FARMACIA HOSPITALARIA最新文献

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.

Background: Medication reconciliation is relevant in transitional care, however, given limited resources, it is necessary to identify the patients who benefit most from this activity.

Aim: To validate criteria to identify patients at high risk of medication errors undergoing major orthopedic surgery.

Method: Delphi Method in 3 phases, April to June 2023, to obtain consensus on the inclusion criteria, previously defined. Each expert rated criteria according to a 5-point Likert scale. Consensus was assumed in round 1 if the rate average was more than 4 (inclusion) or less than 2 (exclusion) and in round 2 and 3 if 50% of the responses were more than 4 (inclusion) or less than 2 (exclusion). It was possible to suggest the inclusion of new criteria.

Results: 10 experts from Faculties of Pharmacy and Medicine participated. In the first phase, consensus was reached on 18 criteria: polypharmacy, anticoagulants, oral chemotherapy (not hormone), immunosuppressants, antiretrovirals, antimyasthenics, insulin, corticoids, neuroleptics, antiarrhythmics, digoxin, carbamazepine, phenytoin, valproate, thyroid drugs, anti-glaucoma, anti-aggregants, and urgent surgery. Systemic antifungals and opioids were suggested. In the second phase, consensus was reached on eleven criteria: anti-parkinsonics, beta-blockers, age more than65 years, length of stay more than 5 days, lamotrigine, diuretics, antidepressants, angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, anxiolytics, opioids, and systemic antifungals. In the last phase, one criterion reached consensus (sulfonylureas) and one criterion did not reach consensus (calcium channel blockers).

Conclusions: We develop and validate a list of 30 criteria to identify patients at high risk of experiencing medication errors undergoing major orthopedic surgery. These may help improve human resource management for clinical pharmacy activities by prioritizing patients who would benefit most.

Objective: Topical rapamycin is the pharmacological treatment of choice for facial angiofibromas in rare tuberous sclerosis disease. A new, more advanced, and complex formula was developed in our pharmacy service: rapamycin 0.4% liposomal formulation, with better organoleptic characteristics and a more favorable release profile of the active ingredient. The purpose of this study is to evaluate the effectiveness and safety of liposomal topical rapamycin for the treatment of facial injuries in this rare disease.

Method: This was an observational, prospective, and multicenter study. Effectiveness was evaluated mainly through Facial Angiofibroma Severity Index (FASI), Investigator's Global Assessment (IGA) scores and Dermatology Life Quality Index (DLQI) questionnaire. To assess the safety profile of rapamycin, adverse reactions were reported, and blood tests and blood rapamycin levels were performed during treatment.

Results: Eleven patients were included, of which 8/11 (73%) patients obtained successful treatment according to FASI and IGA scores after 24 weeks of treatment. Statistical analysis demonstrated a significant improvement (p < 0.05) in FASI and IGA scores, erythema, and FA size after treatment with rapamycin liposomal formulation (FASI before treatment, median [interquartile range]: 6.0 [2.0], FASI after treatment: 3.5 [2.0], p = 0.0063). Five patients also improved their quality of life after treatment. Regarding safety profile of rapamycin, the most common adverse reaction was mild pruritus and two patients reported erythema, who discontinued treatment prematurely. All hematological tests were normal, and blood rapamycin levels were undetectable.

Conclusions: After galenic improvements and clinical evaluations, the rapamycin liposomal formulation proved to be effective and safe for this therapeutic indication. This new formulation was included as a magistral formula in our hospital pharmacy service, now accessible for prescribing by dermatologists. Drug development in hospital pharmacy is often the only pharmacological alternative available to treat the symptoms of rare diseases, when treatment options are limited or inadequate.

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.

Introduction: Older patients are more susceptible to medication use, and physiological changes resulting from aging and organic dysfunctions presented by critically-ill patients may alter the pharmacokinetic or pharmacodynamic behavior. Thus, critically-ill older people present greater vulnerability to the occurrence of pharmacotherapeutic problems.

Objective: To evaluate pharmacotherapy and the development of potential adverse drug reactions (ADRs) in older patients admitted to an intensive care unit (ICU).

Method: A cohort study was conducted in an ICU for adults of a Brazilian University Hospital during a 12-month period. The patients' pharmacotherapy was evaluated daily, considering the occurrence of ADRs and drug-drug interactions (DDIs), the use of potentially inappropriate medications (PIMs) for older people, and the pharmacotherapy anticholinergic burden (ACB). A trigger tool was used for active search of ADRs, with subsequent causality evaluation. PIM use was evaluated by means of the Beers criteria and the STOPP/START criteria. The ABC scale was employed to estimate ACB. The Micromedex® and Drugs.com® medication databases were employed to evaluate the DDIs.

