Knowledge Type: Clinical Articles

Chronic Kidney Disease (CKD) is a major global public health burden, affecting more than 10% of the general population. The global prevalence estimates indicate that approximately 13.4% (11.7–15.1%) of people are living with CKD, and between 4.9 and 7.1 million individuals with end-stage kidney disease (ESKD) require renal replacement therapy. CKD is a progressive condition marked by a sustained and usually irreversible decline in renal function.

The diagnosis of CKD is primarily based on objective laboratory results, which includes the estimation of glomerular filtration rate (eGFR) using validated equations incorporating filtration biomarkers such as serum creatinine or cystatin C, as well as the assessment of urinary markers of kidney damage, particularly albuminuria. CKD can be formally defined by a persistent reduction eGFR to <60 mL/min/1.73 m² for a duration of at least three months, irrespective of the presence of kidney damage, albuminuria or haematuria.

Risk Factors

CKD arises from a combination of modifiable and non-modifiable factors.

Modifiable risk factors:

• Diabetes: Diabetes is the leading cause of CKD and high blood glucose levels impairs kidney filtration and accelerates diabetic nephropathy. It is a very common underlying cause of CKD progression to end-stage kidney disease, which requires dialysis or kidney transplantation.
• Hypertension: Uncontrolled hypertension is a major contributor to CKD progression, and sustained elevations in blood pressure may damage the blood vessels in the kidney and increase the overall risk of kidney damage.
• Cardiovascular Disease (CVD): CVD can impair kidney function by reducing blood flow to the kidney and it is also a common consequence of CKD.
• Obesity: Overweight and obesity increase the risk of CKD by contributing to hypertension, diabetes and dyslipidemia. Obesity also increases mortality for people who already have CKD.
• Smoking: Smoking contributes to CKD progression by increasing blood pressure, reducing oxygen and damaging the blood vessels.

Non-modifiable risk factors:

• Ageing: The risk of CKD increases markedly in individuals over 60 years of age, attributable to the age-related decline in renal function.
• Genetic predisposition: Family history of CKD and a personal history of CKD, particularly hereditary disorders such as Polycystic Kidney Disease (PKD), are associated with an increased risk of CKD. The severe, recurrent or poorly recovered Acute Kidney Injury (AKI) also increases the risk of progression to CKD particularly among older adults with comorbidities.
• Aboriginal and Torres Strait Islander ≥18 years: Aboriginal and Torres Strait Islander populations experience a higher prevalence of CKD, with earlier onset and more rapid disease progression.
• Low birth weight or premature birth: low birth weight or premature birth may be linked to a reduced nephron number, thereby increasing the lifelong risk of hypertension and CKD.

Pathophysiology

CKD is defined by a gradual and irreversible loss of nephrons, resulting in a gradual decline in renal function. Initial injury to nephrons may damage the glomeruli or tubules and it reduces the number of functional nephrons. Glomerular injury facilitates albuminuria, which triggers tubular inflammation and promotes interstitial fibrosis and cellular injury. Sustained inflammation further reduces microvascular supply, leading to chronic hypoxia and accelerates nephron loss, thereby worsening the renal function over the time.

The progressive decline in kidney function disrupts systemic homeostasis, leading to azotaemia, electrolyte and acid-base imbalances, anemia due to decreased erythropoietin production, mineral and bone disorders, fluid overload, hypertension and multiple other complications, reflecting the multisystem impact of CKD.

Classification

Clinical Practice Guidelines published by Kidney Disease: Improving Global Outcomes (KDIGO) categorise CKD into five stages based on eGFR (G1-G5) or albuminuria (A1-A3) (Table 1 & 2). Guideline suggests that both decreased eGFR and increased levels of albuminuria are independently related to mortality, cardiovascular complications and end-stage kidney disease.

Table 1. GFR categories in Chronic Kidney Disease

Category	GFR (ml/min/1.73 m²)	Terms
G1	≥ 90	Normal or high
G2	60–89	Mildly decreased
G3a	45–59	Mildly to moderately decreased
G3b	30–44	Moderately to severely decreased
G4	15–29	Severely decreased
G5	< 15	Kidney failure

Table 2. Albuminuria categories in Chronic Kidney Disease

Category	Albumin Excretion Rate (mg/24 h)	Albumin-to-Creatinine Ratio (mg/mmol)	Terms
A1	< 30	< 3	Normal to mildly increased
A2	30–300	3–30	Moderately increased
A3	> 300	> 30	Severely increased

Clinical Presentation

CKD is typically asymptomatic until over 90% of kidney function has declined. Early signs may include albuminuria, nocturia and polyuria. As renal impairment progresses, patients may develop uraemic symptoms such as fatigue, nausea, pruritus and cognitive changes.

Advanced disease results in systemic manifestations including:

• CVD (heart failure, left ventricular hypertrophy, hypertension)
• Metabolic acidosis
• Bone and mineral disorders
• Anaemia due to reduced erythropoietin
• Hyperkalaemia and fluid overload
• Reduced drug clearance leading to toxicity risks

These systemic complications contribute to impaired quality of life and increased hospitalisation.

Management Principles

CKD is generally irreversible, but timely and effective management can slow its progression, reduce the risk of CVD and manage complications. Individuals with advanced chronic kidney disease experience a significant polypharmacy burden (average of 12 medications per day). Approximately 70–80% of patients are prescribed five or more medications and which increases the risk of polypharmacy-related adverse effects. With early detection and appropriate management, the progression of CKD may be reduced by up to 50%. Patients with CKD should be referred to nephrologists no later than the point at which the eGFR reaches 30 mL/min. (Coritisidis GN et al., 2011)

Pharmacological Management

Drug class	Role in CKD	Key considerations
ACEi/ARBs	First-line for reducing proteinuria and BP	Titrate to highest tolerated dose
SGLT2 inhibitors	– Recommended with or without diabetes. – Slow progression and improve CVD outcomes	– Avoid initiation at eGFR <25 mL/min/1.73m² – Dapagliflozin can be used until 15 mL/min/1.73m²
Non-steroidal MRAs (finerenone)	Persistent albuminuria in T2DM despite ACEi/ARB	Avoid if potassium >5.0 mmol/L or eGFR <25 mL/min/1.73m²
GLP-1 receptor agonists	Improve glycaemia and reduce CVD risk	TGA-approved for reducing kidney decline in T2DM and CKD
Statins ± ezetimibe	CVD risk reduction	Recommended in most adults with CKD not on dialysis

Abbreviations: Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) blood pressure (BP); Sodium-glucose co-transporter 2 inhibitors (SGLT2i); Mineralocorticoid receptor antagonists (MRA); Glucagon-like peptide-1 (GLP-1)

The STOP-ACEi trial of 411 participants with chronic kidney disease, investigated that discontinuing renin-angiotensin system inhibitors (RASi), including ACEi and ARBs did not result in clinical benefit in patients with advanced and progressive CKD. (Bhandari et al., 2024)

Non-Pharmacological Care

Lifestyle modification remains a cornerstone of CKD management, as it improves the clinical outcomes and slows the rate of disease progression. Important lifestyle strategies include smoking cessation, adequate physical activity, healthy diet and limiting alcohol intake.

