MedsScan, Issue 1, 2026

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.

COMPOUNDING SERVICES

MedsScan Editor for Compounding services SPG: Rachel Berry

Considering molecule size in the risk assessment of biologics

The use of biologics in healthcare continues to expand. Newer biologics are often not included in published lists of hazardous drugs such as the National Institute for Occupational Safety and Health (NIOSH) list and so local hazardous risk assessments are required to determine occupational exposure risk.1 This can affect where and how these products are prepared in a healthcare facility. Risk assessments have focused on factors such as monoclonal antibody origin, immunogenic toxicity and hazardous classification. Where data is lacking, biologics have been classified as hazardous.

Data published on adverse effects from clinical exposure in clinical trials cannot be directly extrapolated to healthcare worker exposure, making risk assessment challenging. The aim of this article was to create a novel risk assessment tree for biologics. The proposed risk assessment considered molecule size in the likelihood of dermal, mucosal and inhalation absorption to healthcare workers.

A literature search was performed, focusing on occupational risk assessments and dermal, mucosal and inhalation bioavailability. Fifteen published studies were identified for review. Mechanisms were given for difficulty of absorption via the dermal, mucosal or inhalation route.

A risk assessment decision tree classifying protein-based biologics as either hazardous or non-hazardous was devised based on a molecular weight >1000 Daltons and factors such as carcinogenicity, genotoxicity, reproductive toxicity and organ toxicity at low doses. The decision tree allowed the authors to reclassify 55 biologics (89%) used in their institution as non-hazardous based on molecular weight. This has a significant impact on the facilities and staff training required to handle these drugs.

In addition to the findings that molecules >1000 Daltons showed minimal to no absorption via dermal, mucosal or inhalation, it should be noted that staff members preparing biologics would ordinarily be wearing personal protective equipment consistent with the preparation of medications, thereby further reducing the likelihood of dermal mucosal or inhalation exposure.

This novel risk assessment decision tree provides a potential tool in the local risk assessment of novel biologic agents.

References

  1. Ovesen JL, Sammons D, Connor TH, MacKenzie BA, DeBord DG, Trout DB, et al. NIOSH list of hazardous drugs in healthcare settings. Publication No. 2025-103. Cincinnati: U.S Centres for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH); 2024.  

Ngo Z, Mayeda S, Yu S, Danek M, Wang A, MacDonald EA, et al. A novel decision tree for performing risk assessments of biologics in a health-system setting. J Oncol Pharm Pract 2025; 31: 827–834.

Stability of mitomycin C 0.04% eye drops in sodium chloride 0.9%

Mitomycin C (MMC) eye drops are used in the treatment of ocular surface squamous neoplasia (OSSN). Interferon alfa-2b eye drops are usually the preferred treatment for OSSN in Australia, which remains available via the Special Access Scheme. In the absence of interferon, MMC is the second line treatment, which requires a compounded formulation. There is limited stability data to support MMC formulations and often poor tolerance. This article proposed a formulation in sodium chloride 0.9% potentially leading to less irritation than formulations in other bases.

MMC 0.04% in sodium chloride 0.9% solution was prepared and filtered into sterile plastic eye dropper bottles. Stability was studied over 21 days in three different storage conditions to simulate anticipated storage conditions: refrigerated at 4oC, room temperature under scattered light and room temperature in a dark room. MMC concentration, pH, sterility and appearance were analysed at intervals during the study period.

MMC concentration was found to be affected by storage conditions, with degradation slowest with refrigerated storage and minimised light exposure. Under refrigerated storage with shaded light, an expiry of 10.8 days was given with a residual MMC concentration of 90%. Importantly, when assigning an expiry to a locally made formulation, consideration must be given to local facilities and procedures. Guidance on assigning an in-use expiry of a sterile preservative free eye drop formulation can be found in reference sources such as the Australian pharmaceutical formulary and handbook (APF).1

A limitation of this study is that the stability of unopened product was tested, which may not be reflective of patient use conditions. Given the relatively unstable nature of MMC, further study of solutions simulating in-use conditions and the effect of temperature fluctuations would be advantageous.

References

  1. Pharmaceutical Society of Australia (PSA). Australian pharmaceutical formulary and handbook: a guide to best practice. 26th edition. Deakin: PSA; 2024.

Nonomiya Y, Yamaguchi K, Yokoyama Y, Nakajima I, Hara R, Shoji D, et al. Analysis of the stability of 0.04% mitomycin C ophthalmic solution under various storage conditions. Keio J Med 2025; 74: 214–220.

Implementing standard operating procedures for the handling of advanced therapeutic products

As gene therapy and biohazardous drugs are introduced into healthcare facilities, robust procedures are needed to permit safe handling and ensure staff and patient safety. It is important to understand the differences between handling traditional hazardous compounds such as cytotoxic drugs and these newer compounds.

This case study describes the implementation of standard operating procedures (SOPs) to handle viral vector gene therapy products in an American tertiary academic medical centre. This article describes key areas and stakeholders considered as local procedures were developed and implemented.

Areas for implementation included a change to pharmacy labelling to distinguish between biohazard medicines and other hazardous medicines Available cleaning agents were evaluated against common viral vectors for effectiveness with optimal available cleaning agents determined to be strong oxidising agents, including CONTEC PeridoxRTU (4.4% hydrogen peroxide + 0.23% peracetic acid) or 0.55% sodium hypochlorite. Quaternary ammonium compounds are commonly used in pharmacy clean rooms but were noted to have low efficacy against non-enveloped viruses, so these were not included in their cleaning regimes.

The compounding procedure was comparable to other hazardous compounding, with the addition of an additional decontamination of the cabinet with peroxide followed by isopropyl alcohol. When considering implementation of a local procedure, the required contact times of cleaning agents should be obtained from manufacturers, as these can vary between products. In addition, a spill procedure was developed using guidelines such as USP <800>1 with local consultation.

This case study provides a useful account of how to implement procedures to handle biohazardous or gene therapy agents. Consideration must also be given to staff training and whether the required infrastructure exists locally to handle these agents or whether collaboration is required with a more specialised facility to provide safe and effective treatment for patients.

References

  1. United States Pharmacopeial (USP) Convention. General chapter <800>: Hazardous drugs — handling in healthcare settings. Rockville: USP; 2023.

‌Wang A, Ngo Z, Yu SJ, MacDonald EA. Implementing standard practices in the safe handling of gene therapy and biohazardous drugs in a health-system setting. Am J Health Syst Pharm 2025; 82: e716–e722‌.

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EMERGENCY MEDICINE

MedsScan Editors for Emergency medicine SPG: Jill Upton and Alicia Thomas

Pyelonephritis in the emergency department

Acute pyelonephritis (APN) is a common presentation in the emergency department (ED). With a global rise in antimicrobial resistance, it is important to assess whether the antibiotics prescribed are appropriate for current causative pathogens. This single-centre retrospective cohort study was conducted at a major metropolitan adult tertiary public hospital in Melbourne.  A retrospective review of patients with an ICD-10 [International statistical classification of diseases and related health problems, tenth revision]1 discharge diagnosis of APN was conducted over a 5-year period from 2018–2022, to determine the appropriateness of antibiotic choice.

Five hundred and fifty-seven patients with APN were included and 569 urine samples were cultured. Escherichia coli (E. Coli) was the most frequently cultured organism and was identified in 40.8% (n = 232) of culture results. Most patients were treated with appropriate antibiotics. However, initial antibiotic therapy was inappropriate in 26patients (4.7%, 95% confidence interval [CI] 3.1–6.6). The most common reason for this was monotherapy with amoxicillin or ampicillin. Seventy-six (13.6%) patients were discharged with inappropriate antibiotic therapy. The most common reason for this was that no antibiotic was prescribed on discharge. Of note, among the 232 specimens where E. coli was cultured, a high proportion (53%) of specimens were resistant to ampicillin or amoxicillin.

The study did not evaluate diagnostic accuracy or appropriateness of management or follow patient outcomes after discharge. Generalisability of the results is limited as the study was conducted at a single site. Further, because this study was retrospective the authors were unable to determine why certain antibiotic regimens were selected or why selection deviated from clinical guidelines. Further research here would be useful to improve prescribing appropriateness.

References

  1. World Health Organization (WHO). International statistical classification of diseases and related health problems, tenth revision. Geneva: WHO; 2019.

Yu J, Koolstra C, De Villiers S, Mitra B. Antibiotic therapy for pyelonephritis in the emergency department. Emerg Med Australas 2025; 37: e70130.

Faster administration of fibrinolytic therapy with pharmacist involvement

Special contributor: Aleksandra Trakilovic

Administration of fibrinolytic therapy in acute ischemic stroke (AIS) is a time-sensitive standard of care. Measured by the metric door-to-needle (DTN) time, earlier administration improves functional outcomes. Pharmacist-assisted Stroke Treatments I (PhAST-1) was a systematic review and meta-analysis that assessed the impact of emergency medicine pharmacist (EMP) involvement and impact on DTN time in adult patients in the emergency department.

