Dexrazoxane is used to reduce the incidence and severity of doxorubicin-associated cardiomyopathy. The Therapeutic Goods Administration (TGA) has recently approved its use for women with metastatic breast cancer who have received a cumulative doxorubicin dose of 300mg/m2 and require continuing doxorubicin therapy to maintain tumour control.
Chronic cardiotoxicity is a dose-dependent adverse effect associated with anthracycline therapy. It may present with reduced left ventricular ejection fraction (LVEF) or congestive heart failure (CHF). This cardiotoxicity can be severe and represents the cumulative dose-limiting toxicity for anthracyclines.
Several mechanisms have been proposed to explain this cardiotoxicity. One involves the iron-mediated generation of free radicals, which leads to oxidative stress in cardiac muscle. Dexrazoxane, a structural analogue of ethylenediaminetetraacetic acid (EDTA), acts as a metal ion chelator. It may prevent the formation of iron-anthracycline complexes and reactive oxygen species. Additionally, dexrazoxane inhibits DNA topoisomerase IIβ, and some evidence suggests that reducing cardiac levels of this enzyme may contribute to its cardioprotective effects.
Studies conducted in patients with breast cancer showed a reduced risk of heart failure (risk ratio: 0.22; 95% CI 0.11-0.43) and no significant difference in oncologic outcomes. Most adverse effects occurred at similar rates in both treatment and control groups. However, some studies conducted in paediatric populations have found a higher risk of secondary malignant neoplasms. It should also be noted that dexrazoxane does not protect against non-cardiac toxicities.
The recommended dose ratio of dexrazoxane to doxorubicin of 10:1. Dexrazoxane is administered as an intravenous infusion over 15 minutes. Doxorubicin administration should occur within 30 minutes after the dexrazoxane infusion is completed.
A new longer-acting formulation of aripiprazole, Abilify Asimtufii®, is now listed on the Pharmaceutical Benefits Scheme (PBS). This injection is administered once every two months and is indicated for the maintenance treatment of schizophrenia and the prevention of manic and mixed episodes in bipolar I disorder.
Currently, PBS subsidy for Abilify Asimtufii® is limited to patients with schizophrenia who have already been stabilised on once-monthly aripiprazole (i.e. Abilify Maintena®). Eligible patients can transition to Abilify Asimtufii® when their next monthly Abilify Maintena® dose is due.
A 32-week open-label study compared the safety and tolerability of aripiprazole two-monthly injection with that of the monthly formulation. Key findings include:
- A similar incidence of treatment-emergent adverse events in each group
- Weight gain and injection-site pain were the most commonly reported adverse events
- Injection-site pain was more frequent in the two-monthly group (18.2% vs 9.0%)
- Plasma concentrations of aripiprazole were comparable in the two groups
- No new safety concerns were identified.
Compared to oral therapy, long-acting injectable antipsychotics are associated with improved adherence and more stable plasma levels. They may offer many clinical benefits, including a reduced risk of relapse and hospitalisation, and an improved quality of life.
A comparison of aripiprazole formulations is shown in Table 1.
Table 1. Comparison of aripiprazole formulations
| Product |
Presentation |
Strengths |
Usual dosing interval |
| Abilify® |
Tablets |
2 mg, 5 mg, 10 mg, 15 mg, 20 mg, 30 mg |
Daily |
| Abilify Maintena®
|
Vials |
300mg
400mg |
Monthly |
| Abilify Asimtufii® |
Pre-filled syringes |
720mg/2.4mL
960mg/3.2mL |
Every 2 months |
From 1 May 2025, esketamine nasal spray became available on the Pharmaceutical Benefits Scheme (PBS) for treatment-resistant major depression.
Intravenous and subcutaneously administered ketamine has been used off-label for this purpose. Ketamine is thought to exert its effect in depression primarily via antagonism of the N-methyl-D-aspartate (NMDA) receptor. Ketamine is a racemic mixture, containing equal parts of the S-enantiomer and R-enantiomer. Studies demonstrate that esketamine, the S-enantiomer of ketamine, has a higher affinity for the NMDA receptor.
