Unraveling elements of value-based pricing from a pharmaceutical industry's perspective: a scoping review.

Health authorities use value-based pricing models to determine the value of innovative drugs and to establish a price. Pharmaceutical companies prefer value-based pricing over cost-based pricing. It is ambiguous whether value-based pricing has the same meaning to these stakeholders. We aimed to identify the elements that attribute to value-based pricing of innovative drugs from a pharmaceutical industry's perspective and as possible starting point for (value-based) contracting of drugs. We performed a scoping review of publications available in scientific databases with terms such as 'value-based pricing', 'pharmacoeconomics', 'drug cost', 'innovative drug' and 'drug therapy'. We included 31 publications, covering value elements of innovative drugs from a pharmaceutical industry's perspective. Overall, all found elements of value-based pricing were congruent with the elements of value-based pricing from a health authority's perspective. However, the emphasis placed on the elements differed. The most frequently mentioned elements in our review were economic considerations and cost aspects. Least mentioned were elements regarding cost-effectiveness, disease characteristics and patient characteristics. Although all elements in the drug value framework were present which indicate congruity, there seems controversy on the importance of cost-effectiveness as an element of value. Consequently, establishing a coherent and to all stakeholders' acceptable framework to value and price innovative drugs seems complicated. Mutual understanding can be found in the value elements societal considerations and healthcare process benefits. Our results supported the importance of economic and cost aspects regarding determination of prices of innovative drugs. Further research is required to quantify the weights of all relevant elements in the drug value framework, observe their possible interlinkages, and to weigh them over time.

Differences in prescribing errors between electronic prescribing and traditional prescribing among medical students: A randomized pilot study.

AIMS: This randomized controlled pilot study aimed to assess the differences in the frequency, type and severity of prescribing errors made by medical students when assessed in an electronic (e-)prescribing system compared to a traditional prescribing method (e.g., typing out a prescription). METHODS: Fourth year medical students in the period of 1 November to 31 July 2023, were asked to participate in this single-centre prospective, randomized, controlled intervention study. Participants performed a prescribing assessment in either an e-prescribing system (intervention group) or in a more traditional prescribing platform (control group). The prescriptions were checked for errors, graded and categorized. Differences in prescribing errors, error categories and severity were analysed. RESULTS: Out of 334 students, 84 participated in the study. Nearly all participants (98.8%) made 1 or more prescribing errors, primarily involving inadequate information errors. In the intervention group, more participants made prescribing errors involving the prescribed amount (71.4 vs. 19.0%; P < .01), but fewer involving administrative errors (2.4 vs. 19.0%; P = .03). Prescribing-method-specific errors were identified in 4.8 and 40.5% of the intervention and control group, respectively, with significant differences in overlapping errors as well. CONCLUSION: This pilot study shows the importance of training e-prescribing competencies in medical curricula, in addition to traditional prescribing methods. It identifies prescribing-method-specific prescribing errors and emphasizes the need for further research to define e-prescribing competencies. Additionally, the need for an accessible real-life-like e-prescribing environment tailored to educators and students is essential for effective learning and incorporation of e-prescribing into medical curricula.

Adjunctive Intravenous Immunoglobulin and Glucocorticoid Therapy in Severe Herpes Simplex Encephalitis with Excellent Outcome Begs for Larger Trials Evaluating Immunomodulatory Therapy.