Nine studies met the inclusion criteria, all of which were single centre, retrospective, observational cohort studies and examined patients receiving alteplase. Studies with patients experiencing an AIS without defined pharmacist involvement and patients who received fibrinolytic therapy outside the study facility were excluded. 

A total of 1064 patients were included for meta-analysis: 441 in the EMP present group and 623 in the EMP absent group.  A mean reduction in DTN time of 14.6 min (95% CI -18.1 to -11.1 min) was found in the EMP present group. EMP presence increased the odds of achieving a DTN time within 60 min (odds ratio [OR] 2.75, 95% CI 1.99–3.79) and within 45 min (OR 2.85, 95% CI 1.4–5.79). There was no difference between the EMPs present and absent groups in hospital length of stay (LOS).

The findings of this meta-analysis should be interpreted with caution due to the low number of studies included, with the majority deemed to be of poor quality with respect to risk of bias. Confounding of daytime presence of EMPs and staff availability, as well as shift-timing (weekday versus weekend), was not explored. While higher-quality studies are required to establish causality, this meta-analysis supports the integration of EMPs in stroke response teams to expedite the administration of fibrinolytics.

Mercer KJ, Howington GT, Brown CS, Gilbert BW, Cole K, Acquisto NM, et al. Assessing the impact of emergency medicine pharmacists on fibrinolytic door-to-needle times in acute ischemic stroke: a systematic review and meta-analysis (Pharmacist-assisted Stroke Treatments I (PhAST-1)). Am J Emerg Med 2025; 98: 57–64.

Rapid administration of antiseizure medicines is safe and efficient

Special contributor: Gary Ward

Rapid control of seizures in important to prevent severe neurological damage. Administration of antiseizure medications by intravenous push (IVP) and intravenous piggyback (IVPB) has been proposed to improve time to administration compared to the licensed administration rate.

This narrative review summarised articles reporting on rapid administration of lacosamide, levetiracetam and valproate. Fourteen articles investigated rapid administration of lacosamide (5–30 min). Administration of undiluted lacosamide was not associated with an increase in adverse effects, although studies were inconsistent in reporting dilution status. Increased efficiency was reported with IVP lacosamide, with similar safety concerns noted between IVP and IVPB administration. There may be an increased risk of cardiac arrhythmias, with a small, dose-dependent increase in the PR interval, although clinical significance is unclear.

Eighteen papers examined rapid administration of levetiracetam (2–10 min), with doses ranging from 1000 mg to 4500 mg. Undiluted levetiracetam appeared to be safe, with no increased incidence of adverse effects compared with diluted drug. Use of IVP was associated with a decreased time to administration compared to IVPB in some reports, and significant cost savings were noted with IVP administration.

Thirteen studies investigated rapid administration of valproate (2–60 min), with most not specifying whether the drug was given via IVP or IVPB.  There were few adverse events, and there was no correlation with faster administration rates or according to dilution status (where reported).  IVP was found to be more efficient than IVPB in the one study measuring this outcome.

Rapid administration of intravenous antiseizure medications appears safe and can improve efficiency. The use of IVP, or faster IVPB administration should be considered by healthcare organisations.

Laswell E, Peterson K, Duan H, Grinalds M. Rapid administration of antiseizure medications: review of safety, effectiveness, and implications for pharmacy practice. Am J Health Syst Pharm 2026; 83: 131–150.

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GENERAL MEDICINE

MedsScan Editor for General medicine SPG: Christina Hanciu

Brexpiprazole for treatment of agitation in Alzheimer's dementia

Special Contributor: Wei Mann Chew

Antipsychotics are widely used to manage behavioural and psychological symptoms of dementia and are reserved as the last line of treatment after failing non-pharmacological measures. This study aimed to evaluate the safety and efficacy of brexpiprazole in managing agitation in patients with Alzheimer’s dementia.

This was a randomised, double-blind, placebo-controlled parallel-arm trial conducted in adults aged ≥55 years with a diagnosis of probable Alzheimer’s disease requiring pharmacological treatment of agitation after trialling non-pharmacological interventions. The study was conducted across 123 sites in Europe and the United States. Over a period of 12 weeks, participants were randomised to receive either placebo, brexpiprazole 2 mg daily or 3 mg daily.

At the conclusion of the study, participants that received brexpiprazole demonstrated a greater change in Cohen-Mansfield Agitation Inventory total score (mean difference -5.32, 95% confidence interval [CI] -8.77 to -1.97, p = 0.003) and Clinical Global Impression-Severity scale related to agitation (mean difference -0.27, 95% CI -0.47 to -0.07, p = 0.008). Treatment-emergent adverse events occurred at higher rates in active treatment than with placebo and the participants receiving the higher dose reported more adverse events than those receiving the 2 mg dose.

This study highlights the efficacy of brexpiprazole in managing symptoms of agitation in patients with Alzheimer’s disease and supports the use of atypical antipsychotics. This study was conducted only over a period of 12 weeks to reflect current accepted practice of withdrawing antipsychotics after this period when appropriate, and therefore, there is insufficient data supporting the long-term use of brexpiprazole in this patient population.

Lee D, Slomkowski M, Hefting N, Chen D, Groes Larsen K, Kohegyi E, et al. Brexpiprazole for the treatment of agitation in Alzheimer dementia: a randomized controlled trial. JAMA Neurol 2023; 80: 1307–1316.

Tirzepatide or semaglutide in people with obesity without type 2 diabetes

Special Contributor: Tom Chun Hong Chan

Tirzepatide and semaglutide have been studied for cardiovascular benefits in people with type 2 diabetes mellitus (T2DM). They have not been compared head-to-head in people with obesity without T2DM. Adipocytes do not have functional glucagon-like peptide-1 (GLP-1) receptors, but they have functional gastric inhibitory polypeptide (GIP) receptors. Since tirzepatide works on both GLP-1 and GIP receptors, it has been proposed that tirzepatide works more effectively in reducing body weight.

This Phase 3b, open-label controlled trial recruited individuals with a body mass index (BMI) of ≥30, or ≥27 and with at least one obesity-related complication (hypertension, dyslipidaemia, obstructive sleep apnoea or cardiovascular disease). Participants received either tirzepatide (at maximum tolerated dose of 10 mg or 15 mg) or semaglutide (at maximum tolerated dose of 1.7 mg or 2.4 mg) for 72 weeks. The body weight changes for the tirzepatide and semaglutide groups were -20.2% (95% CI -21.4 to -19.1) and -13.7% (95% CI -14.9 to -12.6) respectively (p < 0.001). Systolic blood pressure improved more with tirzepatide and haemoglobin A1c and lipid levels also improved for both medicine groups. The main side effects were gastrointestinal reactions. Injection site reactions were more common in the tirzepatide group.

The results were in agreement with previous trials on tirzepatide and semaglutide, the SURMOUNT and STEP trials.1,2 Greater cardiovascular benefits may be conferred by tirzepatide due to the additional mechanism of action on GIP receptors producing greater weight loss, however more studies are required to determine this. Hospital pharmacies in Australia should anticipate a greater use of tirzepatide in patients with obesity who are able to afford the cost of tirzepatide treatment in the community.

References

  1. Aronne LJ, Sattar N, Horn DB, Bays HE, Wharton S, Lin W-Y, et al. Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity: the SURMOUNT-4 randomized clinical trial. JAMA 2023; 331: 38–48.
  2. Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, et al. Once-weekly semaglutide in adults with overweight or obesity. N Eng J Med 2021; 384: 989–1002.

Aronne LJ, Horn DB, le Roux CW, Ho W, Falcon BL, Gomez Valderas E, et al. Tirzepatide as compared with semaglutide for the treatment of obesity. N Engl J Med 2025; 393: 26–36.

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INFECTIOUS DISEASES

MedsScan Editor for Infectious diseases SPG: Minyon Avent

Olorofim: a new agent for the treatment of invasive fungal disease?

Special contributor: Violet Zhu

Invasive fungal disease (IFD) is a significant cause of morbidity and mortality, and infections are increasing in incidence globally. Olorofim is a first in class oral orotomide antifungal which acts by impairing fungal pyrimidine biosynthesis leading to cell death. It specifically treats moulds (i.e. Aspergillus spp., Lomentaspora prolificans, Scedosporium spp.) but has no activity against yeasts or Mucorales.

This was an open-label, single arm, phase 2b study that was conducted across 22 international sites including Australia. Adult participants were enrolled if they had a proven olorofim-susceptible IFD or probable pulmonary aspergillosis where licensed antifungals were unable to be used — due to resistance, intolerance, unachievable therapeutic concentrations or drug–drug interactions — or where clinical response was inadequate after at least 7 days. Initial phases of this study included dose ranging methods and pharmacokinetic analysis which established there was no requirement for weight based dosing or therapeutic drug monitoring.

