MedsScan Issue 4, 2025

These reviews provide updates on the international literature on therapeutics. Expert pharmacy practitioners — via AdPha’s Specialty Practice Groups — scan major peer-reviewed journals in areas relevant to Australian pharmacy practice and present precis on major clinical trials, important pharmacoepidemiology studies and pharmacoeconomic research, and other updates relevant to practice. Interested readers are encouraged to explore the original publications in greater detail.

CARDIOLOGY

MedsScan Editor for Cardiology SPG: Vivek Nooney

Stop-or-Not trial supports the continuation of renin-angiotensin system inhibitors before major noncardiac surgery

Special Contributor: Jennis Kumar

The Stop-or-Not clinical trial has demonstrated that in patients who underwent major noncardiac surgery, a continuation strategy of renin-angiotensin system inhibitors (RASIs) before surgery was not associated with a higher rate of postoperative complications 28 days after surgery compared to a discontinuation strategy. Therefore, only patients with a potentially increased risk of intraoperative hypotension may need to discontinue their RASI therapy.

Previously, there was conflicting evidence on whether continuing or discontinuing RASI medicines was safer for patients. This open label, multicentre, randomised trial across 40 French hospitals has found that RASIs can be safely used before surgery for some patients. A total of 2222 patients (mean age was 67 years and 65% were male) on long term RASI therapy were randomised to either continue their medication until the day of surgery or discontinue it 48 hours prior to surgery, with 1107 patients in the continuation group and 1115 patients in the discontinuation group. Both groups resumed treatment at a median of 1 day (interquartile range [IQR] 1–3 days) after surgery. The primary outcome was a composite of all-cause mortality and major postoperative complications within 28 days of surgery.

The results were similar for both groups. Of the 1115 patients in the discontinuation group and the 1107 patients in the continuation group, the rate of all-cause mortality and major postoperative complications was 22.2% (n = 247) and 22.1% (n = 245) respectively (risk ratio [RR] 1.02, 95% confidence interval [CI] 0.87–1.19, P = 0.85). The continuation group experienced a higher rate of intraoperative hypotension (54%) compared to the discontinuation group (41%, RR 1.31, 95% CI 1.19–1.44) and the median duration of hypotension with a mean arterial pressure below 60 mm Hg was only slightly longer (9 min vs 6 min) in the continuation group. This did not translate to an increased risk of adverse postoperative outcomes.  

This trial provides confidence, addressing a gap in existing evidence and conflicting guidelines. The Stop-or-Not trial demonstrates that either approach is acceptable, depending on patients' circumstances. This new evidence can be used to inform and strengthen clinical guidelines.  

Legrand M, Falcone J, Cholley B, Charbonneau H, Delaporte A, Lemoine A, et al; Continuation vs discontinuation of renin-angiotensin system inhibitors before major noncardiac surgery: the Stop-or-Not randomized clinical trial. JAMA 2024; 332: 970–978.

Beyond blood sugar: cardiovascular outcomes with oral semaglutide

Special Contributor: Bree Murphy

Oral semaglutide may be a viable therapeutic option in cardiovascular risk reduction for people with type 2 diabetes mellitus (T2DM), offering both glucose-lowering and cardiovascular protection. Adults with T2DM have an increased risk of heart disease, which remains the leading cause of morbidity and mortality in this patient population.

Injectable glucagon-like peptide 1 (GLP-1) receptor agonists have shown cardiovascular benefits, but many patients are reluctant to use injections, therefore an oral formulation may improve adherence and broaden access. Evidence from PIONEER 6 demonstrated cardiovascular safety but did not establish cardiovascular benefit, leaving important questions about long-term outcomes unanswered.1

This article presents the SOUL (semaglutide cardiovascular outcomes trial) trial, a double-blind, placebo-controlled, event-driven study assessing the cardiovascular effects of oral semaglutide in T2DM patients with atherosclerotic cardiovascular disease (CVD) and/or chronic kidney disease (CKD). The trial enrolled 9650 high-risk patients aged ≥50 years, across 450 centres in 44 countries. Participants were randomised 1:1 to receive semaglutide or placebo, with a median follow-up of 49.5 months.

The primary outcome was major adverse cardiovascular events, defined as cardiovascular death, nonfatal myocardial infarction or nonfatal stroke. Of the 4825 patients in the semaglutide group, events occurred in 12.0% of patients versus 13.8% of the 4825 patients in the placebo group (hazard ratio [HR] 0.86, 95% CI 0.77–0.96, P = 0.006), with the effect consistent across subgroups. The primary driver of benefit was a 26% reduction in non-fatal myocardial infarction, with additional reductions in nonfatal stroke (12%) and cardiovascular death (7%) in the semaglutide group when compared with placebo.

SOUL confirmed that oral semaglutide reduces cardiovascular events in high-risk T2DM patients, providing an alternative for injection-averse patients. However, the SOUL population had a higher CVD and CKD risk than the global T2DM population, possibly limiting applicability to lower risk groups. The trial tested only the 14 mg dose, which provides lower systemic exposure than injectable semaglutide at higher doses, leaving questions of dose–response unanswered. More trials are needed to determine if one method may be more effective than the other.2

References

  1. Husain M, Birkenfeld AL, Donsmark M, Dungan K, Eliaschewitz FG, Franco DR, et al. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Eng J Med 2019; 381: 841–851.
  2. Therapeutic Goods Administration. Australian public assessment report for rybelsus. Active ingredient: semaglutide. Canberra: Commonwealth of Australia; 2022. Available from https://www.tga.gov.au/sites/default/files/2022-11/auspar-rybelsus-20221027.pdf. Accessed 1 October 2025.  

McGuire DK, Marx N, Mulvagh SL, Deanfield JE, Inzucchi SE, Pop‑Busui R, et al. Oral semaglutide and cardiovascular outcomes in high‑risk type 2 diabetes. N Engl J Med 2025; 392: 2001–2012.

Finerenone: a promising pillar for heart failure with preserved ejection fraction

Special Contributor: Grace Nguyen

Steroidal mineralocorticoid receptor antagonists (MRAs), such as spironolactone and eplerenone are established as one of four pillars of therapies for heart failure (HF) with reduced ejection fraction (rEF), however their efficacy in heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF) remains unclear. The FINEARTS trial, first published online in September 2024, aimed to investigate finerenone, a non-steroidal MRA, in this population.

In this double-blind, international and event-driven trial, patients who had left ventricular ejection fraction of 40% or more were randomised in 1:1 ratio to finerenone (20 mg to 40 mg once daily) versus placebo, in addition to usual therapy. The primary outcome was the composite of worsening HF events and death from cardiovascular causes, whereas the secondary outcomes included total HF events, changes in symptoms, New York Heart Association (NYHA) class and kidney function, and death from any causes. The trial was designed with 90% power to detect a 19% reduction in the primary outcome event rate and was analysed using intention- to- treat and time- to- event approaches.