BACKGROUND Despite the preponderance of evidence of immune-driven pathophysiology of disease in herpes simplex virus-1 (HSV-1) encephalitis, current treatment paradigms do not officially recommend adjunctive immunomodulatory therapy in addition to acyclovir. This may in part explain the poor long-term outcomes in patients with severe HSV encephalitis. This report is of a 21-year-old man presenting with a 4-day history of nausea, headache, and fever and a diagnosis of HSV-1 encephalitis. CASE REPORT We describe the case of a young male with clinically and radiographically severe HSV-1 encephalitis diagnosed by PCR of cerebrospinal fluid (CSF), who demonstrated immediate improvement upon treatment with intravenous immunoglobulin (IVIG, 0.5 g/kg daily ×3 days) in addition to acyclovir and dexamethasone therapy. Acyclovir therapy was extended beyond 21 days due to persistently positive HSV-1 CSF PCR. He developed N-methyl-D-aspartate (NMDA) receptor antibodies at 6 weeks, but his long-term outcome far exceeded expectations. While some of his neurological deficits appear to be permanent, he is living a normal life. CONCLUSIONS Overwhelming evidence demonstrates that brain injury due to HSV encephalitis is driven by immune reactions stimulated by HSV rather than HSV itself. Nevertheless, use of immunomodulatory therapy such as glucocorticoids and IVIG are left to the discretion of individual clinicians rather than being recommended in treatment guidelines, which instead recommend acyclovir therapy. The present case highlights the potential role of immunomodulatory therapy with IVIG in HSV encephalitis and the importance of early diagnosis and treatment.

Combatting the rising costs of cancer drugs; interventions from a university hospital's perspective.

Rapid increase in cost continues to have negative impact on patients' accessibility to life-changing anticancer medications. Moreover, the rising cost does not equate to similar increase in medication effectiveness. We recognise our responsibility as a university hospital to tackle this imbalance and strive to provide high quality, sustainable, affordable and accessible care. An active approach in cost containment of expensive and innovative cancer drugs was adopted in our organisation to safeguard accessibility and improve quality of life for patients. In this article, we described four inverventions: 1) identify right patient and minimise overtreatment, 2) in-house medicine production for selected indications, 3) minimise medicine spillages and 4) effective procurement strategies. We call on other hospitals to take action and, favourably, to collaborate on a European level. Together, we will safeguard the current and future care of our patients.

Do junior doctors make more prescribing errors than experienced doctors when prescribing electronically using a computerised physician order entry system combined with a clinical decision support system? A cross-sectional study.

OBJECTIVES: Prescribing errors can lead to inconvenience, morbidity and mortality. It is therefore crucial to educate doctors to prescribe safely, efficiently and effectively. To create an effective educational programme, it is essential to understand which errors are made and by whom. The aim of this study is to explore if the experience level of the doctor influences how many and which prescribing errors are made in a European academic teaching hospital, where a computerised physician order entry system (CPOE) with a clinical decision support system (CDSS) is exclusively used. METHODS: Prescriptions for all inpatients in an academic teaching hospital were collected in June 2021. All prescriptions with an alert generated by the CDSS which could not be handled by a pharmacy technician according to local protocol were checked for errors. Identified errors were categorised by type and severity. RESULTS: A total of 130 538 prescriptions were newly made or altered by doctors. Of these prescriptions, 1914 (1.5%) were retained for a check by the pharmacist. These contained 430 prescribing errors (0.3% of total prescriptions). Doctors not in specialty training and those in specialty training made more prescribing errors than consultants (0.5% and 0.5% vs 0.1%; p<0.001). Doctors in specialty training made relatively more drug-drug interaction errors than consultants (n=31 (16%) vs n=3 (3%), p<0.05). No significant difference was found regarding the severity of the errors. CONCLUSIONS: Doctors not in specialty training and doctors in specialty training, who are the less experienced doctors, make more prescribing errors than consultants, even with the use of a CPOE combined with CDSS. The type of errors differ between doctors of different experience levels. This finding provides a solid basis for specific additional education to medical students, doctors not in specialty training and doctors in specialty training.

Inpatients' information needs about medication: A narrative systematic literature review.

OBJECTIVE: To provide an overview of inpatients' information needs about medication, including the best moment to provide this information, how, by whom and what patient characteristics influence these needs. METHODS: A systematic literature review was conducted. Studies that reported the information needs from inpatients about medication were included from Medline and Embase. The Crowe critical appraisal tool (CCAT) was used to assess the quality of the studies. RESULTS: Initially, 710 records were retrieved from Medline and Embase. After the forward search, another 609 records were screened and in total, 26 articles were included. The CCAT scores ranged from 17 to 34 points on a 40 point scale and two articles received 0 points. CONCLUSION: Inpatients main needs about medicine information are information about adverse and beneficial effects of medication, and general rules about how to take medication. Preferably, this information is printed and provided at the time of prescribing by a physician that already has a relationship with the patient. The most recent studies show that patients are open to the use of modern technology. PRACTICE IMPLICATIONS: This review provides a starting point for providing medicine information to inpatients. Further research should focus on patient characteristics influencing these information needs.