A total of 202 participants were enrolled and included a range of high (40%), moderate (31%) and low/no immunosuppression (29%). The predominant reason for trial enrolment was failure on available therapy (54%). The primary endpoint of successful global response to disease at day 42 was 28.7% (confidence interval [CI] 95% 22.6–35.5]. However, this definition was expanded to include ‘stable disease’, as other salvage IFD studies had included this, hence, success was confirmed at day 42 in 75.2% (CI 95% 68.7–81.0). Measuring treatment response rate at day 42 and 84 (as was done for the secondary endpoints) may have been too early to determine efficacy as clinical, mycological and radiological improvement in IFD is slow. Olorofim was generally well tolerated in the 202 patients, however drug-induced liver injury was noted in 22% (n = 45) of participants. This resolved with either dose modification (7%) or cessation (3%). Olorofim is a CYP3A4 substrate and a weak inhibitor and this study included participants on common concomitant medications such as ciclosporin, allowing for evaluation of dose adjustments.    

The results from this study demonstrate an alternative antifungal that may address the therapeutic limitations of currently available agents. This study sets the scene for the current active phase 3 trial to investigate its efficacy in comparison to liposomal amphotericin in invasive aspergillosis (Registration no: NCT05101187).  

Maertens JA, Thompson GR 3rd, Spec A, Donovan FM, Hammond SP, Bruns AHW, et al. Olorofim for the treatment of invasive fungal diseases in patients with few or no therapeutic options: a single-arm, open-label, phase 2b study. Lancet Infect Dis 2025; 25: 1177-1188.

The GAME CHANGER?  Cefiderocol for hospital-acquired and health-care-associated Gram-negative bacterial bloodstream infections

Special contributor: Kate Morton

The GAME CHANGER trial was an international, open-label, randomised trial evaluating the efficacy of cefiderocol in patients with bloodstream infections caused by Gram-negative bacilli compared to standard of care antibiotics. Cefiderocol is a novel siderophore cephalosporin antibiotic that has broad in vitro activity against carbapenem-resistant Gram-negative bacilli.

Five hundred and four adult participants were enrolled and included in the main analysis receiving either cefiderocol (mean age 62 years; 43% female) or standard of care (mean age 61 years; 40% female) in patients with Gram-negative bloodstream infections (health-care-associated or hospital acquired), to assess all-cause mortality at 14 days. The standard of care antibiotic treatment was determined by the patient’s clinician. Cefiderocol (2 g) was administered intravenously every 8 hours in patients with normal renal function. The minimum course of cefiderocol was 5 days, with a course of treatment up to 14-days as the maximum.

The primary outcome was all-cause mortality at 14 days from the date of randomisation. The primary outcome occurred in 8% and 7% in the cefiderocol and standard of care groups respectively (absolute risk difference 1%, 95% CI -3 to 6). One hundred and twenty-seven patients had an infection with a carbapenem-resistant organism. At 14 days, 14% (n = 9) of patients in the cefiderocol group had died compared with 10% (n = 6) in the standard care group. All-cause 30-day mortality in those with mannose-binding lectin (MBL)-producing enterobacterales infections was 50% in the cefiderocol group and 18% in the standard of care group.

In summary, cefiderocol was found to be noninferior compared to standard therapy in treating hospital-acquired and health-care-associated Gram-negative infections. In both the main analysis population and the carbapenem-resistant subset, superiority of cefiderocol was not demonstrated. Mortality remained slightly higher in the cefiderocol arm. Targeted research is required to evaluate the role of cefiderocol in this subset. Cefiderocol is available under the Special Access Scheme in Australia and its use within hospitals is limited by individual state and territory hospital formularies.

Paterson DL, Sulaiman H, Liu P-Y, Chatfield MD, Yilmaz M, Salmuna ZN, et al. Cefiderocol versus standard therapy for hospital-acquired and health-care-associated gram-negative bacterial bloodstream infection (the GAME CHANGER trial): an open-label, parallel-group, randomised trial. Lancet Infect Dis 2026; 26: 148–159.

The DOTS trial: dalbavancin for the Treatment of Staphylococcus aureus

Special contributor: Abha Kandalkar

The Dalbavancin as an Option for Treatment of Staphylococcus aureus Bacteraemia (DOTS) study was an open-label, assessor-masked, randomised clinical trial aimed at assessing dalbavancin superiority to standard care in complicated Staphylococcus aureus (S.aureus) bacteraemia by achieving a higher desirable outcome ranking at day 70.

Two hundred adult participants (aged >18 years) from 23 medical centres in the United States (n = 22) and Canada (n = 1) between April 2021 and December 2023 were included. Eligible participants had complicated S.aureus bacteraemia as defined by Infectious Diseases Society of America clinical practice guidelines, had received 3–10 days of intravenous (IV) antibiotic therapy, achieved blood culture clearance and fever resolution.1 Key exclusion criteria included central nervous system infections, left-sided endocarditis, severe immunocompromise, presence of infected prosthetic material or polymicrobial bacteraemia and patients that were pregnant or breastfeeding. Dalbavancin susceptibility was inferred from vancomycin susceptibility. Participants were randomised 1:1 to receive dalbavancin (n = 100, 1500 mg on day 1 and day 8, dose adjusted to 1125 mg if creatinine clearance <30 mL/min) versus 4–8 weeks of single agent standard antibiotic therapy (n = 100, anti-staphylococcal penicillin or cefazolin if susceptible, vancomycin or daptomycin if methicillin resistant). Duration of treatment for standard therapy was clinician-determined.

The primary outcome was desirability of outcome ranking (DOOR) at day 70 which was assessed by a committee of infectious diseases experts blinded to the randomisation. A follow up interval of 70 days was chosen as participants would have completed their treatment and majority of S.aureus bacteraemia relapse occurs within 30 days. The DOOR scale comprised of five criteria:

  1. clinical success: survival and resolution of signs or symptoms of S.aureus bacteraemia
  2. infectious complications: development of infective foci, relapsed bacteraemia, unplanned surgery for source control
  3. safety complications, including serious adverse events
  4. mortality
  5. health-related quality of life.

Secondary outcomes included clinical efficacy, defined as lack of clinical failure (lack of signs or symptoms of bacteraemia, infectious complications or mortality at day 70) and safety.

A total of 200 participants were enrolled. Baseline characteristics were balanced, though chronic kidney disease and bacteraemia greater than 4 days were slightly more common in the standard therapy arm, while immunosuppression and soft‑tissue infections were more frequent in the dalbavancin group. Of note, methicillin-resistant S.aureus (MRSA) accounted for approximately one‑third of infections and people who inject drugs made up 15% of the enrolled population. The most prevalent sources of infection were soft-tissue (35%), non-vertebral osteomyelitis (18%), septic arthritis (13%) and septic thrombophlebitis (12%). The median duration of antibiotic therapy prior to randomisation was 7–8 days.

Dalbavancin did not demonstrate superiority for the primary outcome. The probability that a randomly selected dalbavancin‑treated participant would have a more desirable outcome than one receiving standard therapy was 47.7% (95% CI 39.8–55.7), crossing the null threshold of 50%. DOOR components were similar between groups. Mortality in both groups was identical at 4%, and lower than in previously reported literature, highlighting a likely lower-risk population was included in this trial.

In terms of secondary outcomes, dalbavancin met the non-inferiority criteria for clinical efficacy: 73% in dalbavancin group and 72% in standard therapy group (difference 1.0%, 95% CI −11.5 to 13.5). Additionally, adverse events leading to treatment discontinuation were more frequent in the standard therapy group compared to the dalbavancin group (12% versus 3%).

Although dalbavancin was not superior to standard therapy by the DOOR measure, its comparable clinical efficacy and favourable safety profile suggests it has a role in select circumstances of complicated S.aureus bacteraemia, particularly when prolonged IV access is impractical. Further trials involving a more diverse patient cohort would help clarify its optimal place in therapy and provide additional guidance for clinical practice.

References

  1. Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 2011; 52: e18–e55.

Turner NA, Hamasaki T, Doernberg SB, Lodise TP, King HA, Ghazaryan V, et al. Dalbavancin for treatment of staphylococcus aureus bacteremia: the DOTS randomized clinical trial. JAMA 2025; 334: 866–877.

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MENTAL HEALTH

MedsScan Editors for Mental health SPG: Judy Longworth and Amy Sieff

Fatal clozapine outcome pharmacovigilance data from around the world

Clozapine has been associated with the lowest mortality of any antipsychotic drug. Conversely, it has also been well established that clozapine can cause some significant adverse effects which may be fatal.1

The aim of this study was to examine fatal outcomes from clozapine use based on global pharmacovigilance data, according to age and gender. Data from reports of actual and suspected adverse drug reactions and events from all national pharmacovigilance bodies is received by VigiBase, the World Health Organization’s database for the reporting of adverse effects. The authors used SPSS (IBM, Armonk, NY, USA) to analyse VigiBase data regarding reported fatal clozapine outcomes for 6402 female patients and 11 222 male patients.

