Midazolam MaleateZyamis
Treatment of generalised convulsive status epilepticus (GCSE) in patients with epilepsy aged over 6 months and at high risk of status epilepticus.
Decisions on record
- Meeting Nov 2023 Recommended Generalised convulsive status epilepticus (ages 6 months+)
- Meeting Nov 2022 Recommended Generalised convulsive status epilepticus in patients aged over 6 months
- Meeting Jul 2022 Not recommended Epilepsy, generalised convulsive status epilepticus
Access path
- TGA registered · Zyamis
TGA label narrower than the PBS population
- Jul 2022Recommended · restricted
vs midazolam hydrochloride solution for…
- PBS listing · Authority Required
From the public summary
The PBAC did not recommended midazolam oromucosal solution for the treatment of generalised convulsive status epilepticus. The PBAC considered that the proposed population was not well defined, and that expert clinical advice would be needed to refine the PBS restriction.PSD · Jul 2022
The PBAC noted the input from health care professionals and organisations highlighting quality use of medicines benefits associated with midazolam oromucosal solution as compared with off-label use of midazolam ampoules in terms of more effective use of the drug due to correct dosages being given, and less risk of harm from incorrect dosing.PSD · Jul 2022
The submission presented a cost-consequences analysis of the use of midazolam oromucosal solution for the treatment of GCSE events in adults and children over 6 months of age with a diagnosis of epilepsy, compared to buccal midazolam hydrochloride, based on the claim of noninferior effectiveness and safety.PSD · Jul 2022
The cost consequences analysis presented in the submission compared the costs of medicines for the treatment of GCSE, the costs of epilepsy management, and the claimed benefits of improved accuracy and timely administration of midazolam during an acute health emergency for midazolam oromucosal solution versus midazolam hydrochloride.PSD · Jul 2022
The submission described midazolam oromucosal solution as non-inferior in terms of effectiveness and safety compared to buccal or intranasal midazolam hydrochloride.PSD · Jul 2022
The therapeutic conclusion presented in the submission was not supported by the evidence presented in the submission, given the included studies do not inform the comparison between midazolam oromucosal solution and the main comparator, buccal or intranasal midazolam hydrochloride (off-label). However, the clinical evidence presented in the submission suggests the efficacy of buccal administration of midazolam is similar to rectal diazepam.PSD · Jul 2022
The PBAC noted and welcomed the input from health care professionals (3), a medical organisation (1) and health consumer organisations (2) via the Consumer Comments facility on the PBS website. The PBAC acknowledged the advice received from Epilepsy Australia and Epilepsy Action Australia, which supported the proposed listing. The input included a consumer survey with 48 responses.PSD · Jul 2022
The PBAC noted the advice received from the National Paediatric Medicines Forum clarifying the likely use of midazolam oromucosal solution in clinical practice. The advice supported the proposed listing, and noted potential for less dose confusion, improved safety and reduced risk of midazolam loss/abuse.PSD · Jul 2022
Cost-effectiveness
Cost-consequences analysis conducted; no ICER calculated as the submission was based on cost comparison rather than cost-utility analysis.
Decision context
PopulationPatients aged over 6 months with diagnosed epilepsy and high risk of status epilepticus, who have experienced at least one prolonged seizure (>5 minutes duration) requiring emergency medical attention within the previous 5 years, and assessed to be at significant risk of status epilepticus.
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Jul 2022 | Recommended · restricted | midazolam hydrochloride solution for intravenous/intramuscular injection, administered buccally or intranasally | — | Cost-minimisation · Seizure cessation |
Consumer voice
Consumer input from health professionals, medical organisations, and consumer groups (including a 48-response survey from Epilepsy Australia and Epilepsy Action Australia) supported the listing of midazolam in pre-filled syringes, citing improved safety, easier administration, and reduced risk of dosing errors compared to current off-label ampoule use, particularly for those in remote areas.
compared with the current off-label use of ampoules, pre-filled syringes would lead to more effective use of the drug as correct dosages would be given, and there was less risk of harm from incorrect dosing. Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to patients with diagnosed epilepsy and documented prolonged seizure within 5 years; TGA label has no such prerequisites.