Section A: Pre-market registration applications referred for advice
At this meeting, the committee's advice was sought on 11 applications under evaluation by the TGA. The applications included:
- six for the registration of a new chemical entity
- two for the registration of a new biological entity
- two seeking extension of indications
- one for the registration of an OTC medicine
Following the standing meeting, one application for registration of a new biological entity for the treatment of COVID-19 was considered at an out-of-session ACM meeting on Friday 8 October.
Further details of the ACM discussion and advice associated with these items are released within the Australian Public Assessment Reports (AusPARs). Please note that there is a delay from when an application was considered at ACM and the publication of the AusPAR. To browse all AusPARs see AusPAR search.
Section B: Post-market items referred for advice
Antiepileptic medicines and use in pregnancy
The ACM has previously provided advice on the antiepileptic medicine sodium valproate and use in pregnancy and women of child-bearing age.
In January 2021 the United Kingdom Medicines and Healthcare Products Regulatory Agency (MHRA) published Antiepileptic drugs: review of safety of use during pregnancy.
The ACM noted that the antiepileptic medicines discussed in the review may also be approved, or used, for conditions other than epilepsy, such as migraine, bipolar disorder, trigeminal neuralgia, anxiety and neuropathic pain.
The ACM supported revision to Product Information for phenobarbital, phenytoin, primidone and zonisamide to better communicate and characterise the risks of these agents in pregnancy.
The ACM supported the Delegate's view that warnings in the Product Information for carbamazepine, lamotrigine, levetiracetam, topiramate, gabapentin, pregabalin and clobazam appear to adequately describe the risks.
The ACM supported ongoing communications with relevant medical colleges and public health networks, to provide information to consumers and general practice to emphasise the importance of adequate contraception and preconception care.
The ACM supported the work of the Australian Pregnancy Register for Women on Antiepileptic Medication.
Antidepressants and youth suicide
The ACM has previously provided advice on whether there is a causal association between increasing rates of antidepressant dispensing on the Pharmaceutic Benefits Scheme and rates of youth suicide in Australia.
The TGA published an alert on Antidepressant utilisation and risk of suicide in young people in December 2020 and a revised report Antidepressant utilisation and risk of suicide in young people in April 2021.
The TGA report found that while the increasing use of antidepressants in young people is a concern, the current available evidence was not sufficient to conclude that a causal relationship exists between prescribing of antidepressants and rates of youth suicide.
The TGA commissioned further work from NPS MedicineInsight, which was reviewed by the ACM.
The ACM did not identify additional risk minimisation measures that should be undertaken at this time. The ACM agreed with the Delegate that while the MedicineInsight analysis provides additional information about trends and utilisation of antidepressants in young people, this analysis has not identified a clear need for further regulatory action.
Clozapine and intestinal obstruction
Clozapine is an atypical antipsychotic, used in patients with treatment-resistant schizophrenia.
This medicine can cause serious side effects including inflammation of heart muscle and reduction in white blood cells (which are necessary to fight infection in the body). These risks are managed by regular blood tests and regular review by the prescriber and pharmacist.
Clozapine may also cause constipation, which may progress to intestinal obstruction, which may be fatal. Monitoring of patients on clozapine typically includes assessment for constipation, for example, by use of the Bristol stool chart.
The ACM provided advice on the likely knowledge among the prescribing community of severe clozapine-associated adverse gastrointestinal effects.
The ACM advised that the current warning and precaution in the Product Information is somewhat hidden within another warning (on anticholinergic adverse event) and may be overlooked.
The ACM strongly supported revision of the current warnings and precautions in the Product Information, to separate and highlight with a distinct subheading the warning on severe constipation, gastrointestinal hypomotility and intestinal obstruction. The ACM noted that this approach is used in the US prescribing information.
Whether the current boxed warning on myocarditis and cardiomyopathy should be expanded to include intestinal obstruction was a matter for the TGA to consider.
The warning in the Consumer Medicine Information could emphasise that 'constipation' is not trivial. Patients also need evidence-based information on prevention and management of constipation.
Further information
For further information on the Advisory Committee on Medicines, please visit: Advisory Committee on Medicines or contact the ACM Secretary by email: ACM@health.gov.au.