Over a median follow-up of 32 months, 6001 patients were included for analysis. The finerenone arm showed significant reduction in the composite primary outcome (RR 0.84, 95% CI 0.74–0.95, p = 0.007), with a total number of 842 worsening of HF events compared to 1024 in the placebo arm (RR 0.82, 95% CI 0.71–0.94, p = 0.006). Fewer cardiovascular deaths occurred in patients receiving finerenone (n = 242 [8.1%]) compared to patients receiving placebo (n = 260 [8.7%] HR 0.93, 95% CI 0.78–1.11). In terms of secondary outcomes, the symptom score improved modestly (+1.6 points, p < 0.001), while improvement in NHYA class, kidney outcomes or all-cause mortality showed no significant differences. Hyperkalaemia was more frequent in the finerenone group which is consistent with findings from the FIDELIO-DKD and FIGARO-DKD trials.1,2

In summary, finerenone significantly reduced HF events and cardiovascular death in patients with HFmrEF/HFpEF, with an event rate of 14.9 versus 17.7 per 100 patient-years (RR reduction 16%, RR 0.84, p = 0.007). It is worth mentioning that these primary cardiovascular outcomes outperformed that of the TOPCAT trial where neither total deaths nor hospitalisations for any reason were significantly reduced in the spironolactone group versus placebo in the HFpEF population.3 The Australian Pharmaceutical Benefit Scheme (PBS) currently restricts finerenone use to patients with chronic kidney disease (CKD) and type 2 diabetes  with residual albuminuria, and already taking a renin-angiotensin system (RAS) inhibitor and an SGLT-2 inhibitor (unless medically contraindicated), and as such further studies are warranted to compare finerenone head-to-head with other steroidal MRAs for potential superior efficacy in heart failure subgroup populations, such as HFrEF or heart failure with renal failure and/or diabetes as a comorbidity.4

References

  1. Bakris GL, Agarwal R, Anker SD, Pitt B, Ruilope LM, Rossing P, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med 2020; 383: 2219–2229.
  2. Pitt B, Filippatos G, Agarwal R, Anker SD, Bakris GL, Rossing P, et al. Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N Engl J Med 2021; 385: 2252–2263.
  3. Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med 2014; 370: 1383–1392.
  4. Pharmaceutical Benefits Scheme (PBS). FINERENONE (PBS Item 13316W). Canberra: Commonwealth of Australia; 2025. Available from https://www.pbs.gov.au/medicine/item/13316W. Accessed 13 October 2025.

Solomon SD, McMurray JJV, Vaduganathan M, Claggett B, Jhund PS, Desai AS, et al. Finerenone in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med 2024; 391: 1475–1485.

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CLINICAL TRIALS

MedsScan Editor for Clinical trials SPG: June Challen

Precision gene editing medicine makes history

This news article, published in Nature Biotechnology outlines the use of gene editing technology to rewrite the DNA of a baby born with a rare genetic disease. Gene editing allows for precision targeting and modification of the human genome, making it possible to correct mutations and potentially treat genetic causes of disease. The patient was the first person in the world to successfully receive a personalised gene-editing therapy and the full case, led by researchers at the University of Pennsylvania, was first published in the New England Journal of Medicine.1

Until recently, gene-editing of human cells was through nucleases (enzymes that cut or make breaks in DNA) like CRISPR-Cas9, which disrupts target gene sequences by making double-stranded breaks in DNA.  A new generation of gene editing technologies has emerged which now includes base and prime editors. This new technology allows precise nucleotide changes without the need for generating harmful double-strand breaks. Base editing is a highly efficient method of changing one DNA base into another, and prime editing is a newer but more versatile editing technology that can perform base edits as well as rewrites to parts of a gene. 

This article provides a table detailing at least 20 clinical trials that are currently underway using base or prime editors. A number of these trials have published some initial results and the editors then go on to discuss some of these results in detail.

As to the future for this exciting science, the article suggests that the ideal would be for these therapies to be available on demand as soon as a baby is diagnosed with a genetic disease.

References

  1. Musunuru K, Grandinette SA, Wang X, Hudson TR, Briseno K, Berry AN, et al. Patient-specific in vivo gene editing to treat a rare genetic disease. N Engl J Med 2025; 392: 2235–2243.

DeFrancesco, L.  Precision gene editing medicine makes history, and it’s just getting started. Nat Biotechnol 2025; 43: 1019–1022.

Justice for placebo in clinical trials and everyday practice

As clinical trial pharmacists, we all know the placebo as a pharmaceutically inert substance (a sugar pill) used by clinical researchers as a control to prove a new treatment effective. The placebo-controlled double-blind trial is widely regarded as the gold standard for testing the efficacy of new treatments.

There are however psychological and physiological responses associated with administration of a placebo.  Use of placebo injections and sham procedures have demonstrated therapeutic effects in conditions including pain and other neurological conditions. This review article begins by providing an indication of factors that potentially contribute to the placebo response in both the medical and clinical contexts. Suggestions include patient expectations, the relationship between the patient and the caring physician, and the time spent in the healthcare setting, among others.

The aim of this publication was to investigate the placebo effect by reviewing evidence from published studies using a total of 74 studies.  The authors’ discussion of the history of the placebo follows its use in the early 19th century to placate patients, to its evolution in the 1930s as a control in clinical trials. Following on from this, the authors discuss the published evidence of placebo interventions, noting a relationship between the complexity of the medical intervention and the magnitude of the placebo effect observed.

While indicating that further research is needed into the placebo effect, the authors conclude that there is potential for their use in some symptom- driven conditions, such as pain.

Knezevic NN, Sic A, Worobey S, Knezevic E. Justice for placebo: placebo effect in clinical trials and everyday practice. Medicines 2025; 12: 5.

Two workshops on the application of the teletrial model in early-phase clinical trials 

Special contributor: Anne-Lyn Lee

Teletrials (TT) are a model of clinical trial (CT) that utilise telehealth to increase accessibility and equity, and are increasingly used to improve outcomes in rural and remote areas. They provide a type of ‘decentralised’ CT using a monitoring framework to clarify duties across a broader network. TT were considered more suitable for late-phase trials because of lower risks related to late-phase trials and the reduced capacity that smaller or regional CT units are often operating with and so, early phase TT were generally not recognised as a teletrial. To encourage efforts towards “all trials being considered a teletrial”,1 the authors of this article document their experiences conducting two workshops as part of the Victorian Teletrial Collaborative (VTC).

The potential challenges and drivers to improve early-phase TT required identifying. The VTC group organised two national workshops on early-phase cancer TT to create an operational framework. These were held in 2022-2023. The first workshop focused on gathering an understanding of how useful the TT model could be for early-phase trials, while the second was more specific, examining problems and developing solutions for use in early-phase trials. This article outlines the findings of these workshops.