Smoking cessation is strongly recommended, as tobacco use accelerates renal decline through vascular injury, oxidative stress and promoting systemic inflammation. Nutritional intervention should be individualised and adjusted according to the metabolic changes associated with each stage of CKD. In earlier stages, a general healthy balanced diet is recommended, including balanced nutrition, sodium intake reduction, and limiting highly processed foods. In later stages, dietitian involvement is essential, as patients may need to restrict foods high in potassium and phosphate to prevent complications such as hyperkalaemia and bone disease. Alcohol consumption should be no more than 10 standard drinks per week and no more than 4 drinks on a single day. Regular physical activity is also strongly encouraged. The goal is to achieve 2.5–5 hours of moderate to intensity aerobic exercise each week, along with strength training to maintain muscle mass and physical function.

Conclusion

CKD represents a major public health challenge in Australia, affecting a substantial proportion of the population and contributing markedly to morbidity and mortality. According to the Australian Institute of Health and Welfare (AIHW), CKD contributed to approximately 11% of all deaths in 2022, emphasising its significant burden on national health outcomes.

CKD imposes a significant economic burden, particularly in advanced stages requiring dialysis or transplantation. It is also associated with high rates of hospitalisation and healthcare services. Cardiovascular complications are the predominant drivers of both morbidity and mortality among CKD patients, highlighting the need for integrated care strategies that address both renal and cardiovascular health. With early recognition and appropriate treatment, progression to kidney failure can often be significantly delayed and improve the quality of life and reducing healthcare burden.

Dyshidrotic eczema, also known as pompholyx, vesicular dermatitis, or vesicular hand and foot dermatitis, is a type of dermatitis which presents as small 1-2 mm fluid-filled vesicles on the palms, along the fingers and on the soles of the feet (1). It usually resolves after two to three weeks with scaling and peeling, and is typically extremely itchy, chronic, recurrent and often symmetric (2).

It is unclear what causes dyshidrotic eczema, but it is associated with atopic dermatitis and the occurrence does not seem to correlate with any specific age or gender (2). The condition may be precipitated by acute inflammatory tinea, or molluscum contagiosum. Other aggravating factors include overheating, irritants, stress, immunoglobulin therapy, hyperhidrosis, smoking, and taking the oral contraceptive pill or aspirin (1,2).

Early treatment is important as dyshidrotic eczema is often difficult to treat and specialist involvement is usually required (1). Secondary infections may occur and a bacterial swab should be taken if clinical signs of infection are present. The condition may also lead to inflammation of the skin around the finger or toenail as well as nail dystrophy (2).

First line treatment for dyshidrotic eczema includes potent corticosteroids, such as betamethasone dipropionate 0.05% cream or ointment, or betamethasone valerate 0.1% cream or ointment, or mometasone furoate 0.1% cream or ointment (1). The cream or ointment should be applied once or twice daily until the skin is clear and with or without a modified dressing (1).

For recurrent episodes of acute dyshidrotic eczema, betamethasone dipropionate 0.05% ointment in an optimised vehicle should be used once or twice daily until the skin is clear or for up to two weeks, with or without a modified dressing (1).

Oral corticosteroids such as prednisolone or prednisone may be required for dyshidrotic eczema where significant blistering and extreme itching occurs (1). The recommended dose is 15-25mg orally once daily for 3 to 4 days, then tapered over 1-2 weeks to minimise rebound flares (1).

General measures to treat dyshidrotic eczema include avoiding aggravating factors where possible, and using potassium permanganate soaks during the acute phase, which helps to dry exudative lesions (2). Regular use of emollients and moisturisers and antihistamines for itching may also be helpful (2). Dermatologists may also use phototherapy with ultraviolet light A, as well as second-line agents such as methotrexate, depending on the severity and behaviour of the disease (2).

 

 

 

 

Psychotropic medicines are central to the management of many mental health conditions. However, their use is associated with clinically significant metabolic adverse effects, including weight gain, dyslipidaemia, impaired glucose tolerance and type 2 diabetes, hypertension, and ultimately increased cardiovascular risk. These adverse effects are commonly associated with antipsychotics, although some antidepressants and mood stabilisers may also contribute.

Monitoring of metabolic adverse effects is not always optimal, which may contribute to the substantial morbidity and premature mortality in people living with severe mental illness.

Why metabolic monitoring matters

People with severe mental illness already experience poorer physical health outcomes than the general population.

An Australian report found that people living with mental illness are:

• Twice as likely to have cardiovascular disease;
• Twice as likely to have respiratory disease;
• Twice as likely to have metabolic syndrome;
• Twice as likely to have diabetes;
• Twice as likely to have osteoporosis;
• 65% more likely to smoke; and
• Six times more likely to have dental problems.

This population also accounts for around one third of all avoidable deaths. People living with severe mental illness are particularly at risk and are estimated to die between 14 and 23 years earlier than the general population.

Cardiovascular disease is a leading cause of premature death in this population. People with serious mental illness are more likely to have risk factors, such as smoking and poor diet. However, psychotropic medicines can further exacerbate this risk through multiple mechanisms, including:

• Weight gain (via increased appetite, reduced satiety, sedation-related inactivity);
• Reduced insulin sensitivity;
• Dyslipidaemia; and
• Hypertension.

Some studies have found that around 40% of people with chronic schizophrenia meet the criteria for metabolic syndrome.

Antipsychotics and relative metabolic risk

While all antipsychotics may contribute to metabolic abnormalities, the risk differs significantly between agents. Clozapine and olanzapine are considered high risk, while chlorpromazine is considered medium to high risk. It may be appropriate to avoid these agents in patients who are overweight, at high risk of cardiovascular disease, or have a family history of diabetes.

Antipsychotics associated with a medium risk include quetiapine, risperidone, and paliperidone. Asenapine, aripiprazole, brexpiprazole, cariprazine, haloperidol, lurasidone, and ziprasidone are considered low risk, although metabolic adverse effects can still occur.

Significant weight gain can occur within 6-8 weeks of initiating an antipsychotic, and early weight gain may be a predictor of long-term weight gain. Weight gain may be the most visible sign of metabolic disturbances and is often the most concerning for patients. However, it is important that weight is not the only focus of monitoring.

Dyslipidaemia and impaired glucose tolerance can develop even with minimal weight change, particularly in people with pre‑existing risk factors. Therefore, normal weight does not necessarily equal low cardiometabolic risk. Routine laboratory monitoring is essential, even when weight appears stable.

The potential for metabolic effects to develop early highlights the importance of baseline assessment and early follow-up.

Baseline assessment

Baseline data should be documented so that early changes can be identified. The Therapeutic Guidelines recommend assessment of the following parameters prior to initiating a psychotropic:

• Blood pressure and heart rate
• Weight, waist circumference and body mass index (BMI)
• Blood glucose and glycated haemoglobin (HbA1c) concentration
• Lipid concentrations, including triglycerides
• Level of physical activity
• Movement (involuntary or voluntary)
• Full blood count
• Blood prolactin concentration
• Electrocardiogram (as many antipsychotics can prolong the QT-interval).

Waist circumference is particularly important, as it may identify central adiposity even when weight or BMI fall within a healthy range.

Ongoing monitoring

Metabolic abnormalities often develop soon after antipsychotic initiation or dose escalation and guidelines emphasise the importance of early follow‑up. The Therapeutic Guidelines recommend monitoring of weight, waist circumference and BMI at 1 month, 2 months, 3 months, and 6 months after starting treatment, and every 6 months thereafter. Fasting blood glucose and HbA1c should be measured at 3 months and 6 months after initiating therapy and every 6 months thereafter. It is also recommended to measure fasting lipids every 6 months.