Short-term studies demonstrate that esketamine plus a newly initiated oral antidepressant provides clinically meaningful improvement in depressive symptoms compared to an antidepressant plus placebo nasal spray. In some cases, symptom reduction was apparent at 24 hours after the first dose and continued throughout the four-week trials. Long-term studies demonstrate that patients in stable remission who continued with esketamine plus an oral antidepressant were 51% less likely to relapse compared to patients who continued the oral antidepressant but were switched to the placebo nasal spray.
Esketamine must be prescribed by a psychiatrist and be started in combination with a newly initiated oral antidepressant. Esketamine nasal spray can be self-administered, but this must always occur under the direct supervision of a healthcare professional at an accredited treatment centre. Supervised administration reduces the risk of abuse, misuse, and diversion. It also allows appropriate monitoring for adverse effects, such as elevated blood pressure, sedation, and dissociation.
Esketamine is presented in a single-use device that delivers 28 mg of esketamine in two actuations. One spray is administered into each nostril, and patients should then rest in a semi-reclined position for five minutes. If more than one device is required, a five-minute rest should be taken between each device to facilitate absorption.
The Australian Technical Advisory Group on Immunisation (ATAGI) has published advice on seasonal influenza vaccines for 2025. Annual vaccination is recommended for all people six months of age and older, and is particularly important for those at increased risk of severe illness. Protection from an influenza vaccine is expected to last throughout the year. However, optimal protection occurs in the three to four months after vaccination.
The National Immunisation Program (NIP) provides free influenza vaccines to the following high-risk groups:
- Children aged six months to less than five years;
- All adults aged 65 years or older; and
- The following populations of people aged 5 years up to 65 years due to an increased risk of severe influenza
- All Aboriginal and Torres Strait Islander people
- People with certain medical conditions (e.g. certain cardiac, respiratory, neurological, immunocompromising, metabolic, renal, and haematological conditions; and children aged 5-10 years on long-term aspirin therapy)
- Pregnant women (at any stage during pregnancy).
People 65 years of age and older are at higher risk of developing severe influenza. However, the effectiveness of influenza vaccines is reduced in this age group. Two higher-immunogenicity influenza vaccines are available and are preferred over standard vaccines in this population. Fluad® Quad contains an adjuvant to increase immunogenicity, while Fluzone® High-Dose Quad is a higher strength, containing 240mcg influenza virus haemagglutinin in 0.7mL (compared to 60mcg in 0.5mL for the standard dose vaccines). Both of these vaccines are equally preferred for people 65 years of age and older, although only the adjuvanted vaccine is funded on the NIP in this age group.
Table 1 shows the influenza vaccines and their registered age groups for the 2025 season.
Table 1. 2025 influenza vaccines by age group
| Age group |
Vaxigrip Tetra |
Flucelvax Quad |
FluQuadri |
Afluria Quad |
Influvac Tetra |
Fluad Quad |
Fluzone High-Dose |
| 6 months to <5 years |
Yes^ |
Yes |
Yes^ |
No |
Yes |
No |
No |
| 5 to <60 years |
Yes* |
Yes* |
Yes |
Yes |
Yes |
No |
No |
| 60 to < 65 years |
Yes* |
Yes* |
Yes |
Yes |
Yes |
No |
Yes |
| ≥ 65 years |
Yes |
Yes |
Yes |
Yes |
Yes |
Yes^ |
Yes |
^ Available under the NIP
* Available under the NIP only for the populations listed as being at an increased risk of severe influenza
The Therapeutic Guidelines: Antibiotic has recently had a major update. One of the more significant changes relates to the empirical antibiotic treatment of acute cystitis. The updated recommendations are shown in Table 1.