Challenges identified from the first workshop included insufficient remuneration setting up a CT via telehealth and protocol templates excluding the teletrial model, while drivers included sharing expertise and networks between sites and study documents to have TT context. Recommendations for improvement from the second workshop included having increased funding for TT and using telehealth to improve accessibility for those with limited access to healthcare.

Using the teletrial model for early phase CTs will invite wider participation and allow accelerated recruitment to these trials. This article advocated for a shared role to promote using TT in early-phase trials. Positive stories of later-phase trials using the teletrial model were essential for circulation to provide assurance to main stakeholders, hence leading to this model being used more widely in early-phase trials.

References

  1. Seidler AL, Willson ML, Aberoumand M, Williams JG, Hunter KE, Barba A, et al. The changing landscape of clinical trials in Australia. Med J Aust 2023; 219: 192–196.

Freeman J, Underhill C, Evans W, Long D, Harris S, Burbury K, et al. Teletrial implementation in early phase clinical trials: two national workshops. Trials 2025; 26: 199.

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CRITICAL CARE

MedsScan Editors for Critical Care SPG: Melissa Faehrmann and Grainne Hughes

Tirofiban infusion post-thrombolysis for acute ischaemic stroke

Should we start using tirofiban intravenous glycoprotein IIb/IIIa inhibitor tirofiban as an early intervention for acute ischaemic stroke? How do the outcomes compare with current standard care; where no antiplatelet or anticoagulant therapy is administered for the first 24 hours after thrombolysis, pending repeat imaging to exclude haemorrhagic transformation? This phase 3, multicentre, double-blind randomised controlled trial aimed to answer these questions.

Conducted across 38 facilities in China, adult patients thrombolysed (75% alteplase and 25% tenecteplase) within 4.5 hours of acute ischaemic noncardioembolic stroke and not eligible for thrombectomy, were randomised to receive a 24-hour infusion of tirofiban (n = 414) or placebo (n = 418) within 60 minutes of thrombolysis. Tirofiban was dosed at 0.4 microgram/kg/minute for 30 minutes, followed by 0.1 microgram/kg/minute for 23.5 hours.

The primary efficacy outcome was the proportion of patients with an excellent functional outcome (modified Rankin Scale score 0–1) at 90 days. This occurred more often with tirofiban than placebo (65.9% versus 54.9%; risk ratio [RR] 1.20, 95% confidence interval [CI] 1.07–1.34, p = 0.001). Safety outcomes were symptomatic intracranial haemorrhage within 36 hours and death at 90 days. Symptomatic haemorrhage occurred in 1.7% of tirofiban patients and in none of the placebo group; mortality was similar at 4.1% in the tirofiban group versus 3.8% in the placebo group.

In this study, early tirofiban infusion after thrombolysis improved 90-day outcomes without increasing mortality, though with a small rise in symptomatic haemorrhage. The applicability of these findings, based on 832 Chinese patients, to the Australian population is unknown. Given potential pharmacogenomic differences, the study should be repeated in a wider cohort. Tirofiban use for acute ischaemic stroke in Australia remains off-label and is not currently recommended in any guidelines.

Tao C, Liu T, Cui T, Liu J, Li Z, Zhao RX, et al. Early tirofiban infusion after intravenous thrombolysis for stroke. N Eng J Med 2025; 393: 1191–1201.

Melatonin for the prevention of delirium in patients receiving mechanical ventilation

Special Contributor: Nicole Harris

Delirium is associated with poor outcomes in critically ill patients. Disturbances in sleep and circadian rhythm have been implicated in delirium pathophysiology.  This article aimed to determine if a dose of melatonin with an optimal pharmacokinetic profile can prevent delirium in critically ill, mechanically ventilated patients.

The DEMEL (Prevention of DElirium in intensive care by MELatonin) trial was a multicentre, randomised, double-blind, placebo-controlled adaptive phase 2b/3 trial including patients from 20 centres in France. Three hundred and fifty-five adult patients receiving mechanical ventilation with an expected intensive care unit (ICU) stay of more than 48 hours were randomised to receive placebo, low-dose (0.3 mg) of melatonin or high-dose (3 mg) melatonin for 14 nights, with 334 patients included in the analysis after 13 patients withdrew or were later determined ineligible. An activity stage assessed the pharmacokinetic profile of melatonin, selecting the optimal dose to continue in the efficacy stage. Local protocols for sedation, ventilation and ICU care were followed. Delirium was assessed twice daily using the Confusion Assessment Method for ICU (CAM-ICU).

In the interim primary endpoint (activity stage), 75 patients’ pharmacokinetic profiles were analysed, including 24 patients from the low-dose melatonin group, 25 patients from the high-dose melatonin group and 26 patients in the placebo group; the low-dose melatonin group had the highest rate of optimal pharmacokinetic profiles (n = 12, 50%) compared with the high-dose group (n = 6, 24%) and the placebo group (n = 0). Three hundred and one patients were included in the end of the efficacy stage; of these, there was no difference in the final primary outcome of delirium incidence between the 147 patients in the low-dose group (n = 80, 54.4%) and the 154 patients in the placebo group (n = 85, 55.2%).

The DEMEL trial found that low-dose (0.3 mg) melatonin achieved a better pharmacokinetic profile than the high-dose, demonstrating that higher doses cause prolonged supratherapeutic levels. Despite optimal pharmacodynamic targeting, low-dose melatonin failed to reduce delirium incidence compared to placebo. This trial argues against routine melatonin, for delirium prophylaxis, in ventilated patients.

Dessap AM, Ricard J-D, Contou D, Desnos C, Decavéle M, Sonneville R, et al. Melatonin for prevention of delirium in patients receiving mechanical ventilation in the intensive care unit: a multiarm multistage adaptive randomized controlled clinical trial (DEMEL). Intensive Care Med 2025; 51: 1292–1305.

The PROACTIVE trial: propranolol use for critically ill adults receiving mechanical ventilation

The PROACTIVE study looked at using propranolol to reduce the use of routine intravenous (IV) sedatives in patients requiring more than 48 hours of mechanical ventilation, following significant shortages of sedative medications during the COVID-19 pandemic.

Seventy-two patients were randomised in this open-label study across three ICU sites in Canada, with 71 patients included in the final analysis Patients in the intervention arm (n = 36) received enteral propranolol, starting at 20 mg every 6 hours for two to four doses (reassessed every 24 hours to a maximum of 60 mg every 6 hours) and increased accordingly with down titration of their parenteral sedative doses, guided by the Richmond Agitation-Sedation Scale (RASS) and haemodynamic markers.  Control group patients (n = 35) received parenteral sedative doses, titrated to a RASS target specified by their treating team.

Results showed a significantly larger decrease in the sedative doses required on day 3 in the intervention group (53.9%) compared to control (33.9%, p = 0.048). The propranolol group also had a higher proportion of RASS scores in the target range, compared to control (48% versus 35%, p < 0.0001). Opioid doses on day 3 and adverse events overall were similar in both groups, though more propranolol patients received antipsychotics.