Clozapine requires especially close metabolic and physical health surveillance in addition to mandatory haematological monitoring.

Metabolic risk persists throughout treatment and may accumulate over time. Therefore, monitoring must continue long term. Transitions of care, such as discharge from inpatient units or changes between prescribers, are high‑risk points where monitoring responsibility can be lost.

Addressing abnormal results

Abnormal findings should trigger timely intervention, which may include lifestyle support or adjustment of psychotropic therapy.

Weight gain is often considered clinically significant when it increases by 7% or more from baseline. Lifestyle interventions are the first-line options and should be tailored to the patient. Studies suggest that a weight loss of at least 5% of body weight is associated with reduced cardiovascular risk and mortality.

A review of all other concurrent medications should be undertaken to identify any other drugs that may be contributing to the metabolic abnormalities. For example, hyperglycaemia is a common adverse effect of glucocorticoids, and weight gain can occur with the antiepileptics valproate and carbamazepine.

In some cases, switching to an antipsychotic with a lower metabolic risk profile may be considered. However, this must be carefully weighed against the risk of psychiatric destabilisation.

Where lifestyle interventions are not effective and adjusting antipsychotic therapy is either ineffective or inappropriate, metformin may be considered to treat antipsychotic-associated weight gain. Studies in patients with schizophrenia or schizoaffective disorder found a mean weight loss of 3.27kg (95% CI: −4.66 to −1.89, p < 0.001) and a reduction in BMI of −1.13 kg/m² (95% CI: −1.61 to −0.66). Additional benefits may include improved insulin sensitivity, reduced hepatic glucose production, and improved peripheral glucose uptake.

Pharmacological treatment may also be required for established dyslipidaemia, hypertension, or diabetes, in line with standard clinical guidelines.

Summary

Metabolic monitoring is a core safety requirement for patients receiving psychotropic medicines, particularly antipsychotics. Baseline assessment, early follow‑up, and long‑term monitoring is required to ensure the safe use of these medicines.

Monoclonal antibodies (mAbs) are biologic medicines that bind to specific antigens with high specificity. The targets for these proteins are varied and include cancer cells, inflammatory mediators, and pathogens. Their use has grown considerably over the past few years with an expanding range of indications.

It is important to identify medicines that fall into this category as mAbs often have specific requirements for storage, administration, and monitoring. Currently, these medicines can be easily identified by the suffix -mab. However, this suffix has been discontinued and mAbs named after 2021 will no longer end in -mab.

Naming conventions

Biological medicines supplied in Australia are identified using the Australian Approved Biological Name. This name is invariably an international non-proprietary name (INN), supplied by the INN committee of the World Health Organization (WHO). In the absence of an INN, an appropriate name is agreed between the sponsor of the new medicine and the Therapeutic Goods Administration (TGA) during the medicine registration process.

Monoclonal antibody names follow a structured naming convention established by the WHO. The original system, introduced in 1991, assigned all mAbs the suffix –mab (e.g. adalimumab, infliximab). However, a large number of mAbs with increasing structural complexity have been developed since then which has led to various revisions of the nomenclature system.

Original naming pattern: Prefix + Target Substem + Source Substem + Suffix

1. Prefix

• Unique and arbitrary
• Helps distinguish between drugs

2. Target Substem

Indicates what the antibody targets:

• -tu-: tumour (e.g., cancer therapies)
• -li-: immune system (e.g., inflammatory diseases)
• -vi-: viral targets

3. Source Substem

Historically indicated how “human” the antibody is:

• -o-: murine (mouse)
• -xi-: chimeric
• -zu-: humanized
• -u-: fully human

4. Suffix

• -mab: identifies the drug as a monoclonal antibody

Example: Adalimumab

• ada- (prefix)
• -li- (immune system target)
• -u- (fully human)
• -mab (monoclonal antibody)

This tells us that adalimumab is a fully human monoclonal antibody targeting the immune system.

Recent Changes to Nomenclature

In recent years, the WHO has simplified mAb naming by removing the source substem (e.g., -xi-, -zu-). This change reflects advances in biotechnology and reduces confusion, as most modern antibodies are highly humanised regardless of classification.

While mAbs have previously shared the common suffix -mab, this naming system has become unsustainable. With over 800 mAbs already named using “-mab”, it has become increasingly harder to create distinct, recognisable, and clinically meaningful names. Secondly, the structural diversity of this drug class has also increased (e.g., fragments, bispecific antibodies, engineered constructs), making the single suffix overly simplistic.

In response, the WHO formally revised the INN system in 2021, eliminating the universal “-mab” suffix for new agents. Medicines named prior to 2021 retain their original names..

The New Naming System

Under the updated INN scheme, monoclonal antibody-based therapies are now grouped into four categories, each with a unique suffix that reflects structure and function:

1. -tug → Unmodified immunoglobulins

• Full-length antibodies with no engineered changes in constant regions
• Structurally closest to naturally occurring antibodies

2. -bart → Engineered (artificial) immunoglobulins

• Full-length antibodies with intentional modifications (e.g., altered Fc function, glycoengineering)

3. -mig → Multispecific antibodies

• Includes bispecific or multispecific constructs
• Designed to bind multiple targets simultaneously

4. -ment → Antibody fragments

• Includes partial antibodies or fragments lacking full Fc regions
• Often used for improved tissue penetration or specific targeting

These four suffixes will be used in place of the suffix mab for all mAbs approved after 2021.

There are also some new infixes which denote the target, as shown in the updated list below:

• ami – serum amyloid protein (SAP)/amyloidosis
• ba – bacterial
• ci – cardiovascular
• de – endocrine
• eni – enzyme inhibition
• fung- fungal
• gro – skeletal muscle mass related growth factors & receptors
• ki – cytokine & cytokine receptor (formerly: interleukin)
• ler – immunomodulating allergen
• pru – immunomodulating immunosuppressive
• sto – immunomodulating immunostimulatory
• ne – neural
• os – bone
• ta – tumour
• toxa – toxin
• vet – veterinary use
• vi – viral

While the infix can provide an idea of how the drug works, it is important to remember that this is assigned according to the proposed mechanism of action at the time of naming. The mechanism of action may not be completely understood at that time and may vary by indication.

The new naming structure follows the pattern of: Prefix + infix + suffix

• Prefix: unique, arbitrary (chosen by pharmaceutical company for distinctiveness)
• Infix: may indicate therapeutic target
• Suffix: indicates structural class

The pipeline for biologics is rapidly expanding. Many investigational therapies already use the new naming scheme. For example, etentamig is currently being evaluated in phase 3 clinical trials for the treatment of relapsed or refractory multiple myeloma.

Understanding the new naming conventions helps to avoid confusion once these drugs reach clinical practice.

Conclusion

The shift away from the “-mab” suffix reflects the evolution of mAb therapies, which have emerged as a diverse and complex class of medicines.

While the naming changes occurred in 2021, the average clinical development time for mAbs is around six to nine years. As a result, the full impact of this naming system is only beginning to emerge and will become increasingly relevant in clinical practice as new therapies are approved.

Around two thirds of Australian adults are living with overweight or obesity, and around a third are obese. Obesity presents a significant clinical challenge in the safe use of medicines.