Pneumonia was the most common label associated with fatal clozapine outcomes in both male and female consumers in the geriatric and middle-aged groups. In younger males and females, the most common labels were suicide and pulmonary embolism respectively. Myocarditis and agranulocytosis were uncommon labels across all ages and sexes, despite rigorous monitoring requirements and recommendations in relation to these adverse effects, particularly in Australia.2,3

Among the most significant limitations of this study is the quality, reliability and variability in global pharmacovigilance reporting. Additionally in this work, it was found that around one-third of reports only listed ‘death’ associated with clozapine, with no further detail. This effectively reduced the sample size available for analysis. Analysis itself is also limited in that confounding factors and relevant clinical details cannot be accounted for. There would be value in the authors utilising the data they were able to access. For instance, data from different countries could have been compared and considered in relation to relevant literature about clozapine adverse effects.

References

  1. Meltzer HY. Clozapine: balancing safety with superior antipsychotic efficacy. Clin Schizophr Relat Psychoses 2012; 6: 134–144.
  2. Ronaldson KJ, Fitzgerald PB, Taylor AJ, Topliss DJ, McNeil JJ. A new monitoring protocol for clozapine induced myocarditis based on an analysis of 75 cases and 94 controls. Aust N Z J Psychiatry 2011; 45: 458–465.
  3. Siskind D, Northwood K, Pillinger T, Chan S, Correll C, Cotes RO, et al. Absolute neutrophil count and adverse drug reaction monitoring during clozapine treatment: consensus guidelines from a global Delphi panel. Lancet Psychiatry 2026; 13: 77–86.

De Las Cuevas C, Sanz EJ, de Leon J. Fatal outcomes in use of clozapine: a VigiBase study of 6402 women and 11,222 men. J Clin Psychopharmacol 2025; 45; 547–553.

Psychotropic pharmacogenetics: precision can reduce harm and improve patient outcomes

Psychotropic pharmacogenetics (PGx) has great potential in psychiatric care by allowing for optimised dosing and medication selection based on one’s genetic profile.  Common barriers to successful treatment of psychiatric illness are treatment resistance and adverse drug reactions (ADRs), which may be able to be avoided or reduced by accounting for a patient’s genetic profile. The authors of this perspective article explore the challenges and possibilities emerging in this space, arguing that the broad implementation of psychotropic PGx can both improve patient outcomes and reduce healthcare costs.,  

This expanding field has already shown metabolic differences of many psychotropic agents through the identification of variations in the genetic makeup of the cytochrome P450 (CYP450) enzymes. When trying to determine the value or usefulness of clinical trials of psychotropic PGx, there is a need for researchers and clinicians to have greater clarity regarding commercial interests and publication biases, with most studies being both industry-dependent and industry-independent, with the ideal being a combination of both.

The authors discuss several studies, demonstrating there have been significant improvements in reducing ADRs and rates of major depressive disorder when comparing groups treated with psychotropic PGx and treatment as usual groups. There is scope for further research in attention-deficit/hyperactivity disorder, autistic spectrum disorder and psychedelic-assisted treatment, as well as schizophrenia, to utilise the potential benefits from psychotropic PGx.

Improving outcomes of these major psychiatric disorders with psychotropic PGx has health economic benefits in the long term by reducing ADRs, hospitalisations and readmissions, although initial testing can be cost prohibitive. Further work in this expanding field is needed and should move beyond industry funded trials.

Truong TT, Lago J, Neil J, Wilkes FA, Barnes R, Hopwood M, et al. Psychotropic pharmacogenetics in adult populations: from basic science to clinical trials and health economics – an evidence-based overview for decision makers. Aust N Z J Psychiatry 2025; 59: 950–956.

A timely reminder: the risk of venous thromboembolism in psychiatric inpatients

People with severe mental illness are not immune to physical health conditions and being confined to bed or restrained for any length of time is known to contribute to the incidence of venous thrombosis. This paper is a timely reminder to all pharmacists working in mental health and non-mental health wards, to advocate for the patient by reminding others in the multidisciplinary team of the significance of antithrombosis treatments.

This case controlled, retrospective chart review covered a period of fourteen years (January 2007–December 2021) of psychiatric inpatient treatment in adults (aged ≥18 years) in Saskatchewan, Canada. Psychiatric patients taking anticoagulants for venous thromboembolism (VTE) were matched to four (case-to-control ratio 1:4) non-VTE controls whose discharge diagnosis did not include VTE. A total of 32 patients with VTE and 159 patients without VTE were included.

Patients in the VTE group tended to have more complex clinical profiles, including a greater burden of both psychiatric and medical comorbidities compared to patients without VTE (22.0% versus 2.0%, p < 0.001). Psychiatric interventions and acute medical diagnoses emerged as potential VTE-associated factors, with more than two-thirds of VTE cases involving a pulmonary embolism (PE). The use of both mechanical restraints and electroconvulsive therapy were independently associated with VTE in this study. Univariate analysis showed significance with a diagnosis of catatonia, which is supported by current literature, with one study reporting that 61.1% of catatonic patients developed VTE.1

One suggestion for ongoing work is the development of a predictive risk assessment model specific for psychiatric inpatients as there is no current protocol in Australasia. Overseas examples include the Caprini score for VTE or the Padua prediction score for risk of VTE, but these do not account for psychiatric risk.2,3

References

  1. Takeshima M, Ishikawa H, Shimizu K, Kanbayashi T, Shimizu T. Incidence of venous thromboembolism in psychiatric inpatients: a chart review. Neuropsychiatr Dis Treat 2018; 14: 1363–1370.
  2. Caprini J. Caprini score for venous thromboembolism. NY: MD+Calc; 2005. Available from https://www.mdcalc.com/calc/3970/caprini-score-venous-thromboembolism-2005. Accessed 26 February 2026.
  3. Barbar S, Noventa F, Rossetto V, Ferrari A, Brandolin B, Perlati M, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost 2010; 8: 2450–2457.

Chan RR, Hamis E, Le T, Alaverdashvili M, Wanson A, Halpape K. Bridging the mind and body: exploring venous thromboembolism in psychiatric inpatients. Australas Psychiatry 2026; 34: 23–30.

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NEPHROLOGY

MedsScan Editor for Nephrology SPG: Laura Johnstone

When finerenone met empagliflozin: a critical look at the fine print

Special Contributor: Bec Livori

Background: Chronic kidney disease (CKD) affects approximately 10% of adults worldwide and diabetes mellitus is the primary cause of CKD.1 While individual therapies of sodium-glucose cotransport-2 (SGLT2) inhibitors and mineralocorticoid receptor antagonists have shown renoprotective effects, limited evidence supports initiating these treatments together. The rationale for combination therapy is based on their differing and complementary mechanisms of action in reducing proteinuria and slowing CKD progression.

Aim: The CONFIDENCE [COmbinatioN effect of FInerenone and EmpaglifloziN in participants with chronic kidney disease and type 2 diabetes using a UACR Endpoint] trial aimed to evaluate whether simultaneous initiation of finerenone (a nonsteroidal mineralocorticoid receptor antagonist) plus empagliflozin (an SGLT2 inhibitor) would result in greater reduction in urinary albumin-to-creatinine ratio (UACR) compared to either therapy alone in patients with CKD with albuminuria and type 2 diabetes mellitus (T2DM).

Method: CONFIDENCE was a randomised, active-controlled, double-blind, multicentre phase 2 clinical trial enrolling adults with CKD and T2DM. Participants had an estimated glomerular filtration rate (eGFR) of 30–90 mL/min/1.73 m², glycated haemoglobin (HbA1c) <11% and UACR of ≥100 mg/g to <5000 mg/g. All participants were required to already be receiving an angiotensin converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB) at the maximally tolerated dose prior to the trial period. The study employed a three-arm design comparing combination therapy (finerenone plus empagliflozin) against each monotherapy arm. The primary endpoint was the percentage change in UACR from baseline to Day 180, with secondary endpoints including safety parameters and additional efficacy measures.

Results: Participant screening was undertaken from 23 June 2022–14 August 2024, with 1664 patients screened. Ultimately, 800 participants were included in the full efficiency analyses (combination therapy group: n = 269, finerenone only group: n = 264, empagliflozin only group: n = 267).

Over a period of six months, when compared to baseline, combination therapy yielded a 52% reduction in UACR (least-squares mean [LSM] ratio 0.48, 95% confidence interval [CI] 0.44–0.54). The combination therapy group reduction in UACR was 29% greater than the finerenone group (LSM ratio 0.71, 95% CI 0.61–0.82, p < 0.001), and 32% greater than the empagliflozin alone group (LSM ratio 0.68, 95% CI 0.59–0.79, p < 0.001). The combination therapy resulted in a notably larger reduction in albuminuria than either treatment alone. Safety profiles appeared consistent with the known effects of each individual drug profile. Adverse effects leading to treatment discontinuation were noted in 30 (3.8%) of the 798 participants included in the safety analyses (after receiving at least one dose of a trial drug) and hyperkalaemia occurred in 9.3% of participants in the combination arm, 11.4% in the finerenone arm and 3.8% in the empagliflozin arm.

