levetiracetam
Brand: Keppra, Spritam
Prototype Drug
Drug Class: antiepileptic
Drug Family: antiepileptic
Subclass: synaptic vesicle protein modulator
Organ Systems: cns
Mechanism of Action
Binds selectively to synaptic vesicle protein SV2A, modulating neurotransmitter release; also inhibits N-type calcium channels and reduces GABA inhibition reversal.
synaptic vesicle protein SV2A
Indications
- focal-onset seizures
- juvenile myoclonic epilepsy
- tonic-clonic seizures
- status epilepticus (IV)
Contraindications
- known hypersensitivity to levetiracetam
Adverse Effects
Common
- somnolence
- dizziness
- irritability
- behavioral changes
- nasopharyngitis
Serious
- serious behavioral/psychiatric symptoms (aggression, agitation, psychosis)
- Stevens-Johnson syndrome (rare)
- anaphylaxis
Pharmacokinetics (ADME)
| Absorption | Nearly complete (>95%); not affected by food |
| Distribution | Minimal protein binding (<10%); Vd ~0.5–0.7 L/kg |
| Metabolism | Not hepatically metabolized; hydrolysis of acetamide group (non-CYP pathway) |
| Excretion | 66% excreted unchanged renally; dose adjustment required for CrCl <80 mL/min |
| Half-life | 6–8 hours |
| Onset | 1 hour |
| Peak | 1–1.3 hours |
| Duration | 12 hours |
| Protein Binding | <10% |
| Vd | 0.5–0.7 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| CNS depressants | additive sedation | moderate |
| probenecid | inhibits renal tubular secretion of levetiracetam metabolite | minor |
Nursing Considerations
- Monitor renal function; dose reduce when CrCl <80 mL/min (dose by renal function tier: 60–80, 30–60, <30, and ESRD on dialysis)
- Monitor for behavioral changes including irritability, agitation, and depression; psychiatric symptoms may require dose reduction or discontinuation
- IV levetiracetam can be infused over 15 minutes; compatible with NS, LR, and D5W
- Advise patients not to abruptly discontinue; taper over at least 2 weeks to minimize seizure recurrence risk
Clinical Pearls
- Levetiracetam has no hepatic metabolism and minimal drug interactions, making it highly useful in polytherapy and in patients on complex medication regimens
- Behavioral side effects (irritability, aggression) are the main limiting factor; sometimes called 'Keppra rage' — pyridoxine (vitamin B6) supplementation may reduce these effects
Safety Profile
Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.