Age Moderates the Effect of Obesity on Mortality Risk in Critically Ill Patients With COVID-19: A Nationwide Observational Cohort Study.

OBJECTIVES: A high body mass index (BMI) is associated with an unfavorable disease course in COVID-19, but not among those who require admission to the ICU. This has not been examined across different age groups. We examined whether age modifies the association between BMI and mortality among critically ill COVID-19 patients. DESIGN: An observational cohort study. SETTING: A nationwide registry analysis of critically ill patients with COVID-19 registered in the National Intensive Care Evaluation registry. PATIENTS: We included 15,701 critically ill patients with COVID-19 (10,768 males [68.6%] with median [interquartile range] age 64 yr [55-71 yr]), of whom 1,402 (8.9%) patients were less than 45 years. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In the total sample and after adjustment for age, gender, Acute Physiology and Chronic Health Evaluation IV, mechanical ventilation, and use of vasoactive drugs, we found that a BMI greater than or equal to 30 kg/m 2 does not affect hospital mortality (adjusted odds ratio [OR adj ] = 0.98; 95% CI, 0.90-1.06; p = 0.62). For patients less than 45 years old, but not for those greater than or equal to 45 years old, a BMI greater than or equal to 30 kg/m 2 was associated with a lower hospital mortality (OR adj = 0.59; 95% CI, 0.36-0.96; p = 0.03). CONCLUSIONS: A higher BMI may be favorably associated with a lower mortality among those less than 45 years old. This is in line with the so-called "obesity paradox" that was established for other groups of critically ill patients in broad age ranges. Further research is needed to understand this favorable association in young critically ill patients with COVID-19.

How would final-year medical students perform if their skill-based prescription assessment was real life?

AIMS: Prescribing errors occur frequently, especially among junior doctors. Our aim was to investigate prescribing errors made by final-year medical students. Information on these errors can help to improve education on and assessment of clinical pharmacotherapy (CPT). METHODS: This was a retrospective cohort study amongst final-year medical students at Erasmus Medical Centre, The Netherlands. Errors made in the final prescribing assessment were analysed. Errors were categorized by type, possible consequence and possibility of reaching the patient in real life. RESULTS: A total of 381 students wrote 1502 analysable prescriptions. Forty per cent of these contained at least one error, and 54% of errors were of the inadequate information type. The rating of prescriptions for children was lower than for other question categories (P = <.001). Fifty per cent of errors were classified as "would have reached the patient but would not have had the potential to cause harm". In total, 253 (29%) errors would not have been intercepted by an electronic prescribing system or a pharmacist. Ten (4%) of these would probably have caused harm in the patient. CONCLUSIONS: There is a high rate of errors in prescriptions written by final-year medical students. Most errors were of the inadequate information type, indicating that students had difficulties determining the content and amount of information needed to make treatment successful. Prescriptions for children contained most errors. Curricula could be improved by offering more case-based CPT education, focusing on the practical issues of prescribing, especially for paediatric cases, and offering more practice time for prescribing during clerkships.

Control in the Hospital by Extensive Clinical rules for Unplanned hospitalizations in older Patients (CHECkUP); study design of a multicentre randomized study.

