Levetiracetam
Actions
- Incompletely understood.
- Binds to the synaptic vesicle glycoprotein SV2A and inhibits presynaptic Ca++ channels reducing neurotransmitter release.
- Modulates kainate receptor activity.
- Reverses inhibition of GABA and glycine gated currents induced by negative allosteric modulators.
Metabolism
Hepatic
Elimination
Renal
Therapeutic serum concentration range
20-60 μg/ml
Half-life
4-8 hours
Plasma protein binding
<10%
Important side-effects
Suicidal behavior and ideation.
Blood dyscrasias (rare).
Renal injury (rare).
Indications
Focal seizures with or without generalization.
Primarily generalized tonic-clonic seizures.
Myoclonic seizures.
Treatment of status epilepticus.
Dosing recommendation
Start with 500 mg/day or 1000 mg/day divided in 2 doses.
Increase if indicated after 2 weeks.
Target dose: 1000–3000 mg/day divided in 2 doses.
Renal impairment
Dose adjustment is necessary in patients with impaired renal function.
| Creatinine clearance (ml/min/1.73 m2) | Dose and frequency |
|---|---|
>80 | 500–1500 mg twice daily |
| 50–79 | 500–1000 mg twice daily |
| 30–49 | 250–750 mg twice daily |
<30 | 250–500 mg twice daily |
| On dialysis | 500–1000 mg once daily.* |
* After dialysis give an extra 250–500 mg.
Hepatic impairment
No adjustment is necessary in patients with impaired hepatic function.
Serum concentration changes during pregnancy
Total level decreases by 40–50%. Free fraction level decreases by 40–50%.