Odevixibat has recently been added to the Pharmaceutical Benefits Scheme (PBS) for the treatment of progressive familial intrahepatic cholestasis (PFIC). PFIC is a collection of rare genetic conditions of impaired bile formation and secretion. Signs and symptoms of cholestasis typically begin in infancy and can progress to liver failure.
Odevixibat acts locally in the distal ileum to inhibit the ileal bile acid transporter (IBAT). This reduces the reabsorption of bile acids, thereby increasing their clearance from the body.
The safety and efficacy of odevixibat was evaluated in a double-blind study of children with PFIC who had pruritus and elevated serum bile acids at baseline. Patients were randomly assigned to receive odevixibat (40 mcg/kg or 120 mcg/kg daily) or placebo for 24 weeks. Compared to placebo, odevixibat was associated with statistically significant improvements in pruritus. A serum bile acid response was observed in 33% of patients in the odevixibat group, while no patients met the response threshold in the placebo group. Data from the PEDFIC 2 extension study suggest these benefits are sustained with ongoing treatment.
Odevixibat is typically dosed once daily in the morning. The capsules may be swallowed whole, or the contents sprinkled on food. Odevixibat is minimally absorbed, and the most common adverse events are diarrhoea or frequent bowel movements.
The Therapeutic Goods Administration (TGA) has updated the product warnings for GLP-1 and dual GIP/GLP-1 receptor agonists due to a potential risk of suicidal thoughts. Glucagon-like peptide‑1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretins that play important roles in glucose metabolism and energy homeostasis. Medications acting as agonists at GIP and GLP-1 receptors are used in the treatment of type 2 diabetes and weight management.
These medications include:
- Semaglutide;
- Liraglutide;
- Dulaglutide; and
- Tirzepatide.
A potential signal for self-harm and suicidality prompted investigations by the TGA and international regulatory agencies. As of September 2025, the TGA had received 85 such reports, including two reports of completed suicide. While there is insufficient evidence to support a causal link, the TGA notes the complex interaction between mental illness and the disorders for which these medicines are prescribed.
Use of GLP-1 agonists has increased significantly in recent years, particularly for weight loss. The TGA advises healthcare professionals to evaluate the benefits and risks of starting or continuing these medicines in patients with suicidal ideation or a history of suicide attempts. Patients should be monitored for any new or worsening mental health symptoms and encouraged to promptly report any concerning symptoms to their healthcare professional.
The subcutaneous formulation of ocrelizumab is now available on the Pharmaceutical Benefits Scheme (PBS) for relapsing-remitting multiple sclerosis (MS). While the intravenous infusion has been PBS listed since 2018, the subcutaneous option may improve the convenience and accessibility of therapy.
Ocrelizumab is a monoclonal antibody that targets CD20-expressing B cells. It reduces the number and function of these cells which are thought to play an important role in the initiation and progression of MS.
The pivotal OPERA I and OPERA II studies demonstrated the efficacy of ocrelizumab in relapsing MS. Patients were randomly assigned to receive intravenous ocrelizumab every 24 weeks or subcutaneous interferon beta-1a three times a week. The primary end point of annualised relapse rate was 46% and 47% lower for ocrelizumab in the respective studies. Pooled analyses showed a 40% risk reduction for confirmed disability progression at 12 weeks and 24 weeks, and a 33% relative increase in confirmed disability improvement at 12 weeks. The recently published OCARINA II study found subcutaneous ocrelizumab (920mg) to be non-inferior to intravenous ocrelizumab (600mg) for drug exposure, with comparable safety and efficacy.
The usual dose of subcutaneous ocrelizumab is 920mg/23mL injected in the abdomen over ten minutes. The subcutaneous formulation contains the permeation enhancer, vorhyaluronidase alfa. This enzyme hydrolyses hyaluronic acid in the subcutaneous tissue, temporarily increasing tissue permeability and allowing a larger volume to be injected.
Both the intravenous and subcutaneous formulations are administered every six months, although the first intravenous dose is split between two infusions. Premedication with a corticosteroid and an antihistamine reduces the risk of infusion-related reactions. An antipyretic, such as paracetamol, may also be considered.
The product information documents have been updated for denosumab medicines used in the treatment of osteoporosis. These revisions strengthen existing warnings regarding the risk of multiple vertebral fractures following treatment delay or discontinuation.
Bone metabolism is a dynamic process balancing activity between bone-forming osteoblasts and bone-resorbing osteoclasts. A key regulator of this process is the RANK/RANKL/OPG pathway. Denosumab binds to RANKL, preventing it from activating the RANK receptor. This inhibits osteoclast formation and activation, effectively reducing bone resorption.
However, accelerated bone turnover and rapid loss of bone mineral density can occur following discontinuation of denosumab. While the mechanism is not completely understood, denosumab may cause osteoclasts to fission into daughter cells, called osteomorphs. These cells accumulate during denosumab treatment and can quickly fuse to form functional osteoclasts once the inhibitory effect of denosumab is removed. This may explain the increased risk of multiple vertebral fractures, particularly in patients with a history of vertebral fracture.
Denosumab is administered subcutaneously every six months. Patients should be advised of the importance of adhering to the dosing schedule as dosing delays of just 30 days have been associated with a significant increase in fracture risk. If treatment must be stopped, Healthy Bones Australia recommends patients be started on a bisphosphonate within four weeks of the next scheduled denosumab dose.
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.