BACKGROUND: Due to ageing of the population the incidence of multimorbidity and polypharmacy is rising. Polypharmacy is a risk factor for medication-related (re)admission and therefore places a significant burden on the healthcare system. The reported incidence of medication-related (re)admissions varies widely due to the lack of a clear definition. Some medications are known to increase the risk for medication-related admission and are therefore published in the triggerlist of the Dutch guideline for Polypharmacy in older patients. Different interventions to support medication optimization have been studied to reduce medication-related (re)admissions. However, the optimal template of medication optimization is still unknown, which contributes to the large heterogeneity of their effect on hospital readmissions. Therefore, we implemented a clinical decision support system (CDSS) to optimize medication lists and investigate whether continuous use of a CDSS reduces the number of hospital readmissions in older patients, who previously have had an unplanned probably medication-related hospitalization. METHODS: The CHECkUP study is a multicentre randomized study in older (≥60 years) patients with an unplanned hospitalization, polypharmacy (≥5 medications) and using at least two medications from the triggerlist, from Zuyderland Medical Centre and Maastricht University Medical Centre+ in the Netherlands. Patients will be randomized. The intervention consists of continuous (weekly) use of a CDSS, which generates a Medication Optimization Profile, which will be sent to the patient's general practitioner and pharmacist. The control group will receive standard care. The primary outcome is hospital readmission within 1 year after study inclusion. Secondary outcomes are one-year mortality, number of emergency department visits, nursing home admissions, time to hospital readmissions and we will evaluate the quality of life and socio-economic status. DISCUSSION: This study is expected to add evidence on the knowledge of medication optimization and whether use of a continuous CDSS ameliorates the risk of adverse outcomes in older patients, already at an increased risk of medication-related (re)admission. To our knowledge, this is the first large study, providing one-year follow-up data and reporting not only on quality of care indicators, but also on quality-of-life. TRIAL REGISTRATION: The trial was registered in the Netherlands Trial Register on October 14, 2018, identifier: NL7449 (NTR7691). https://www.trialregister.nl/trial/7449 .

Understanding the association between sleep, shift work and COVID-19 vaccine immune response efficacy: Protocol of the S-CORE study.

This protocol describes an innovative study to investigate the relationship between sleep, shift work and the immune response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2; coronavirus disease 2019 [COVID-19]) vaccination. As the COVID-19 pandemic is a global crisis with devastating health, social and economic impacts, there is a pressing need for effective vaccination programmes. Previous influenza and hepatitis vaccination studies suggest that lack of sleep can negatively alter immune responsiveness, while circadian misalignment most likely may also play an important role in the immune response to vaccination. Our present study will be the first to address this question in actual shift workers and in relation to COVID-19 vaccination. We hypothesise that the occurrence of recent night shifts and diminished sleep will negatively alter the immune response to vaccination in shift workers compared to dayworkers. We aim to recruit 50 shift workers and 50 dayworkers. Participants will receive an mRNA-based vaccination, through the Dutch vaccination programme. To assess immune responsiveness, blood will be drawn at baseline (before first vaccination), 10 days after first vaccination, the day prior to the second vaccination; and 28 days, 6 and 12 months after the second vaccination. Actigraphy and daily sleep e-diaries will be implemented for 7 days around each vaccination to assess sleep. The Pittsburgh Sleep Quality Index will be used to monitor sleep in the long term. Optimising the efficacy of the COVID-19 vaccines is of outmost importance and results of this study could provide insights to develop sleep and circadian-based interventions to enhance vaccination immunity, and thereby improve global health.

Better performance of medical students on pharmacotherapy knowledge and skills tests is associated with practising with e-learning program P-scribe.

AIMS: Junior doctors write most hospital prescriptions, yet are more than twice as likely to make an error in their prescriptions compared to senior doctors. A possibility to enhance pharmacotherapy education is through the use of e-learning modules. The aim of this study was to determine whether P-scribe, as the chosen e-learning resource, helps students in passing their pharmacotherapy assessments. METHODS: This retrospective study was undertaken in the Erasmus Medical Center, the Netherlands. All 270 medical students who started their master's curriculum in the academic session of 2017-2018 were included. Data were analysed to identify the frequency of student's use per e-learning module, total time students spent on e-learning modules and timing of the use of e-learning modules in relation to their assessments. The results of the assessments were analysed to identify possible correlations between the time students spent using P-scribe, their timing of use and their assessment results. RESULTS: Students who passed their knowledge-based assessment first time had a mean practice time of five more hours than students who did not pass first time (P < .05, 95% CI: 3.4-6.6). These students practised on average six e-learning modules more (P < .05, 95% CI: 4.1-7.0) than students who failed their first attempt. Students who passed their skill-based prescription test first time, practised on average five more e-learning modules (P = .006, 95% CI: 1.4-8.3) than students who failed their first attempt. CONCLUSION: Students who passed their pharmacotherapy assessments first time spent more time, and practised more frequently, with e-learning modules.