Physiological changes associated with increased body mass can include:

• Altered cardiac output
• Increased adipose tissue
• Altered plasma protein binding
• Modified renal and hepatic function.

These physiological changes can all influence how drugs are absorbed, distributed, metabolised, and eliminated. Therefore, there is the potential for underdosing (which may lead to treatment failure) or overdosing (which may cause toxicity) if standard dosing strategies are used.

Pharmacokinetic changes in obesity:

• Absorption
  • Gastrointestinal transit time is typically accelerated, which can reduce the solubilisation and absorption of some orally administered drugs. However, absorption is not significantly affected for most oral drugs.
  • Absorption following subcutaneous, intramuscular, and transdermal administration may be less predictable. The increased amount of subcutaneous adipose tissue with its reduced blood flow could affect bioavailability.
  • Consideration of needle size is required to avoid administration errors for drugs administered intramuscularly. In some cases, standard needles may be too short and result in administration to the subcutaneous space.
• Distribution
  • Lipophilic drugs generally have a large volume of distribution as they readily distribute into adipose tissue. In patients with obesity, accumulation in adipose tissue may slow the elimination of the drug. This prolongs the drug half-life, increasing the risk of accumulation during chronic dosing. Examples of highly lipophilic drugs are phenytoin, diazepam, midazolam, propranolol, and verapamil.
  • Hydrophilic drugs are more likely to remain in the extracellular fluid, giving them a lower volume of distribution which more readily correlates with lean body mass. Examples of highly hydrophilic drugs are aminoglycosides, lithium, aciclovir, glycopeptides, beta-lactams, low-molecular-weight heparins
  • Plasma protein binding may be altered.
• Metabolism
  • Liver size and blood flow may increase, potentially enhancing the metabolism of some drugs.
  • Fatty liver disease may impair hepatic metabolism in some patients.
  • Some evidence suggests that glucuronidation reactions are significantly increased in obesity. Drugs metabolised via this pathway include paracetamol, some opioids (e.g. codeine, morphine), benzodiazepines (e.g. lorazepam, oxazepam, temazepam), and lamotrigine.
• Elimination
  • Kidney size and renal blood flow may increase which can enhance renal elimination of drugs. However, obesity is a risk factor for chronic kidney disease (CKD), which can lead to significantly reduced drug clearance.
  • Estimating renal function can be more challenging in obesity as standard equations can be inaccurate. The Cockcroft-Gault equation may overestimate clearance if total body weight is used; using adjusted body weight may improve accuracy.

Weight metrics

There are many weight metrics available, including:

• Total body weight (TBW): actual weight
  • Using TBW to dose drugs in patients who are obese makes the assumption that the pharmacokinetics of the drug are linearly scalable regardless of body weight. Relying on TBW may lead to significant overdosing.
• Ideal body weight (IBW): based on height
• Adjusted body weight (ABW): used when TBW significantly exceeds IBW
• Lean body weight (LBW): reflects metabolically active tissue.
  • This is often a useful metric to use when dosing drugs in obesity. Calculators are available in the Therapeutic Guidelines which simplifies the use of this metric.

The most appropriate metric will depend on the pharmacokinetic profile of the drug being dosed.

Medications that may require dose adjustments

1. Antimicrobials

• Vancomycin – dosed using TBW, requires therapeutic drug monitoring
• Aminoglycosides (e.g. gentamicin) – expert advice is recommended for dosing and monitoring of aminoglycosides in obesity. The volume of distribution is difficult to predict. Methods used to calculate doses include LBW, ABW, and dosing nomograms. Prompt plasma concentration monitoring is recommended as initial doses can vary significantly depending on the method used, particularly for patients at the higher end of the weight range.
• Beta-lactams – may require higher or more frequent dosing due to increased volume of distribution and clearance. For example, studies show that a 2g dose of cefazolin for surgical antibiotic prophylaxis is associated with a higher rate of postoperative infections in obese patients. The Therapeutic Guidelines now recommend a cefazolin dose of 3 g for surgical prophylaxis for patients who weigh more than 120 kg (with a GFR > 40 mL/min).
• Linezolid – standard dosing may be insufficient in obesity.

2. Anticoagulants

• Low molecular weight heparins (e.g. enoxaparin) – often dosed by TBW, but requires caution in obesity. Dose adjustment may be required for patients with a body weight > 150kg or a BMI > 40kg/m².
• Unfractionated heparin – weight-based dosing, but monitoring is essential.
• Direct oral anticoagulants (DOACs) – limited data in morbid obesity.

3. Sedatives and anaesthetics

• Propofol – induction dosing often based on LBW, maintenance may use TBW.
• Midazolam – increased volume of distribution; prolonged effects possible.
• Opioids – lipophilic; dose adjustment may be required to avoid accumulation.

4. Chemotherapy

• Historically underdosed due to toxicity concerns.
• Current evidence supports using TBW for most agents to avoid compromising efficacy.

5. Cardiovascular drugs

• Beta-blockers and calcium channel blockers – variable effects; lipophilic agents may accumulate.
• Digoxin – IBW may be used due to limited distribution into adipose tissue.

Medications that typically do not require dose adjustments

1. Medications with a wide therapeutic index

• This includes many penicillins as well as some cephalosporins. Standard dosing is often sufficient unless severe obesity is present.

2. Hydrophilic drugs with limited distribution

• Drugs that primarily remain in the plasma or extracellular fluid may not require dose adjustment. Ideal body weight may be used for these agents. An example would be atenolol.

3. Antidepressants

• Selective serotonin reuptake inhibitors (SSRIs) typically do not require dose adjustment, although clinical response should guide therapy.

Special considerations

Therapeutic drug monitoring (TDM) is important for drugs with a narrow therapeutic index, e.g. vancomycin, aminoglycosides. It is also important to remember that evidence is limited at extremes of body weight, i.e. BMI ≥ 40 kg/m². Individualised dosing and monitoring is essential.

Practical considerations:

• Identify drug characteristics (i.e. lipophilicity, therapeutic index)
• Choose appropriate weight scalar (e.g. TBW, IBW, etc.)
• Initiate therapy with recommended obesity-specific dosing, if available
• Monitor clinical response and drug levels where appropriate
• Adjust dose based on efficacy and toxicity.

Conclusion

Drug dosing in obese patients requires careful consideration as pharmacokinetics and pharmacodynamics may be altered. While some medications can be safely administered using standard dosing, others require individualised dosing to avoid toxicity or therapeutic failure. Evidence-based guidelines and therapeutic monitoring should be utilised to optimise outcomes.

As the prevalence of obesity continues to rise, refining dosing strategies for this population is an important aspect of safe and effective clinical care.

Patient safety is a shared responsibility across the healthcare team. Healthcare professionals often work within complex systems where high workloads, time pressures, communication challenges, and human factors can increase the risk of incidents. Incident reporting, including the reporting of near misses, is a cornerstone of clinical governance and continuous quality improvement. When used effectively, it supports learning, strengthens systems, and reduces the risk of patient harm.

What Is Incident Reporting?

