Levetiracetam
| Evidence Level: L5 | Predicted Indications: 1 |
Table of Contents
Levetiracetam: Beta-ketothiolase deficiency
One-Sentence Summary
Levetiracetam is an antiseizure medication originally used to treat partial (focal) epilepsy.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Beta-ketothiolase deficiency |
| TxGNN Prediction Score | 0.9990 |
| Evidence Level | L5 (for visual epilepsy; L1 for the related prediction, status epilepticus) |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Hold (for visual epilepsy); Proceed with Guardrails for status epilepticus |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known information, levetiracetam binds to synaptic vesicle protein 2A (SV2A) and modulates neurotransmitter release. This plausibly reduces the cortical hyperexcitability seen in photosensitive or visually triggered seizures.
The beta-ketothiolase deficiency prediction has no evident mechanistic link. Its score comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT01960075 | Phase 3 | Completed | 478 | ESETT: fosphenytoin vs valproic acid vs levetiracetam in benzodiazepine-refractory status epilepticus; comparable efficacy |
| NCT01150331 | Phase 3 | Completed | 203 | IV levetiracetam plus clonazepam vs clonazepam alone in prehospital generalised tonic-clonic status epilepticus |
| NCT02920060 | Phase 2 | Completed | 80 | Levetiracetam vs sodium valproate in children with refractory generalised convulsive status epilepticus |
| NCT04926844 | Phase 2 | Completed | 144 | Levetiracetam plus midazolam in paediatric generalised convulsive status epilepticus |
| NCT06403150 | Phase 4 | Completed | 62 | Open-label levetiracetam vs fosphenytoin in convulsive status epilepticus |
| NCT04176887 | Phase 4 | Unknown | 60 | Levetiracetam vs phenytoin in paediatric status epilepticus |
| NCT07046611 | Phase 2/3 | Recruiting | 124 | Ketamine plus levetiracetam vs levetiracetam alone in children with benzodiazepine-refractory convulsive status epilepticus |
| NCT06907173 | Phase 3 | Recruiting | 770 | KESETT: ketamine plus levetiracetam vs levetiracetam alone in established status epilepticus |
| NCT00362141 | Phase 2 | Unknown | 12 | Safety and tolerability of add-on levetiracetam in status epilepticus |
| NCT07052136 | Not specified | Completed | 138 | Levetiracetam vs valproic acid in paediatric status epilepticus |
No ANZCTR identifiers were included in the data compiled for this report.
Literature Evidence
For visual epilepsy, the retrieved literature is general to seizures and not disease-specific. Selected items:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 32385134 | 2020 | RCT | Pediatrics | Levetiracetam vs phenobarbital for neonatal seizures |
| 35963261 | 2022 | RCT (Phase 3) | Lancet Neurol | PEACH: prophylactic levetiracetam for seizure prevention in acute intracerebral haemorrhage |
| 34286461 | 2022 | Meta-analysis | Neurocrit Care | Levetiracetam for seizure prophylaxis in neurocritical care |
| 39808752 | 2025 | Network meta-analysis | Neurology | Antiseizure medications in poststroke seizures |
| 40450767 | 2025 | Meta-analysis | Epilepsy Behav | Levetiracetam for myoclonic seizures in idiopathic generalised epilepsy |
| 38678766 | 2024 | RCT | Seizure | Phenytoin vs levetiracetam for acute symptomatic seizures in children with encephalitis |
| 21936590 | 2011 | Review | CNS Drugs | Overview of levetiracetam in epilepsy |
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 31774955 | 2019 | RCT | N Engl J Med | Three anticonvulsants (including levetiracetam) in benzodiazepine-refractory status epilepticus |
| 32203691 | 2020 | RCT | Lancet | ESETT by age group: levetiracetam, fosphenytoin and valproate |
| 33190679 | 2020 | RCT | Health Technol Assess | EcLiPSE: levetiracetam as an alternative to phenytoin in children |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 13937M | Levactam | Tablet 1 g (oral) | Not recorded in the data compiled for this report |
Safety Considerations
Contraindication and warning text from the product label was not available. The knowledge graph links levetiracetam to the following conditions through drug-disease contraindication edges (these are not label text and need verification against the PI):
- Psychiatric: anxiety disorder, neurotic disorder, dysthymic disorder, psychotic disorder, schizophreniform disorder, schizoaffective disorder, mental disorder, depersonalisation disorder
- Haematological: neutropenia, agranulocytosis, leukopenia, pancytopenia
- Organ disease: kidney disease, liver disease, gallbladder disease, pyoureter
Drug interactions: The interaction query returned 100 records. Those rated Moderate include morphine (including liposomal), dronabinol, metoclopramide, nabilone, opium and sibutramine. Other entries have an unknown severity rating.
The retrieved literature also reports adverse effects including hyponatraemia and gingival hyperplasia (case reports), and renal dose adjustment is relevant given the pharmacokinetic studies in haemodialysis and haemofiltration.
Please refer to the TGA-approved Product Information (PI) for full safety information.
Conclusion and Next Steps
Decision: Hold (visual epilepsy)
Rationale:
To proceed, the following is needed:
- Disease-specific clinical data for visual or photosensitive epilepsy (for example, a photoparoxysmal response study, noting the related SV2A ligand seletracetam has a Phase 2 trial in this setting)
- Mechanism of action data to be confirmed from DrugBank
- TGA Product Information, including the approved indication text, warnings and contraindications, which were missing from the data compiled for this report
- Clarification of whether the status epilepticus use is already covered by the current ARTG indication, and which formulations (IV) are available in Australia, since the single ARTG entry is an oral 1 g tablet
- For any reflex-epilepsy extension, a safety monitoring plan covering behavioural and psychiatric effects, haematological effects and renal dose adjustment
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.