The Pharmaceutical Benefits Scheme (PBS) listing for daratumumab has been extended to include first-line treatment of multiple myeloma. Patients must be ineligible for a primary stem cell transplant and treatment must form part of triple combination therapy that is limited to daratumumab, lenalidomide, and dexamethasone.
Daratumuab is a targeted immunotherapy that inhibits the growth of cells expressing the CD38 protein. This protein is overexpressed on the surface of cells in many haematological malignancies, including multiple myeloma. Studies have shown that daratumumab induces multiple myeloma cell death via several mechanisms, including complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, antibody-dependent cellular phagocytosis, and apoptosis.
A Phase 3 trial in patients with newly diagnosed multiple myeloma compared the safety and efficacy of daratumumab plus dexamethasone and lenalidomide to dexamethasone and lenalidomide alone. Median progression-free survival was significantly longer in the daratumumab group (44.5 months vs 17.5 months), and the risk of disease progression or death was 44% lower compared to the control group.
The most common serious adverse events reported were neutropenia, anaemia, lymphopenia, and pneumonia. Daratumumab may also cause infusion-related reactions, particularly with the first dose. Reactions can include nasal congestion, chills, and throat irritation. However, serious reactions, including anaphylaxis have been reported. Infusion-related reactions are more common with intravenous administration than subcutaneous.
Empagliflozin is available on the Pharmaceutical Benefits Scheme (PBS) for the treatment of type 2 diabetes, chronic heart failure, and chronic kidney disease (CKD). From 1 November 2025, the CKD listing expanded to cover patients with an eGFR of 20-90mL/min/1.73m2 prior to initiation.
Empagliflozin and dapagliflozin are sodium-glucose co-transporter 2 (SGLT2) inhibitors. While originally approved for the management of type 2 diabetes, studies have demonstrated that these medicines can also slow the progression of CKD regardless of diabetes status.
The primary effect of SGLT2 inhibitors is to inhibit the reabsorption of sodium and glucose in the proximal tubules. This produces glucosuria, natriuresis, and osmotic diuresis. Increased delivery of sodium to the distal tubules activates tubuloglomerular feedback mechanisms that lead to reduced intraglomerular pressure. This has been proposed as their mechanism of preserving renal function and reducing proteinuria, although additional processes may be involved.
A meta-analysis compared the safety and efficacy of SGLT-2 inhibitors, glucagon-like peptide-1 (GLP-1) agonists, and non-steroidal mineralocorticoid receptor antagonists (ns-MRA) in CKD. The authors concluded that all three medication classes are associated with significant reductions in cardiovascular and kidney disease risks in patients with CKD. However, SGLT-2 inhibitors may be the most attractive option when considering efficacy together with safety.
Empagliflozin is generally well tolerated. One of the safety concerns is the risk of ketoacidosis. The risk is minimal and largely limited to patients with diabetes. However, cases have been reported in patients without a diagnosis of diabetes. Clinical situations that may predispose to this event include acute intercurrent illness and surgery. Withholding SGLT2 inhibitors during these periods is recommended to prevent ketoacidosis in patients with diabetes. Evidence to guide perioperative dosing in patients without diabetes is currently lacking. Until further evidence is available, the Council of Australian Therapeutic Advisory Groups (CATAG) advise practitioners to refer to the Periprocedural Diabetic Ketoacidosis (DKA) with SGLT2 Inhibitor use in People with Diabetes.
The Therapeutic Goods Administration (TGA) has issued a safety update regarding the use of prilocaine/lidocaine cream (e.g. EMLA®) in infants. This follows two serious adverse events involving seizures and methaemoglobinaemia. Both cases occurred in neonates and are believed to have involved overdose.
Methaemoglobinaemia is a potentially life-threatening condition where methaemoglobin, the oxidised form of haemoglobin, accumulates in the blood. As this form of haemoglobin cannot bind oxygen, raised levels can lead to hypoxia.
Infants may be more likely to develop methaemoglobinaemia due to:
- A higher proportion of foetal haemoglobin, which is more readily oxidised to methaemoglobin compared to adult haemoglobin; and
- Lower activity of NADH cyb5r reductase, the enzyme responsible for reducing methaemoglobin back to haemoglobin.
The manufacturer advises against using EMLA® in pre-term infants with a gestational age of less than 37 weeks, and in infants up to 12 months of age who are receiving treatment with a methaemoglobin-inducing agent. Examples of methaemoglobin-inducing agents include dapsone, sulphonamides, other local anaesthetics, and nitrites and nitrates. EMLA® is also contraindicated in glucose-6-phosphate dehydrogenase deficiency and congenital or idiopathic methaemoglobinaemia as these patients have a higher risk of drug-induced methaemoglobinemia.
The EMLA® product label and package insert have been updated to emphasise the importance of adhering to the maximum recommended dose and application time. The TGA is also in the process of ensuring these updates are applied to generic products.
Capivasertib has been added to the Pharmaceutical Benefits Scheme (PBS) for the treatment of locally advanced or metastatic breast cancer. Eligibility requires the condition to be human epidermal growth factor receptor-2 (HER2) negative and estrogen receptor positive, and treatment must be in combination with fulvestrant.