The Australian Commission on Safety and Quality in Healthcare (the Commission) defines clinical incidents as “an event or circumstance that resulted, or could have resulted, in unintended or unnecessary harm to a patient or consumer; or a complaint, loss or damage.” Examples of clinical incidents include:

• Medication errors (prescribing, dispensing, administration, or monitoring);
• Patient falls or pressure injuries;
• Delays or failures in diagnosis or treatment;
• Documentation or handover errors;
• Procedural errors;
• Equipment or system failures; and
• Inappropriate treatment.

The most serious patient incidents are classified as sentinel events. Sentinel events are those that are completely avoidable and result in serious harm or death of a patient.

In Australian hospitals, incidents are reported through local electronic reporting systems and managed within organisational clinical governance frameworks. Incident reporting aligns with the National Safety and Quality Health Service (NSQHS) Standards, particularly the Clinical Governance, Medication Safety, Communicating for Safety, and Comprehensive Care standards.

Near Misses

A near miss is an incident that did not cause harm. This may be because it was identified and corrected in time, or because circumstances prevented harm. Examples of near misses include:

• A pharmacist identifying an incorrect dose before dispensing;
• A nurse detecting a mismatch between a medication order and the patient;
• A doctor identifying a prescribing error during chart review; and
• A clinician recognising incorrect equipment settings before use.

Near misses are just as important to report as incidents causing harm. The root cause of near misses and adverse clinical incidents are likely similar. Therefore, reporting near misses can identify vulnerabilities in systems and processes and provide an opportunity to improve safety before a patient is affected.

A further consideration for reporting near misses is that only a small proportion of incidents lead to adverse events. Therefore, only reporting events that led to serious outcomes provides insufficient data for analysis.

The Commission encourages the reporting of near misses, emphasising that they should be viewed as opportunities for improvement.

Why Reporting Matters

Reporting incidents and near misses is important to:

• Improve patient safety and care quality.
  • Incident and near miss reports allow organisations to identify patterns, trends, and high‑risk areas. This information supports system-level improvements, e.g. changes to policies, workflows, or electronic systems, and the implementation of education programs.
• Support a just and learning culture.
  • Australian healthcare organisations promote a just culture, where staff are encouraged to report incidents without fear of blame or punishment. The focus is on understanding what went wrong and why, rather than who was involved.
• Facilitate learning across disciplines.
  • Many incidents involve multiple points in the care pathway. Reporting enables shared learning across medical, nursing, pharmacy and other allied health teams.
• Meet professional and regulatory expectations.
  • All healthcare professionals have ethical and professional obligations to promote patient safety.
  • Incident reporting supports compliance with NSQHS Standards and organisational risk management processes.

Common Barriers to Reporting

Underreporting of clinical events remains a problem, particularly for near misses. One study found that only 13% of medication events are reported.

Barriers to reporting may include:

• Fear of blame, disciplinary action, or reputational impact;
• Time pressures and competing clinical priorities;
• Belief that the incident was minor;
• Uncertainty about what should be reported; and
• Lack of feedback on submitted reports.

In one Australian study, lack of feedback was the most commonly stated barrier for reporting (57.7% for doctors and 61.8% for nurses). Providing feedback to healthcare professionals in the form of newsletters and discussions at departmental meetings has been found to increase reporting rates. Timely and meaningful feedback should also be provided to patients and carers, as appropriate.

Responsibilities

Frontline clinicians have a number of important roles and responsibilities in incident management, including:

1. Recognising reportable events

• All clinicians should report
  • Incidents that resulted in patient harm;

• • Near misses with the potential for harm;
  • Recurrent unsafe conditions or system issues; and
  • Errors intercepted at any stage of care.

2. Contributing to high-quality reports

• Effective incident reports should be:
  • Objective and factual – describe what happened, while avoiding assumptions or judgments;

• • Clear and specific – include relevant details such as timing, location, and contributing factors; and
  • Timely – submitted as soon as practicable after the event.
• Reports should focus on system factors (e.g. communication gaps, workload, design of charts or electronic systems) rather than individual performance.

3. Escalating Immediate Risks

• If an incident presents an ongoing or immediate risk to patient safety, concerns should be promptly escalated through clinical and managerial pathways, in addition to completing an incident report.

 

4. Learning from near misses

• Near misses are powerful learning tools as they can reveal system weaknesses without patient harm.
• Learning from near misses involves:
  • Reviewing reports to identify recurring themes or trends;

• • Analysing contributing factors such as interruptions, unclear documentation, or handover issues;
  • Implementing targeted improvements (e.g. standardised processes, decision support, double-checks); and
  • Sharing lessons learned with clinical teams to prevent recurrence.
• Feedback to staff about changes resulting from these reviews is critical. When clinicians can see that reporting leads to real improvements, engagement and reporting rates increase.

5. Building a strong reporting culture

• Clinicians can contribute to a strong reporting culture by supporting colleagues, discussing safety concerns openly, and reinforcing the fact that reporting is a professional responsibility and a positive action.
• Healthcare organisations and leaders can also support effective incident reporting by:
  • Promoting psychological safety and a just culture;
  • Providing education on incident and near miss reporting;
  • Ensuring reporting systems are easy to access and use;
  • Communicating outcomes and improvements arising from reports; and
  • Encouraging multidisciplinary review and learning.

Conclusion

Incident reporting and learning from near misses are essential to the provision of safe, high‑quality care. Nurses, doctors, and pharmacists each bring unique perspectives to identifying risks and improving systems. By reporting incidents and near misses, clinicians contribute to shared learning, stronger systems, and better outcomes for patients.

Every incident report, regardless of harm, has the potential to prevent future incidents and improve care.

Further information on incident management, including specific resources published by states and territories, are available from the Commission.

 

The product information for pegylated liposomal doxorubicin (Caelyx®) has been updated. The adverse effects section now includes advice that renal-limited thrombotic microangiopathy (TMA) has been reported in association with high cumulative exposure.

Pegylated liposomal doxorubicin (PLD) is a specialised formulation of the anthracycline chemotherapeutic, doxorubicin. Encapsulation of doxorubicin in polyethylene-glycol (PEG)-coated liposomes prolongs its circulation time, enhances tumour targeting, and may reduce key toxicities such as cardiotoxicity and myelosuppression. These properties have made PLD a valuable option in the treatment of a range of malignancies, including Kaposi sarcoma, ovarian cancer, and breast cancer.

While pegylation reduces some toxicities, this formulation is associated with higher rates of palmar-plantar erythrodysesthesia. More recently, rare reports have emerged of renal-limited TMA.

What is renal-limited thrombotic microangiopathy?

Thrombotic microangiopathy refers to a group of conditions characterised by:

• Endothelial injury in microvessels;
• Microvascular thrombosis; and
• Organ dysfunction.

The condition is often drug-induced, although other causes include autoimmune diseases, malignant hypertension, and infections.

When TMA affects the kidneys without systemic haemolysis or thrombocytopaenia, it is classified as renal-limited TMA. While not a common finding, renal-limited TMA has a poor prognosis. One recent study demonstrated that 30% of these patients will progress to end-stage kidney disease.

Case reports

Renal‑limited TMA has previously been reported in association with PLD, although many early cases involved patients also taking other medications known to cause TMA. More recently, the American Journal of Kidney Diseases published a case report of two patients who developed this condition in association with PLD without exposure to other TMA-causing drugs.

Case details include:

• High cumulative PLD doses (760mg/m² and 1240mg/m²)
• Proteinuria and rising serum creatinine
• Kidney biopsy consistent with chronic TMA
• No exposure to other drugs known to cause TMA
• Stabilisation or improvement occurred once PLD was ceased. Neither patient required dialysis.

