Introduction
Extravasation by conventional cytotoxics has been well documented. While monoclonal antibodies are not considered to have the necrotic potential of some cytotoxic medicines, they require ...appropriate management in case of extravasation. However, fewer data are available on their classification and appropriate management when extravasation occurs. As monoclonal antibodies are being more commonly used in current daily oncology practice, this is an issue that cannot be ignored.
Methods
A scientific literature review on PubMed was conducted. All findings were critically appraised independently by 6 clinical pharmacists in order to provide a classification according to the extravasation hazard.
Results
A classification of non-conjugated and conjugated monoclonal antibodies according to extravasation hazard has been elaborated for different molecules frequently used in oncology. In addition, general management, in case extravasation of monoclonal antibodies occurs, has been proposed and the role of the pharmacist in the extravasation process has been described.
Conclusion
A classification of hazard extent of extravasation of monoclonal antibodies with concurrent management based on literature data and expert consensus has been elaborated. In addition, the role of the oncology pharmacist is crucial in terms of follow-up and documentation of the extravasated monoclonal antibody and management is described.
Background and ImportanceEvolocumab, an inhibitor of proprotein convertase subtilin-kexin type 9, represents an alternative therapeutic option for individuals who exhibit intolerance to standard ...low-density lipoprotein cholesterol (LDL-C) treatments or fail to attain desired LDL-C levels.Aim and ObjectivesThis study aims to assess the effectiveness, safety and adherence to evolocumab among patients with hypercholesterolemia.Material and MethodsObservational, retrospective, and multidisciplinary study that included patients who started treatment with evolocumab in a tertiary hospital between July 2016 and August 2022. Data variables (clinical history and dispensing program) were sex, age, indication, statins treatment, evolucumab dosage, treatment duration, LDL-C levels at baseline, 3, 6, 12 and 36 months, adverse effects (AEs) and adherence (medication possession rate). SPSS-27 statistical program (Wilcoxon test) was used to compare the decrease in LCL-C levels at different times.ResultsThe study enrolled 63 patients (52.4% women), with an average age at initiation of 61.8 (SD:11.1) years. The primary diagnoses included familial hypercholesterolemia (57.1%), established cardiovascular disease (33.3%) or both (9.5%). 63.5% of patients were intolerant to statins, 1.6% had contraindications, and 34.9% received statins at maximum tolerated doses without achieving target LDL-C levels. Dosage was 140 mg/14 days, with an average treatment duration of 3.0 (SD:1.6) years and an adherence rate of 91.3 (SD:14.9)%. The average LDL-C levels was 169.9 (SD:57.5)mg/dl, 84.9 (SD: 62.6) mg/dl, 77.2 (SD: 47.5)mg/dl, 75.7 (SD: 39.0) mg/dl and 84.0 (SD: 44.5) mg/dl at basal, 3, 6, 12 and 36 months, respectively. These LDL-C levels were significantly reduced (p<0.01) when compared to basal. Currently the majority (85.7%) of patients continue their treatment, 1.6% lost to follow-up, and 12.7% discontinued due to death (4.8%), AEs (6.3%) and lack of response (1.6%). Only four patients had AEs (headache; pseudo catarrhal symptoms, haematomas, spasms; anaphylaxis; skin reaction, diarrhoea and myopathies), and evolocumab was withdrawn in all of them.Conclusion and RelevanceEvolocumab emerges as a compelling therapeutic option for LDL-C reduction and cardiovascular risk mitigation, particularly for patients with statin intolerance or inadequate statin response. The results obtained in our real clinical practice (55.4% decrease in LDL-C levels at 12 months) were similar to those of the pivotal clinical trials. Further research is warranted to ascertain its impact on major cardiovascular events in real-world settings.References and/or AcknowledgementsConflict of InterestNo conflict of interest.
Background
Dose banding (DB) is a strategy to rationalise antineoplastic production at Hospital Pharmacy Aseptic Compounding Units (ACUs) and to reduce patient’s waiting time. DB allows for ...optimizing workflows and workloads, facilitating adoption of new technologies, and increasing safety, quality and efficiency of the compounding process.
Objective
To evaluate the potential impact of implementation of Logarithmic DB and to identify antineoplastic agents and preparations that fulfil criteria published and establish the number and standard doses that could be compounded in advance at the ACU.
Setting
University and Polytechnic third level general hospital.