Key limitations: As a phase 2 trial with 180-day follow-up, CONFIDENCE provides only intermediate-term efficacy data without demonstrating impacts on hard clinical endpoints such as kidney failure, cardiovascular events or mortality. The relatively short study duration precludes assessment of long-term safety concerns or sustained therapeutic benefits that would be essential for clinical practice recommendations.

The CONFIDENCE trial was sponsored by the pharmaceutical company Bayer, who own finerenone. This introduces an inherent bias to the trial, with a financial conflict of interest. For CONFIDENCE, this was mediated with double-blinding, computer randomisation, an independent data and safety monitoring committee and registration of the trial with ClinicalTrials.gov (ID: NCT05254002).

Impact on practice: The CONFIDENCE trial represents a significant next step in the evidence base for treating CKD in T2DM, building directly upon the foundational work established by FIGARO-DKD [Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease] and FIDELIO-DKD [Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease]. While FIGARO-DKD2,3 and FIDELIO-DKD2,4 demonstrated that finerenone was effective when added to standard care (including renin-angiotensin system [RAS] blockade), CONFIDENCE demonstrated the additional benefit to UACR and CKD management in combining finerenone with SGLT2 inhibition from the start, rather than following traditional step-by-step methods.

The CONFIDENCE trial has demonstrated that simultaneous introduction of finerenone and empagliflozin to baseline RAS blockade is safe, provides additive therapeutic benefit and may reduce clinical inertia when compared with a traditional stepwise method. This is a shift towards early, aggressive combination treatment in diabetic kidney disease, mirroring established strategies in heart failure care. The magnitude of UACR reduction with the combination treatment indicates clinically meaningful renoprotection, given the established links between albuminuria reduction and long-term cardiovascular and kidney outcomes.

The trial’s diverse patient population enhances generalisability, though individual patient factors, including baseline kidney function, potassium levels, cardiovascular status and diabetic control should guide pharmacists recommending combination therapy. CONFIDENCE excluded patients with HbA1c >11% and with UACR <100 mg/g, which may limit external validity to patient cohorts. Additionally, risk of hyperkalaemia (finerenone) and volume depletion or urogenital infections (empagliflozin) should be evaluated for individuals. Cost-effectiveness analyses and real-world safety data will be essential for broad implementation, but the CONFIDENCE results provide the efficacy basis for combination therapy strategies.

The CONFIDENCE results fundamentally challenge the traditional sequential approach to CKD management, advocating for more proactive early intervention strategies that could greatly influence the course of diabetic kidney disease progression. Future research priorities may include long-term outcome studies, understanding optimal CKD stage for starting combination therapy and identifying patient subgroups most likely to benefit from dual therapy approaches. Some of these are underway, including evaluating the effect of finerenone with and without SGLT2 inhibition in other types of CKD, and in heart failure as well, and a cost-effectiveness study of RAAS inhibition alongside finerenone and SGLT2 inhibition: imagine if there could be a polypill for all three pillars of therapy for our CKD patients!

References

  1. Global Burden of Disease (GBD) Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2020; 395 (10225): 709–733.
  2. Kidney Disease Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2022 clinical practice guideline for diabetes management in chronic kidney disease. Kidney Int 2022; 105 (5S): S1–S127.
  3. 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 Eng J Med2021; 385: 2252–2263.
  4. 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 Eng J Medew England Journal of Medicine 2020; 383: 2219–2229.

Agarwal R, Green JB, Heerspink HJL, Mann JFE, McGill JB, Mottl AK, et al. Finerenone with empagliflozin in chronic kidney disease and type 2 diabetes. N Eng J Med 2025; 393: 533–543.

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ONCOLOGY AND HAEMATOLOGY

MedsScan Editor for Oncology and haematology SPG: Alborz Soroush

Comparing apixaban and rivaroxaban in gastrointestinal cancer-associated venous thromboembolism

The risk of venous thromboembolism (VTE) and bleeding is higher for patients who have gastrointestinal (GI) malignancies. The selection of the best anticoagulant treatment for these patients continues to be a matter of debate. The SELECT-D1 and CARAVAGGIO2 randomised trials showed patients that receive direct oral anticoagulants (DOACs) or low molecular weight heparin (LMWH) experience different bleeding patterns, which result in higher gastrointestinal bleeding risks for DOAC recipients, although this finding was more prominent in the SELECT-D trial.

This study used a single-site retrospective chart analysis to evaluate the real-world safety outcomes and therapeutic efficacy of apixaban and rivaroxaban for treating cancer-associated VTE in adult patients with primary GI cancers at Winship Cancer Institute, located in Atlanta, USA, between 2017 and 2021. The study included patients who were at least 18 years old and had a main GI cancer who received standard-dose apixaban or rivaroxaban for proven DVT or PE. The primary study endpoint consisted of major bleeding defined by haemoglobin reduction by at least 2 g/dL during 24 h, requirement of two or more red blood cell units for transfusion, critical-site bleeding or bleeding that needs surgical intervention. Secondary outcomes consisted of clinically relevant non-major bleeding (CRNMB), VTE recurrence during the first 6 months and death caused by bleeding.

In 300 included patients, the study recorded three major bleeding events in 3.4% (n = 3) of the 89 apixaban patients but 8.5% (n = 18) of patients experienced major bleeding events among the 211 rivaroxaban patients (odds ratio [OR] 0.42, 95% confidence interval [CI] 0.13–1.37, p = 0.152). The study showed that CRNMB occurred in 2.2% of patients who received apixaban and 8.5% of patients who received rivaroxaban (OR 0.34, 95% CI 0.09–1.32, p = 0.119). The research findings showed that VTE recurrence happened to 4.5% of patients treated with apixaban and to 2.8% of patients treated with rivaroxaban (OR 1.10, 95% CI 0.30–4.05, p = 0.882).

The study found no instances of death caused by bleeding in both groups and showed no statistically significant differences but apixaban produced less bleeding events (major and non-major) while maintaining similar VTE recurrence rates as rivaroxaban for patients with primary GI cancers.

References

  1. Young AM, Marshall A, Thirlwall J, Chapman O, Lokare A, Hill C, et al. Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELECT-D). J Clin Oncol 2018; 36: 2017–2023.
  2. Agnelli G, Becattini C, Meyer G, Muñoz A, Huisman MV, Connors JM, et al. Apixaban for the treatment of venous thromboembolism associated with cancer. N Eng J Med 2020; 382: 1599–1607.

Gundersen P, Basillio A, Draper A, Watson M, Tiao E, Abousaud M, et al. Evaluation of bleeding risk with apixaban versus rivaroxaban in patients with gastrointestinal cancer. J Hem Onc Pharm 2025; 15: 192–198.

Cytarabine consolidation in acute myeloid leukaemia: which dose is best?

Special contributor: Rahul Kumar

Cytarabine is commonly used as consolidation therapy for newly diagnosed acute myeloid leukaemia (AML), but the optimal dosing is uncertain. A large, multicentre phase 3 non-inferiority randomised controlled trial compared intermediate-dose cytarabine (IDAC) with high-dose cytarabine (HiDAC) to determine whether lower doses could achieve similar efficacy with less toxicity. The study included younger adults aged 18–60 years with AML, excluding patients with favourable-risk core-binding factor, acute promyelocytic or Philadelphia chromosome–positive AML.

Following induction, 1221 patients were randomised to receive either IDAC (1500 mg/m² every 12 h) or HiDAC (3000 mg/m² every 12 h) on days 1, 3 and 5 for up to three cycles. The primary endpoint was overall survival (OS), assessed in 1132 patients. At five years, estimated OS was 59.3% in the IDAC group and 57.5% in the HiDAC group, demonstrating noninferiority of IDAC (adjusted hazard ratio 0.96, 95% CI 0.80–1.15, noninferiority test p = 0.0042). Despite some favourable trends in specific subgroups for IDAC, no significant differences in treatment effect were observed across age groups, European LeukemiaNet (ELN) 2022 risk categories,1 induction regimens (type of anthracycline) or key molecular mutations such as nucleophosmin 1 (NPM1) and FMS-like tyrosine kinase 3 (FLT3).

Secondary outcomes including event-free survival, relapse-free survival and cumulative incidence of relapse were nearly identical between treatment arms. Rates of allogeneic stem cell transplantation were also similar. Although HiDAC produced a slightly higher salvage rate in patients’ refractory to induction (51.6% versus 38.5%), when compared to the IDAC group, this did not result in improved overall survival.