Additional clinical reports:

• Renal-limited TMA was reported in an 80-year old man after extended PLD monotherapy for metastatic Kaposi sarcoma. Acute kidney injury resulted and the patient required haemodialysis. The patient’s clinical history, laboratory, and kidney biopsy data all support PLD as the primary aetiologic factor.
• A case was reported in a kidney transplant recipient with Kaposi sarcoma in remission following treatment with PLD. This patient developed a slowly progressive renal-limited TMA that was proven on biopsy. Kidney function improved following discontinuation of PLD. The patient presented with Kaposi sarcoma recurrence and, due to poor tolerance to alternative therapies, was restarted on PLD. Kidney function started to deteriorate again three months after resuming PLD therapy.

Across case reports, high cumulative PLD exposure (often >700-800mg/m²) is a common factor. However, one report occurred at a lower cumulative dose (~300mg/m²) in a patient with preexisting chronic kidney disease (CKD) and hypertension. This highlights the potential for patient-specific susceptibilities.

Clinical features

Renal-limited TMA linked to PLD tends to present with:

• Gradual rise in serum creatinine;
• Proteinuria;
• Hypertension; and
• Little or no evidence of systemic haemolysis or thrombocytopaenia.

The mechanism for how PLD may cause this condition is not understood. However, processes implicated in other drug-induced cases of TMA include:

• Endothelial cell injury due to oxidative stress;
• Platelet aggregation triggered by damaged microvascular endothelium; and
• Impaired microcirculatory blood flow in glomeruli.

Management and monitoring

Early recognition is critical to minimise renal impairment. Increases in creatinine, new proteinuria or hypertension in patients on PLD may warrant evaluation for renal-limited TMA. Renal biopsy is required for definitive diagnosis.

Management of renal-limited TMA includes removal of the causative agent along with supportive care. Cessation of the causative agent often stabilises or improves kidney function if implemented early.

A wide range of medications have been associated with drug‑induced TMA, with chemotherapeutics and quinine most commonly implicated. However, establishing causal relationships with drugs is challenging and the condition is thought to be under-recognised. Some medications linked with TMA are shown in Table 1.

Table 1. Drugs associated with TMA (adapted from Mazzierli 2023)

Chemotherapeutic drugs	Targeted cancer drugs	Immunosuppressants	Antimicrobials	Other drugs
Docetaxel	Alemtuzumab	Certolizumab pegol	Levofloxacin	Valproic acid
Gemcitabine	Imatinib	Cyclosporin	Ciprofloxacin	Quetiapine
Mitomycin C	Lenvatinib	Tacrolimus	Metronidazole	Quinine
Oxaliplatin	Nintedanib	Interferon	Penicillins	Cocaine
Pentostatin	Palbociclib	Leflunomide	Rifampicin	Oxycodone hydrochloride SR (drug misuse)*
Vincristine	Regorafenib	Sirolimus	Trimethoprim-sulfamethoxazole	Clopidogrel
Lomustine	Sunitinib	Everolimus	Famciclovir	Bupropion
Bortezomib	Bevacizumab	Adalimumab	Valaciclovir	Estrogen/ Progesterone
Carfilzomib	Ramucirumab			Hydroxychloroquine
Ixazomib	Pazopanib			Simvastatin
Daunorubicin
Tamoxifen
Trastuzumab

*Cases of TMA secondary to the intravenous use of the sustained-release product intended for oral use. This is suspected to be related to the polyethylene oxide coating on these tablets which may be directly toxic to endothelial cells. Other excipients may also play a role.    

Conclusion

Pegylated liposomal doxorubicin has some potential advantages over conventional doxorubicin in terms of reduced cardiotoxicity and enhanced pharmacokinetics. However, it may be associated with renal-limited TMA. While this adverse event is rare, the clinical outcome is often poor.

Awareness of this association, along with active monitoring of renal function and early investigation of kidney injury are vital. These steps can prevent irreversible kidney damage and preserve renal function in affected patients.

Infusion reactions are unexpected adverse responses that occur during or shortly after the infusion of a medication. These reactions can be allergic or non-allergic and may affect any organ system. Many reactions are mild, but severe and even life-threatening reactions can occur. Therefore, early recognition and prompt intervention is essential.

There is a wide spectrum of signs and symptoms associated with infusion reactions, including:

• Flushing;
• Itching;
• Urticaria;
• Fever or chills;
• Dyspnoea or chest tightness;
• Hypotension or hypertension;
• Back or abdominal pain; and
• Gastrointestinal effects (e.g. nausea, vomiting).

Infusion reactions can have a significant impact on patients and the healthcare system. They may necessitate prolonged infusion times, dose reductions or delays, discontinuation of therapy, or hospitalisation.

The onset and severity of these reactions can also differ widely which impacts their management:

• Mild to moderate infusion reactions
  • Often non-allergic and related to cytokine release.
  • Typical features include flushing, mild dyspnoea, fever, pruritus
• Severe infusion reactions
  • May involve airway compromise
  • Typical features include bronchospasm, angioedema, severe hypotension.
• Delayed reactions
  • May occur hours to days after administration. These reactions are less common and may present with symptoms such as fever, fatigue, joint pain, and muscle aches.
  • Drugs associated with delayed infusion reactions include monoclonal antibodies, parenteral iron, and enzyme replacement therapies.

Clinically, it is often difficult to distinguish allergic from non‑allergic infusion reactions. Anaphylaxis is the most severe presentation of an allergic reaction. This is characterised by rapidly developing and life-threatening problems affecting the airway, breathing and circulation which is often accompanied by skin or mucosal changes. This is a medical emergency requiring prompt intervention.

Anaphylactoid reactions mimic the signs and symptoms of anaphylaxis. However, these reactions are not IgE-mediated and can occur upon first exposure to an agent. The immediate management of these two conditions is the same.

Risk factors

Infusion reactions can occur with a wide range of medicines. Drug classes that are more commonly implicated include:

• Monoclonal antibodies;
• Taxanes;
• Platinum-based chemotherapy;
• Pegylated liposomal doxorubicin; and
• Asparaginase.

Non-allergic infusion reactions are typically more likely to occur with the first or second exposure to a drug. The rate of infusion is a significant factor, and concomitant medications may also have an impact. The formulation may be important to consider as some excipients may contribute to these reactions (e.g. polysorbate 80).

Infusion reactions can occur with subcutaneous administration, although the incidence is much lower than intravenous. When a medication is administered subcutaneously, serum levels rise more slowly than when the same medication is administered intravenously. This results in later and lower peak serum concentrations (C_max). It is thought that a faster and higher C_max is associated with a more rapid release of cytokines. Therefore, subcutaneous administration may reduce the risk of cytokine-mediated reactions. However, this is often at the expense of an increase in local injection site reactions.

Monoclonal antibodies

Many monoclonal antibodies are associated with infusion reactions. Studies suggest that the origin of the drug (i.e. human, chimeric, or mouse) does not correlate with the risk of reaction. This supports the understanding that most of these reactions are caused by cytokine release, rather than an IgE-mediated allergy. However, anaphylaxis has also been reported with monoclonal antibodies.