The results look promising and statistically significant, albeit marginally. RASS targets were not explicitly discussed — targets between day 1 versus day 3 could be significantly different — making it hard to determine if propranolol was the confounding factor. Presenting values of sedative doses at baseline and day 3 would have made it more indicative of impact. Large scale studies are required to more conclusively determine if propranolol reduces sedative use in mechanically ventilated adults. The authors suggest propranolol could be used as a sedative-sparing agent if another surge in medication demand occurs, similar to that during the COVID-19 pandemic, as opposed to acting as an alternative to IV sedatives.

Downar J, Lapenskie J, Kanji S, Watpool I, Haines J, Saeed U, et al. Propranolol as an anxiolytic to reduce the use of sedatives for critically ill adults receiving mechanical ventilation (PROACTIVE): an open-label randomized controlled trial. Crit Care Med 2025; 53: e257–e268.

Erratum: Downar J, Lapenskie J, Kanji S, Watpool I, Haines J, Saeed U, et al. Propranolol as an anxiolytic to reduce the use of sedatives for critically ill adults receiving mechanical ventilation (PROACTIVE): an open-label randomized controlled trial: erratum. Crit Care Med 2025; 53: e1869–e1870.

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DISPENSING AND DISTRIBUTION

MedsScan Editors for Dispensing and distribution SPG: Ashley Crawford and Anna Wood

How do medicines shortages impact Australian pharmacists and their patients?

Medicines shortages have become a daily reality for pharmacists, with many Australian pharmacists required to undertake additional logistical tasks to have the medicines the community needs. The Therapeutic Goods Administration (TGA), supports national regulatory activities which have been designed to reduce the impact of medicines shortages in Australia, including publishing the medicines shortage reports database,1 however it is unclear whether these activities also support community pharmacists to be better equipped to manage the large list of medicines in shortage.

This report outlined the results from a national survey of Australian community pharmacists, conducted in 2023, with pharmacists from all states and the ACT responding to the survey. In 2023, the vulnerabilities of the medication supply chain were exacerbated following the COVID-19 pandemic, particularly noting that approximately 90% of the medicines used in Australia are imported. The survey sought to understand the personal impact of managing medicines shortages on community pharmacists, as well quantifying some pharmacist reported impacts of shortages on patients.

Pharmacists across Australia responded to the survey sharing personal insights on the impact of shortages. The study highlighted increased workloads for pharmacists, with most pharmacists reporting medicine shortages were contributing negatively to their stress levels. The survey results indicated that pharmacists were frequently, or were very frequently, needing to substitute medicines for patients and frequently, or very frequently, needing to turn patients away due to insufficient stock. Pharmacists also reported that medicines shortages negatively impacted their motivation and engagement at work. Additionally, survey participants highlighted that patients were experiencing delayed access to treatment and increased levels of stress resulting from medicines shortages.

The negative experiences community pharmacists reported in this survey from managing shortages demonstrates the importance of investing in a connected system for managing medicines shortages: from regulators, suppliers, wholesalers, health professionals, and consumers. One of the recommendations of the report was to improve awareness of medicines in shortage, and further consideration could be given to how to balance the awareness with equitable distribution to prevent stock piling. The report didn’t specifically cover the cost impacts of alternatives, with many substitute medicines during a shortage costing more than the Australian registered product, however this is another area for future assessment to understand the financial implications of shortages on patients and the health system. Australians expect pharmaceuticals to be available for treatment when they are needed and more can, and should be, done to improve supply through to the patient. 

References

  1. Therapeutic Goods Administration. Medicine shortage reports database [ updated 11 November 2025]. Canberra: Commonwealth of Australia; 2023. Available from https://apps.tga.gov.au/prod/MSI/search/.

Janetzki JL, Chai WC, Ngoc Thi Bui T, Fei Sim T, Suppiah V, Impact of medicine shortages on Australian pharmacists’ professional practice and patient care: a nationwide survey. J Pharm Pract Res 2025; 55: 146–153.

The influence of medication dispensing on medication knowledge and adherence

Medication dispensing is a core pharmacy activity, involving not only the supply of prescribed medicines but also patient education. A lack of patients’ understanding about medications contributes to adverse drug events and poorer health outcomes. Interactions with the pharmacy team during the dispensing process provide opportunities to enhance medication knowledge and adherence.

This systematic review and meta-analysis assessed available evidence on how the dispensing process impacts health outcomes, specifically focusing on patient medication knowledge and adherence. A comprehensive literature search was performed across multiple databases, as well as grey literature. Studies were included if the intervention met the following three criteria: it evaluated medication dispensing by pharmacists, was performed in a community pharmacy setting, and assessed patient knowledge and/or adherence. A total of 7590 studies were identified using the agreed search terms, of which 11 met the inclusion criteria for further analysis.

Four studies examined the influence of medication dispensing on patients' medication knowledge, all using structured questionnaires. The medication dispensing process was found to increase patient medication knowledge across these studies. Medication adherence was explored in eight studies using various assessment methods including patient self-reported pill counts, questionnaires, and validated rating scales. Results were mixed, with some studies demonstrating improvements in adherence following pharmacist dispensing interventions, while others found no significant effect.

Medication knowledge and adherence are complex outcomes influenced by multiple factors beyond the dispensing interaction alone. Although medication dispensing by pharmacists has the potential to improve both knowledge and adherence, the findings of this review demonstrate a lack of robust evidence supporting this assumption. Future research incorporating hospital pharmacy environments and using standardised outcome measures may provide a more comprehensive understanding of the impact of dispensing on patient outcomes. Despite limited evidence, these findings reinforce the importance of the dispensing process, as this remains a key touchpoint with patients to support safe and appropriate medicines use.

Santana EPC, Javarini HRV, de Araújo DCSA, Cerqueira-Santos S, Reis TM, Dos Santos-Junior GA, et al. Does drug dispensing influence patients’ medication knowledge and medication adherence? A systematic review and meta‑analysis. BMC Health Serv Res 2025; 25: 172.

Impact of workplace distractions on medication safety: a review of pharmacy practice

Pharmacists, technicians and pharmacy assistants operate in an environment of constant interruptions — phone calls, emails, alerts and notifications all compete for attention during critical dispensing tasks. These distractions and interruptions can contribute to medication errors and preventable patient harm, making them a threat to patient safety. Understanding the types of distractions that commonly occur in pharmacy settings and implementing effective mitigation strategies are essential for supporting safe medication practices.