Fall incidents in nursing home residents: development of a predictive clinical rule (FINDER).

OBJECTIVES: To develop (part I) and validate (part II) an electronic fall risk clinical rule (CR) to identify nursing home residents (NH-residents) at risk for a fall incident. DESIGN: Observational, retrospective case-control study. SETTING: Nursing homes. PARTICIPANTS: A total of 1668 (824 in part I, 844 in part II) NH-residents from the Netherlands were included. Data of participants from part I were excluded in part II. PRIMARY AND SECONDARY OUTCOME MEASURES: Development and validation of a fall risk CR in NH-residents. Logistic regression analysis was conducted to identify the fall risk-variables in part I. With these, three CRs were developed (ie, at the day of the fall incident and 3 days and 5 days prior to the fall incident). The overall prediction quality of the CRs were assessed using the area under the receiver operating characteristics (AUROC), and a cut-off value was determined for the predicted risk ensuring a sensitivity ≥0.85. Finally, one CR was chosen and validated in part II using a new retrospective data set. RESULTS: Eleven fall risk-variables were identified in part I. The AUROCs of the three CRs form part I were similar: the AUROC for models I, II and III were 0.714 (95% CI: 0.679 to 0.748), 0.715 (95% CI: 0.680 to 0.750) and 0.709 (95% CI: 0.674 to 0.744), respectively. Model III (ie, 5 days prior to the fall incident) was chosen for validation in part II. The validated AUROC of the CR, obtained in part II, was 0.603 (95% CI: 0.565 to 0.641) with a sensitivity of 83.41% (95% CI: 79.44% to 86.76%) and a specificity of 27.25% (95% CI 23.11% to 31.81%). CONCLUSION: Medication data and resident characteristics alone are not sufficient enough to develop a successful CR with a high sensitivity and specificity to predict fall risk in NH-residents. TRIAL REGISTRATION NUMBER: Not available.

Association between Clinical Frailty Scale score and hospital mortality in adult patients with COVID-19 (COMET): an international, multicentre, retrospective, observational cohort study.