Rituximab is known to have a particularly high incidence of infusion reactions. In clinical trials of lymphoma patients, the incidence was as high as 77% for the first infusion, reducing to 30% for the fourth infusion. Most of these reactions could be classified as mild to moderate, with severe reactions reported in around 10% of patients. The incidence of infusion reactions when rituximab is used for non-cancer indications appears to be significantly lower.

These reactions are typically non-allergic and can be reduced with premedication and adherence to a slower infusion rate for the first dose (refer to the product information and/or clinical guidelines for recommendations). Particular care is required in patients with a high tumour burden or a high number of circulating malignant cells as they may be at greater risk of severe infusion reactions.

Platinum agents

Carboplatin, cisplatin, and oxaliplatin are all associated with infusion reactions. In most cases these reactions are IgE-mediated, and their incidence tends to increase with each treatment cycle. For oxaliplatin, cycles 9-10 are reported to be the average time of infusion reactions to first occur. For carboplatin, they tend to occur around cycle 5-6.

Vancomycin

Rapid administration of vancomycin can cause non-allergic infusion reactions. Symptoms can include hypotension, flushing, erythema, urticaria, pruritus, and pain or muscle spasms of the chest and back. Recovery is typically rapid with discontinuation of the infusion. Other potential causes of the reaction (e.g. anaphylaxis) must be ruled out.

Depending on the severity of the reaction, it may be appropriate to restart the infusion at a lower rate once the symptoms have resolved. In these cases, the patients should be closely monitored in case of further reaction.

Response

Infusion reactions should be managed according to local policies. The following is a general overview of how a reaction may be managed, although strategies may differ for specific drugs.

1. Stop the infusion
2. Assess the patient
   • Check airway, breathing, circulation, vital signs, and symptom severity
3. Maintain IV access
4. Notify the prescriber
   • Drug, dose, and timing
   • Symptoms and vital signs
   • Any interventions already performed
5. Administer emergency medication as ordered. Depending on the severity, this may include
   • Antihistamines
   • Corticosteroids
   • Bronchodilators
   • Adrenaline for anaphylaxis
6. Supportive care as appropriate
   • g. oxygen, fluids, continuous monitoring
7. Document
   • Comprehensively document details of reaction, including onset, symptoms, interventions, patient response.
   • Thorough documentation can help to distinguish between allergic and non-allergic reactions. E.g. anaphylactic reactions typically occur within the first few minutes of the infusion, while reactions related to cytokine release usually begin within 30-120 minutes of beginning the infusion.
8. Prepare for rechallenge (if appropriate)
   • Some therapies may be restarted at a slower rate once symptoms resolve, depending on prescriber directions and local policy.
   • Patients who experience mild to moderate infusion reactions are more likely to tolerate re-challenge (with a slower infusion rate and appropriate premedication) compared to patients who experience severe reactions.

Immediate escalation is required for patients who show any of the following signs or symptoms:

• Airway compromise
• Respiratory distress
• Hypotension
• Altered consciousness
• Rapidly progressing symptoms.

The presence of these symptoms may indicate anaphylaxis or a severe reaction requiring an emergency response.

Prevention strategies

There are many strategies to reduce the risk of infusion-related reactions.

Pre-medication protocols

Many high-risk drugs have pre-medication protocols to reduce the risk of reactions. These protocols may include the administration of an antihistamine, steroid, and/or antipyretic prior to the infusion.

Slow initial infusion rates

Gradual titration reduces the risk of cytokine-mediated reactions. For some medications, a reduced dose may also be recommended for the first infusion.

Close monitoring

Close monitoring is particularly important during the first 15-30 minutes of the infusion and during dose escalations.

Patient education

Encourage patients to report early symptoms such as itching, throat tightness, or dizziness. Patients should also be educated on the potential for delayed reactions following discharge and should understand what symptoms require prompt reporting to their healthcare professional.

Conclusion

Infusion reactions are unpredictable but can be managed with careful observation, rapid assessment and prompt intervention. Adherence to the recommended infusion rate and any premedication requirements may minimise patient risk. Recognising early symptoms and following clear escalation pathways further improves patient safety. Comprehensive documentation may also assist in differentiating non-allergic reactions from true allergies. This may avoid the inappropriate discontinuation of first-line therapies.

The decision to restart an infusion will depend upon the nature of the infusion reaction. In the case of mild and moderate infusion reactions, rechallenge can often be considered. Factors that will influence this decision include the drug in question, the type of reaction, treatment goals, and the preferences of the patient and prescriber. If rechallenge is attempted, premedication and a reduced infusion rate may be implemented.

While most infusion-related reactions are mild to moderate, severe reactions can occur. It is important that healthcare professionals recognise these reactions and act quickly to ensure optimal outcomes.

A new presentation of abiraterone has been added to the Pharmaceutical Benefits Scheme (PBS). Abiraterone is available in several formulations that differ in strength, bioavailability, and administration instructions.

Abiraterone is an antiandrogen used in the treatment of prostate cancer. It selectively inhibits the CYP17 enzyme (17α hydroxylase/C17,20-lyase). This enzyme is involved in androgen biosynthesis in the testes, adrenal glands, and prostate tumour tissue. Blocking this enzyme significantly reduces the production of testosterone and other androgens, leading to suppression of tumour growth.

The CYP17 enzyme also plays a role in glucocorticoid production. When this enzyme is inhibited, there is a reduction in cortisol production which reduces negative feedback on adrenocorticotropic hormone (ACTH). As ACTH levels rise, there is an excess production of mineralocorticoids.

Some patients may experience symptoms of mineralocorticoid excess. This can include hypertension, hypokalaemia and fluid retention. Co-administration with a corticosteroid suppresses ACTH release. This reduces the incidence and severity of adverse effects associated with mineralocorticoid excess.

There are many brands of abiraterone available, as well as two products that also contain a corticosteroid, as shown in Table 1.

	Zytiga®*	Andriga®	Yonsa Mpred™
Abiraterone content	250mg	500mg	125mg
	500mg
Formulation	Standard	Standard	Fine particle
Corticosteroid included	Nil	Prednisolone 5mg	Methylprednisolone 4mg
Typical abiraterone dose**	1,000mg daily	1,000mg daily	500mg daily
Administration instructions	Take on empty stomach	Take on empty stomach	Swallow whole without regard to food

*Multiple generic brands available

**Dose may be reduced in response to toxicity

Andriga®

Andriga® is a composite pack containing 500mg abiraterone tablets and 5mg prednisolone tablets. It is marketed as Andriga-5® and Andriga-10® with both products containing the same strength and quantity of abiraterone. Andriga-5® is intended to provide 5mg per day of prednisolone while Andriga-10® provides 10mg per day of prednisolone.

The absorption of abiraterone is highly affected by food. Depending on the fat content of a meal, taking the tablet with food can increase systemic exposure up to 17 times compared to administration in a fasted state. As meals typically vary in composition, the manufacturer advises that the abiraterone tablets must be taken on an empty stomach, i.e. at least two hours after food and at least one hour before food.

The usual daily dose is abiraterone 1,000mg plus prednisolone 5mg (for hormone sensitive prostate cancer) or prednisolone 10mg (for metastatic castration-resistant prostate cancer).

Yonsa Mpred™

Yonsa Mpred™ is a composite pack containing 125mg abiraterone tablets and 4mg methylprednisolone tablets.