This systematic review aimed to identify existing knowledge on distractions and interruptions in pharmacy settings. Specifically, it examined the types and frequency of distractions, their impact on patient safety and educational or workflow strategies recommended or implemented to reduce the risk of consequent medication errors. A comprehensive literature search was conducted across multiple databases including Web of Science, Ovid Medicine, CINAHL, Embase and Scopus using search terms related to pharmacy practice, distractions, interruptions and medication safety. Following a robust screening process, 51 articles met the inclusion criteria for analysis. The included studies representing both community and hospital pharmacy settings across multiple countries, providing diverse perspectives.

Analysis of the included articles revealed that phone calls and face-to-face enquiries from consumers were the most commonly reported types of interruptions and distractions. Among studies that reported frequency data, rates varied from fewer than 5 interruptions per hour to more than 20 per hour. This reflects significant variation across different pharmacy settings and contexts. Eight studies explored strategies aimed at reducing the impact of distractions on medication safety. Documented approaches included modifications to the physical working environment, implementation of new systems and protocols and changes to communication strategies between staff and patients.

While it is widely accepted that distractions and interruptions contribute to adverse medication events, this systematic review highlights the need for further research in this area. As technology and healthcare delivery continue to evolve, maintaining a contemporary understanding of potential sources of distraction is essential to develop effective workflow modifications and educational strategies that minimise risks to patient safety.

Ayanaw M, Lim A, Khera H, Vu T, Goordeen D, Malone D. How do interruptions and distractions affect pharmacy practice? A scoping review of their impact and interventions in dispensing. Res Social Adm Pharm 2025; 21: 667–678.

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EDUCATION AND EDUCATIONAL VISITING

MedsScan Editors for Education and Educational Visiting SPG: Michelle Hansen and Diana Bortoletto

Promoting resilience through pedagogical interventions

Healthcare professionals encounter many workplace challenges that can impact their mental health and wellbeing, with building resilience commonly recommended to better equip individuals to manage in these environments. Much of the research in this space centres on medical and nursing fields with limited data relating to allied health professionals (AHPs), specifically pre-registration and student positions. A systematic review was undertaken to identify resilience strategies that could be applied within educational environments for pre-registration and student AHPs.

A literature search was conducted to identify relevant studies published between January 2000–January 2024. The search identified 2067 articles, with 110 identified for full-text screening and 13 articles meeting the inclusion criteria. The majority of included studies were published in the United States (n = 8) with two of the studies based in Australia. Three narrative synthesis groupings were identified, these were: holistic mind-body interventions, inclusion of a resilience course within the pre-existing curriculum and the use of peer mentoring and group support. The review identified a range of approaches to teaching, delivering and measuring resilience, however limitations and variability in the studies made it difficult to identify the most effective methods. The potential need for repeated training to avoid loss of skills was also highlighted.  

The promotion of practices that support mental health and wellbeing for healthcare professionals is of ongoing importance. Whilst an ideal pedagogical approach has not been clearly identified, supporting mental health and wellbeing requires a multimodal approach with the suggested strategies for building resilience aligning with broader literature.

Wells LK, Bullock AF, Killingback C. Educational interventions to promote resilience in pre-registration allied health professions curricula: a systematic review. J Furth High Educ 2025; 49: 799–817.

The role of pharmacy preceptors in supporting professional identity formation

Professional identity formation (PIF) is a key step when transitioning from a student role to that of a qualified practitioner. Pharmacy preceptors are well placed to support PIF during workplace learning however they may require further professional development to take on this role.

This North American study aimed to identify priorities in developing preceptors to support PIF and to create a framework to support preceptor training. A multicomponent approach was used including focus groups and a modified nominal group technique to identify the needs and priorities for preceptor development. The findings from these activities, in combination with relevant literature, were then used to create a framework to guide preceptor development in supporting PIF.

Focus groups were completed with twenty participants who had experience with preceptor training and/or experiential education programs, with five insights identified from analysis of the focus group data. A preceptor development framework was created including recommendations for content, program design and learning outcomes. Key areas included exploring PIF and the preceptor’s own journey, applying a PIF lens to precepting practices and creating a learning environment that supports PIF.

Whilst this was a small, overseas study, the increased demand for experiential placements and need for preceptor support is a common challenge encountered in Australia. Given the importance of PIF it is worth considering whether benefit could be achieved by implementing strategies to further develop preceptors in this area.

Kennie-Kaulbach N, Cooley J, Anksorus H, Janke KK, Riley B, O'Sullivan TA. Building a pharmacy preceptor development framework for nurturing learner professional identity formation. Am J Pharm Educ 2025; 89: 101862.

Teaching compassion and self-compassion

Compassion and self-compassion are linked to the development of ethical character and have been shown to benefit one’s mental health and wellbeing. For healthcare professionals, who are exposed to high pressure environments and are focused on delivering person centred care, these traits are highly relevant.

This article is a conceptual paper written by two Australian authors with experience as allied health educators and professional backgrounds in social work and occupational therapy. Drawing on existing literature, the authors explore the proposed impact a pedagogy of compassion and self-compassion could have on learning for allied health university students. 

The authors present three key claims to support the inclusion of a compassionate pedagogy in higher education, arguing it would improve student and staff personal wellbeing, support motivation and self-improvement and develop the knowledge and skills that align with professional allied health roles. It is proposed that a compassionate pedagogical approach could enhance learning in areas of critical thinking, reflection, emotional awareness and compassionate listening; critically important skills for allied health professionals, as well as a range of other professions. Whilst some examples are provided, further guidance on how to teach these traits and embed them within higher education is required. 

The needs and benefits of compassion and self-compassion are represented across the pharmacy profession within educational and workplace environments. As changes occur in higher education pathways for pharmacy, it is timely to consider whether there is a need and opportunity to introduce a compassionate pedagogy for future students.

Hatfield M, Hodgson D. Compassionate pedagogy: principles and methods for allied health education. J Uni Teach Learn Pract 2025; 22(1): 1–20.

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GENERAL MEDICINE

MedsScan Editor for General Medicine SPG: Christina Hanciu

Update on the American Standards of care in diabetes

Special Contributor: Chun Hong Chan, Tom

The American Diabetes Association updated the existing Standards of care in diabetes in January 2025. This summary discussed a few main areas that are relevant to Australian day-to-day practice for people with diabetes in hospital settings.

Standard 5.26 discusses the need to avoid ketogenic eating patterns, and to educate on ketoacidosis risk and how to avoid it. Ketogenic diets haves been found not to improve glycated haemoglobin (HbA1c) but increase low-density lipoprotein (LDL) cholesterol, in a 12-week study in 2022. When people adopting ketogenic diets use sodium-glucose cotransporter 2 (SGLT2) inhibitors at the same time, the risk of diabetic ketoacidosis (DKA) increases further.1

The treatment algorithm for intravenous (IV) fluids, insulin and potassium in DKA and the hyperosmolar hyperglycaemic state (HHS) is new to this version of the American standards of care. There are great similarities with existing Australian standards, such as those of the NSW Agency for Clinical Innovation,2  with the focus on correcting potassium for both DKA and HHS. Additionally, the revised standards also focus on reducing ketoacidosis with supportive fluid management in DKA, while fluid replacement is achieved through controlling blood glucose level (BGL) in HHS.