Table 1. Empiric antibiotic therapy recommendations from the Therapeutic Guidelines
| |
1st line |
2nd line |
3rd line |
| Non-pregnant adult females* |
Nitrofurantoin |
Fosfomycin |
Trimethoprim |
| During pregnancy |
Nitrofurantoin |
Cefalexin |
Fosfomycin |
| Adult males* |
Nitrofurantoin |
Trimethoprim |
|
| Children who can swallow tablets/capsules |
Nitrofurantoin |
Trimethoprim |
|
| Children who cannot swallow tablets/capsules |
Cefalexin |
Trimethoprim +/- sulfamethoxazole |
|
* Cefalexin is considered an alternative option if the other recommended agents cannot be used for empirical therapy.
Trimethoprim is no longer recommended as a first-line agent due to rising rates of resistance among Escherichia coli. The most recent AURA report (Australian report on antimicrobial use and resistance in human health) states that 22.6% of urinary E. coli isolates were resistant to trimethoprim in 2021. In contrast, only 0.9% were resistant to nitrofurantoin.
Nitrofurantoin is now the first-line agent in most cases. The typical adult dose is 100 mg six-hourly for five days in women and seven days in men. Doses should be administered with food or milk to reduce nausea and vomiting.
Fosfomycin is now the second-line choice for non-pregnant adult females. It is administered orally as a 3 g single dose. Fosfomycin is available in single-dose sachets that are mixed with water immediately before use. Doses should be taken on an empty stomach, preferably before bedtime and after emptying the bladder. At this time, fosfomycin is not subsidised on the Pharmaceutical Benefits Scheme (PBS).
For a full list of new and updated topics, please refer to the summary provided by the Therapeutic Guidelines.
From 1 May 2025, Ryeqo® will be available on the Pharmaceutical Benefits Scheme (PBS) for the treatment of endometriosis. Each Ryeqo® tablet contains relugolix (40mg), estradiol (1mg), and norethisterone acetate (0.5 mg).
Relugolix is a gonadotrophin-releasing hormone (GnRH) receptor antagonist. Inhibition of this receptor reduces the release of luteinising hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary gland. This, in turn, leads to a reduction in ovarian estrogen and progesterone production.
As endometriosis is an estrogen-dependent condition, relugolix can significantly improve symptoms. However, reduced estrogen is also associated with significant adverse effects such as hot flushes and reduced bone mineral density (BMD). Estradiol is included in the formulation in a low dose to minimise hypoestrogenic effects; norethisterone is added to protect the endometrium from the effects of unopposed estrogen.
The SPIRIT trials assessed the efficacy of Ryeqo® in premenopausal women with endometriosis-associated pain ranging from moderate to very severe. Ryeqo® was associated with a significant improvement compared to placebo, with benefits seen as early as eight weeks for dysmenorrhea and twelve weeks for non-menstrual pelvic pain. The SPIRIT open-label extension study demonstrated that these benefits are maintained with continued treatment of 104 weeks.
Relugolix may offer some advantages over GnRH agonists in the management of endometriosis: it is orally administered, does not trigger an initial disease flare-up, and can be used long-term. Assessment of BMD by dual-energy X-ray absorptiometry (DXA) is recommended at baseline and annually thereafter. The decision to continue treatment should be dependent upon stable DXA results.
Osilodrostat has been added to the Pharmaceutical Benefits Scheme (PBS) for the treatment of endogenous Cushing’s syndrome. This is a rare condition caused by glucocorticoid overproduction, often due to a pituitary tumour. Excess cortisol is associated with significant morbidity and mortality, largely related to cardiovascular disease and infections.
Osilodrostat inhibits 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2), enzymes responsible for the final step of cortisol and aldosterone production in the adrenal gland. Cortisol levels must be regularly monitored throughout therapy. Adverse effects related to low cortisol levels can occur, including dizziness, nausea, vomiting, fatigue, and reduced appetite. Accumulation of adrenal steroid precursors and increased testosterone levels can also occur. In female patients, elevated testosterone may be associated with hirsutism or acne.