The abiraterone in this product is formulated as a fine particle which is intended to improve its bioavailability and reduce pharmacokinetic variability. Randomised studies found that 500mg fine particle abiraterone is bioequivalent to 1000mg in healthy subjects under fasted conditions. The effect of food on this formulation is not considered to be significant. Therefore, patients may take these tablets without regard to meals.

Therapeutic equivalence has also been demonstrated between 500mg fine particle abiraterone and 1000mg standard abiraterone in a study in men with progressive metastatic castration-resistant prostate cancer. Testosterone levels and prostate-specific antigen (PSA) were monitored after treatment with either 500mg fine particle abiraterone or 1000mg standard abiraterone. The study found comparable testosterone suppression, and a similar proportion of patients achieved at least 50% reduction in PSA from baseline.

The other key difference with Yonsa Mpred™ is the choice of glucocorticoid. Yonsa Mpred™ contains methylprednisolone instead of prednisolone. Methylprednisolone is a more potent corticosteroid, with 0.8mg methylprednisolone being approximately equivalent to 1mg of prednisolone.

The usual dose is abiraterone 500mg daily plus 4mg methylprednisolone (taken daily for metastatic hormone sensitive prostate cancer or twice daily for metastatic castration resistant prostate cancer).

Summary

Abiraterone is available in several presentations, and it is important to understand their differences. Standard abiraterone tablets must be taken on an empty stomach to reduce variations in drug exposure. Fine particle abiraterone (i.e. Yonsa Mpred™) has greater bioavailability and may be taken without regard to food. The two presentations are not interchangeable.

The current criteria for PBS subsidy is shown in Table 2.

Medication	PBS criteria
Abiraterone 250mg	Castration resistant metastatic carcinoma of the prostate
Abiraterone 500mg
Yonsa Mpred®	Metastatic castration sensitive carcinoma of the prostate
	Castration resistant metastatic carcinoma of the prostate
Andriga-5®	N/A
Andriga-10®	Castration resistant metastatic carcinoma of the prostate

 

Hereditary fructose intolerance (HFI) is a rare genetic disorder where individuals lack aldolase B, an enzyme required for the metabolism of fructose-1-phosphate. When an individual with HFI is exposed to fructose, fructose 1-phosphate accumulates in the liver and kidney. Symptoms of acute toxicity may include nausea, vomiting, abdominal pain, and hypoglycaemia. Chronic symptoms can include failure to thrive, fatigue, persistent abdominal pain, jaundice, and severe liver and kidney damage.

Fructose is primarily derived from the diet. It is found in its free form in honey, fruits, and some vegetables. Fructose can also be derived from the ingestion of sucrose and sorbitol. Sucrose is a disaccharide containing one glucose and one fructose molecule joined together, while sorbitol is converted to fructose in the liver.

When exclusively breastfed, infants with HFI are asymptomatic with normal growth and development. Symptoms typically become apparent when solid foods are introduced. However, symptoms can occur earlier when infant formula containing these sugars is used.

If this condition is identified and managed before organ damage occurs, quality of life and life expectancy are normal. Management requires the dietary restriction of fructose, sucrose, and sorbitol.

Hereditary fructose intolerance should not be confused with fructose malabsorption. Fructose malabsorption is a common condition where individuals cannot absorb fructose properly. The ingestion of fructose can produce gastrointestinal issues such as diarrhoea and bloating in these individuals. In contrast, HFI is a metabolic disorder that can lead to serious and life-threatening reactions upon exposure to fructose.

Sugars in medicines

Many medications and nutritional supplements contain sugars that must be avoided in HFI. Sorbitol is found in many medicines for oral use, particularly oral liquid medicines (e.g. analgesics, antibiotics). However, some capsules and tablets also contain this sugar.

The risk of harm is significantly higher when fructose or sorbitol is administered parenterally, particularly when the intravenous route is used. Fatal outcomes have been reported in adults with HFI following the intravenous administration of 25g of sorbitol. These reactions involve hepatorenal failure associated with bleeding.

Sorbitol is used as an excipient in some products for parenteral use. It can be used to adjust tonicity or as a stabilising agent for proteins and peptides. Products containing sorbitol include some monoclonal antibodies, immunoglobulins, growth factors, and vaccines. However, the amount can vary significantly. For example, Flebogamma® (human normal immunoglobulin) contains sorbitol 50mg/ml, while Stamaril® (yellow fever vaccine) contains only 8mg/dose of sorbitol.

The ingestion of large quantities of fructose can be particularly problematic for infants. Life-threatening events can occur when young children with HFI receive medicines containing fructose intravenously. As young children with this condition may not yet be diagnosed, it recommended to avoid the use of intravenous medicines containing fructose in children under two years unless there is an overwhelming need and no appropriate alternative.

Some vaccines routinely recommended for use in children under two years do contain sorbitol or sucrose as excipients (e.g. MMR and varicella zoster vaccines). However, the amounts are low and absorption slower due to their administration via the subcutaneous or intramuscular routes. Severe events due to HFI have not been reported with these vaccines.

Some examples of medicines containing sugars of concern in HFI are shown in Table 1.

Table 1. Medications containing fructose, sucrose, or sorbitol.

Medication	Sugar	Comment
Oral medications
Rotarix®	Sucrose	Infants with severe adverse reactions (e.g. hypoglycaemia, pallor, hypotonia) should be investigated for HFI.
Melatonin (Voquily® oral solution)	Sorbitol	Contains 140mg/mL sorbitol. Should not be used in HFI.
Icosapent ethyl (Vazkepa®)	Sorbitol	Contains 83mg sorbitol per capsule. Should not be used in HFI.
Lopinavir/ ritonavir (Kaltera®)	Fructose	Kaletra® oral liquid contains fructose; tablets are fructose-free.
Injectable medications
Anidulafungin (eraxis®)	Fructose	Contains 120mg fructose per 100mg vial. Avoid in HFI
Lipegfilgrastim (Lonquex®)	Sorbitol	Avoid in HFI. Each pre-filled syringe contains 30mg sorbitol.
Filgrastim (Nivestim®, Zarzio®)	Sorbitol	Avoid in HFI.
Pegfilgrastim (Pelgraz®, Ziextenzo®)	Sorbitol	Avoid in HFI. Each pre-filled syringe contains 30mg sorbitol.
Immunoglobulin solutions	Sorbitol	Some products use sorbitol as a stabiliser. E.g. Flebogamma® contains sorbitol 50mg/mL and is contraindicated in HFI.
Other
Micolette enema	Sorbitol	Contains sorbitol 625 mg/mL

The polysorbate content of medicines should also be considered as these agents are derived from sorbitol. Polysorbates may be used as a surfactant to improve the dissolution of poorly water-soluble drugs (e.g. docetaxel, amiodarone) or to stabilise protein-based medicines (e.g. some monoclonal antibodies).

Summary

There is currently no established and generally accepted safe dose of fructose for patients with HFI. Some reports consider amounts up to 40mg/kg/day (up to 1.5g) safe. However, evidence suggests that inadequate restriction of fructose can cause growth deficiency even in patients who are clinically asymptomatic.

Maintaining a low fructose diet can be challenging due to the widespread presence of fructose in foods. Support groups can assist with practical dietary strategies.

During hospitalisation, additional care is required to avoid the administration of medicines and fluids containing fructose, sucrose, or sorbitol to patients with HFI.