The revised standards advise that collaboration between pharmacists and dietitians is particularly helpful for surgical patients that are experiencing acute illness or are not eating well. Dietitians can provide advice on meal planning that is not ketogenic, while pharmacists can discuss the signs and symptoms of DKA, providing patients with a sick day management plan and, working with treating doctors, can advise when to withhold medications. The NSW Therapeutic Advisory Group (NSWTAG) has a useful Consumer Medicine Information (CMI) on SGLT2 inhibitors that pharmacists can utilise.3

References

  1. Gardner CD, Landry MJ, Perelman D, Petlura C, Durand LR, Aronica L, et al. Effect of a ketogenic diet versus mediterranean diet on HbA1c in individuals with prediabetes and type 2 diabetes mellitus: the interventional keto-med randomized crossover trial. Am J Clin Nutr 2022; 116: 640–652.
  2. Agency for Clinical Innovation, NSW Government. Management of diabetic ketoacidosis and hyperosmolar hyperglycaemic state in adults in the emergency department. Sydney: State of New South Wales; 2021. Available from https://aci.health.nsw.gov.au/__data/assets
    /pdf_file/0004/699097/ACI-Management-diabetic-ketoacidosis-hyperosmolar-hyperglycaemic-state-adults-ED-flow-chart.pdf    . Accessed 23 October 2025. 

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GERIATRIC MEDICINE

MedsScan Editors for Geriatric medicine SPG: Gauri Godbole and David Nguyen

Impact of central nervous system-active medicines at discharge and risk of readmission

Central nervous system (CNS)-active medicines are commonly prescribed in older adults and are linked to an increased risk of adverse events such as falls, cognitive impairment and hospital readmission. A prospective cohort study examined the association between CNS-active medicines prescribed at hospital discharge and the risk of readmission and mortality in older adults with multiple chronic conditions.

The European study included 2008 hospitalised patients, aged 65 years and older, who were discharged with five or more medicines and at least three chronic conditions. Outcomes were tracked over one year, including all-cause and drug-related readmission, mortality, quality of life and functional status. CNS-active medicines comprised antidepressants, antipsychotics, benzodiazepines, opioids and antiepileptics.

Each additional CNS-active medicine at discharge was associated with a 7% higher risk of all-cause readmission, a 7% higher risk of drug-related readmission and a 14% higher risk of mortality after adjusting for demographic, clinical and psychosocial factors. No significant relationship was found between CNS-active medicine count and changes in quality of life or functional status. Common causes of drug-related admissions included falls, fractures, bleeding and heart failure, with CNS drugs frequently implicated in falls and confusion.

The findings suggest CNS-active medicines may contribute to adverse outcomes in multimorbid older adults, likely through sedation, cognitive decline or increased fall risk. Limitations included assessing medicines only at discharge without accounting for post-discharge changes, dosage or treatment duration. The association with higher one-year risk reiterates the need for polypharmacy and high-risk medicines prescribed for older adults to be carefully assessed.

Stuber MJ, Brockhus LA, Spinewine A, O'Mahony D, Jennings E, Dalleur O, et al. Central nervous system-active medications and risk of hospital readmission in older multimorbid adults. J Am Geriatr Soc 2025; 73: 3113–3122.

No mortality benefits of deprescribing antihypertensives in nursing home residents with frailty

Special contributor: Ashley Webb

Treating hypertension in older adults with frailty is complex, as excessive intervention can raise the risk of adverse events. Evidence for deprescribing in nursing home residents remains limited, despite concerns about polypharmacy.

The RETREAT-FRAIL randomised controlled trial recruited 1048 French nursing home residents, aged 80 years and older, treated with multiple antihypertensives and with systolic blood pressure below 130 mmHg. Participants were randomised to a protocol-driven ‘step-down’ deprescribing strategy or usual care, with median follow-up of 38.4 months, assessing mortality, cardiovascular events, and changes in blood pressure, function and medication use.

Antihypertensive therapy declined from 2.6 to 1.5 agents in the step-down group compared with 2.5 to 2.0 in the usual care group, whilst systolic blood pressure rose modestly (adjusted mean difference 4.1 mmHg). Mortality was similar (61.7% vs 60.2%, hazard ratio 1.02, 95% confidence interval [CI] 0.86–1.21), with no significant differences in cardiovascular events or falls.

The study suggests structured deprescribing of antihypertensives in older adults with frailty is safe but does not lower all-cause mortality. Strengths included a large cohort and objective primary endpoint however it was limited given its single-country setting, low proportion of male participants, open-label design and possible crossover in the control arm, which may have diluted differences.

The results contrast with previous observational studies that have linked higher mortality in frail patients with low blood pressure and high antihypertensive burden, reiterating the importance of personalising medicines recommendations for older adults with frailty. Whilst the deprescribing interventions did not demonstrate improvements on outcomes, they also demonstrated no additional harm to patients.

Benetos A, Gautier S, Freminet A, Metz A, Labat C, Georgiopoulos I, et al. Reduction of antihypertensive treatment in nursing home residents. N Engl J Med 2025; [online ahead of print]. https://www.nejm.org/doi/10.1056/NEJMoa2508157.

Enhancing patient experiences at transitions of care

Special contributor: Jessica Domzalski

There is currently limited evidence on interventions that actively engage older patients in their own care during a hospital stay to enhance safety and improve their experience during the transition back home. The Your Care Needs You (YCNY) cluster randomised controlled trial aimed to assess an intervention designed to educate and encourage older patients to be involved in their care plans to improve outcomes during transition from hospital across 42 wards (clusters) in 11 organisational units (known as trusts) in the National Health Service.

Of the 42 wards included, 21 were randomised to the YCNY group and 21 to the care as usual group, with three wards withdrawing during the trial. Additionally, four wards withdrew from the nested cohort, but did provide data. The inclusion criteria were as follows: aged 75 years and above, were anticipated to be discharged home from hospital, were staying overnight in hospital and were able to read and understand English and 4947 patients were included in the primary analysis, with 2525 patients in the YCNY group and 2444 patients in the care as usual group. The intervention included a booklet, film and discharge care summary to encourage patient involvement in their care through four domains: health and wellbeing, medicines, daily activities and escalating care needs.

At 30 days post-discharge, unplanned readmission rates were slightly lower in the intervention group (17%) than the control group (19%), but it was not statistically significant (odds ratio 0.93, 95% CI 0.78–1.10, p = 0.37). At 90 days, a 13% reduction in total readmissions emerged (incidence rate ratio 0.87, 95% CI 0.76–0.99, p = 0.039), alongside fewer reported safety events and improved transition experiences at 30 days. Serious adverse events were similar between the groups.

