|
Levetiracetam is the drug of choice for post-transplant seizures given its
broad-spectrum efficacy across a broad range of seizure types throughout the lifespan, including
infants, children, and adults, as well as its rapid and linear oral absorption conferring rapid
efficacy; favorable side effect profile; flexible availability as oral tablet, syrup, and
intravenous formulations; and lack of significant hepatic metabolism or drug–drug
interactions [57, 60,
65, 66]. The CNS
target for levetiracetam is binding of intravesicular synaptic vesicle protein 2A, thereby
modulating neuro-transmitter release in rapidly discharging neurons [67]. |
Standard dosage |
Initiate levetiracetam at 1,000 mg/d(2×500-mg tablets once daily) and
titrate in increments of 1,000 mg every 1 to 2 weeks up to 3,000 mg/d. Intravenously, 1,000 mg
infusions can be given safely and rapidly over 15 to 60 min or faster. |
Contraindications |
Hypersensitivity to levetiracetam. |
Main drug interactions |
No interactions were found between levetiracetam and 11 different drug-metabolizing
enzymes [68]. Of particular relevance to transplant patients,
levetiracetam does not affect cyclosporine metabolism [58]. |
Main side effects |
Somnolence, asthenia, infection, and dizziness are the most frequent adverse
effects. Behavioral abnormalities such as irritability, personality change, and psychosis, and mild
leukopenia are possible. The US Food and Drug Administration has issued a class warning for
antiepileptic drugs that an increase in suicidal thoughts may occur during treatment, applying
generally to every AED [69]. |
Special points |
Patients with impaired renal function may require a dosage decrease, as
levetiracetam is excreted largely unchanged and almost entirely renally, and the rate of elimination
correlates with creatinine clearance [42–47, 50, 60, 70, 71]. An intravenous formulation has been demonstrated as
bioequivalent to the oral formulation, providing another potential option for acute seizure
management, preferably for those who are not in convulsive status epilepticus, as the evidence basis
for acute seizure termination remains limited and uncontrolled [72, 73]. Ongoing randomized trials of intravenous
levetiracetam in status epilepticus may yield more definitive data on efficacy in the near future
[74]. |
Cost |
Expensive (especially the intravenous formulation). |