumab (bsTCZ) for patients with moderate-severe RA in Spain from a healthcare system perspective. METHODS: A Markov model was developed with a lifetime horizon including 5 health states: remission of the disease; low, moderate, or high activity; and death. A PICO-S-T search retrieved efficacy of treatments in meta-analysis and network meta-analysis, and was further complemented with published clinical trials. Pharmacological costs were obtained from the BotPlus database, and medical resources costs from regional tariffs. Deterministic and probabilistic sensitivity analysis were performed to validate the robustness of results. Incremental cost-effectiveness ratio (ICER) for cost/percentage of remission and cost/quality-adjusted life year (QALY) gain were calculated. RESULTS: Lifetime cost of bsTCZ was 183 741€ (lowest) versus comparative costs ranging from 184 317€ for infliximab to 201 972€ (highest) for certolizumab. QALYs were 13.74 for upadacitinib and 13.73 for sarilumab and tocilizumab with values between 13.53 and 13.72 for the comparators. ICERs as €/remission and €/QALY showed that bsTCZ was either dominant in most of the comparisons or the most cost-effective alternative. The sensitivity analysis showed that bsTCZ long term cost, and transition from low to moderate disease activity health status were the most influential factors. Moreover, bsTCZ was either dominant or cost-effective in all the comparisons. CONCLUSIONS: bsTCZ demonstrated to be a cost-effective and cost-saving alternative for the treatment of patients with RA in Spain when compared to all the available therapeutic alternatives.
INTRODUCTION: Infections caused by multidrug-resistant gram-negative bacilli (MDR-GNB) in critically ill patients present a challenge for timely and appropriate antibiotic treatment. This is particularly important in pat...INTRODUCTION: Infections caused by multidrug-resistant gram-negative bacilli (MDR-GNB) in critically ill patients present a challenge for timely and appropriate antibiotic treatment. This is particularly important in patients undergoing extracorporeal life-support techniques such as renal replacement therapy and extracorporeal membrane oxygenation. These techniques can introduce additional pharmacokinetic alterations, potentially leading to suboptimal exposure to antibiotics. This study aims to outline dosing strategies and therapeutic drug monitoring protocols for new β-lactam antibiotics effective against MDR-GNB in critically ill patients undergoing extracorporeal life-support techniques at a national level. Additionally, the study seeks to develop a consensus document, based on available evidence. METHODS: The project will comprise two main phases: I) a national survey and II) the development of a consensus document. This consensus document, undertaken according to ACCORD guidelines, will encompass: a) establishment of a multidisciplinary panel of experts, b) prospective registration of the consensus, c) evidence synthesis, d) modified Delphi rounds. The antimicrobials to be included will be: meropenem, ceftazidime/avibactam, ceftolozane/tazobactam, cefiderocol, meropenem/vaborbactam, imipenem/relebactam, and aztreonam. Extracorporeal life-support techniques will include continuous renal replacement therapy, conventional intermittent hemodialysis, and extracorporeal membrane oxygenation. DISCUSSION: The availability of extracorporeal life-support techniques has expanded significantly in recent years, alongside a rise in the prevalence of infections caused by MDR-GNB. There is a need to develop evidence-based tools of high quality to standardize dosing and monitoring strategies for new β-lactam antibiotics.