The trial was strengthened by its large sample size and patient co-designed interventions. The use of routinely collected data enhanced generalisability and reduced selection bias. It was however limited by potential contamination between wards, pandemic-related recruitment barriers and limited participant diversity, particularly in the 90-day follow-up group where most of the benefits were recorded.

Although primary endpoints were not met, delayed reduction in readmissions suggests an ‘investment effect’, where enhanced patient engagement yields longer-term benefits. YCNY highlights the importance of patient-centred involvement in discharge readiness.

Murray J, Baird K, Brealey S, Mandefield L, Richardson G, O’Hara J, et al. Improving the safety and experience of transitions from hospital to home: a cluster randomised controlled trial of an intervention to involve older people in their care (Your Care Needs You). Age Ageing 2025; 54: afaf142.

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RESEARCH

MedsScan Editor for Research SPG: Jacinta Johnson

A capability framework for allied health research in health services

Equipping health service staff with research capabilities is essential for building a strong, practice-relevant evidence base, yet existing research frameworks are largely academic-focused and do not reflect the needs of Allied Health (AH) professionals — including pharmacists — who conduct research while embedded in health services. A shared understanding of the capabilities required for research careers in health settings is important for growing and supporting the AH workforce.

This Queensland study developed a research career capability framework tailored to AH research careers within health services, using four sequential research phases: a rapid review to identify potential capabilities; refinement of these findings into an initial set of capabilities and domains by a Project Reference Group; an e-Delphi survey with a broad range of stakeholders to build consensus; and finally, a survey of, and consultation with, the Project Reference Group to refine and confirm the framework elements.

The review phase of the study examined 12 articles and included 2125 capabilities. These were refined to 73 capabilities that were used during the 2-round e-Delphi with 48 participants. Ultimately, a research framework of 61 capabilities under five domains was developed. The five domains included: research knowledge and skills; research impact and translation; clinical and healthcare research context; research leadership and strategy; and research capacity building and mentorship.

The complete framework is presented within this paper and may be useful to guide pharmacy departments in developing and nurturing a workforce of practice-based pharmacist, pharmacy technician and assistant researchers.

Bandenburg C, Ward EC, Stoikov S, Pitt R, McBride L-J. 2025 Development of capability framework for allied health research careers in health services. BMC Health Serv Res 2025; 25: 231.

Updated guidelines for reporting randomised trials: CONSORT 2025

High-quality reporting of randomised controlled trials (RCTs) is essential for clinicians to critically appraise evidence and apply it safely in patient care. Incomplete or unclear reporting can undermine the reliability of trial findings and limit their translation into practice, particularly in hospital settings where pharmacists rely on evidence to guide medication therapy and service delivery. The Consolidated Standards of Reporting Trials (CONSORT) 2025 statement updates previous CONSORT guidelines to enhance the transparency, completeness and usability of RCT reports.

Developed through a rigorous consensus process involving trialists, methodologists, journal editors and other stakeholders, the CONSORT 2025 statement introduces several key updates. It adds seven new checklist items, revises three existing ones, and deletes one: resulting in a streamlined 30-item checklist covering trial design, conduct, analysis and reporting. A notable addition is the new section on ‘open science’, emphasising the importance of sharing research artefacts, such as data and code. The checklist also incorporates items from key CONSORT extensions, providing a more comprehensive framework for reporting RCTs. An accompanying explanation and elaboration document offers rationale, examples of good reporting and guidance for authors and reviewers.

For hospital pharmacy departments, CONSORT 2025 helps pharmacists, pharmacy technicians and assistants critically appraise and evaluate published trial evidence to inform routine practice. It also provides guidance for those involved in designing, conducting or supporting RCTs. By promoting consistent and transparent reporting, the guidelines support evidence-based decision-making, service optimisation and improved patient care in hospital settings.

Hopewell S, Chan A-W, Collins GS, Hróbjartsson  A, Moher D, Schulz KF, et al. CONSORT 2025 statement: updated guideline for reporting randomised trials. BMJ 2025; 389: e081123. 

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TECHNICIANS AND ASSISTANTS

MedsScan Editor for Technicians and assistants SPG: Bryan Walker

The technological future of pharmacy: navigating to 2050

The pharmacy profession, and healthcare more broadly, face significant pressures to adapt to increasing and changing public health needs. These pressures have only been exacerbated by the recent challenges of COVID-19. In this commentary article, August explores each decade until 2025 and argues technological advancements are critical in meeting these challenges with the introduction of digital health technologies (DHT), artificial intelligence (AI) and automation able to transform patient-pharmacist interactions and the dispensing of medicines. The key now is how the profession can proactively adapt and make changes to meet the rapidly changing landscape due to the introduction of these technologies. This is not just a challenge, but an opportunity for professional growth and development.

The first challenges will emerge during the 2030s, as more remote pharmacists will be needed to provide services with increased automation and increased consumer demand for prescription medicines The author theorises technology, such as drones, will be increasingly deployed to help patients access their medicines, while the focus of the community pharmacy will turn to providing clinical services and meeting on-demand needs, while hospital pharmacy will experience further integration of alternative care models, such as Hospital in the Home, and development of transitions of care.

In the 2040s, DHTs and AI may be sophisticated enough to be able to handle direct, patient-facing interactions, such as having AI acting to triage certain healthcare contexts or even making an initial clinical decision. However, these actions will still need to be reviewed by a healthcare professional for accuracy and execution of the treatment plan. Drone use will increase on-demand prescription delivery, and AI will be used for drug discovery and automation of medication therapy management.

By 2050, the pharmacy profession will have undergone massive change, with most things we do with labour now being automated. Despite the trepidation around AI and other technologies, the author remains hopeful that these changes will provide space for new avenues for pharmacists, technicians and assistants to grow.  For example, one possible new role could be a digital health technologies consultant. This person would advise on selecting, implementing and optimising digital tools to enhance patient care and pharmacy operations. The education and training needed for this role would be courses in digital health, health informatics and cybersecurity basics. This person would have to be technologically aware, able to adapt to new situations, have strategic planning abilities and be an effective communicator.

As a profession, we must be versatile and proactive in learning, advocating for policy changes and establishing more sustainable financial models to help pharmacy flourish and not atrophy.

Aungst TD Beyond the fill: navigating pharmacy's technological future in 2050. J Am Pharm Assoc 2025; 65: 102285.

Safe staffing standards for hospital pharmacy technicians

Pharmacy technicians and assistants provide essential services to hospital pharmacies, performing various clinical and technical duties. With increasing healthcare demands, adequate staffing levels of pharmacy technicians and assistants must be provided to help support the safe and efficient care of patients. Drawing on literature, guidelines and recommendations from North America, the United Kingdom (UK) and the World Health Organization, the authors demonstrate that inadequate staffing levels lead to excessive workloads, poor staff outcomes and higher risk of medication errors, arguing appropriate guidelines must define appropriate staffing levels for technicians and assistants for hospital and community settings.