Method
Retrospective observational study (December 2015–May 2016). Antineoplastic dose production was analysed. Investigational drugs were excluded. Three criteria were applied following bibliography reviewed to select candidates to be compounded at our ACU as standardised using logarithmic DB: (a) Antineoplastic preparations > 250 per year; (b) psychochemical stability in optimal storage conditions at least 14 days; (c) maximum five logarithmic standardised doses that include at least 60% of all individualised doses compounded for a given drug.
Main outcome measure
Number of antineoplastic agents, preparations and logarithmic standard doses candidates to DB.
Results
15,436 antineoplastic individualised doses corresponding to 69 antineoplastic agents were analysed. At our institution applying selection criteria, 19 (27%) antineoplastic drugs (3 monoclonal antibodies, 16 cytotoxic) were potential candidates to DB. 6285 (40%) of compounded individualised dose preparations could be prepared in 84 logarithmic standard doses in advance.
Conclusion
Dose banding implementations could contribute to rationalise antineoplastic production and increase the ACUs compounding capacity.
— Because they are designed to produced just one tree, neighbor‐joining programs can obscure ambiguities in data. Ambiguities can be uncovered by resampling, but existing neighbor‐joining programs ...may give misleading bootstrap frequencies because they do not suppress zero‐length branches and/or are sensitive to the order of terminals in the data. A new procedure, parsimony jackknifing, overcomes these problems while running hundreds of times faster than existing programs for neighbor‐joining bootstrapping. For analysis of large matrices, parsimony jackknifing is hundreds of thousands of times faster than extensive branch‐swapping, yet is better able to screen out poorly‐supported groups.
BackgroundPaclitaxel is commonly associated with infusion reactions (IR) with no clear influence of different paclitaxel formulations.PurposeTo analyse the number and severity of IR related to ...administration of different generic formulations of paclitaxel registered by means of an adverse drug reactions reporting programme (ADRRP).Material and methodsObservational, retrospective study from January 2010 to March 2015. Identification of IR was carried out by an active collaboration of day hospital nursing staff based on voluntary reporting of adverse drug reactions (ADRs) documented centrally at the pharmacy department (chemotherapy unit) using the application Farmis-Oncofarm within the framework of ADRRP. Variables collected: sex, age, generic brand name, cycle, IR severity (CTCAE v4.03), ADRs medication management and re-administration tolerance.5 different generic formulations (A-E) were used during the study period, with no significant differences in type and concentration of the excipients. All patients received premedication with corticosteroids, antihistamines and H2 antagonists, as recommended by the summary of product characteristics.Relative frequencies and severity were calculated, and χ2 and Fisher exact tests were used for statistical comparison (SPSS v.19).ResultsDuring the study period, 648 patients (401 women (61.9%)), median age 59.5 years (range 23–86) received a total of 4845 paclitaxel intravenous infusions: 61.3% (paclitaxel A), 28.4% (B), 6.7% (C), 3.3% (D) and 0.4% (E).61 IR were recorded. Paclitaxel A: 36 (1.21%), B: 14 (1.02%), C: 6 (1.86%), D: 1 (0.62%) and E: 4 (23.53%). No statistically significant differences (SSD) were observed in IR number or severity except with E paclitaxel (p < 0.001). 41% of IR occurred during the first administration. 46/61 grade 2; 14/61 grade 3; and 1 grade 4 (ICU admission after the second cycle). All IR were managed by temporarily stopping the current infusion and symptomatic treatment with corticosteroid+antihistamine±paracetamol as per protocol. 18/61 did not tolerate re-administration.ConclusionSSD were only observed with E paclitaxel without finding out the cause. Sample imbalance among formulations was due to the regional health department centralised purchasing system through public tenders and several shortage supplies over the study period. The ADRRP based on the active voluntary collaboration of nurses was effective in detecting drug related problems and implementing interventions accordingly (notification to national surveillance programme, laboratory involved and changing the available presentation at the hospital) to enhance drug safety.No conflict of interest.
Because they are designed to produced just one tree, neighbor-joining programs can obscure ambiguities in data. Ambiguities can be uncovered by resampling, but existing neighbor-joining programs may ...give misleading bootstrap frequencies because they do not suppress zero-length branches and/or are sensitive to the order of terminals in the data. A new procedure, parsimony jackknifing, overcomes these problems while running hundreds of times faster than existing programs for neighbor-joining bootstrapping. For analysis of large matrices, parsimony jackknifing is hundreds of thousands of times faster than extensive branch-swapping, yet is better able to screen out poorly-supported groups.