Results: The sample of this study consisted of 41 patients, with a mean age of 66.8 years old (±5.2). The 22 triggers used assisted in identifying 15 potential ADRs, and 26.8% of the patients developed them. The mean estimated ACB score was 3.0 (±1.8), and the patients used 3.1 (±1.4) and 3.3 (±1.6) PIMs according to the Beers and the STOPP criteria, respectively. A total of 672 DDIs were identified, with a mean of 16.8 (±9.5) DDIs/patient during ICU hospitalization. Our findings show an association between occurrence of ADRs in the ICU and polypharmacy (p = 0.03) and DDIs (p = 0.007), corroborating efforts for rational medication use as a preventive strategy.

Conclusions: Using tools to evaluate the pharmacotherapy for older people in intensive care can assist in the recognition and prevention of pharmacotherapeutic problems, with emphasis on the identification of ADRs through the observation of triggers and subsequent causality analysis.

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%.

Aims: Tyrosine kinase inhibitors (TKIs) have been successful in changing the course of chronic myeloid leukaemia (CML) due to their high efficacy. However, their effectiveness is conditioned by adherence to treatment. The aim of this study was to analyse the adherence of CML patients treated with TKIs and to evaluate the impact of pharmaceutical care on adherence in a prospective and interventional manner.

Methods: Multicentre, prospective study including CML patients on treatment with TKIs attending the outpatient units of the Pharmacy Services. Adherence was assessed using a combination of two methods: the Simplified Adherence Problems Scale and the treatment dispensing register (a patient with a percentage <90% being considered "non-adherent"); patients who demonstrated a non-adherence in either of these two methods were classified as "non-adherent patients". In individuals with inadequate adherence, PC was reinforced for 8 months by means of a specific programme.

Results: A total of 130 patients were included, 56.9% had optimal adherence to treatment. Pharmaceutical care in the oncohaematology-specific outpatient units of the Pharmacy Services improved adherence (from 67.1% to 90.9%; p < 0.001) while the generalist outpatient units kept it constant (from 70.2% to 72.4%; p = 0.509).

Conclusions: Adherence is one of the most relevant parameters in the effectiveness of chronic treatments. Approximately half of our CML patients showed inadequate adherence to TKIs. This is the first prospective study to determine that the pharmacist's actions in oncohaematology-specific outpatient units of the Pharmacy Services are capable of influencing adherence and improving it.

Background: Adalimumab biosimilar MSB11022 (Idacio®) has been approved for the same indications as its originator (Humira®), based on findings from clinical trials in plaque psoriasis. Data on its efficacy and safety in inflammatory bowel disease, however, are scarce.

Methods: Retrospective, observational study of 44 patients with inflammatory bowel disease: 30 were treated with originator adalimumab, five were directly started on MSB11022, and nine switched from originator to biosimilar adalimumab. To evaluate the effectiveness of the use of adalimumab in inflammatory bowel disease, both laboratory markers (fecal calprotectin and C-reactive protein) and scales that measure the activity of inflammatory bowel disease using specific scales (Harvey-Bradshaw Index [HBI] have been used for Crohn's disease and Mayo Score for ulcerative colitis). Efficacy was evaluated by recording the adverse effects that could occur with the administration of adalimumab (original or biosimilar). The success of the switch was determined by analyzing meaningful differences in effectiveness and safety criteria. Concomitant therapy and the need for dose intensification were also analyzed. Objective of this study was to assess the effectiveness and safety of biosimilar adalimumab in adalimumab-naïve patients and patients switched from originator adalimumab.

Results: No significant differences were observed in clinical disease activity (p = 0.317) or biochemical parameters (fecal calprotectin [p = 0.445] and C-reactive protein [p = 0.661]) after the switch from the originator adalimumab to MSB11022. There was not a significant reduction in the concomitant use of corticosteroids and thiopurines (p = 0.157). No emergency room visits or hospitalizations were observed during the study period and none of the patients experienced serious adverse effects.

Conclusions: Between originator adalimumab and biosimilar-start cohorts no differences were observed, between originator adalimumab and switch cohorts no significant differences were found either, and with the pre- and post-switch to biosimilar comparison two of the nine patients experienced adverse effects after the switch. The biosimilar showed a favorable safety profile (one patient with a serious adverse effect [rash] with biosimilar discontinued treatment) and no significant changes to clinical or biochemical parameters were observed after the switch.

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.