The dose of osilodrostat is adjusted according to individual response and tolerability. The usual initial dose is 2mg twice daily. However, a lower starting dose of 1mg twice daily is recommended for patients of Asian descent as this population demonstrates higher relative bioavailability.
The product information for Flagyl® (metronidazole) has recently been updated to include a warning regarding posterior reversible encephalopathy syndrome (PRES). This rare neurological condition has a variable presentation. Symptoms may include visual disturbances, seizures, headaches, and altered consciousness. Life-threatening complications, such as status epilepticus or cerebral haemorrhage, can occur.
There are many potential causes of this syndrome, including autoimmune disorders, eclampsia, and some medications. A recent review of antibiotic-associated PRES found that metronidazole was one of the most frequently implicated agents. While metronidazole-induced encephalopathy (MIE) has previously been described in the literature, few cases presenting as PRES have been reported. Prompt diagnosis is crucial as outcomes are generally good when appropriate treatment is started early. The Flagyl® product information now advises radiologic imaging for any patient who presents with symptoms suggestive of PRES.
Metronidazole is a commonly used antibiotic that is generally well tolerated. However, it is associated with rare and potentially serious neurotoxicity. In the past ten years, the Therapeutic Goods Administration (TGA) has received 74 reports of nervous system disorders in association with metronidazole and three reports of encephalopathy.
Selpercatinib has been added to the Pharmaceutical Benefits Scheme (PBS) for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC). This is a targeted therapy for patients with RET (rearranged during transfection) fusion-positive disease.
While NSCLC is the most common type of lung cancer, RET fusions are only found in 1-2% of cases. Data suggests that RET fusions may be more likely to occur in patients who are female, younger than 60 years, non-smokers, or of Asian background.
Selpercatinib is a highly selective inhibitor of the RET receptor tyrosine kinase. Under normal conditions, RET plays an important role in the development of a variety of tissues. However, genetic alterations are associated with uncontrolled cellular proliferation and the development of cancer.
A recent randomised clinical trial compared the efficacy of selpercatinib with platinum-based chemotherapy (with or without pembrolizumab) in advanced RET fusion-positive NSCLC. Median progression-free survival was 24.8 months for selpercatinib (95% CI: 16.9 to not estimable) and 11.2 months for control (95% CI: 8.8 to 16.8).
Selpercatinib is usually administered twice daily without regard to food. However, patients who are also taking a proton pump inhibitor should take their selpercatinib dose with food. Metabolism is primarily via CYP3A4. Selpercatinib dose reduction may be required if co-administered with a strong CYP3A4 inhibitor (e.g. itraconazole, voriconazole, ritonavir, saquinavir, posaconazole). The concomitant use of strong inducers of CYP3A4 (e.g. carbamazepine, phenobarbital, phenytoin, rifabutin, rifampicin, St. John’s Wort) is not recommended.
The Therapeutic Goods Administration (TGA) has issued a new safety alert for montelukast. A boxed warning highlighting possible neuropsychiatric adverse events is being added to all montelukast product information and consumer medicine information documents.
The TGA previously released an alert regarding this issue in 2018. A further investigation was undertaken in 2024 after international regulators strengthened their warnings. While this most recent review did not uncover any new risks, the Australian Advisory Committee on Medicines recommended enhanced warnings to address consumer concerns and better align with international practice.
Montelukast is a leukotriene antagonist that is indicated in the management of chronic asthma and seasonal allergic rhinitis. Neuropsychiatric events have been reported in all age groups taking montelukast. The most common of these reactions are aggression, anxiety, suicidal ideation, depression, and sleep disturbances. While reactions are typically mild, the TGA has received seven reports of completed suicide in association with montelukast over the past ten years.
It is important to note that causality has not been established for montelukast. However, the TGA advises healthcare professionals to inform patients and their carers of the possibility of neuropsychiatric reactions and to seek immediate medical advice if they occur.
The TGA encourages the reporting of all suspected adverse events.