Introduction. Antineoplastic drug therapy errors represent a high iatrogenic potential due to antineoplastic drugs narrow therapeutic ranges and the complexity of chemotherapy regimens that may ...increase the risk of morbidity and mortality for oncology patients.
Setting. We report a 57-year-old man with head and neck cancer who mistakenly received 180 mg/ m2 of cisplatin overdose despite the safety measures and validations carried out during preparation. The patient developed moderate nausea and vomiting, acute renal failure, hearing difficulty (tinnitus), and severe myelodepression.
Patient management. Prophylactic and symptomatic treatments were applied in order to prevent and correct toxicity during the 9 days stay at hospital.
Result. He recovered with mild tinnitus and mild renal impairment as the only sequelae. This case presents a hospital stay and treatment quite different to others used to reverse all cisplatin overdose toxicity and it shows the benefits of prompt management.
According to currently accepted theories, rapidly evolving nucleotide sites are phylogenetically less informative than more slowly evolving ones, especially for recognizing more ancient groupings. ...For this reason third codon positions are often regarded as less reliable than first and second positions as indicators of phylogeny. Analysis of the largest nucleotide matrix treated to date—2538 rbc L sequences covering all major lineages of green plants—shows the opposite: although rapidly evolving and highly homoplastic, third positions contain most of the phylogenetic structure in the data. Frequency of change should thus be used with caution as a criterion for weighting or selecting characters.
Studies on bioavailability are part of the clinical development of drugs for oral use in order to identify potential drug-food interactions. For oral antitumor drugs, their clinical importance is ...currently recognized although regrettably the information available presents variability concerning the scientific evidence.
To review the available scientific evidence about oral anti-tumor medications and establish the recommendations for their administration with foods.
We carried out a bibliographic search in Medline and The Cochrane Library for the period January of 1966 to March of 2008, focused on identifying those publications about drug-food interactions with oral antitumor medications. The bibliographical analysis was made in two steps. During the first phase, we excluded those articles in which the title or their content did not correspond with the objective settled; during the second phase, we deleted all the references duplicated in both databases. The inclusion criteria to select the articles were: design (systematic reviews, meta-analysis, Phase I and Phase II randomized clinical trials), population (adult patients; >19 years of age), intervention evaluated (administration of oral anti-tumor drugs under fasting conditions or with food) and measurement of the iFA results (calculation of the 90% CI of the odds ratio between the geometric mean of the values under the curve of the plasma concentrations (ABC) or the maximal plasma concentration (Cmax) with and without foods). We excluded those publications that did not make reference to the bioequivalence dictamen established by the Food and Drugs Administration (FDA) in their outcomes measurement. A critical appraisal of the selected articles was done according to the recommendations that the FDA established to be met by these studies.
At the initial search we obtained 850 references (98.5% Medline + and 1.4% Cochrane). During the first phase, we excluded 87.7% (746) of the articles, 100% of them corresponding to the search in Medline. During the second phase, 40 studies remained (5.2% of the initial ones) for full-text critical appraisal, to which four studies were added not indexed in Medline. From the critical appraisal of the 44 final articles, 25 were excluded (20 original articles, 4 short communications, and 1 meta-analysis) because they did not include as an outcome measure the bioequivalence dictamen. The 19 (2.2%) remaining articles provided information on 19 oral anti-tumor drugs in 210 patients and 146 healthy volunteers. Of these 19 drugs, 63% did not present drug-food interactions, with the possibility of administering them either with or without food; 21% have to be administered with foods and only 16% present drug-food interactions, so they have to be administered without foods.
Currently, the clinical importance of drug-food interactions with oral anti-tumor drugs is identified more directly with the patient's safety than with the efficacy of the therapy. Given the development of these oral agents, their incorporation into the oncologic strategy displacing parenteral therapy, with monthly costs of thousands of Euros, it is necessary to perform well-designed studies on pharmacokinetics and pharmacodynamics. Their goal has to be comparing their bioavailability in the presence or absence of foods with the clinical response. In the meanwhile, to establish recommendations for their administration in relation to foods is inconsistent for some of these drugs and their results is uncertain given the lack of studies based on the FDA bioequivalence dictamen.
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