BACKGROUND: During the COVID-19 pandemic, the scarcity of resources has necessitated triage of critical care for patients with the disease. In patients aged 65 years and older, triage decisions are regularly based on degree of frailty measured by the Clinical Frailty Scale (CFS). However, the CFS could also be useful in patients younger than 65 years. We aimed to examine the association between CFS score and hospital mortality and between CFS score and admission to intensive care in adult patients of all ages with COVID-19 across Europe. METHODS: This analysis was part of the COVID Medication (COMET) study, an international, multicentre, retrospective observational cohort study in 63 hospitals in 11 countries in Europe. Eligible patients were aged 18 years and older, had been admitted to hospital, and either tested positive by PCR for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or were judged to have a high clinical likelihood of having SARS-CoV-2 infection by the local COVID-19 expert team. CFS was used to assess level of frailty: fit (CFS1-3), mildly frail (CFS4-5), or frail (CFS6-9). The primary outcome was hospital mortality. The secondary outcome was admission to intensive care. Data were analysed using a multivariable binary logistic regression model adjusted for covariates (age, sex, number of drugs prescribed, and type of drug class as a proxy for comorbidities). FINDINGS: Between March 30 and July 15, 2020, 2434 patients (median age 68 years [IQR 55-77]; 1480 [61%] men, 954 [30%] women) had CFS scores available and were included in the analyses. In the total sample and in patients aged 65 years and older, frail patients and mildly frail patients had a significantly higher risk of hospital mortality than fit patients (total sample: CFS6-9 vs CFS1-3 odds ratio [OR] 2·71 [95% CI 2·04-3·60], p<0·0001 and CFS4-5 vs CFS1-3 OR 1·54 [1·16-2·06], p=0·0030; age ≥65 years: CFS6-9 vs CFS1-3 OR 2·90 [2·12-3·97], p<0·0001 and CFS4-5 vs CFS1-3 OR 1·64 [1·20-2·25], p=0·0020). In patients younger than 65 years, an increased hospital mortality risk was only observed in frail patients (CFS6-9 vs CFS1-3 OR 2·22 [1·08-4·57], p=0·030; CFS4-5 vs CFS1-3 OR 1·08 [0·48-2·39], p=0·86). Frail patients had a higher incidence of admission to intensive care than fit patients (CFS6-9 vs CFS1-3 OR 1·54 [1·21-1·97], p=0·0010), whereas mildly frail patients had a lower incidence than fit patients (CFS4-5 vs CFS1-3 OR 0·71 [0·55-0·92], p=0·0090). Among patients younger than 65 years, frail patients had an increased incidence of admission to intensive care (CFS6-9 vs CFS1-3 OR 2·96 [1·98-4·43], p<0·0001), whereas mildly frail patients had no significant difference in incidence compared with fit patients (CFS4-5 vs CFS1-3 OR 0·93 [0·63-1·38], p=0·72). Among patients aged 65 years and older, frail patients had no significant difference in the incidence of admission to intensive care compared with fit patients (CFS6-9 vs CFS1-3 OR 1·27 [0·92-1·75], p=0·14), whereas mildly frail patients had a lower incidence than fit patients (CFS4-5 vs CFS1-3 OR 0·66 [0·47-0·93], p=0·018). INTERPRETATION: The results of this study suggest that CFS score is a suitable risk marker for hospital mortality in adult patients with COVID-19. However, treatment decisions based on the CFS in patients younger than 65 years should be made with caution. FUNDING: LOEY Foundation.

No association between use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers prior to hospital admission and clinical course of COVID-19 in the COvid MEdicaTion (COMET) study.

Since the outbreak of SARS-CoV-2, also known as COVID-19, conflicting theories have circulated on the influence of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) on incidence and clinical course of COVID-19, but data are scarce. The COvid MEdicaTion (COMET) study is an observational, multinational study that focused on the clinical course of COVID-19 (i.e. hospital mortality and intensive care unit [ICU] admission), and included COVID-19 patients who were registered at the emergency department or admitted to clinical wards of 63 participating hospitals. Pharmacists, clinical pharmacologists or treating physicians collected data on medication prescribed prior to admission. The association between the medication and composite clinical endpoint, including mortality and ICU admission, was analysed by multivariable logistic regression models to adjust for potential confounders. A total of 4870 patients were enrolled. ACEi were used by 847 (17.4%) patients and ARB by 761 (15.6%) patients. No significant association was seen with ACEi and the composite endpoint (adjusted odds ratio [OR] 0.94; 95% confidence interval [CI] 0.79 to 1.12), mortality (OR 1.03; 95%CI 0.84 to 1.27) or ICU admission (OR 0.96; 95%CI 0.78 to 1.19) after adjustment for covariates. Similarly, no association was observed between ARB and the composite endpoint (OR 1.09; 95%CI 0.90 to 1.30), mortality (OR 1.12; OR 0.90 to 1.39) or ICU admission (OR 1.21; 95%CI 0.98 to 1.49). In conclusion, we found no evidence of a harmful or beneficial effect of ACEi or ARB use prior to hospital admission on ICU admission or hospital mortality.

COvid MEdicaTion (COMET) study: protocol for a cohort study.

