Levetiracetam

Common indications

1. Seizure prophylaxis in epilepsy. Epilepsy is classified by seizure type which, in turn, guides antiepileptic drug choice. Levetiracetam is an option for monotherapy or add-on therapy of focal seizures (with or without secondary generalisation) if carbamazepine or lamotrigine are unsuitable or not tolerated. It may be used for add-on therapy for myoclonic seizures and generalised tonic–clonic seizures if the first agent is insufficient.
2. Selected cases of established convulsive status epilepticus that have not responded to adequate treatment with a benzodiazepine.

 

Mechanisms of action

• The molecular target of levetiracetam is synaptic vesicle protein 2A (SV2A). 
• SV2A is expressed throughout the brain, in both excitatory and inhibitory synapses, as a glycoprotein located within the membranes of synaptic vesicles. Synaptic vesicles are where neurotransmitters are stored in the presynaptic nerve terminal. 
• During depolarisation, synaptic vesicles fuse with the pre-synaptic membrane to release neurotransmitters into the synaptic cleft. 
• It is presumably through interfering with synaptic vesicle function that levetiracetam modulates neuronal excitability and reduces the risk of seizures. 
• The intermediate steps in this mechanism are, however, poorly understood.

 

Important adverse effects

• In comparison with many other antiepileptic drugs, levetiracetam is generally well tolerated. Most patients have only mild adverse effects, or none at all. 
• Drowsiness (affecting about 10), weakness, dizziness and headache are the most common adverse effects. 
• Mood disturbance and psychiatric adverse effects are less common (about 5% and 2.5%, respectively), but more likely to cause discontinuation. 
• Suicidal ideation and serious hypersensitivity reactions have been reported rarely.

 

Warnings

• Levetiracetam is eliminated by the kidneys, so dosage reduction may be required in renal impairment. 
• There is no evidence that levetiracetam increases the overall risk of congenital malformation when taken during pregnancy, although it is difficult to exclude effects on specific congenital defects.

 

Important interactions

• In contrast to many other antiepileptic drugs, levetiracetam has few clinically significant interactions, and this is one of its major advantages. 
• In particular, it does not have important interactions with other antiepileptic drugs, hormonal contraception, or warfarin.