Importantly, IDAC was associated with lower treatment-related toxicities as patients experienced fewer febrile days, less severe gastrointestinal and bleeding complications and required fewer blood product transfusions with the greatest safety benefit seen in patients aged 50 years or older. Overall, the trial supports IDAC as an effective and less toxic consolidation strategy for adults aged 18–60 years with AML.

References

  1. Döhner H, Wei AH, Appelbaum FR, Craddock C, DiNardo CD, Dombret H, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood 2022; 140: 1345–1377.

Hunault M, Pautas C, Bertoli S, Dumas P-Y, Raffoux E, Hospital M-A, et al. Intermediate-dose cytarabine as postinduction AML therapy. NEJM Evid 2025; 4: EVIDoa2400326.

Trastuzumab deruxtecan plus pertuzumab compared to standard taxane–trastuzumab–pertuzumab treatment for HER2-positive breast cancer: interim results from the DESTINY-Breast09 trial

The phase 3 DESTINY‑Breast09 trial evaluated trastuzumab deruxtecan plus pertuzumab (T‑DXd‑P) as an initial therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients who had progressed to advanced or metastatic disease against the standard taxane–trastuzumab–pertuzumab (THP) treatment. The study included adult patients who had HER2-positive metastatic breast cancer which had been confirmed through central testing, Eastern Cooperative Oncology Group (ECOG) performance 0–1 and had not received any previous treatment for metastatic breast cancer although one prior line of endocrine monotherapy was allowed.

Participants were assigned (1:1:1) to groups to receive T‑DXd‑P, T‑DXd plus placebo or THP. This article provides an interim analysis and compared T‑DXd-P (n = 383) with the taxane-based group (THP) (n = 387). The study excluded patients who had active central nervous system metastases and who had previously developed interstitial lung disease (ILD) or pneumonitis. Interestingly, almost half of the study population was from Asia (T-DXd-P: 49.6% versus THP: 50.6%) and lacked sufficient representation from Black participants (T-DXd-P: 3.1% versus THP: 1.3%).

According to the blinded independent central review, the T‑DXd-P treatment resulted in a 40.7-month median progression-free survival (primary endpoint) but THP patients only achieved 26.9 months (hazard ratio [HR] 0.56, 95% CI 0.44–0.71, p < 0.00001). The T‑DXd-P group achieved superior outcomes across‑ all secondary endpoints — 85.1% confirmed objective response rate versus 78.6% in THP group — as well as 15.1% complete responses versus 8.5% in the THP group. Median duration of response reached 39.2 months compared to 26.4 months in the THP group.

In the T-DXd-P group, 63.5% (n = 242) of participants showed grade ≥3 adverse events whereas THP treatment led to such events in 62.3% (n = 238) of patients. Neutropenia, hypokalaemia and anaemia were the most severe side effects in the T‑DXd-P group, but THP patients’ most severe reactions were neutropenia, leukopenia and diarrhoea. The results demonstrated that 46 (12.1%) of T‑DXd-P patients developed any grade of ILD/pneumonitis (mostly grade 1–2) but two patients developed grade 5 (fatal) symptoms and in the THP group, four (1%) patients developed equal or less than grade 2 symptoms. Left-ventricular dysfunction required monitoring because it occurred in 11.0% (n = 42) of T‑DXd-P patients and 7.1% (n = 27) of THP patients respectively without demonstrating any new safety risks.

DESTINY-Breast03 shifted second-line practice by demonstrating a significant progression-free survival benefit with T-DXd over trastuzumab emtansine which resulted in PBS approval of T-DXd for unresectable or metastatic HER2-positive breast cancer after prior HER2-directed therapy (not first line).3 More recently, DESTINY-Breast09 results led to FDA approval of T-Dxd in combination with pertuzumab as first-line therapy in December 2025.

References

  1. Cortés J, Kim S-B, Chung W-P, Im S-A, Park YH, Hegg R, et al. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. N Eng J Med 2022; 386: 1143–1154.
  2. Hurvitz SA, Hegg R, Chung W-P, Im S-A, Jacot W, Ganju V. et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-postive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial. Lancet 2023; 401 (10371): 105–117.
  3. Cortés J, Hurvitz SA, Im S-A, Iwata H, Curigliano G, Kim S-B, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-postive metastatic breast cancer: long-term survival analysis of the DESTINY-Breast03 trial. Nat Med 2024; 30: 2208–2215.

Tolaney SM, Jiang Z, Zhang Q, Barroso-Sousa R, Park YH, Rimawi MF, et al. Trastuzumab deruxtecan plus pertuzumab for HER2-positive metastatic breast cancer. N Eng J Med 2026; 394: 551–562.

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PAEDIATRICS AND NEONATOLOGY

MedsScan Editor for Paediatrics and neonatology SPG: Rachael Worthington

The SCALE of impact of liraglutide on obesity in children

Treating nonmonogenic, nonsyndromic obesity in children (aged <12 years) is challenging because while liraglutide has been shown to induce weight loss in adults and adolescents with obesity, safety and efficacy have not been established in children and currently, there are no medicines approved for use in children. This phase 3 study sought to investigate the efficacy and safety of liraglutide, a glucagon-like peptide-1 (GLP-1) agonist in children with obesity.

Eighty-two children (aged 6 to <12 years) with obesity were randomly assigned (2:1) to either once-daily subcutaneous liraglutide at a dose of 3.0 mg (or the maximum tolerated dose) (n = 56) or placebo (n = 26), with both groups also including lifestyle interventions. The study was conducted over 56-weeks and included a 26-week follow up period. The primary end point was the percentage change in body-mass index (BMI) and secondary end points were the percentage change in body weight and a reduction in BMI of at least 5%.

At the end of the treatment period (week 56), the mean percentage change in BMI from baseline was –5.8% in the liraglutide group compared to +1.6% in the placebo group (mean difference −7.4%, 95% confidence interval [CI] −11.6 to −3.2, p < 0.001). The liraglutide group experienced a mean percentage change in body weight of 1.6% compared to 10.0% in the placebo group (mean difference –8.4%, 95% CI −13.4 to −3.3, p = 0.001) and a  BMI reduction of >5% (adjusted odds ratio 6.3, 95% CI 1.4 to 28.8, p=0.02) was seen in 46% and 9% of patients in the liraglutide and placebo groups respectively. Adverse events occurred in 89% of liraglutide recipients and 88% of placebo recipients, with gastrointestinal (GI) adverse events more common for patients in the liraglutide group (80% versus 54% in the placebo group). Serious adverse events were reported in 12% and 8% of participants in the liraglutide and placebo groups, respectively.

The authors concluded that among children (aged between 6 and <12 years) with obesity, treatment with liraglutide reduced BMI compared to lifestyle interventions alone and improved the proportion of patients with a clinically significant decrease in BMI. GI adverse effects were more common with liraglutide and no differences in height velocity or bone age were detected. The limited data suggest that liraglutide is moderately effective with no significant safety concerns, but its potential use in this age group requires further investigation.

Fox CK, Barrientos-Pérez M, Bomberg EM, Dcruz J, Gies I, Harder-Lauridsen NM, et al. Liraglutide for children 6 to <12 years of age with obesity – a randomized trial. N Engl J Med 2025; 392: 555–565.

Oral ivermectin or topical permethrin to cure classic scabies

Scabies is one of the most common illnesses internationally and is a parasitic skin disease caused by the Sarcoptes scabiei var. hominis mite. Oral ivermectin and 5% permethrin cream are frequently used treatments for classic scabies, but robust data are lacking or contradictory: showing permethrin superiority or no difference in efficacy between the drugs.

This study, the Scabies Randomised Trial in Children and Adults (SCRATCH), sought to investigate whether oral ivermectin or topical 5% permethrin can clinically cure scabies in index cases (adults and children weighing >15kg) and members of their households. The trial took place in 28 French hospitals from 19 January 2016–16 December 2021 with participants randomly assigned (1:1) to the ivermectin group or permethrin group. Each member of a ‘cluster’ — defined as the household of each index case — received the same treatment as the index case, except for children weighing <15 kg who were prescribed topical 5% permethrin. All participants received oral ivermectin 200 mcg/kg or 5% permethrin cream on day 0 and day 10, applied head to toe. The primary outcome was clinical cure (disappearance of clinical signs and symptoms of scabies) of the index participant by day 28, assessed by dermatologists blinded to assigned treatment group and their respective cluster (if available or self-assessment if cluster was not available).

Five hundred and seven index participants in 142 households (clusters) were treated with ivermectin and 568 index participants in 147 clusters received permethrin. Cluster level cure rates were 71.8% for ivermectin versus 88.5% for permethrin (mean difference –16.7 %, 95% CI –26.3 to –7.1). Secondary outcomes also demonstrated the inferiority of ivermectin compared with 5% permethrin for index cases (76.6% versus 91.5%; mean difference –14.9%, 95% CI –23.6 to –6.2) and for all participants (index cases and clusters) (85.3% versus 94.2%; mean difference –9.2%, –14.9 to –3.5).Cutaneous adverse events were found in 9.9% and 13.6% of index case participants,  including eczema (n = 6; n = 10), itching or burning (n = 11; n = 12) and drug-induced urticaria (n = 0; n = 1) in the  ivermectin and permethrin groups, respectively.