Pharmacy technicians and assistants have increasingly adopted expanded roles and responsibilities as healthcare systems face increasing demands due to an aging population, chronic diseases and complex treatments. According to a survey undertaken by the Pharmacy Technician Certification Board (PTCB) in the United States in 2022, despite adequate staffing levels, staffing shortages continue, with more than 60% of survey respondents indicating a significant increase in their workload and stress. Insufficient staff levels can also delay patient care and impede operational delivery.

The authors argue healthcare managers must implement internal audit systems to monitor work efficiency and ensure essential hospital tasks can be completed safely. Drawing on the UK Hepatology pharmacy staffing standards, maintaining 20% additional staffing resources to cover leave and ensure service delivery is recommended, as well as adopting training and professional development programs for pharmacy technicians and assistants. Activities such as mentoring programs and providing leadership opportunities for technicians and assistants can help support the workforce and growth and retention goals. Pharmacies also need to emphasise work-life balance and adequate compensation for pharmacy technicians' duties.

Silva V, Joaquim JJ, Desselle S, Quaye S, Matos C. Safe staffing standards for pharmacy technicians in hospital settings. J Mark Access Health Policy 2025; 13: 45.

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WOMEN’S AND NEWBORN HEALTH

MedsScan Editor for Women’s and Newborn Health SPG: Kate Luttrell

Extended summary: A close examination of optimised intermittent vancomycin dosing in infants

Special Contributor: Josephine Wen

Background: Vancomycin is frequently used within the neonatal intensive care unit and special care nursery for empiric and directed treatment of systemic gram-positive infections.1,2 During infancy, rapid developmental changes in renal function, weight and body composition create highly variable pharmacokinetics, making standard vancomycin dosing regimens challenging.1 Currently, intermittent dosing regimens for vancomycin vary significantly worldwide and fail to achieve trough concentrations of 10–20 mg/L in the majority of young infants. This is possibly due to these dosing regimens not routinely accounting for post-menstrual age and serum creatinine. To our knowledge, there is currently no consensus guidelines for empiric intermittent vancomycin dosing in Australia, where dosing practices vary between institutions.

Historically, vancomycin has been monitored using trough concentrations, aiming for a target between 10–20 mg/L. More recent evidence demonstrates that efficacy is better predicted by total exposure over 24 hours in relation to the pathogen’s minimum inhibitory concentration (MIC), expressed as the AUC24/MIC ratio. Adopting a 24-hour area under the curve (AUC24) target is associated with lower rates of nephrotoxicity. For Staphylococcus aureus, guidelines recommend targeting AUC24 400 to 600 mg.hr/L, though the target value for coagulase-negative staphylococci is less well defined.  

Aim: This study aimed to create and evaluate an optimised vancomycin dosing strategy for infants between 0 and 90 days of age. The objectives were to determine whether the new regimen achieved the recommended AUC24 target range, to compare this with trough attainment and to assess its safety when implemented in routine clinical practice.

Method: A validated pharmacokinetic model for infants was used to simulate various regimens, with the goal of identifying one most likely to achieve an AUC24 of 400–650 mg.hr/L. The probability of attaining the conventional trough range of 10–20 mg/L was also estimated. The optimised regimen was then introduced at the study centre, The Royal Children’s Hospital, located in Melbourne. Over twelve months, infants under 90 days of age who required vancomycin received this protocol. Clinical data included patient demographics, dosing and serum concentrations at steady state; AUC24 values were then derived. Outcomes included the proportion of courses achieving therapeutic AUC24 and trough concentrations, the frequency of subtherapeutic or supratherapeutic exposure and any evidence of toxicity.


Results: The simulated model suggested that the new regimen would achieve the AUC24 target in about two-thirds of infants but with lower trough level attainment, with only a little over half of the cohort reaching the desired range.

In clinical practice, 24 infant patients received 26 treatment courses under the protocol. Their median post-menstrual age was forty weeks, with a wide range reflecting both premature and term infants, and weights ranged from 650 g to nearly 6 kg. Of the 26 treatment courses, the regimen successfully achieved the target AUC24 in 23 (88%) of the courses. Two courses were subtherapeutic and one course was supratherapeutic. Trough concentrations fell between 10–20 mg/L in 21 (81%) courses. Notably, there were no observed cases of nephrotoxicity or ototoxicity.

Key Limitations: This study was a single-centre clinical validation, retrospective study design with a small sample size, including few with positive blood cultures and only four infants with a post-menstrual age of less than 29 weeks. Another limitation is that the study excluded infants: with a post-menstrual age of less than 25 weeks, weighing less than 500 g, with renal impairment, and receiving renal replacement therapy or extra-corporeal membrane support. Therefore, these results cannot be directly generalised and applied to these populations.

Commentary and Implications for Practice: This study demonstrates the value of model-informed dosing in a population where conventional approaches often fail. By designing a regimen specific to infants’ physiology and validating its implementation in practice, the authors show how pharmacokinetic modelling can improve both efficacy and safety. The contrast between AUC24 and trough target attainment highlights the limitations of trough monitoring and supports the growing move toward AUC-based approaches for vancomycin dosing, where resourcing and support allows.

Although the numbers are small, the results suggest that better target attainment can be achieved without observed toxicity. The evidence presented makes a strong case for precision dosing tools as part of antimicrobial stewardship strategies in the neonatal setting.

For clinicians, the main challenge will be implementation. AUC-based monitoring requires therapeutic drug monitoring expertise, resources, training and end-user support, while trough monitoring remains simpler and more accessible. Further research should assess whether optimised dosing leads to measurable improvements in clinical outcomes, such as time to infection resolution, and to evaluate vancomycin dosing in premature infants.

Conclusion: The optimised dosing regimen, developed through pharmacokinetic modelling and validated prospectively, proved effective and safe in most infants up to 90 days of age. Almost 90% of treatment courses achieved therapeutic AUC24 and the absence of renal or ototoxic adverse effects supports its clinical use. The authors conclude that this regimen should be considered for routine practice and that AUC-based monitoring provides a more reliable framework than trough monitoring.

References

  1. Sosnin N, Curtis N, Cranswick N, Chiletti R, Gwee A. Vancomycin is commonly under-dosed in critically ill children and neonates. Br J Clin Pharmacol 2019; 85: 2591–2598.
  2. Harvey EJ, Ashiru-Oredope D, Hill LF, Demirjian A, United Kingdom Health Security Agency Staphylococcus capitis Incident Management Team. Need for standardized vancomycin dosing for coagulase-negative staphylococci in hospitalized infants. Clin Microbiol Infecti 2023; 29: 10–12.

Wilkins AL, Yang W, Duffull SB, Cranswick N, Curtis N, Zhu X, et al. Evaluation of an optimized intermittent vancomycin dosing regimen in infants. J Antimicrob Chemother 2025; 80: 1635–1639.

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