Capivasertib is an inhibitor of AKT, a serine/threonine kinase that is important in various cellular processes, including cell survival and proliferation. Inhibition of AKT has been shown to reduce growth in breast cancer cell lines.
The efficacy and safety of capivasertib was investigated in the CAPItello-291 study. Patients with hormone receptor-positive, HER2-negative advanced breast cancer were randomised to receive fulvestrant plus either capivasertib or placebo. The median progression-free survival was 7.2 months in the capivasertib group and 3.6 months in the placebo group. Patients receiving capivasertib maintained their global health status and quality of life for longer. The median time to deterioration was 24.9 months, compared to 12.0 months for the placebo group.
Diarrhoea, rash, and nausea were the most commonly reported adverse events. Hyperglycaemia has also been reported, including severe cases associated with diabetic ketoacidosis and ketoacidosis. Patients should be counselled to seek medical advice if they experience symptoms of hyperglycaemia (e.g. excessive thirst, increased urination).
Capivasertib is usually administered twice daily for four consecutive days, followed by three days off treatment. Cycles should continue until disease progression or unacceptable toxicity. Co-administration with strong CYP3A4 inhibitors should be avoided and dose adjustment considered with moderate CYP3A4 inhibitors.
Two new indications have been added to the product information of guselkumab. Guselkumab is now indicated for the treatment of ulcerative colitis and Crohn’s disease, in addition to the original indications of plaque psoriasis and psoriatic arthritis.
Guselkumab is a monoclonal antibody that is selective for interleukin-23, a key cytokine involved in inflammatory and autoimmune diseases. Interleukin-23 drives intestinal inflammation by activating T helper 17 (Th17) cells, which release pro-inflammatory cytokines, and by directly stimulating other immune cells. Elevated levels of interleukin-23 have been observed in the colon tissue of patients with inflammatory bowel disease.
The QUASAR induction and remission studies evaluated guselkumab in patients with moderately to severely active ulcerative colitis:
- Induction study – clinical remission at 12 weeks was achieved in 23% of patients receiving IV guselkumab vs 8% with placebo
- Maintenance study – clinical remission at week 44 was 50% (200 mg SC every 4 weeks) and 45% (100 mg SC every 8 weeks), compared to 19% with placebo.
The GALAXI-3 study assessed the efficacy of guselkumab in patients with Crohn’s disease. There were two active treatment groups which both received guselkumab 200mg IV every four weeks for induction. For maintenance, the high-dose group continued on 200mg SC every four weeks, and the low-dose group received 100mg SC every eight weeks. The composite endpoint of clinical response at week 12 and clinical remission at week 48 was achieved in 48% of the high dose group and 47% of the low dose group, compared to 13% of the placebo group. The safety outcomes were favourable and consistent with its use in other approved indications.
Note: guselkumab is not currently subsidised on the Pharmaceutical Benefits Scheme (PBS) for ulcerative colitis or Crohn’s disease.
The Pharmaceutical Benefits Scheme (PBS) listing for dupilumab has been expanded to include the treatment of uncontrolled severe asthma in children from six years of age.
The VOYAGE study evaluated the efficacy of dupilumab in children aged 6–12 years with uncontrolled asthma. When added to standard therapy, dupilumab produced a 59.3% relative risk reduction for severe exacerbations compared to placebo (95% CI: 39.5 – 72.6, P<0.001).
The frequency of adverse effects was similar in the dupilumab and placebo groups (83.0% vs 79.9%). The most commonly reported events included injection site reactions and viral upper respiratory tract infections. Eosinophilia occurred more frequently in the dupilumab group (5.9% vs 0.7%), although most cases were asymptomatic laboratory findings that resolved without intervention.
A 52-week open-label extension study assessed the long-term safety and efficacy of dupilumab in this population. Dupilumab was associated with sustained reductions in exacerbations and systemic corticosteroid use, along with improved lung function. Children switched from placebo to dupilumab showed rapid improvements in lung function.
Uncontrolled asthma in children causes significant morbidity, frequent hospitalisation, and disruption to education, social and sporting activities. It may also lead to irreversible airflow limitation and an increased risk of chronic obstructive pulmonary disease (COPD) later in life. The addition of dupilumab to the PBS provides another specialised option for younger children with uncontrolled severe asthma.
A new indication has been added to the product information of ipilimumab and nivolumab. Combination therapy with these medicines is now a first-line treatment option for unresectable or metastatic hepatocellular carcinoma in adults.
This approval was based on objective response rate and duration of response from a single-arm study. The recently published CheckMate 9DW study provides further evidence to support this indication. This open-label randomised, phase 3 trial compared the efficacy and safety of nivolumab plus ipilimumab with investigator’s choice of oral kinase inhibitor (lenvatinib or sorafenib).
With a median follow-up period of 35.2 months, overall survival (OS) was found to be significantly higher for the combination therapy:
- Nivolumab plus ipilimumab: median OS of 23.7 months (95% CI: 18.8–29.4)
- Oral kinase inhibitor: median OS of 20.6 months (95% CI: 17.5–22.5).