The authors concluded that the results of the SCRATCH trial did not show the non-inferiority of oral ivermectin compared with 5% permethrin cream and that 5% permethrin cream could be used as first line treatment in classic scabies in children and young adults, where application of a scabicide is not contraindicated, with oral ivermectin an alternative when topical application is not practical or appropriate.

Boralevi F, Simon G, Bernigaud C, Brun J, Goujon E, Perrot JL, et al. Oral ivermectin versus 5% permethrin cream to treat children and adults with classic scabies: multicentre, assessor blinded, cluster randomised clinical trial. BMJ 2026; 392: e086277.

Tirzepatide to treat youth-onset type 2 diabetes mellitus

This article outlines the findings of the SURPASS-PEDS trial which assessed the use of tirzepatide — a glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist — compared with placebo in patients with youth-onset type 2 diabetes mellitus (T2DM) and aimed to address the limited treatment options for this patient cohort. SURPASS-PEDS was a phase 3, double-blind, placebo-controlled, trial conducted over 30 weeks, across 39 sites in eight countries between 12 April 2022 and 27 December 2023.

One hundred and forty-six participants, aged 10 to <18 years, with poorly controlled (with metformin and/or basal insulin) youth-onset T2DM were initially screened, with 99 included in the trial. Participants were randomly assigned (1:1:1), stratified by age and anti-hyperglycaemic medicine use, into tirzepatide 5 mg (n = 32), tirzepatide 10 mg (n = 33) or placebo groups (n = 34). Tirzepatide or placebo was administered via subcutaneous injection (single dose pen). The primary endpoint was a change in glycated haemoglobin (HbA1c) from baseline to week 30. Following this period, an a open-label extension for 22 weeks was conducted, where all participants received tirzepatide. Across the entire cohort, participants were 61% female, with a mean age (±standard deviation [SD]) of 14.7 (±1.8) years and mean HbA1c (±SD) of 8·04% (±1.23). The trial was funded by Eli Lilly and Company and all participants, investigators and the sponsor were blinded to treatment assignment during the 30-week double-blind period.

At week 30, tirzepatide was superior to placebo in reducing HbA1c. The tirzepatide 5 mg and 10 mg groups were pooled and experienced a mean reduction of HbA1c of 2.23% versus an increase of 0.05% in the placebo group (mean difference −2·28%, 95% CI −2.87 to −1.69, p < 0.0001), sustained up to 52 weeks with the additional period of tirzepatide treatment. Tirzepatide also resulted in significant reductions in BMI, a secondary endpoint, with reductions of 7.4% and 11.2% for the 5 mg and 10 mg groups, respectively, compared with 0.4% in the placebo group at 30 weeks. Participants in the tirzepatide groups experienced some adverse events, the most serious causing two participants to withdraw; the most common adverse events were mid-to-moderate gastrointestinal issues which decreased over time.

The authors concluded that tirzepatide is effective in glycaemic control and resulted in significant and clinically meaningful improvements in weight-related parameters compared with placebo in patients with youth-onset T2DM, with effects sustained for up to one year. These results support tirzepatide as a potentially safe and efficacious treatment option for the treatment of youth-onset T2DM.

Hannon TS, Chao LC, Barrientos-Pérez M, Pamidipati KC, Fernández Landó L, Lee CJ, et al. Efficacy and safety of tirzepatide in children and adolescents with type 2 diabetes (SURPASS-PEDS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet, Volume 2025; 406 (10511): 1484–1496.

Errata: Department of Error. Lancet 2025; 406 (10511): 1472.

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PAIN MANAGEMENT

MedsScan Editor for Pain management SPG: Jeremy Szmerling

Incretin-based therapies as emerging options for neuropathic pain management

This review summarised mechanistic and emerging clinical evidence for incretin-based therapies, including glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors and their potential role in neuropathic pain management.

The authors conducted a thematic synthesis of literature published between January 2000 and March 2025, using PubMed, Scopus and Web of Science, and included literature that examined the therapeutic effect of GLP1- and DPP-4 inhibitors on neuropathic pain. Articles were grouped by therapeutic agent and neuropathic pain model, with findings categorised based on mechanism of action, therapeutic efficacy and clinical outcomes.

Incretin-based therapies may alleviate neuropathic pain through suppression of neuroinflammation, reduction of oxidative stress, restoration of mitochondrial function and inhibition of glial cell activation. In animal models, particularly diabetic neuropathy, modulation of key pain signalling pathways produced antinociceptive effects and reduced allodynia and hyperalgesia. Human evidence remains limited but suggests potential improvements in neuropathic symptoms, quality of life, and possible opioid-sparing effects, primarily in patients with diabetes treated with GLP-1 agonists.

For Australian hospital pharmacists, these findings highlight potential dual benefits of incretin-based therapies for patients with diabetes and co-existing neuropathic pain, including symptom improvement and possible opioid-sparing effects. In the short term, this evidence may support consideration of neuropathic pain outcomes when reviewing incretin-based therapy in eligible patients, rather than prompting initiation solely for analgesia. However, as the current evidence base is predominantly pre-clinical with limited pain-focused clinical trials, these agents cannot yet be recommended for routine neuropathic pain management. Well-designed, adequately powered clinical trials across diverse neuropathic pain populations are required before translation into standard practice.

Kuthati Y, Davuluri VNG, Wong C-S. Therapeutic effects of GLP‑1 receptor agonists and DPP‑4 inhibitors in neuropathic pain: mechanisms and clinical implications. Biomolecules 2025; 15: 622.

Artificial intelligence in pain management: promise tempered by implementation challenges

Pain is highly prevalent, costly and multifactorial, and current approaches often fail to adequately predict treatment response or prevent transition from acute to chronic pain. This systematic review aimed to characterise current applications of artificial intelligence (AI) in acute and chronic pain management and identify barriers to clinical integration.

The authors conducted a systematic review, with four electronic databases searched from inception–October 2023, identifying 197 eligible studies. Included studies described AI applications for pain treatment rather than diagnosis of underlying causes of pain or the identification and assessment of pain intensity measurement alone. Multiple AI domains were represented across diverse clinical settings.

AI applications were most commonly used to predict acute and chronic pain, forecast treatment response and opioid related risk, support treatment decision making, guide interventional procedures and facilitate patient self management. Many tools demonstrated good predictive accuracy, however few studies assessed whether these predictions translated into meaningful improvements in patient reported outcomes. Key barriers to implementation included lack of validation in diverse patient groups and clinical settings, lack of technological infrastructure and limited real world clinical evaluation. Study limitations also included heterogeneous study designs, limited external validation and variable reporting of AI methods.

AI holds clear potential to enhance individualised pain management, including within analgesic stewardship frameworks. However, Australian pharmacists and pain clinicians should remain cautious given gaps in validation, infrastructure and clinician understanding. Successful integration will require robust clinical trials, interdisciplinary collaboration and education to ensure AI tools support, rather than obscure, clinical judgment in pain management.

Antel R, Whitelaw S, Gore G, Ingelmo P. Moving towards the use of artificial intelligence in pain management. Eur J Pain 2025; 29: e4748.

Multi‑level analgesic stewardship effects on opioid prescribing at discharge

Special contributor: Ka Jor Renny Chan

Analgesic stewardship programs aim to balance effective pain control with minimisation of opioid‑related harm. This multisite study evaluated whether adding pharmacy-led, patient‑level interventions to an existing organisational stewardship framework improved opioid‑related outcomes at discharge.

This 12‑month retrospective cohort study was run across four metropolitan Australian hospitals. Patients exposed to both organisation‑level stewardship interventions (e.g. governance structures, prescribing guidelines, EMR optimisation, education, KPI monitoring) and pharmacy-led, patient‑level stewardship interventions (pharmacist assessment, SafeScript review, individualised analgesia plans) were compared with patients that received organisation‑level interventions alone.

Among opioid‑naïve patients, exposure to patient‑level stewardship interventions was associated with significantly lower odds of discharge on modified-release opioids (odds ratio [OR] 0.23, 95% confidence interval [CI] 0.11–0.49, p < 0.001), while there was no difference in 2‑week readmission rates. In the non‑opioid‑naïve cohort, patient‑level interventions were associated with lower odds of readmission within 2 weeks (OR 0.39, 95% CI 0.15–0.98, p = 0.045), with significant within group, but not between‑group, differences in change in oral morphine equivalent daily dose from preadmission to discharge.