Various theories about drugs such as ACE inhibitors or angiotensin II receptor blockers (ARBs) in relation to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and clinical outcomes of COVID-19 are circulating in both mainstream media and medical literature. These are based on the fact that ACE2 facilitates SARS-CoV-2 cell invasion via binding of a viral spike protein to ACE2. However, the effect of ACE inhibitors, ARBs and other drugs on ACE2 is unclear and all theories are based on conflicting evidence mainly from animal studies. Therefore, clinical evidence is urgently needed. The aim of this study is to investigate the relationship between use of these drugs on clinical outcome of patients with COVID-19. Patients will be included from several hospitals in Europe. Data will be collected in a user-friendly database (Digitalis) on an external server. Analyses will be adjusted for sex, age and presence of cardiovascular disease, hypertension and diabetes. These results will enable more rational choices for randomised controlled trials for preventive and therapeutic strategies in COVID-19.

Review on the relevance of therapeutic drug monitoring of levetiracetam.

Therapeutic Drug Monitoring (TDM) of anti-epileptic drugs (AEDs) is not routinely performed, although this can guide the dosage regimen to achieve greater efficacy and safety. Levetiracetam (LEV) has been introduced as an AED with an almost perfect pharmacokinetic (PK) profile. Nonetheless, recent research challenges this statement and therefore we aimed to explore factors that modify LEV PK. Age and enzyme-inducing drugs (EIDs) appear to be major factors influencing the PK profile of LEV. Therefore, 30-50% lower dosages should be used in the elderly (> 65 years of age) and the dosing regimen should be guided by monitoring SDC (TDM). In contrast, higher LEV dosages are necessary in children aged between 2 months and 12 years (compared to adults) due to a 30-70% increase of LEV clearance (CL). Higher dosages are also required if a patient receives EIDs, again due to a higher CL of LEV (range 24-60%). This could also be true for pregnant women. LEV TDM is currently not common in the clinical setting due to the wide therapeutic range and the low prevalence of side-effects. However, LEV dose should on the one hand be increased in certain physiological situations (pregnancy, neonates) and patients on EIDs (especially carbamazepine). On the other hand, dose reductions are necessary when the LEV CL is impaired (elderly). Nevertheless, current data to support regular LEV TDM are lacking. Prospective research is needed to explore the importance of LEV TDM in elected patient groups; i.e. neonates, elderly, patients on EIDs and pregnant women.

Medication surveillance on intravenous cytotoxic agents: a retrospective study.

BACKGROUND: Medication surveillance is not commonly performed for cytotoxic agents. Cytotoxic agents generally have a narrow therapeutic range and therefore it might be necessary to adjust the dose. Interactions may not only cause supratherapeutic ranges, but can also lead to subtherapeutic levels. Up till now, only a few studies have demonstrated the value and importance of medication surveillance in ambulatory cancer patients. OBJECTIVE: The objective of this study is to determine the prevalence and relevance of interactions with cytotoxic agents in ambulant cancer patients receiving one or more intravenous cytotoxic administrations. SETTING: This retrospective study was undertaken in the Orbis Medical Centre in Sittard, the Netherlands. METHODS: All ambulatory cancer patients receiving one or more intravenous cytotoxic treatments during the period October 2008 to April 2010 were included. Cytotoxic agent related information was determined using the hospital information system and medication history was determined using the Electronic Prescribing System (EPS) and an open care information system. Medication was entered into the EPS and medication surveillance was performed electronically using the G-standard. All alerts were generated retrospectively. MAIN OUTCOME MEASURE: The prevalence and relevance of interactions between cytotoxic agents and other drugs in ambulatory cancer patients. RESULTS: A total of 527 ambulatory cancer patients was enrolled. The mean age of the patients was 63.6 years and 303 were female (55 %). In 24 patients a total of 58 cytotoxic agent-related interactions was detected of whom five were clinically relevant. The most frequent cytotoxic agent-related interaction was with acenocoumarol; the most relevant interactions were with antiepileptic drugs. CONCLUSION: A total of 58 potential cytotoxic agent-related interactions was found. This corresponds to 11 cytotoxic agent-related interactions per 100 ambulatory cancer patients, of which one was indicated clinically relevant and should have required an intervention. The most frequently involved drug was acenocoumarol. Most drug-related interactions with cytotoxic agents are manageable and can be monitored. Prospective studies are needed to confirm the relevance of medication surveillance on cytotoxic agents.