Immune-mediated adverse events were reported in 58% of patients in the nivolumab plus ipilimumab group. These events included hepatitis, thyroid disorders, rash, and diarrhoea/colitis. The incidence of severe to life-threatening adverse events was similar between the two groups (41% for nivolumab plus ipilimumab and 42% in the group receiving oral therapy).
The usual dosing regimen is nivolumab 1 mg/kg plus ipilimumab 3 mg/kg via intravenous infusion every three weeks for up to four doses. This is followed by nivolumab monotherapy until disease progression, unacceptable toxicity, or for up to two years.
Vyalev® (foslevodopa + foscarbidopa) has been added to the Pharmaceutical Benefits Scheme (PBS) for the management of advanced Parkinson’s disease in patients with severe disabling motor fluctuations not adequately controlled by oral therapy.
Many patients with Parkinson’s disease require complex treatment regimens with frequent oral dosing. In contrast, Vyalev® is administered as a continuous subcutaneous infusion. While patients require training to use the delivery system, Vyalev® may simplify therapy, potentially improving adherence and overall quality of life. Studies demonstrate a reduction in “off” time and an increase in “on” time without dyskinesia when compared to immediate-release levodopa + carbidopa tablets.
General administration considerations include:
- Dosing is individualised and requires specialist oversight.
- Infusion site and infusion set must be changed at least every 3 days.
- Pump must be disconnected for bathing and swimming.
- Disconnections > 1 hour require a new infusion set and a different infusion site.
- Interruptions > 3 hours may require a loading dose.
- Sudden discontinuation or rapid dose reduction should be avoided unless alternative dopaminergic therapy is used.
Vyalev® is presented in 10 mL vials containing foslevodopa 240 mg/mL and foscarbidopa 12 mg/mL (equivalent to approximately 170 mg levodopa and 9 mg carbidopa per 1 mL). The solution is high in sodium which should be considered for patients on a low salt diet.
Ivosidenib has recently been added to the Pharmaceutical Benefits Scheme (PBS) for the treatment of locally advanced or metastatic cholangiocarcinoma. Eligibility requires the presence of an IDH1 R132 mutation and prior treatment with systemic therapy.
Isocitrate dehydrogenase (IDH) is a key enzyme in cellular metabolism, catalysing the rate-limiting step in the citric acid cycle. Mutations in the genes encoding IDH, particularly the IDH1 and IDH2 isoforms, are implicated in several malignancies. Mutant IDH1 has altered enzymatic function, causing it to produce 2-hydroxyglutarate, an oncometabolite that can disrupt several enzymes involved in cellular growth and differentiation.
Ivosidenib is a potent inhibitor of mutated IDH1. Its efficacy and safety were evaluated in a clinical study involving patients with previously treated IDH1-mutant cholangiocarcinoma. Ivosidenib was associated with a significant improvement in median progression-free survival (2.7 months [95% CI 1.6–4.2]) compared to placebo (1.4 months [95% CI 1.4–1.6]). The most common adverse events were low-grade diarrhoea, nausea, and fatigue.
The recommended dose of ivosidenib is 500 mg once daily, continued until disease progression or unacceptable toxicity. Tablets may be taken with or without food, but should not be taken with a high fat meal. As ivosidenib is primarily metabolised by CYP3A4, co-administration with strong CYP3A4 inhibitors should be avoided. If unavoidable, dose reduction is required. Ivosidenib may prolong QTc interval and patients should be monitored closely during therapy. Concurrent use of other QTc-prolonging medications should also be avoided.
The Therapeutic Goods Administration (TGA) has issued a medicines safety update regarding the administration of respiratory syncytial virus (RSV) prevention products. These products include the two vaccines, Arexvy® and Abrysvo®, and the monoclonal antibody nirsevimab (Beyfortus®).
As of 13 June 2025, the TGA has received 84 medication error reports involving the administration of these products outside their approved indications. While most cases did not result in adverse events, concerns remain about the level of protection provided to patients when these products are used incorrectly.
The TGA acknowledges that the introduction of three RSV preventative medicines, each with different indications, within a short timeframe may be contributing to these errors. To help reduce the risk of further incidents, the TGA recommends the following strategies:
- Education on the differences between RSV prevention products;
- Use of both generic and brand names when prescribing these products;
- Improving storage practices to better differentiate between adult and paediatric vaccines;
- Following recommended checking protocols; and
- Implementation of local risk mitigation strategies.
A summary of the approved indications for these three products is shown in Table 1.
Table 1. Summary of RSV preventative therapies
| Medication |
Population for administration |
Dose frequency |
Immunity provided |
| ≤ 24 months |
Pregnant women |
≥ 60 years |
| Arexvy® |
No |
No |
Yes* |
Once |
Active |
| Abrysvo® |
No |
Yes |
Yes |
Once |
Active |
| Nirsevimab |
Yes |
No |
No |
Once |
Passive |
* Arexvy® is also approved for use in patients 50-59 years old who are at higher risk for RSV disease
