levetiracetam
antiepileptic· Brands: Keppra, Levira, EpitamIVPO
Mechanism of action
Levetiracetam is a pyrrolidine derivative with a unique mechanism of action. It binds to synaptic vesicle protein 2A (SV2A), modulating neurotransmitter release and reducing seizure activity. It may also affect voltage-gated calcium channels and GABAergic transmission. Unlike many antiepileptics, it does not act on sodium channels or GABA receptors.
Pharmacokinetics
Levetiracetam is rapidly and almost completely absorbed after oral administration, with peak plasma concentrations occurring about 1 hour after dosing. It has low protein binding (<10%) and is not significantly metabolized by cytochrome P450 enzymes. The major metabolic pathway is hydrolysis of the acetamide group to an inactive metabolite. About 66% of the dose is excreted unchanged in urine. The elimination half-life is approximately 6-8 hours in adults, increasing in elderly patients and those with renal impairment. Intravenous administration gives equivalent exposure to oral.
Indications & dosing
Adjunctive therapy for focal (partial-onset) seizures
Initial dose 250 mg twice daily; titrate as needed. Licensed for adjunctive use.
- adult · PO: 250–1500 mg twice daily · Initial dose 250 mg twice daily; titrate as needed. Licensed for adjunctive use.
Adjunctive therapy for primary generalised tonic-clonic seizures
Start 500 mg twice daily; titrate to response.
- adult · PO: 500–1500 mg twice daily · Start 500 mg twice daily; titrate to response.
Adjunctive therapy for myoclonic seizures in juvenile myoclonic epilepsy
Usual dose 500 mg twice daily; may be increased.
- adult · PO: 500–1500 mg twice daily · Usual dose 500 mg twice daily; may be increased.
Status epilepticusoff-label
Off-label. Loading dose 60 mg/kg (max 4.5 g) over 15 minutes, followed by maintenance 500 mg IV twice daily.
- adult · IV: 60 mg/kg single dose · Off-label. Loading dose 60 mg/kg (max 4.5 g) over 15 minutes, followed by maintenance 500 mg IV twice daily.
Adjunctive therapy for focal seizures
Dosed by weight. Refer to paediatric formulary for titration.
- pediatric · PO: 10–20 mg/kg twice daily · Dosed by weight. Refer to paediatric formulary for titration.
Contraindications & precautions
- Known hypersensitivity to levetiracetam or other pyrrolidone derivatives · Includes rash, angioedema, or anaphylaxis.
- History of psychiatric disorders such as psychosis or severe depression · Levetiracetam may worsen psychiatric symptoms or precipitate behavioural changes.
- Monitor for psychiatric symptoms such as depression, aggression, or psychotic episodes; advise patients to seek help if these occur.
- Adjust dose in renal impairment based on creatinine clearance; avoid in severe renal impairment unless benefit outweighs risk.
- Do not stop treatment abruptly; gradual withdrawal is required to avoid seizure recurrence.
- Caution patients operating machinery or driving due to somnolence and dizziness.
- Monitor for skin reactions; discontinue treatment if rash, mucosal lesions, or other signs of hypersensitivity develop.
- Use with caution in pregnancy; weigh potential benefits against fetal risk.
Adverse effects
- Somnolence
- Fatigue
- Dizziness
- Headache
- Irritability or agitation
- Suicidal ideation or behaviourserious
- Stevens-Johnson syndromeserious
- Angioedemaserious
- Anaphylaxisserious
- DRESS syndromeserious
Renal & hepatic adjustment
- eGFR 50–80: 500-1000 mg twice daily
- eGFR 30–50: 250-750 mg twice daily
- eGFR 15–30: 250-500 mg twice daily
- eGFR 0–15: 500-1000 mg once daily; supplemental dose 250-500 mg after haemodialysis
Monitoring, pregnancy & toxicity
- Seizure frequency · At each clinical assessment
- Renal function (serum creatinine/eGFR) · Baseline and periodically, especially in renal impairment
- Neuropsychiatric adverse effects (e.g., irritability, agitation, depression) · Throughout treatment
- CNS adverse effects (e.g., somnolence, dizziness, coordination difficulties) · Throughout treatment
- Pregnancy: Levetiracetam is an antiepileptic with a relatively low risk of congenital malformations; it is generally preferred over valproate. Specialist advice is recommended. Continue treatment to prevent seizures, as maternal seizures can harm the foetus. Use the lowest effective dose, and monitor for foetal effects. Consider monitoring serum levetiracetam levels as they may change during pregnancy.
- Toxicity: Somnolence, dizziness, and ataxia · Supportive care; monitor vital signs and neurological status
- Toxicity: Agitation, confusion, and behavioural changes · Supportive care; avoid additional CNS depressants; consider benzodiazepines for severe agitation
- Toxicity: Respiratory depression and coma · Airway management, ventilatory support, and haemodialysis may be considered in severe cases or renal impairment
Clinical notes
Levetiracetam is indicated for partial-onset seizures, myoclonic seizures, and primary generalized tonic-clonic seizures, as monotherapy or adjunctive therapy. It is also used intravenously in status epilepticus. Common adverse effects include somnolence, dizziness, fatigue, and headache. Rare but serious side effects include Stevens-Johnson syndrome, agranulocytosis, and psychiatric symptoms such as agitation or depression. Dose adjustment is necessary in renal impairment. Avoid abrupt discontinuation to prevent seizure rebound. Consult local formulary for specific indications and dosing.
Log in to read the full levetiracetam monograph
A free account unlocks the complete drug reference, the interaction checker, prescription practice and every other learning tool.
BNF; local formulary