This study highlights the clinical value of embedding pharmacists within analgesic stewardship models and suggests that patient‑level interventions may confer benefits beyond those achieved through organisational measures alone. Strengths included multisite implementation and the use of parallel control groups, although non‑randomisation and potential selection bias limit causal inference. Importantly, these findings build upon existing evidence supporting stewardship frameworks and suggest that targeted pharmacist involvement may enhance discharge prescribing quality and reduce avoidable readmissions. Future research exploring sustainability, cost‑effectiveness and scalability will be critical to determine broader applicability across health services.

Szmerling J, Maleki S, Mar G, Gu G, Schembri E, Buntine P, et al. The effectiveness of a multisite, multidisciplinary analgesic stewardship program: a 12-month retrospective cohort study. Pain Rep 2025; 10: e1339.

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PHARMACY INFORMATICS AND TECHNOLOGY

MedsScan Editor for Pharmacy informatics and technology SPG: James Grant

Digital health implementation: useful frameworks and missing realities

This systematic review examines how two established implementation frameworks — the Nonadoption, Abandonment, Scale-up, Spread, and Sustainability (NASSS) framework and the Theoretical Domains Framework (TDF) — have been applied to the deployment of digital health solutions. While this review is well grounded in implementation science, its findings highlight the value and the current limitations of framework-driven evidence for real-world pharmacy informatics practice.

From a pool of 2704 studies, only 12 met the inclusion criteria for final analysis. This degree of attrition is notable given the extensive literature on digital health implementations. It seems to reflect a deliberate methodological choice to include only studies that explicitly used NASSS and/or TDF, rather than broader implementation research using alternative frameworks or pragmatic approaches. While this strengthens theoretical consistency, it significantly narrows the evidence base and likely under-represents the breadth of implementation experience documented across health care. 

For readers less familiar with these frameworks, NASSS and TDF serve complementary purposes. NASSS provides a system-level lens, examining complexity across domains such as the technology itself, organisational capacity and wider system context. TDF focuses on behavioural determinants, helping to explain how beliefs, skills, social influences and professional roles affect adoption and sustained use. Together, they offer a structured way to diagnose why digital solutions succeed or struggle. Other commonly used frameworks of this type include Consolidated Framework for Implementation Research (CFIR) and Normalisation Process Theory (NPT). CFIR maps contextual barriers and facilitators, while NPT focuses on how to embed and sustain innovations in daily work.

However, the systematic review has notable gaps. Several NASSS domains that are frequently decisive in pharmacy informatics — political context, regulatory and legal constraints, organisational readiness and changes to routines and work practices — were absent from the included studies. This is surprising given the heavily regulated nature of medicines and the central role of workflow change in any healthcare or work setting. The omission likely reflects limitations in primary study reporting rather than a lack of relevance, surfacing a disconnect between implementation research and the operational realities faced by health services.

The review also does not meaningfully engage with established change management frameworks. While NASSS and TDF are valuable for analysis and diagnosis, they are not, in themselves, actionable change methodologies. For pharmacy leaders and informaticians, the practical challenge lies in delivering structured actions to enable change including engagement, training, governance and reinforcement, using recognised change management approaches. The absence of this linkage limits the paper’s utility in isolation, though extensive information is available on change management methodologies such as Kotter’s 8-Steps or Prosci’s 5-Step ADKAR [Awareness, Desire, Knowledge, Ability, and Reinforcement] models.

Overall, this review provides a methodologically rigorous focus on selected methods to assess a digital solution implementation. It demonstrates how NASSS and TDF can be applied, although it is not a comprehensive account of implementation challenges in pharmacy informatics or digital health. It is suggested that this review prompt readers to plan to assess deployments post-‘go-live’ using frameworks for consistency and to consider the barriers they measure in advance alongside change management processes. 

Patel SB, Iqbal FM, Lam K, Acharya A, Ashrafian H, Darzi A. Characterizing behaviors that influence the implementation of digital-based interventions in health care: systematic review. J Med Internet Res   2025; 27: e56711.

Newer tech, same barriers: lessons from global health IT implementations

Special contributor: Jessica Hosking

This editorial reviewed the implementation of health technology across diverse healthcare settings in Australia, Africa, Europe and the United States. The authors cite the proven positive impact of health technology in the Australian hospital context, however they also note that many implementations they reviewed focused on implementation challenges and barriers that prevented potential patient benefits from being fully realised.

Among these barriers were themes related to staff training and workarounds and issues with the technology’s design, which will feel familiar to all who have been involved in the digital health space. Indeed, the authors themselves commented that these aligned with barriers identified from hospital implementations two decades prior.

A theme that emerged in this editorial as a key factor for successful implementation was “the importance of context”, with the authors emphasising the need to thoroughly consider the real-world setting in which these technologies were implemented. Additionally, the authors proposed that consistently achieving the benefits of these technologies for patients requires methods with sufficient agility to adapt to the diverse contexts of health. The perspective of using an agile implementation method is an interesting one, particularly in the context of adopting new technology in the tightly regulated healthcare environment, where highly structured change management is often the norm.

Baysari MT, Carland JE, Salwei ME. Editorial: Overcoming challenges in health technology implementation to maximize patient safety. Front Health Serv 2025; 5: 1692601.

AI-assisted medication reconciliation at admission: improving safety and efficiency at the front door

Special contributor: Michael Bakker

Medication reconciliation (MedRec) at hospital admission is a cornerstone of patient safety, yet it remains highly vulnerable to omissions, duplications and dosing or frequency errors, particularly in older adults and patients with polypharmacy. While electronic health records (EHRs) have improved documentation, they have not consistently delivered reductions in clinically meaningful harm. This prospective before-and-after study evaluates whether embedding artificial intelligence (AI) — specifically natural language processing (NLP) — into admission workflows can improve both medication safety and pharmacist efficiency.

The study was conducted in a tertiary academic hospital and compared standard MedRec processes with an AI-assisted workflow over two matched 8-week periods, enrolling 840 adult admissions in total (n = 420 pre-intervention, n = 420 post-intervention). The AI tool automatically assembled a candidate preadmission medication list from heterogeneous sources — such as prior clinical notes, discharge summaries and pharmacy fill data — and flagged likely discrepancies between the best possible medication history (BPMH) and draft admission orders for pharmacist and clinician review. Importantly, final clinical decisions remained with the care team, maintaining a human-in-the-loop model of care.

The mean number of unintentional discrepancies per patient fell from 1.15 at baseline to 0.94 with AI assistance, representing an 18% relative reduction (incidence rate ratio 0.82, 95% confidence interval [CI] 0.72–0.93). This indicates fewer omissions, duplications and dosing or frequency errors entering the inpatient medication list at admission. The proportion of patients experiencing at least one high-severity potential adverse drug event (pADE) at admission declined from 21.7% to 16.0% (odds ratio 0.69, 95% CI 0.51–0.92), suggesting that the discrepancy reduction translated into clinically meaningful risk mitigation. The median time to complete medication reconciliation dropped from 66.9 min to 51.1 min:  approximately a 24% improvement in workflow efficiency. This reflects the benefit of pre-assembled medication lists and targeted, explainable flags that focus attention on high-risk mismatches rather than requiring full manual review.

The study had several key strengths, including being conducted in a real-world context within routine hospital workflows rather than a simulated environment. Maintaining human review within the model and the simultaneous measurement of safety (discrepancies and pADEs) and operational impact (time-to-completion) were also notable strengths. However, there are limitations that require attention. While conducted in a real-world context, the use of a single site limits generalisability.  The ability of the approach to algorithmically match and reconcile medication orders across more heterogeneous data sources would require further evaluation. Additionally, while clinical outcomes were reported, detailed performance metrics of the NLP extraction (e.g. per-attribute precision and recall) were not fully presented which limited the transparency of the model used in the study.

This study strengthens the case for AI as a tool to augment, rather than replace, clinical expertise. By automating the assembly of medication histories and directing clinical attention to high-risk discrepancies, the system delivered concurrent gains in safety and efficiency; an outcome that many traditional electronic MedRec systems have struggled to achieve. For pharmacy departments, the observed 15–20 min reduction in reconciliation time per patient represents meaningful reclaimed capacity. This time could be redirected toward complex medication reviews, emerging workforce demands such as prescribing and charting or other direct patient-facing clinical activities.AI-assisted medication reconciliation shows promise as a pragmatic, scalable approach to improving admission safety while easing the operational burden on pharmacists. However, achieving meaningful clinical and economic benefit at scale will require solution designs that accommodate semantic variation in how medicines are recorded across different systems. Progress toward a single, contiguous medication narrative across transitions of care will depend on robust interoperability frameworks, particularly in health services operating across diverse EHRs and ancillary clinical systems that each contribute incremental insight into the patient’s medication management continuum.

Kabir F, Tabassum N, Haque MdR, Akter S, Rehman A. Clinical impact of AI-assisted medication reconciliation at admission: a prospective before-and-after study. J Pharm Hosp Pharm 2025; 2(2): 18–25.

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